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T Barrett

Publications and source records attributed to T Barrett.

At least 73 records · Page 4Linked to original sources
PubMed1998

A conserved p38 mitogen-activated protein kinase pathway regulates Drosophila immunity gene expression.

Accumulating evidence suggests that the insect and mammalian innate immune response is mediated by homologous regulatory components. Proinflammatory cytokines and bacterial lipopolysaccharide stimulate mammalian immunity by activating transcription factors such as NF-kappaB and AP-1. One of the responses evoked by these stimuli is the initiation of a kinase cascade that leads to the phosphorylation of p38 mitogen-activated protein (MAP) kinase on Thr and Tyr within the motif Thr-Gly-Tyr, which is located within subdomain VIII. We have investigated the possible involvement of the p38 MAP kinase pathway in the Drosophila immune response. Two genes that are highly homologous to the mammalian p38 MAP kinase were molecularly cloned and characterized. Furthermore, genes that encode two novel Drosophila MAP kinase kinases, D-MKK3 and D-MKK4, were identified. D-MKK3 is an efficient activator of both Drosophila p38 MAP kinases, while D-MKK4 is an activator of D-JNK but not D-p38. These data establish that Drosophila indeed possesses a conserved p38 MAP kinase signaling pathway. We have examined the role of the D-p38 MAP kinases in the regulation of insect immunity. The results revealed that one of the functions of D-p38 is to attenuate antimicrobial peptide gene expression following exposure to lipopolysaccharide.

Amino Acid Sequence↗
PubMed1998

New approaches to the development of virus vaccines for veterinary use.

The marked progress in recombinant deoxyribonucleic acid (DNA) technology during the past decade has led to the development of a variety of safe new vaccine vectors which are capable of efficiently expressing foreign immunogens. These have been based on a variety of virus types--poxviruses, herpesviruses and adenoviruses--and have led to the production of many new potential recombinant vaccines. Of these recombinant vaccines, the rabies vaccine, in which the rabies G protein is expressed in a vaccinia vector, has been widely used in the field to prevent the spread of rabies both in Europe and in the United States of America. A recombinant Newcastle disease virus vaccine, using fowlpox virus as the vector to express immunogenic proteins from the Newcastle disease virus, has been licensed as the first commercial recombinant vectored vaccine. Many other recombinant virus vaccines are still at the stage of laboratory or field testing. The most recent breakthrough in vaccinology has been the success with the use of naked DNA as a means of vaccination. This approach has shown great promise in mouse model systems and has now become the most active field in new vaccine development. Molecular redesigning of conventional ribonucleic acid (RNA) viruses to obtain more stable attenuated vaccines was previously possible only for positive-strand RNA viruses, such as poliovirus. However, recent advances in molecular biological techniques have enabled the rescuing of negative-strand viruses from DNA copies of their genomes. This has made it possible to engineer specific changes in the genomes of Rhabdoviridae and Paramyxoviridae, both of which include several viruses of veterinary importance. The authors describe the current progress in the development of vector vaccines, DNA vaccines and vaccines based on engineered positive- and negative-strand RNA virus genomes, with special emphasis on their application to diseases of veterinary importance.

Adenoviridae↗
PubMed1997

Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase.

The c-Jun NH2-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases is activated by phosphorylation on Thr and Tyr. Here we report the molecular cloning of a new member of the mammalian MAP kinase kinase group (MKK7) that functions as an activator of JNK. In vitro protein kinase assays demonstrate that MKK7 phosphorylates and activates JNK, but not the p38 or extracellular signal-regulated kinase groups of MAP kinase. Expression of MKK7 in cultured cells causes activation of the JNK signal transduction pathway. MKK7 is therefore established to be a novel component of the JNK signal transduction pathway.

Amino Acid Sequence↗
PubMed1997

The structure of the GTPase-activating domain from p50rhoGAP.

Members of the Rho family of small G proteins transduce signals from plasma-membrane receptors and control cell adhesion, motility and shape by actin cytoskeleton formation. They also activate other kinase cascades. Like all other GTPases, Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form. The active conformation is promoted by guanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins (GAPs) which stimulate the intrinsic GTPase activity of small G proteins. Rho-specific GAP domains are found in a wide variety of large, multi-functional proteins. Here we report the crystal structure of an active 242-residue C-terminal fragment of human p50rhoGAP. The structure is an unusual arrangement of nine alpha-helices, the core of which includes a four-helix bundle. Residues conserved across the rhoGAP family are largely confined to one face of this bundle, which may be an interaction site for target G proteins. In particular, we propose that Arg 85 and Asn 194 are involved in binding G proteins and enhancing GTPase activity.

Amino Acid Sequence↗
PubMed1997

Risk factors for sporadic infection with Escherichia coli O157:H7.

BACKGROUND: Little is known about risk factors for sporadic infection with Escherichia coli O157:H7. In response to a sharp increase in reported cases in New Jersey during July 1994, we conducted a case-control study to identify principal sources of infection and contributing practices. METHODS: Standardized questionnaires were used to evaluate (1) potential exposures of case patients and matched controls and (2) knowledge, attitudes, and practices of food preparers in case and control households. Patient isolates were subtyped by pulsed-field gel electrophoresis. RESULTS: Patients with E coli O157:H7 infection (N = 23; median age, 9 years; 55% female) were more likely than healthy controls to have eaten a hamburger in the week preceding illness (matched odds ratio, undefined; P < .001); 80% of the hamburgers eaten by ill persons were prepared at home. Food preparers in case households were less likely than those in control households to report washing their hands (odds ratio, 8.5; P < .005) and work surfaces (odds ratio, 10.5; P < .05) after handling raw ground beef. Pulsed-field gel electrophoresis yielded 17 unique subtypes among the 23 patient isolates, indicating multiple sources of infection. CONCLUSIONS: Hamburgers prepared at home are an important source of sporadic E coli O157:H7 infections. We estimate that adequate hand washing by food preparers could have prevented 34% of E coli O157:H7 infections in the study population.

Adolescent↗
PubMed1997

Analysis of the haemagglutinin gene of current wild-type canine distemper virus isolates from Germany.

The haemagglutinin (H) gene sequences from three wild-type canine distemper viruses (CDV) isolated during 1994-1995 were sequenced to determine whether contemporary strains had undergone significant genetic changes relative to the currently used vaccine strains. The new isolates were closely related to each other (> 99%) and displayed about 90-91% sequence homology to the Onderstepoort and Convac vaccine strains. There were one to four additional potential glycosylation sites compared to the vaccine strains which were also present in a German dog CDV isolate dating from 1990. However, only a very slight reduction in neutralizing titre against the new isolates was found when compared with the Onderstepoort and Rockborn vaccine strains. Cysteine and proline residues were well conserved indicating a conserved three dimensional structure for the protein. By phylogenetic analysis the recent isolates showed a narrow clustering close to the previous canine isolates indicating a linear pattern of evolutionary changes. A comparison with published CDV H gene sequences suggested the presence of different lineages of CDV on a global scale and possible cocirculation of more than one genotype of CDV.

Amino Acid Sequence↗
PubMed1997

Trial of a capripoxvirus-rinderpest recombinant vaccine in African cattle.

Cattle were vaccinated with differing doses of an equal mixture of capripox-rinderpest recombinant viruses expressing either the fusion protein (F) or the haemagglutinin protein (H) of rinderpest virus. Animals vaccinated with 2 x 10(4) p.f.u. or greater of the combined viruses were completely protected against challenge, 1 month later, with both virulent rinderpest and lumpy skin disease viruses. Vaccination with any of the doses did not induce any adverse clinical response in the animals or transmission of the vaccine virus between animals. All cattle challenged 6 or 12 months after vaccination with 2 x 10(5) p.f.u. of the mixture of recombinant viruses were protected from severe rinderpest disease. Ten out of 18 were completely protected while the remaining 8 developed mild clinical signs of rinderpest. Cattle vaccinated with the recombinant vaccines after prior infection with the parental capripox virus showed more marked clinical signs of rinderpest after challenge with virulent rinderpest, but 9 out of 10 recovered, compared with 80% mortality in the unvaccinated controls.

Animals↗
PubMed1997

Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping.

Thiamine-responsive megaloblastic anemia, also known as "TRMA" or "Rogers syndrome," is an early-onset autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and sensorineural deafness, responding in varying degrees to thiamine treatment. On the basis of a linkage analysis of affected families of Alaskan and of Italian origin, we found, using homozygosity mapping, that the TRMA-syndrome gene maps to a region on chromosome 1q23.2-23.3 (maximum LOD score of 3.7 for D1S1679). By use of additional consanguineous kindreds of Israeli-Arab origin, the putative disease-gene interval also has been confirmed and narrowed, suggesting genetic homogeneity. Linkage analysis generated the highest combined LOD-score value, 8.1 at a recombination fraction of 0, with marker D1S2799. Haplotype analysis and recombination events narrowed the TRMA locus to a 16-cM region between markers D1S194 and D1S2786. Several heterozygote parents had diabetes mellitus, deafness, or megaloblastic anemia, which raised the possibility that mutations at this locus predispose carriers in general to these manifestations. Characterization of the metabolic defect of TRMA may shed light on the role of thiamine deficiency in such common diseases.

Alaska↗
PubMed1997

Studies on the discontinuous N-oxidation of trimethylamine among Jordanian, Ecuadorian and New Guinean populations.

Whilst the majority of individuals within a British white population are able to convert greater than 90% of their dietary-derived trimethylamine to its N-oxide, outliers exist who show varying degrees of impairment. Such individuals excrete unoxidized trimethylamine in their urine and, if sufficiently compromised, may experience malodour problems (Fish-Odour Syndrome). Little information concerning this polymorphic N-oxidation process is available in other ethnic groups and the present study explores Jordanian, Ecuadorian and New Guinean populations. Subjects with a relative deficiency in N-oxidation were found in all three groups, with 1.7% (2/116) Jordanian, 3.8% (3/8) Ecuadorian and 11.0% (11/100) New Guinean excreting 80% or less of their total trimethylamine as the N-oxide. Two subjects from the Ecuadorian population (4% and 33% total trimethylamine as the N-oxide) exhibited frank trimethylaminuria. These observations suggest that a compromised ability to N-oxidize trimethylamine is detectable in several ethnic groups and that this polymorphic phenomenon may have a widespread existence.

Adolescent↗
PubMed1997

Rescue of rinderpest virus from cloned cDNA.

Rinderpest virus is a morbillivirus and is the causative agent of a widespread and important disease of cattle. The viral genome is a single strand of RNA in the negative sense. We have constructed plasmids containing cDNA copies of the 5' and 3' termini of the virus separated by a reporter gene and have shown that antigenome-sense RNA transcripts of these model genomes can be replicated, transcribed, and packaged by helper virus, both rinderpest virus and the related measles virus. Further, these genome analogs can be replicated and transcribed by viral proteins expressed from cDNA clones by using a recombinant vaccinia virus expressing T7 RNA polymerase (MVA-T7). Using this latter system, we have rescued live rinderpest virus from a full-length cDNA copy of the genome of the RBOK vaccine strain. The recombinant virus appears to grow in tissue culture identically to the original virus.

Animals↗
PubMed1997

Particulate-cell interactions and pulmonary cytokine expression.

The type II cell plays an important role in the response of the alveolar epithelium after lung injury through its synthesis and secretion of pulmonary surfactant, and by acting as the stem cell for the replacement of damaged type I epithelial cells. The nonciliated bronchiolar epithelial (Clara) cell is thought to play a similar role during repair of the bronchiolar epithelium. Recent evidence has suggested that epithelial cells may participate in aspects of the inflammatory response and regulation of fibroblast growth during pulmonary fibrosis through the production of and response to specific growth factors and cytokines. The cellular and molecular responses of epithelial cells and how they lead to the progression of events that defines the pulmonary parenchymal response to a class of particles is unclear. We used particles differing in size, chemical composition, and fibrogenicity in vivo and in vitro to elucidate early changes in proinflammatory and profibrotic cytokine and antioxidant gene expression in lung cells. Early increases in mRNA and protein for the proinflammatory cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha have been observed in epithelial cells following exposure. These are accompanied by changes in specific epithelial genes including surfactant protein C and Clara cell secretory protein. The data indicate that effects on the epithelium are due to direct interactions with particles, not a result of macrophage-derived mediators, and suggest a more significant role in the overall pulmonary response than previously suspected. These results suggest that type II cell growth factor production may be significant in the pathogenesis of pulmonary fibrosis.

Animals↗
PubMed1997

Nonmigraine headaches.

The easiest-to-treat nonmigraine headaches for the 18-to-64 year old population have an average duration of 60 days. The most common diagnostic imaging test used is the computed tomography scan performed on the head or brain. Two out of 1,000 patients have a hospital admission. About 43% of the PTEs are treated without prescription. When a single prescription drug group is used, 56.7% of the prescriptions are for pain relief drugs. Nonsteroidal anti-inflammatory drugs are the most prescribed single drug group for this condition.

Adolescent↗
PubMed1996

A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila.

The Drosophila MAP kinase DJNK is a homolog of the mammalian c-Jun amino-terminal kinase (JNK). Mutations in the DJNK gene correspond to the complementation group basket. DJNK is phosphorylated and activated by the Drosophila MAP kinase kinase HEP. Substrates of DJNK include the transcription factor DJun. DJNK participates in multiple physiological processes. Exposure to endotoxic lipopolysaccharide initiates an insect immune response and leads to DJNK activation. In addition, embryos lacking DJNK are defective in dorsal closure, a process in which the lateral epithelial cells migrate over the embryo and join at the dorsal midline. These data demonstrate that the DJNK signal transduction pathway mediates an immune response and morphogenesis in vivo.

Alleles↗
PubMed1996

Binding of zinc finger protein ZPR1 to the epidermal growth factor receptor.

ZPR1 is a zinc finger protein that binds to the cytoplasmic tyrosine kinase domain of the epidermal growth factor receptor (EGFR). Deletion analysis demonstrated that this binding interaction is mediated by the zinc fingers of ZPR1 and subdomains X and XI of the EGFR tyrosine kinase. Treatment of mammalian cells with EGF caused decreased binding of ZPR1 to the EGFR and the accumulation of ZPR1 in the nucleus. The effect of EGF to regulate ZPR1 binding is dependent on tyrosine phosphorylation of the EGFR. ZPR1 therefore represents a prototype for a class of molecule that binds to the EGFR and is released from the receptor after activation.

Amino Acid Sequence↗
PubMed1996

Selective interaction of JNK protein kinase isoforms with transcription factors.

The JNK protein kinase is a member of the MAP kinase group that is activated in response to dual phosphorylation on threonine and tyrosine. Ten JNK isoforms were identified in human brain by molecular cloning. These protein kinases correspond to alternatively spliced isoforms derived from the JNK1, JNK2 and JNK3 genes. The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. Treatment of cells with interleukin-1 (IL-1) caused activation of the JNK isoforms. This activation was blocked by expression of the MAP kinase phosphatase MKP-1. Comparison of the binding activity of the JNK isoforms demonstrated that the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors. Individual members of the JNK group may therefore selectively target specific transcription factors in vivo.

Activating Transcription Factor 2↗
PubMed1996

Canine distemper virus in Lake Baikal seals (Phoca sibirica).

The virus epizootic which resulted in significant mortality in Siberian seals (Phoca sibirica) in Lake Baikal during 1987/88 was caused by canine distemper virus. Sequence analysis of the virus glycoprotein genes revealed that it was most closely related to recent European field isolates of canine distemper virus. This paper presents evidence that the same virus continued to circulate in seals in Lake Baikal after the initial epizootic. Three out of 45 brain tissue samples collected from seals culled in the spring of 1992 were positive for canine distemper virus-specific nucleic acid by the reverse transcription/polymerase chain reaction and the sequences were closely related to that of the original virus isolated in 1988.

Animals↗