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J Brownlie

Publications and source records attributed to J Brownlie.

At least 55 records · Page 3Linked to original sources
PubMed1992

Rearrangement of viral sequences in cytopathogenic pestiviruses.

Two cytopathogenic isolates of bovine viral diarrhea virus (cpBVDV) have been analyzed. For both viruses two regions of their genomic RNAs were found to be duplicated and rearranged. The viral genomes contain a small duplicated element (SD) derived from the genomic 5' end far downstream of its original context. This sequence is followed by a larger duplication which encompasses the region coding for the protein p80(LD), a molecular marker for cpBVDV. The SD element codes for the viral protease p20. In the case of the viruses analyzed here the aminoterminus of p80 is generated by autoproteolytic removal of the preceding SD-encoded protease. For one of the cpBVDV isolates a specific fusion protein (p28) could be identified which is composed of p20 and part of p10, another viral protein. Molecular characterization of the respective noncytopathogenic counterpart revealed that duplication and rearrangement of sequences as well as the expression of p28 and p80 are specific for the cytopathogenic virus.

Amino Acid Sequence↗
PubMed1992

Immunity to bovine virus diarrhoea virus in calves: the role of different T-cell subpopulations analysed by specific depletion in vivo with monoclonal antibodies.

Gnotobiotic calves were injected intravenously with murine monoclonal antibodies (mAb) directed against the BoCD4, BoCD8 or BoWC1 antigens that define the three major T-lymphocyte subpopulations in cattle. This produced a transient, specific depletion of each cell type in the circulation. Calves were then infected intranasally with a non-cytopathogenic biotype of bovine virus diarrhoea virus and the effect of the specific depletion with the mAb on viraemia and shedding of virus from the nasopharynx determined. Depletion of the cells expressing the BoCD4 antigen resulted in an extension of the duration of viraemia and an increase in the titre of virus in blood. No effect on nasopharyngeal shedding was noted. Depletion of either of the other two T-cell subsets that expressed the BoCD8 antigen or the BoWC1 antigen present on the gamma/delta T-cells had no demonstrable effect. These findings are interpreted as showing that the BoCD4+ cells play a pivotal role in controlling a primary infection with this virus but MHC class I restricted BoCD8+ T-cells are not a major effector mechanism. The BoCD4+ cells may be acting directly or be mediators of T-cell help.

Administration, Intranasal↗
PubMed1992

Protein C activity in severely ill newborns with congenital heart disease.

Levels of protein C functional activity were studied in twenty-nine full-term infants with symptomatic congenital heart disease, who presented in the neonatal period. Protein C levels on admission ranged from < 10% to 61% (mean 37.7% S. D. 14.1%). Eight of the twenty-nine babies had protein C levels between 1.5 and > 3.0 S. D. below the normal neonatal mean with no parental evidence of familial deficiency. Of these infants with low protein C two developed thrombotic complications and four had evidence of coagulation factor consumption. Critically ill infants were over-represented in the group with low protein C. Severely ill newborn infants with protein C at or below the lower limit of the normal neonatal range may be at increased risk of either a consumptive coagulopathy or major thrombosis.

Blood Coagulation Factors↗
PubMed1991

The pathways for bovine virus diarrhoea virus biotypes in the pathogenesis of disease.

BVDV infections of cattle ranges from the transient acute infections, which may be inapparent or mild, to mucosal disease which is inevitably fatal. On occasions the acute infections can lead to clinical episodes of diarrhoea an agalactia but as these syndromes cannot be reproduced experimentally, the pathogenesis remains unclear. The immunosuppressive effect of acute BVDV infections can enhance the clinical disease of other pathogens and this may be an important part of the calf respiratory disease complex. Although BVDV antigen has been demonstrated within the lymphoid tissues, for prolonged periods, the evidence for viral latency remains to be proven. Venereal infection is shown to be important in the transfer of virus to the foetus and congenital infections can cause abortions, malformations and the development of persistently viraemic calves. The two biotypes of BVDV, non-cytopathogenic and cytopathogenic, are described. Their sequential role in the pathogenesis of mucosal disease arises from the initial foetal infection with the non-cytopathogenic virus and the subsequent production of persistently viraemic calves. These calves may later develop mucosal disease as a result of superinfection with a "homologous" cytopathogenic virus and the possible origin of this biotype by mutation is discussed. Chronic disease is defined as a progressive wasting and usually diarrhoeic condition; it is suggested that this may develop following superinfection of persistently viraemic cattle with a "heterologous" cytopathogenic biotype.

Animals↗
PubMed1991

Enhanced thrombin generation in patients receiving intensive care.

Thrombin-antithrombin III complex (TAT) concentration was measured in 27 control and 155 intensive care patients to (a) establish normal reference ranges, (b) measure thrombin generation in critically ill patients, and (c) determine the characteristics of the TAT assay for the diagnosis of disseminated intravascular coagulation (DIC) in children. The normal reference range was 1-4.3 micrograms/l (median 2.3 micrograms/l), and 89.7% of patients had raised TAT concentrations. Median TAT concentrations in the presence of DIC (27 micrograms/l) were significantly higher than in its absence (8 micrograms/l). Sensitivity, specificity, and positive and negative predictive values of the assay were 97.3%, 28.3%, 76.3%, and 81.3%, respectively, at a cut off of 4 micrograms/l. Excess thrombin production occurs in the majority of critically ill children. The TAT assay is potentially useful in the diagnosis of DIC in children.

Adolescent↗
PubMed1990

The coding region for the 54-kDa protein of several pestiviruses lacks host insertions but reveals a "zinc finger-like" domain.

We sequenced cDNAs, amplified by the polymerase chain reaction (PCR), which correspond to the carboxy-terminal portion of the 54-kDa protein of various cytopathic (cp) or noncytopathic (ncp) pestiviral strains. Except for the previously described insertions in two cp strains of the bovine viral diarrhea virus (BVDV), we did not find comparable insertions in this gene in eight pestiviral strains. The predicted amino acid sequences of this 54-kDa protein portion contain a conserved cysteine-rich stretch remarkably similar to a "zinc finger-type" binding domain found in many gene-regulatory proteins. Thus, this protein may be involved in the binding to viral RNA.

Amino Acid Sequence↗
PubMed1990

Pathogenesis of mucosal disease and molecular aspects of bovine virus diarrhoea virus.

Studies carried out over three decades, on the pathogenesis and epidemiology of bovine virus diarrhoea virus (BVDV), have provided the basis for our understanding of the aetiology of mucosal disease. Experimental reproduction of the disease has demonstrated the mechanism of sequential infection and the role of the two virus biotypes. The need for "homogeneity" between the biotypes, causing mucosal disease, has demonstrated the precision of immunotolerance. The origin of the cytopathogenic biotype remains unclear but molecular studies may provide the solution. Recent findings have revealed the absence of an 80 kDa polypeptide in the non-cytopathogenic isolates. This protein is related to the 120 kDa polypeptide that is present in both biotypes. Genomic sequences for two isolates have been reported. An extensive homology to the protein ubiquitin has been identified only within the Osloss sequence in the region flanking coding sequences for the 80 kDa and 120 kDa proteins. Advances in the development of molecular gene probes and monoclonal antibodies will provide new tools for furthering our understanding of the pathogenesis, epidemiology and interrelationships of pestiviruses that infect pigs, cattle and sheep.

Animals↗
PubMed1990

Increased concentrations of D-dimers in newborn infants.

The concentrations of D-dimers (the D fragments of fibrinogen) were measured in blood from 15 preterm infants, and 45 born at full term, to establish normal ranges. The adult normal range is less than 0.25 mg/l; 31 of the 60 infants (52%) had values less than 0.25 mg/l, in 16 (27%) they were 0.25-0.5, in eight (13%) 0.5-1, in three (5%) 1-2, and in two (3%) 2-4. D-dimer concentrations measured during the neonatal period should be interpreted with caution.

Fibrin Fibrinogen Degradation Products↗
PubMed1990

Bovine virus diarrhoea virus: speculation and observations on current concepts.

This final chapter highlights the advances and some of the unanswered questions concerning bovine virus diarrhoea virus (BVDV) presented in this Review by specialists from around the world. Persistently viraemic cattle play an essential role in the dissemination of BVDV but it is suggested that acute infections with the virus are also important. The role of latency is considered but, as yet, there is no evidence that it plays a part in pathogenesis. It is well established that BVDV, Border disease virus and hog cholera virus infect sheep and pigs. There is also some indication that pestiviruses may be involved in other infections of ruminants, such as syndrome X and hyena disease. They also infect other ruminants, such as deer, and human infections have been reported. It is now known that the pathogenesis of mucosal disease is due to the combined action of the two BVDV biotypes. However, the cause of death remains an enigma. It is suggested that, due to the importance of this syndrome, it may be an appropriate time to reconsider the use of "mucosal disease virus" to replace the ungainly name "BVDV".

Animals↗
PubMed1990

The pathogenesis of bovine virus diarrhoea virus infections.

Bovine virus diarrhoea virus (BVDV) disease in cattle ranges from the transient acute infections, which may be inapparent or mild, to mucosal disease which is inevitably fatal. On occasions the acute infections can lead to clinical episodes of diarrhoea and agalactia but as these syndromes cannot be reproduced experimentally, the pathogenesis remains unclear. The immunosuppressive effect of acute BVDV infections can enhance the clinical disease of other pathogens and this may be an important part of the calf respiratory disease complex. Although BVDV antigen has been demonstrated within the lymphoid tissues, for prolonged periods, the evidence for viral latency remains to be proven. Venereal infection is shown to be important in the transfer of virus to the foetus and congenital infections can cause abortions, malformations and the development of persistently viraemic calves. The two biotypes of the virus, non-cytopathogenic and cytopathogenic, are described. Their sequential role in the pathogenesis of mucosal disease arises from the initial foetal infection with the non-cytopathogenic virus and the subsequent production of persistently viraemic calves. These calves may later develop mucosal disease as a result of superinfection with a "homologous" cytopathogenic virus. The possible origin of this biotype by mutation is discussed. Chronic disease is defined as a progressive wasting and usually diarrhoeic condition; it is suggested that this may develop following superinfection of persistently viraemic cattle with a "heterologous" cytopathogenic biotype.

Acute Disease↗
PubMed1989

Protection against respiratory infection with bovine virus diarrhoea virus by passively acquired antibody.

Susceptibility to infection with bovine virus diarrhoea virus (BVDV) was compared for calves with varying amounts of specific antibody in their sera passively acquired from the ingestion of colostrum. Challenge consisted of intranasal exposure to a strain of BVDV isolated from an outbreak of respiratory disease. Resistance to infection, as judged by nasopharyngeal shedding of virus, was directly related to the titre of neutralizing antibodies in sera. Besides protecting against infection of the upper respiratory tract, passive antibody, which was mainly IgG1, also protected against viraemia and, to a lesser extent, leukopenia. In the presence of colostral antibody, neutralizing and IgG1 antibody responses were apparently inhibited, but a specific IgG2 response occurred.

Animals↗
PubMed1989

Experimental infection of cattle in early pregnancy with a cytopathic strain of bovine virus diarrhoea virus.

Nine pregnant heifers, in early gestation (63 to 107 days), were infected intranasally or in utero with cytopathic bovine virus diarrhoea virus (BVDV) and each dam seroconverted. All nine calves developed to full term; four were stillborn, of which one had seroconverted but virus was not recovered from their tissues. One of the five liveborn calves appeared to have seroconverted in utero to an adventitious BVDV infection in late pregnancy but the remaining four were not viraemic and showed a normal secondary antibody response to BVDV infection at about six months old. Thus, in contrast to results with noncytopathic virus there was no evidence that infection in utero with cytopathic virus could result in a persistent viraemia or immunotolerance. It is suggested that cells able to support a persistent viraemia with cytopathic virus may not be developed in the young fetus.

Animals↗
PubMed1987

Variation in the intracellular polypeptide profiles from different isolates of bovine virus diarrhoea virus.

Variation of the intracellular polypeptides induced in calf testis cells by 5 cloned isolates of bovine virus diarrhoea virus (BVDV) was examined. Three of the isolates were cytopathic (NADL, C 2415 and Pe 515 c) and two were non-cytopathic (C 1226 and Pe 515 nc) in these cells. The isolates Pe 515 c and Pe 515 nc were both isolated from an animal with clinical signs of mucosal disease. In cells infected with NADL, 8 virus specific proteins (vp 1 to vp 8) with molecular weights ranging from 120,000 (vp 1) to 23,000 (vp 8) were detected. Isolates C 2415 and Pe 515 c gave a similar array of polypeptides to NADL, but the 3 cytopathic isolates could be distinguished by the variation in the molecular weights of some of the proteins. The non-cytopathic isolates could also be distinguished from each other by this type of molecular variation; however, one feature that characterised these strains, when compared to the cytopathic isolates, was the absence of vp 2. Comparison of the polypeptides induced by Pe 515 c and Pe 515 nc showed that apart from the lack of vp 2 in the Pe 515 nc virus profile, the molecular weights of the other viral proteins were similar. This supports serological evidence that for mucosal disease to occur the pair of cytopathic and non-cytopathic viruses must be closely related. Four of the polypeptides induced by Pe 515 c were shown to be glycoproteins.

Animals↗
PubMed1987

Comparison by the neutralisation assay of pairs of non-cytopathogenic and cytopathogenic strains of bovine virus diarrhoea virus isolated from cases of mucosal disease.

Neutralising antibody to non-cytopathogenic and cytopathogenic strains of bovine virus diarrhoea virus (BVDV) was assayed in a microtitre test in which cultures of calf testis cells were stained by the immunoperoxidase method to detect viral replication. Fourteen BVDV strains were compared in cross neutralisation tests with antisera prepared in gnotobiotic calves. Ten of the strains comprised five pairs of non-cytopathogenic and cytopathogenic BVDV. Each pair was isolated from an animal with mucosal disease. All five animals were from five separate outbreaks of the disease. Each pair of strains from the same outbreak was found to be antigenically indistinguishable. In contrast, when the coefficient of antigenic similarity was calculated 11 of 45 comparisons between the pairs and 46 of 91 comparisons between all 14 viruses gave R values that distinguished strains. The observations suggest that an antigenic spectrum within a single related group exists for BVDV strains, rather than distinct serotypes. The findings are also consistent with the suggestion that cytopathogenic strains from natural outbreaks of mucosal disease arise by mutation from non-cytopathogenic virus.

Animals↗
PubMed1987

Pathogenesis and epidemiology of bovine virus diarrhoea virus infection of cattle.

An outline of the clinical diseases that arise following BVDV infection is given. Isolates of BVDV can be separated into two forms non-cytopathic and cytopathic depending on their effect on cell cultures. In utero infection of the foetus with non-cytopathic virus may result in a number of syndromes, such as abortions, stillbirths or weak calves. It may also result in the birth of calves with a persistent viraemia and these animals may later develop mucosal disease as a result of superinfection with a "homologous" cytopathic strain of BVDV. Acute infection of seronegative animals in usually mild and subclinical. A chronic disease also occurs and this can be protracted with progressive wastage and diarrhoea. This condition has not yet been well defined but it is suggested that it may be the result of superinfection of a viraemic animal with a "heterologous" cytopathic strain of virus. The maintenance of non-cytopathic virus within the cattle population can be either by the slow spread following acute infections of seronegative animals or, more importantly, by spread from persistently viraemic cattle. The cytopathic virus is usually found in association with cases of mucosal disease and may be maintained in the population only by continually arising, possibly by mutation, from the non-cytopathic virus. It is recommended that persistently viraemic animals are eliminated from the herd to avoid in utero infections and the possibility of subsequent mucosal disease.

Animals↗
PubMed1986

Serial inoculation of sheep with two bluetongue virus types.

Groups of sheep inoculated with bluetongue virus type 4 were challenged at various intervals after inoculation (from seven to 70 days) with bluetongue virus type 3. Examination of the clinical and serological response showed that animals were protected from challenge with a second bluetongue virus for up to 14 days after the inoculation of the first virus type. An adoptive transfer experiment in monozygotic sheep involving both antibody and T lymphocytes was carried out. Only partial protection was observed against heterologous virus challenge, indicating that although the T cell response has a cross-protective component, antibody is not involved. These observations indicate that current vaccination procedures should be reappraised, particularly in terms of revaccination with multiple bluetongue virus type.

Animals↗
PubMed1985

An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to bovine viral diarrhoea virus (BVDV) in cattle sera.

A microtitre ELISA has been established for the quantitation of antibodies to bovine viral diarrhoea virus (BVDV). Single dilutions of sera were assayed and units of antibody were calculated from a standard curve. In order to detect the maximum number of responding animals both IgG1 and IgG2 antibody should be assayed, although detection of IgG1 alone was nearly as effective. The ELISA was as sensitive as the virus neutralization test for detection of antibody; comparison of an ELISA that detected IgG1 plus IgG2 antibody to BVDV with the virus neutralization test gave a correlation coefficient (r) of 0.89 (P less than 0.001 for 95 compared sera). Although similar amounts of IgG1 and IgG2 antibodies were present in sera from both experimentally- and naturally-infected cattle, antibody to BVDV in colostrum and in the sera from young calves was predominantly IgG1. The number of adult cows with antibody was 40 out of 41 while 36 of 44 calves reared in a beef unit were found to have produced antibody by the time they were 31.5 weeks old, an indication of the high prevalence of BVDV in the cattle population.

Animals↗