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Biomedical subjects

T Barrett

Publications and source records attributed to T Barrett.

At least 127 records · Page 7Linked to original sources
PubMed1994

Protection of cattle against rinderpest and lumpy skin disease with a recombinant capripoxvirus expressing the fusion protein gene of rinderpest virus.

Cattle were protected against challenge with rinderpest and lumpy skin disease viruses by vaccination with a recombinant capripoxvirus containing the fusion protein (F) gene of rinderpest virus. The minimum protective immunising doses for rinderpest and lumpy skin disease were 5.5 x 10(4) plaque forming units (pfu) and 1.5 x 10(3) pfu, respectively.

Animals↗
PubMed1994

JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain.

The ultraviolet (UV) response of mammalian cells is characterized by a rapid and selective increase in gene expression mediated by AP-1 and NF-kappa B. The effect on AP-1 transcriptional activity results, in part, from enhanced phosphorylation of the c-Jun NH2-terminal activation domain. Here, we describe the molecular cloning and characterization of JNK1, a distant relative of the MAP kinase group that is activated by dual phosphorylation at Thr and Tyr during the UV response. Significantly, Ha-Ras partially activates JNK1 and potentiates the activation caused by UV. JNK1 binds to the c-Jun transactivation domain and phosphorylates it on Ser-63 and Ser-73. Thus, JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation. These properties indicate that JNK1 activation may play an important role in tumor promotion.

Amino Acid Sequence↗
PubMed1994

Cloning and sequence analysis of the matrix (M) protein gene of rinderpest virus and evidence for another bovine morbillivirus.

We have cloned and sequenced the entire M gene of the vaccine strain of rinderpest virus and that of the virulent Kabete "O" strain from which it was derived. The sequences of these two genes are essentially identical (99% at the nucleotide level), but were very different from a previously published Kabete O M gene sequence (M. Limo and T. Yilma, 1990, Virology 175, 323-327). Inspection of the nucleotide and deduced amino acid sequences of known morbillivirus M genes showed that the earlier sequence was clearly from a morbillivirus, but neither from rinderpest virus nor from peste des petits ruminants virus.

Amino Acid Sequence↗
PubMed1994

Recombinant capripoxvirus expressing the hemagglutinin protein gene of rinderpest virus: protection of cattle against rinderpest and lumpy skin disease viruses.

A cDNA clone containing the complete coding sequence of the hemagglutinin (H) protein gene of the RBOK vaccine strain of rinderpest virus, under the control of the vaccinia late promoter p11, was inserted by homologous recombination into the thymidine kinase gene of the KS-1 strain of capripoxvirus. The recombinant virus produced authentic H protein as judged by its electrophoretic mobility, transport to the cell surface of infected lamb testis cells, and reactivity with monoclonal antibodies specific for the H protein of rinderpest virus. The recombinant virus induced significant levels of rinderpest virus neutralizing antibodies in vaccinated cattle and protected them from clinical rinderpest after challenge with a lethal dose of a highly virulent heterologous strain of the virus. Protection was achieved using vaccine doses lower than those used with a similar recombinant expressing the fusion protein gene of rinderpest. The parental KS-1 virus is widely used as a vaccine against capripox viruses and so the rinderpest recombinant acts as a dual vaccine to protect cattle against both rinderpest and lumpy skin disease.

Animals↗
PubMed1994

Peste des petits ruminants in Ethiopian goats.

An outbreak of disease characterised by fever, ocular and nasal discharge, coughing and sneezing, oral necrosis, diarrhoea, enteritis and pneumonia in goats was shown by the use of specific cDNA probes to have been peste des petits ruminants, confirmed for the first time in Ethiopia. Both morbidity and mortality rates were high in goats but sheep were not affected.

Animals↗
PubMed1994

Protection against turkey rhinotracheitis pneumovirus (TRTV) induced by a fowlpox virus recombinant expressing the TRTV fusion glycoprotein (F).

A recombinant fowlpox virus was produced which expressed the fusion protein (F) of turkey rhinotracheitis virus (TRTV), a pneumovirus. Turkey poults were vaccinated twice, at an interval of 2 weeks, intramuscularly and by wing web on each occasion, with the recombinant or a control fowlpox virus. Two weeks after the second vaccination the poults were challenged superconjunctivally and intranasally with virulent TRTV. A partially protective immune response was achieved; turkeys vaccinated with the F recombinant showed milder clinical signs and 1000-fold less challenge virus was recovered from the nose and trachea compared with turkeys that had been vaccinated with control fowlpox virus. Expression of the F protein induced antibodies which were detectable both by an ELISA and a virus neutralization test. These results show that the immune responses to the F protein play a major role in protection against TRTV and indicate that recombinant viruses expressing the TRTV F protein have potential as vaccines against TRT.

Animals↗
PubMed1994

Cloning of the nucleocapsid protein gene of peste-des-petits-ruminants virus: relationship to other morbilliviruses.

Two independent cDNA clones, identified as representing the mRNA of the nucleocapsid protein gene of peste-des-petits-ruminants virus, were sequenced. The longest insert was 1662 nucleotides, not counting the poly(A) tail, and it was estimated that about 21 nucleotides were missing from the complete gene sequence. The sequence contained one long open reading frame encoding a protein of 525 amino acids with a predicted relative molecular mass of 58,008. Comparisons of the nucleic acid and protein sequences of all the morbillivirus nucleoproteins so far determined indicated two major subgroups in the morbillivirus genus of the Paramyxoviridae: one group included canine and phocine distemper viruses, and the other rinderpest, measles and peste-des-petits-ruminants viruses. Peste-des-petits-ruminants virus was found to be slightly more related to canine and phocine distemper viruses than were measles and rinderpest viruses.

Amino Acid Sequence↗
PubMed1994

Nucleotide sequence comparisons of the fusion protein gene from virulent and attenuated strains of rinderpest virus.

We have cloned and sequenced the entire fusion (F) protein gene of the RBOK vaccine strain of rinderpest virus and the coding regions for the F genes of two mild field isolates of the virus from Africa. Analysis of the nucleotide and the predicted amino acid sequences showed that the vaccine virus was more than 99% identical in the protein coding region to the virulent Kabete O strain from which it was derived, whereas the field isolates differed by 10 to 12% from each other and from the vaccine strain. No changes were found in the F protein which could explain attenuation of the vaccine; however, each of the mild field isolates had amino acid changes in important functional areas which may be related to their attenuated phenotype.

Africa↗
PubMed1994

Signal transduction by tumor necrosis factor mediated by JNK protein kinases.

JNK protein kinases are distantly related to mitogen-activated protein kinases (ERKs) and are activated by dual phosphorylation on Tyr and Thr. The JNK protein kinase group includes the 46-kDa isoform JNK1. Here we describe the molecular cloning of a second member of the JNK group, the 55-kDa protein kinase JNK2. The activities of both JNK isoforms are markedly increased by exposure of cells to UV radiation. Furthermore, JNK protein kinase activation is observed in cells treated with tumor necrosis factor. Although both JNK isoforms phosphorylate the NH2-terminal activation domain of the transcription factor c-Jun, the activity of JNK2 was approximately 10-fold greater than that of JNK1. This difference in c-Jun phosphorylation correlates with increased binding of c-Jun to JNK2 compared with JNK1. The distinct in vitro biochemical properties of these JNK isoforms suggest that they may have different functions in vivo. Evidence in favor of this hypothesis was obtained from the observation that JNK1, but not JNK2, complements a defect in the expression of the mitogen-activated protein kinase HOG1 in the yeast Saccharomyces cerevisiae. Together, these data indicate a role for the JNK group of protein kinases in the signal transduction pathway initiated by proinflammatory cytokines and UV radiation.

Amino Acid Sequence↗
PubMed1994

Progress in the development of a heat-stable recombinant rinderpest vaccine using an attenuated vaccinia virus vector.

Rinderpest is a fatal infectious disease of cattle and buffalo, and is prevalent in many parts of the developing world. Eradication campaigns are at present under way in Africa, the Middle East and South Asia. As these regions have very hot climates, it is difficult and expensive to establish reliable cold chains to deliver heat-sensitive vaccines and, for this reason, many previous vaccination/eradication campaigns have been ineffective. To overcome the problem of vaccine heat-lability, a recombinant rinderpest vaccine (RRV) has been developed by inserting the haemagglutinin gene of rinderpest virus into the attenuated smallpox vaccine (vaccinia virus) and using this as heat-stable vaccine vector system to deliver the foreign antigens. This rinderpest vaccine, as with the smallpox vaccine, could be used for the global eradication campaign, without the need to establish a cold chain. Both the efficacy and the safety of the RRV have been confirmed in experiments in cattle. In addition to heat stability, the RRV has several other advantages over the current rinderpest tissue-culture vaccine. DNA viruses have greater genetic stability than RNA viruses (this may be easily checked by restriction enzyme analysis), and the use of RRV enables vaccinated animals to be distinguished from naturally-infected animals, as the vaccine generates a more restricted antigenic response to rinderpest virus. The current situation in relation to the efficacy and safety of the RRV is discussed.

Animals↗
PubMed1994

Fate of dimethylamine in man.

1. The fate of [14C]-dimethylamine was investigated following oral administration to four male volunteers. 2. The major route of excretion was urine, with 94% of the administered radioactivity being voided over 3 days (87% during the first 24 h). Small amounts (1-3%) of radioactivity were found in the faeces and expired air. 3. Metabolism was limited with only 5% being demethylated to methylamine. The remainder of the dose was excreted unchanged. 4. Pharmacokinetic studies indicated rapid (t1/2ab = 8 min) and extensive absorption (bioavailability = 82%) from the gastrointestinal tract followed by widespread distribution and a fairly prompt excretion (t1/2el = 6-7 h) with a plasma clearance of 190 ml/min.

Administration, Oral↗
PubMed1993

Accessory cell function of human eosinophils. HLA-DR-dependent, MHC-restricted antigen-presentation and IL-1 alpha expression.

Although peripheral blood eosinophils express little of the class II MHC protein, HLA-DR, eosinophils could be induced to express HLA-DR by exposures to cytokines, including granulocyte-macrophage-CSF, IL-4, and IFN-gamma, with granulocyte-macrophage-CSF eliciting the greatest level of HLA-DR expression as assessed by flow cytometry. The capacity of HLA-DR+ eosinophils to function as APC was evaluated with blood eosinophils isolated free of mononuclear cells, cultured with granulocyte-macrophage-CSF to induce HLA-DR expression and then exposed to the Ag tetanus toxoid. HLA-DR+ eosinophils fixed with paraformaldehyde after Ag exposure stimulated T cell proliferation, whereas HLA-DR+ eosinophils fixed with paraformaldehyde before Ag exposure failed to stimulate lymphocyte proliferation. The lymphocyte proliferative responses elicited by Ag-pulsed HLA-DR+ eosinophils were inhibited by anti-HLA-DR mAb and were restricted to HLA-DR compatible lymphocytes. Moreover, eosinophils from a hypereosinophilic donor, both before and more prominently after stimulation with PMA, contained transcripts for IL-1-alpha mRNA detectable by Northern blot hybridization and in situ hybridization and expressed IL-1-alpha protein detectable by immunohistochemistry. These findings indicate that human eosinophils can process Ag, express the costimulatory cytokine IL-1-alpha, and after cytokine-elicited induction of HLA-DR expression can function as HLA-DR-dependent, MHC-restricted APC in stimulating T lymphocyte responses.

Antigen-Presenting Cells↗
PubMed1993

Immunisation of cattle with a recombinant vaccinia vector expressing the haemagglutinin gene of rinderpest virus.

The efficacy of a recombinant rinderpest vaccine, constructed by inserting the rinderpest virus haemagglutinin gene into attenuated vaccinia virus, LC16mO strain, was tested in cattle. After subcutaneous inoculation of 10(8) plaque-forming units (pfu) of the recombinant vaccine, neither palpable skin lesions nor increases in body temperature were observed, indicating the absence of detectable clinical reactions. All the vaccinated cattle were completely protected from challenge with the Saudi 1/81 strain of virulent rinderpest virus. Contact control cattle housed in the same pen with the vaccinated animals did not develop antibodies to rinderpest or vaccinia viruses, and developed typical clinical signs of rinderpest after challenge with virulent rinderpest virus, indicating that there was no contact transmission of the recombinant virus. The 50 per cent protective doses of the vaccine, estimated by the mortality and morbidity rates respectively. were 10(4) and 10(5) pfu. To observe the effect of pre-existing immunity to vaccinia virus on the efficacy of the vaccine, cattle inoculated with the Lister strain of vaccinia virus three weeks earlier, were vaccinated with the recombinant virus. These animals developed antibodies to rinderpest virus and were protected from challenge with virulent rinderpest virus, showing that the vaccine was effective in animals already immune to vaccinia virus. The effectiveness and safety of the vaccine demonstrated in this study suggest that it has potential as a new vaccine against rinderpest.

Animals↗
PubMed1993

Dolphin and porpoise morbilliviruses are genetically distinct from phocine distemper virus.

The morbilliviruses recently isolated from two cetacean species in the North and Mediterranean Seas have been shown to differ from phocine distemper virus isolated from European seals using monoclonal antibodies. We have identified a "universal" morbillivirus primer set, based on highly conserved regions of the morbillivirus phosphoprotein (P) gene and used this to amplify a region surrounding the RNA editing site from all known members of the group. Sequence analysis of this region of the gene shows that the dolphin and porpoise viruses are related but quite different from all other members of the group, forming a distinct lineage more closely related to the ruminant morbilliviruses than to the carnivore viruses.

Animals↗
PubMed1993

Single capripoxvirus recombinant vaccine for the protection of cattle against rinderpest and lumpy skin disease.

A recombinant capripoxvirus has been constructed containing a full-length cDNA of the fusion protein gene of rinderpest virus. The gene was inserted in the thymidine kinase gene of the capripox genome under the control of the vaccinia virus major late promoter p11 together with the Escherichia coli gpt gene in the opposite orientation under the control of the vaccinia early/late promoter p7.5. A vaccine prepared from this recombinant virus protected cattle against clinical rinderpest after a lethal challenge with a virulent virus isolate. In addition, the vaccine protected the cattle against lumpy skin disease.

Animals↗
PubMed1993

Delayed onset of coagulopathy following amniotic fluid embolism: two case reports.

Two cases of amniotic fluid embolism with markedly similar clinical presentations occurred in the same unit in a 6 month period. Both patients were under general anaesthesia for caesarean section at the time of embolism. Having been successfully extubated and found to be haemodynamically stable, they developed a coagulopathy after an interval of 2 hours. There had been initial uncertainty as to the diagnosis in the first patient and the haematological sequelae were not fully anticipated. Experience in dealing with the first patient who died, may have influenced the survival of the second. The diagnosis of amniotic fluid embolism should be considered at an early stage in all cases of maternal collapse and the appropriate preparations made to combat a potential coagulopathy.

Journal Article↗
PubMed1993

Evidence for different lineages of rinderpest virus reflecting their geographic isolation.

Sequence analysis of part of the fusion protein gene from recent isolates of rinderpest virus revealed that distinct lineages of the virus exist which reflect the geographical location of their isolation in Africa and Asia. Current strains circulating in Kenya and Sudan were most similar, both in terms of nucleotide sequence and pathogenic nature, to viruses isolated in Egypt and in Nigeria in 1983/1984 and they were quite distinct from an East African isolate (RBT-1) from the 1960s. Two older isolates of the virus, the Japanese avianized/lapinized vaccine strain dating from the 1930s and the Old Kabete strain dating from 1911, each differed considerably from the other viruses. The sequence data were derived from the region where the precursor protein is cleaved to yield the biologically active F1/F2 heterodimer; all strains analysed had a highly basic connecting peptide which is required for efficient cleavage by endogenous host cell proteases. No correlation was found between amino acid changes at this site and the rinderpest virus pathogenicity unlike the association reported for Newcastle disease virus.

Africa↗