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J Harwood

Publications and source records attributed to J Harwood.

At least 19 recordsLinked to original sources
PubMed1992

The alternative sigma factor katF (rpoS) regulates Salmonella virulence.

Nutrient limitation is a critical signal in Salmonella virulence gene regulation. The katF (rpoS) gene mediates the expression of the Salmonella spv plasmid virulence genes during bacterial starvation. A katF Salmonella mutant has increased susceptibility to nutrient deprivation, oxidative stress, acid stress, and DNA damage, conditions which are relevant to the intraphagosomal environment of host macrophages. Moreover, the katF mutant has significantly reduced virulence in mice. katF encodes an alternative sigma factor of RNA polymerase which coordinately regulates Salmonella virulence.

Animals↗
PubMed1992

Quantitative investigations of the epidemiology of phocine distemper virus (PDV) in European common seal populations.

This paper uses simple mathematical models to examine the long-term dynamic consequences of the 1988 epizootic of phocine distemper virus (PDV) infection in Northern European common seal populations. In a preliminary analysis of single outbreaks of infection deterministic compartmental models are used to estimate feasible ranges for the transmission rate of the infection and the level of disease-induced mortality. These results also indicate that the level of transmission in 1988 was probably sufficient to eradicate the infection throughout the Northern European common seal populations by the end of the first outbreak. An analysis of longer-term infection dynamics, which takes account of the density-dependent recovery of seal population levels, corroborates this finding. It also indicates that a reintroduction of the virus would be unlikely to cause an outbreak on the scale of the 1988 epizootic until the seal population had recovered for at least 10 years. The general ecological implications of these results are discussed.

Animals↗
PubMed1992

The descriptive epizootiology of phocine distemper in the UK during 1988/89.

The 'time, place, individual' approach, widely used in characterising human epidemics, was applied to the 1988 phocine distemper virus (PDV) epizootic affecting North Sea seals. Estimates of time of death from 157 (69%) of the 228 dead seals necropsied in 1988 indicated that the number of carcasses which were found more than 14 days post mortem increased as the epizootic progressed. Although information provided by epizootic curves based on when and where carcasses were reported are affected by the accuracy of such data, the PDV epizootic curves were characteristic of a propagative epidemic. The individual characteristics of the carcasses provided more useful information. 1. Common seals were more susceptible than grey seals. 2. Males and older seals had a greater exposure to the virus than females and younger animals. 3. The likelihood of viral transmission was greater on land. Seasonal, sex and age related variation in haul-out behaviour affected transmission probabilities and rates. 4. The risk of infection for a susceptible individual during August was higher for seals in England and Northern Ireland than for those in Scotland. These findings illustrate the importance of population characteristics including behaviour and social organisation in determining the pattern and spread of wildlife epizootics.

Animals↗
PubMed1992

Plasma thymulin concentrations, the thymus and organochlorine contaminant levels in seals infected with phocine distemper virus.

Blood samples collected from live common seals (Phoca vitulina) and grey seals (Halichoerus grypus) around the coast of Scotland and Northern Ireland during, and immediately after, an epizootic caused by phocid distemper virus (PDV) were analysed for thymulin content. Thymulin levels were compared with neutralization titres and concentrations of organochlorine contaminants (DDT and its metabolites, seven chlorinated biphenyl congeners) derived from blood and blubber samples collected from the same animals and analysed independently. Thymulin levels in grey seals (mean 2827 +/- 1355 fg/ml) were negatively correlated with the logarithm of virus neutralization titre. In common seals they varied significantly between age classes. There was no direct relationship between thymulin levels and contaminant levels in either species. However, when an estimate of time since exposure was included in the regression analysis for common seals, there was a highly significant relationship between thymulin and the two chlorinated biphenyl congeners with the highest concentrations in blubber.

Adipose Tissue↗
PubMed1992

Organochlorine levels in common seals (Phoca vitulina) which were victims and survivors of the 1988 phocine distemper epizootic.

We compared concentrations of organochlorines in the blubber of common seals (Phoca vitulina) found dead during the 1988 phocine distemper epizootic with levels in animals which survived it. There were highly significant differences between the live and dead animals, and between sample sites. These were not fully accounted for by seasonal and condition-related changes in blubber thickness.

Adipose Tissue↗
PubMed1992

The Salmonella typhimurium virulence plasmid complement resistance gene rck is homologous to a family of virulence-related outer membrane protein genes, including pagC and ail.

A fragment of the Salmonella typhimurium virulence plasmid containing the rck locus, when cloned in the recombinant cosmid pADE016, was shown previously to confer high-level complement resistance on both rough and smooth Escherichia coli, Salmonella minnesota, and S. typhimurium and was associated with the production of an outer membrane protein. We determined the nucleotide sequence of the fragment containing the rck locus. Mutations in the two major open reading frames confirmed that the complement resistance mediated by pADE016 was due to a single 555-bp rck gene encoding a 17-kDa outer membrane protein. Analysis of the rck gene revealed that the Rck outer membrane protein consisted of 185 amino acid residues, with a calculated postcleavage molecular mass of 17.4 kDa. Rck is homologous to a family of outer membrane proteins expressed in gram-negative bacteria, two of which have been associated with virulence-related phenotypes: PagC, required by S. typhimurium for survival in macrophages and for virulence in mice; and Ail, a product of the Yersinia enterocolitica chromosome capable of mediating bacterial adherence to and invasion of epithelial cell lines. Rck, most closely related to PagC, represents the third outer membrane protein in this five-member family with a distinct virulence-associated phenotype.

Amino Acid Sequence↗
PubMed1992

Helicobacter pylori and hypergastrinaemia during proton pump inhibitor therapy.

The rise in serum gastrin and pepsinogen I after 5 days' treatment with the proton pump inhibitor pantoprazole (40 mg/day) was examined in eight duodenal ulcer patients with Helicobacter pylori infection and compared with eight in whom it had been eradicated. Before treatment, the post-prandial serum gastrin concentrations were higher in the H. pylori-positive than -eradicated patients (p less than 0.05). The median rise in pre-prandial serum gastrin concentrations on treatment was similar in the H. pylori-positive (41%) and -eradicated patients (45%). The rise in post-prandial serum gastrin was also similar in the H. pylori-positive (81%) and -eradicated patients (69%), resulting in significantly higher gastrin concentrations during treatment in the former. The median rise in serum pepsinogen I on treatment was greater in the H. pylori-positive (114%) than in the -eradicated patients (8%), resulting in significantly higher concentrations during treatment in the former. These observations indicate that eradication of H. pylori may be a means of moderating the hypergastrinaemia caused by acid-inhibitory therapy. They also indicate that H. pylori-related hypergastrinaemia is not due to an increase of the antral surface pH by the bacterium's urease activity.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1991

Molecular analysis of the virulence locus of the Salmonella dublin plasmid pSDL2.

The virulence properties of various non-typhoid Salmonella serotypes depend on the presence of large plasmids 60-100 kb in size. We have shown previously that the virulence region on the 80 kb plasmid pSDL2 of Salmonella dublin Lane maps within a 14kb SalI fragment. In this report we show that an 8.2 kb region within this fragment is sufficient to express lethal disease in BALB/c mice. Sequence analysis of this segment revealed six sequential open reading frames designated vsdA-F, which encode putative proteins of 13-65kDa. Deletion analysis and location of Tn5-oriT inserts which abolish virulence suggest that vsdA, vsdC, vsdD and vsdE are essential for virulence expression. Downstream of vsdF we discovered a locus involved in stable plasmid maintenance. Deletion of that region resulted in plasmid multimerization and instability.

Amino Acid Sequence↗
PubMed1991

Genetic analysis of homology between the virulence plasmids of Salmonella dublin and Yersinia pseudotuberculosis.

Two segments within the virulence region of Salmonella dublin plasmid pSDL2 that were homologous to regions on Yersinia pseudotuberculosis plasmid pIB1 were located with regard to the four known genes (vsdA, vsdB, vsdC, and vsdD) of pSDL2. One segment mapped upstream of vsdA within an insertion element related to IS630 of Shigella sonnei; the second was confined to a 45-bp sequence containing an inverted repeat between vsdC and vsdD. On pIB1, both areas were located in an intergenic region upstream of yopH. These results indicate that the homology between Yersinia and Salmonella virulence plasmids is not located within structural genes.

Amino Acid Sequence↗
PubMed1991

Multiple dispersed spontaneous mutations: a novel pathway of mutation in a malignant human cell line.

We analyzed the nature of spontaneous mutations at the autosomal locus coding for adenine phosphoribosyltransferase in the human colorectal carcinoma cell line SW620 to establish whether distinctive mutational pathways exist that might underlie the more complex genome rearrangements arising in tumor cells. Point mutations occur at a low rate in aprt hemizygotes derived from SW620, largely as a result of base substitutions at G.C base pairs to yield transversions and transitions. However, a novel pathway is evident in the form of multiple dispersed mutations in which two errors, separated by as much as 1,800 bp, fall in the same mutant gene. Such mutations could be the result of error-prone DNA synthesis occurring during normal replication or during long-patch excision-repair of spontaneously arising DNA lesions. This process could also contribute to the chromosomal instability evident in these tumor cells.

Adenine Phosphoribosyltransferase↗
PubMed1990

Isolation and expression of the gene for a major surface protein of Giardia lamblia.

To study the interactions between the parasitic protozoan Giardia lamblia and its environment, we have cloned the gene that encodes the two major surface-labeled trophozoite protein species. Sequence analysis of this gene reveals a single open reading frame specifying a hydrophilic, cysteine-rich (11.8%) protein of 72.5-kDa molecular mass with an amino-terminal signal peptide and a postulated hydrophobic membrane-spanning anchor region near the carboxyl terminus. Most of the cysteine residues (58 of 84) are in the motif Cys-Xaa-Xaa-Cys, which is dispersed 29 times throughout the sequence. Antibodies against the recombinant protein react with the entire surface of live trophozoites, including flagella and adhesive disc. These antibodies inhibit trophozoite attachment, prevent growth, and immunoprecipitate the major approximately 66- and 85-kDa proteins from surface-labeled live trophozoites. The recombinant Escherichia coli also expresses polypeptides of approximately 66- and 85-kDa molecular mass, which are not fusion proteins. This suggests that the processing and/or conformational changes that lead to production of these two peptide species in E. coli reflect those that occur in Giardia. The abundance of cysteine residues suggests that the native proteins on the parasite surface may contain numerous disulfide bonds, which would promote resistance to intestinal fluid proteases and to the detergent activity of bile salts and would help to explain the survival of Giardia in the human small intestine.

Amino Acid Sequence↗
PubMed1988

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Adult↗
PubMed1985

Does the dexamethasone suppression test predict antidepressant treatment success?

The 1 mg dexamethasone suppression test (DST) was carried out in patients with a major depressive illness in order to establish whether the results of this test, given before antidepressant or ECT treatment, could predict eventual therapeutic outcome. No significant difference could be detected in overall therapeutic improvement between those patients with a normal or abnormal DST response respectively, based on the 50 ng/ml cortisol cut-off point. However, using 100 ng/ml as a cut-off point it was found that patients with an abnormal DST response (i.e. a post-DST plasma cortisol concentration greater than or equal to 100 ng/ml) responded significantly better than those who had a normal DST response. These observations were statistically significant for those patients receiving antidepressants and in the combined treatment groups of those patients receiving either antidepressants or ECT.

Antidepressive Agents↗