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T Barrett

Publications and source records attributed to T Barrett.

At least 37 records · Page 2Linked to original sources
PubMed2002

Rinderpest virus H protein: role in determining host range in rabbits.

A major molecular determinant of virus host-range is thought to be the viral protein required for cell attachment. We used a recombinant strain of Rinderpest virus (RPV) to examine the role of this protein in determining the ability of RPV to replicate in rabbits. The recombinant was based on the RBOK vaccine strain, which is avirulent in rabbits, carrying the haemagglutinin (H) protein gene from the lapinized RPV (RPV-L) strain, which is pathogenic in rabbits. The recombinant virus (rRPV-lapH) was rescued from a cDNA of the RBOK strain in which the H gene was replaced with that from the RPV-L strain. The recombinant grew at a rate equivalent to the RPV-RBOK parental virus in B95a cells but at a lower rate than RPV-L. The H gene swap did not affect the ability of the RBOK virus to act as a vaccine to protect cattle against virulent RPV challenge. Rabbits inoculated with RPV-L became feverish, showed a decrease in body weight gain and leukopenia. High virus titres and histopathological lesions in the lymphoid tissues were also observed. Clinical signs of infection were never observed in rabbits inoculated with either RPV-RBOK or with rRPV-lapH; however, unlike RPV-RBOK, both RPV-L and rRPV-lapH induced a marked antibody response in rabbits. Therefore, the H protein plays an important role in allowing infection to occur in rabbits but other viral proteins are clearly required for full RPV pathogenicity to be manifest in this species.

Animals↗
PubMed2002

Goat immune response to capripox vaccine expressing the hemagglutinin protein of peste des petits ruminants.

Sheep-pox and capripox are contagious diseases of domestic small ruminants for which the causal agent is a poxvirus classified into the Capripoxvirus genus. Viruses of this group have a host range specific to sheep, goats, cattle, and possibly buffalo. Thus, they are clearly indicated as vectors for the development of recombinant vaccines for peste des petits ruminants (PPR). Here we report the immune response of goats inoculated with a recombinant capripox-PPR hemagglutinin.

Animals↗
PubMed2002

Inhibition of in vitro leukocyte proliferation by morbilliviruses.

Immune suppression associated with morbillivirus infections may influence the mortality rate by allowing secondary bacterial infections that are lethal to the host to flourish. Using an in vitro proliferation assay, we have shown that all members of the genus Morbillivirus inhibit the proliferation of a human B-lymphoblast cell line (BJAB). Proliferation of freshly isolated, stimulated bovine and caprine peripheral blood lymphocytes is also inhibited by UV-inactivated rinderpest (RPV) and peste-des-petits ruminants viruses. As for measles virus, coexpression of both the fusion and the hemagglutinin proteins of RPV is necessary and sufficient to induce immune suppression in vitro.

Animals↗
PubMed2001

Beta-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand.

Elevated levels of beta-Amyloid (Abeta) are present in the brains of individuals with either the sporadic or familial form of Alzheimer's disease (AD), and the deposition of Abeta within the senile plaques that are a hallmark of AD is thought to be a primary cause of the cognitive dysfunction that occurs in AD. Recent evidence suggests that Abeta induces neuronal apoptosis in the brain and in primary neuronal cultures, and that this Abeta-induced neuronal death may be responsible in part for the cognitive decline found in AD patients. In this study we have characterized one mechanism by which Abeta induces neuronal death. We found that in cortical neurons exposed to Abeta, activated c-Jun N-terminal kinase (JNK) is required for the phosphorylation and activation of the c-Jun transcription factor, which in turn stimulates the transcription of several key target genes, including the death inducer Fas ligand. The binding of Fas ligand to its receptor Fas then induces a cascade of events that lead to caspase activation and ultimately cell death. By analyzing the effects of mutations in each of the components of the JNK-c-Jun-Fas ligand-Fas pathway, we demonstrate that this pathway plays a critical role in mediating Abeta-induced death of cultured neurons. These findings raise the possibility that the JNK pathway may also contribute to Abeta-dependent death in AD patients.

Alzheimer Disease↗
PubMed2001

An insight into the epidemiology of dolphin morbillivirus worldwide.

Serum samples from 288 cetaceans representing 25 species and originating from 11 different countries were collected between 1995 and 1999 and examined for the presence of dolphin morbillivirus (DMV)-specific antibodies by an indirect ELISA (iELISA) (N = 267) or a plaque reduction assay (N = 21). A total of 35 odontocetes were seropositive: three harbour porpoises (Phocoena phocoena) and a common dolphin (Delphinus delphis) from the Northeastern (NE) Atlantic, a bottlenose dolphin (Tursiops truncatus) from Kent (England), three striped dolphins (Stenella coeruleoalba), two Risso's dolphins (Grampus griseus) and a bottlenose dolphin from the Mediterranean Sea, one common dolphin from the Southwest (SW) Indian Ocean, three Fraser's dolphins (Lagenodelphis hosei) from the SW Atlantic, 18 long-finned pilot whales (Globicephala melas) and a bottlenose dolphin from the SW Pacific as well as a captive bottlenose dolphin (Tursiops aduncus) originally from Taiwan. The presence of morbillivirus antibodies in 17 of these animals was further examined in other iELISAs and virus neutralization tests. Our results indicate that DMV infects cetaceans worldwide. This is the first report of DMV-seropositive animals from the SW Indian, SW Atlantic and West Pacific Oceans. Prevalence of DMV-seropositives was 85.7% in 21 pilot whales from the SW Pacific and both sexually mature and immature individuals were infected. This indicates that DMV is endemic in these animals. The same situation may occur among Fraser's dolphins from the SW Atlantic. The prevalence of DMV-seropositives was 5.26% and 5.36% in 19 common dolphins and 56 harbour porpoise from the NE Atlantic, respectively, and 18.75% in 16 striped dolphins from the Mediterranean. Prevalence varied significantly with sexual maturity in harbour porpoises and striped dolphins; all DMV-seropositives being mature animals. The prevalence of seropositive harbour porpoise and striped dolphins appeared to have decreased since previous studies. These data suggest that DMV is not endemic within these populations, that they are losing their humoral immunity against the virus and that they may be vulnerable to new epidemics.

Animal Diseases↗
PubMed2001

Region-specific transcriptional response to chronic nicotine in rat brain.

Even though nicotine has been shown to modulate mRNA expression of a variety of genes, a comprehensive high-throughput study of the effects of nicotine on the tissue-specific gene expression profiles has been lacking in the literature. In this study, cDNA microarrays containing 1117 genes and ESTs were used to assess the transcriptional response to chronic nicotine treatment in rat, based on four brain regions, i.e. prefrontal cortex (PFC), nucleus accumbens (NAs), ventral tegmental area (VTA), and amygdala (AMYG). On the basis of a non-parametric resampling method, an index (called jackknifed reliability index, JRI) was proposed, and employed to determine the inherent measurement error across multiple arrays used in this study. Upon removal of the outliers, the mean correlation coefficient between duplicate measurements increased to 0.978+/-0.0035 from 0.941+/-0.045. Results from principal component analysis and pairwise correlations suggested that brain regions studied were highly similar in terms of their absolute expression levels, but exhibited divergent transcriptional responses to chronic nicotine administration. For example, PFC and NAs were significantly more similar to each other (r=0.7; P<10(-14)) than to either VTA or AMYG. Furthermore, we confirmed our microarray results for two representative genes, i.e. the weak inward rectifier K(+) channel (TWIK-1), and phosphate and tensin homolog (PTEN) by using real-time quantitative RT-PCR technique. Finally, a number of genes, involved in MAPK, phosphatidylinositol, and EGFR signaling pathways, were identified and proposed as possible targets in response to nicotine administration.

Amygdala↗
PubMed2001

Application of cDNA microarrays to examine gene expression differences in schizophrenia.

Using cDNA microarrays we have investigated gene expression patterns in brain regions of patients with schizophrenia. A cDNA neuroarray, comprised of genes related to brain function, was used to screen pools of samples from the cerebellum and prefrontal cortex from a matched set of subjects, and middle temporal gyrus, from a separate subject cohort. Samples of cerebellum and prefrontal cortex from neuroleptic naive patients were also included. Genes that passed a 3% reproducibility criterion for differential expression in independent experiments included 21 genes for drug-treated patients and 5 genes for drug-naive patients. Of these 26 genes, 10 genes were increased and 16 were decreased. Many of the differentially expressed genes were related to synaptic signaling and proteolytic functions. A smaller number of these genes were also differentially expressed in the middle temporal gyrus. The five genes that were differentially expressed in two brain regions from separate cohorts are: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide; sialyltransferase; proteasome subunit, alpha type 1; ubiquitin carboxyl-terminal esterase L1; and solute carrier family 10, member 1. Identification of patterns of changes in gene expression may lead to a better understanding of the pathophysiology of schizophrenia disorders.

Adult↗
PubMed2001

Rinderpest virus (RPV) ISCOM vaccine induces protection in cattle against virulent RPV challenge.

Rinderpest virus (RPV), a member of genus Morbillivirus in the family Paramyxoviridae, causes an acute and often fatal disease in cattle and other large ruminants. A subunit rinderpest vaccine consisting of an immune-stimulating complex (ISCOM) incorporating the RPV haemaggulutinin (H) protein, was examined for its ability to induce protective immunity in cattle, the natural host of RPV. All of four cattle vaccinated with the ISCOM vaccine survived challenge with virulent virus. Three were solidly protected, showing no clinical signs of infection, while the fourth animal developed only mild and transient symptoms. Virus neutralizing antibodies were produced at a significant level in all vaccinated cattle. These results indicate that this ISCOM vaccine is effective in producing protective immunity in cattle and should be a suitable means of delivering glycoprotein antigens from other morbilliviruses.

Animals↗
PubMed2001

A murine dopamine neuron-specific cDNA library and microarray: increased COX1 expression during methamphetamine neurotoxicity.

Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified by fluorescent-activated cell sorting from embryonic day 13.5 transgenic mice harboring a 4.5-kb rat tyrosine hydroxylase promoter-lacZ fusion. Nine-hundred sixty dopamine neuron cDNA clones were sequenced and arrayed for use in studies of gene expression changes during methamphetamine neurotoxicity. A neurotoxic dose of methamphetamine produced a greater than twofold up-regulation of the mitochondrial cytochrome c oxidase polypeptide I transcript from adult mouse substantia nigra at 12 h posttreatment. This is the first work to describe a gene expression profile for a neuronal subtype and to identify gene expression changes during methamphetamine neurotoxicity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

The relationship between Y chromosome DNA haplotypes and Y chromosome deletions leading to male infertility.

Microdeletions on the short arm of the Y chromosome have defined three non-overlapping regions (AZFa, b, c) recurrently deleted among infertile males. These regions contain several genes or gene families involved in male germ-cell development and maintenance. Even though a meiotic origin for these microdeletions is assumed, the mechanisms and causes leading to microdeletion formation are largely unknown. In order to assess whether some Y chromosome groups (or haplogroups) are predisposed to, or protected against, deletion formation during male meiosis, we have defined and compared Y chromosome haplogroup distribution in a group of infertile/subfertile males harbouring Yq deletions and in a relevant Northwestern European control population. Our analyses suggest that Y chromosome deletion formation is, at least in the study populations, a stochastic event independent of the Y chromosome background on which they arise and may be caused by other genetic and/or environmental factors.

Chromosome Deletion↗
PubMed2001

Is routine fetal karyotyping necessary for patients undergoing amniocentesis for elevated maternal serum alpha-fetoprotein?

OBJECTIVE: The object of the study was to determine the necessity of routine fetal karyotyping in patients undergoing amniocentesis for elevated maternal serum alpha-fetoprotein (AFP). METHODS: Data were collected retrospectively on patients under age 35 who underwent amniocentesis for elevated maternal serum AFP at the University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, between 1 January 1986 and 31 March 1995. A total of 537 patients with maternal serum AFP values greater than 2.5 multiples of the median were included in the study. RESULTS: Of 509 patients in the group with normal amniotic fluid AFP, 505 had a normal karyotype (specificity 94.9%, negative predictive value 99.2%). One of 28 patients in the group with an elevated amniotic fluid AFP demonstrated an abnormal karyotype (sensitivity 20%, positive predictive value 3.6%). CONCLUSIONS: Routine fetal chromosomal analysis of amniotic fluid amniocytes may not be necessary in patients with a normal level of amniotic fluid AFP. A fetal karyotype is recommended in those patients with an elevated amniotic fluid AFP.

Adult↗
PubMed2001

Assembly and use of a broadly applicable neural cDNA microarray.

cDNA microarrays provide an efficient method to analyze gene expression patterns in thousands of genes in parallel. In some cases, large unfocused collections of cDNAs have been used in hybridization studies, in others small logically defined collections of tissue specific arrays have been used. Here we describe the bioinformatic selection of 1152 named human cDNAs specifically designed for neuroscience applications, arrayed on nylon membranes at high density. cDNAs were chosen which represent all the major cellular types of the brain including; neurons, astrocytes, microglia, and oligodendrocytes. Gene families chosen include cell type specific markers, ion-channels, transporters, receptors, and cell adhesion molecules among many others. These arrays were used with region specific samples from human brain to determine MRNA expression profiles for each region. Used with 33p labeled complex probes, this is a low cost, highly sensitive approach for tbc investigator to focus on tissue specific genes of interest where samples of limiting amounts of RNA are used. This selected set of brain-relevant cDNAs should be widely useful in the analysis of gene expression patterns from brain tissues as well as neural cell lines.

Brain↗
PubMed2000

Identifying a series of candidate genes for mania and psychosis: a convergent functional genomics approach.

We have used methamphetamine treatment of rats as an animal model for psychotic mania. Specific brain regions were analyzed comprehensively for changes in gene expression using oligonucleotide GeneChip microarrays. The data was cross-matched against human genomic loci associated with either bipolar disorder or schizophrenia. Using this convergent approach, we have identified several novel candidate genes (e.g., signal transduction molecules, transcription factors, metabolic enzymes) that may be involved in the pathogenesis of mood disorders and psychosis. Furthermore, for one of these genes, G protein-coupled receptor kinase 3 (GRK3), we found by Western blot analysis evidence for decreased protein levels in a subset of patient lymphoblastoid cell lines that correlated with disease severity. Finally, the classification of these candidate genes into two prototypical categories, psychogenes and psychosis-suppressor genes, is described.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Identification of T-helper cell epitopes in the hypervariable region of the nucleocapsid (N) protein of rinderpest virus (RPV) in cattle.

The proliferative responses to synthetic peptides by lymphocytes derived from rinderpest virus (RPV)-infected cattle, the natural host for RPV, were assayed by determining [3H]thymidine incorporation into the DNA. In eight out of twelve cattle tested, significant responses were detected to peptides representing amino acids 452-501 in the C-terminal hypervariable region of the virus nucleocapsid (N) protein. It appears that helper T-cell epitope(s) for cattle which can be broadly recognized within an MHC diverse population, exists in this region of the protein.

Amino Acid Sequence↗
PubMed2000

Bipolar disorder and variation at a common polymorphism (A1832G) within exon 8 of the Wolfram gene.

A number of linkage studies provide evidence consistent with the existence of a bipolar susceptibility gene on chromosome 4p16. The gene for Wolfram syndrome, a rare recessive neurodegenerative disorder, lies in this region and has recently been cloned. Psychiatric disturbances including psychosis, mood disorder, and suicide have been reported at increased frequency in Wolfram patients and in heterozygous carriers of a Wolfram mutation. In the current investigation we have undertaken a case-control association study using a single nucleotide polymorphism (causing an amino acid change) in exon 8 of the Wolfram gene in a UK Caucasian sample of 312 Diagnostic and Statistical Manual of Mental Disorders (fourth edition; DSM IV) bipolar I probands and 301 comparison individuals. We found no evidence that variation at this polymorphism influences susceptibility to bipolar disorder. It remains possible that variation at other sites within or near the Wolfram gene plays important roles in determining susceptibility to affective illness. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:154-157, 2000.

Bipolar Disorder↗