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Biomedical subjects

C J Clarke

Publications and source records attributed to C J Clarke.

At least 37 records · Page 2Linked to original sources
PubMed1996

Increased intestinal TNF-alpha, IL-1 beta and IL-6 expression in ovine paratuberculosis.

Mycobacterium avium subspecies paratuberculosis is an intracellular parasite of intestinal macrophages and causes a chronic granulomatous enteritis in sheep and other ruminants (paratuberculosis or Johne's disease). Macrophages can be produced a variety of immunoregulatory cytokines that may influence mycobacterial killing and produce disordered inflammation within the gut. In this study, messenger RNA (mRNA) was extracted from intestinal tissue from control and multibacillary diseased sheep and profiles for the cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, transforming growth factor-beta1 (TGF-beta1) and granulocyte-macrophage colony stimulating factor (GM-CSF) were semi-quantified using reverse transcriptase polymerase chain reactions (RT-PCR). Infected intestinal tissues had significantly increased mRNA for TNF-alpha, IL-1beta and IL-6 but TGF-beta1 and GM-CSF mRNA levels were significantly different from controls. Supernatants from in vitro intestinal cultures were assayed for TNF-alpha activity using the PK(15)-1512 cytotoxicity bioassay and levels were significantly raised in diseased samples. TNF-alpha was not detected in any serum samples. Further analysis on intestinal tissues from sheep with the different, paucibacillary, form of the disease showed significant elevation of TNF-alpha mRNA but not other cytokines tested. Increased pro-inflammatory cytokine expression in the intestine coincident with a failed or misdirected immune response may contribute to the pathogenesis of paratuberculosis and the persistence of a chronic inflammatory state.

Animals↗
PubMed1996

The pathology of ovine paratuberculosis: gross and histological changes in the intestine and other tissues.

In sheep clinically affected with paratuberculosis, two distinct forms of microscopical pathology were recognized, related to a high or a low degree of mycobacterial colonization ("multibacillary" or "paucibacillary" presence). These forms were characterized by different types of cellular infiltrate in the ileal mucosa and submucosa. Statistical analysis demonstrated strong correlations between the presence of large numbers of acid-fast organisms and macrophage infiltration, and between small numbers and lymphocyte infiltration. Correlations also existed between high numbers of acid-fast bacteria and a positive serum antibody test results; and between the presence of giant cells and lymphocytes in the gut. This study suggests that in ovine paratuberculosis the same clinical and gross pathological changes can result from different pathogenetic mechanisms.

Animals↗
PubMed1996

Phenotypic characterisation of intestinal lymphocytes in ovine paratuberculosis by immunohistochemistry.

Characterisation of the T-cell subsets in intestinal lesions in sheep with paratuberculosis may contribute to our understanding of the pathogenesis of this disease. To determine the phenotype and distribution of lymphocytes in the normal sheep intestinal mucosa and in Mycobacterium avium subspecies paratuberculosis infected sheep, immunohistochemistry was performed on 12 normal sheep and 18 naturally infected, clinically diseased sheep of which 12 showed lepromatous and six tuberculoid forms of the disease. Immunoperoxidase staining was carried out on frozen sections of ileum using monoclonal antibodies against ovine CD4, CD8, and gamma delta T-cell receptor (TCR) markers. In all three sample groups, cells appeared to be non-randomly distributed throughout the lamina propria. Higher densities of lymphocytes were present in villus than in crypt areas. CD8+ cells were located principally around the epithelial basement membrane, whereas CD4+ cells were localised towards the central villus area of the lamina propria. Lymphocytes bearing the gamma delta T-cell receptor were more widely distributed, both in epithelial and lamina propria compartments. Ileum with tuberculoid lesions had higher densities of CD4 and gamma delta T-cell subsets while lepromatous lesions had lower densities of CD4 and CD8 cells compared with normal tissues. The median relative percentage of CD4+ cells was increased and that of CD8+ cells decreased in tuberculoid cases, with a corresponding increase in the CD4:CD8 ratio, while the relative percentage of gamma delta + cells was increased in lepromatous cases.

Animals↗
PubMed1995

Severe post-dipping dermatitis and subcutaneous fluid swellings associated with two outbreaks of sheep scab (Psoroptes ovis infestation)

Large subcutaneous fluid swellings developed on some of the sheep in two flocks infested with Psoroptes ovis during the two weeks after they had been plunge-dipped in phenol-based solutions. The swellings contained between 1 and 10 litres of exudate and affected 4 per cent of the sheep in each flock. The sheep with subcutaneous fluid swellings or exudative dermatitis had significantly lower serum albumin concentrations than the unaffected sheep (P < 0.05). In most cases secondary bacterial infections of the exudate occurred and these necessitated intensive antibiotic therapy. The severity of the skin lesions posed a serious welfare problem.

Animals↗
PubMed1995

Interleukin-4 inhibits kappa light chain expression and NF kappa B activation but not I kappa B alpha degradation in 70Z/3 murine pre-B cells.

The murine pre-B cell line 70Z/3 responds to lipopolysaccharide by up-regulating the surface expression of kappa (kappa) light chain through activation of the transcription factor NF kappa B. Interleukin-4 (IL-4), a T cell cytokine, is a known inhibitor of some LPS-mediated events. We investigated whether IL-4 could inhibit the up-regulation of kappa light chain and activation of NF kappa B by LPS in 70Z/3. IL-4 partially inhibited both the LPS-induced expression of kappa light chain and also the activation of NF kappa B as judged by an NF kappa B reporter gene assay. Additionally, electrophoretic mobility shift assays confirmed this effect on LPS-induced NF kappa B DNA binding activity in the nucleus. Surprisingly, proteolytic degradation of I kappa B alpha (MAD3), a prerequisite for NF kappa B activation, was unaffected by IL-4, implying that this cytokine inhibits some subsequent undefined event in the activation of NF kappa B. IL-4 was also found partially to inhibit NF kappa B activity induced by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta). These results indicate that there may be a common mechanism for the well-documented anti-inflammatory effects of IL-4 and that this mechanism involves the transcription factor NF kappa B.

Animals↗
PubMed1994

Respiratory syncytial virus-associated bronchopneumonia in a young chimpanzee.

A fatal bronchopneumonia in a captive, 14-month-old female chimpanzee (Pan troglodytes) is reported. Clinical, necropsy and histopathological findings, together with immunofluorescence and virus isolation studies implicated respiratory syncytial virus as the causative agent. The probable pathogenesis is discussed.

Animals↗
PubMed1992

Chronic tracheobronchial syndrome in eight dogs.

Chronic tracheobronchial syndrome was diagnosed in eight dogs which had had a chronic mild cough for two to 13 months but were otherwise clinically normal. In five of them there was evidence of contact with other coughing dogs before the appearance of clinical signs and the majority at first responded favourably to antibacterial therapy. The coughing occurred mainly when the dogs pulled on their leads or became excited. Three cases had bronchoscopic evidence of active airway inflammation, and five had varying numbers of inflammatory cells (neutrophils) in bronchial aspirates. There was no evidence of excessive production of mucus in the airways of any of the dogs. Seven had an increased bronchial pattern on radiographs but only one of the dogs has developed chronic bronchitis.

Animals↗
PubMed1992

The intestinal and serum humoral immune response of mice to systemically and orally administered antigens in liposomes: I. The response to liposome-entrapped soluble proteins.

The development of oral vaccines is of great importance in veterinary medicine and new adjuvants and carriers are essential to this aim. Liposomes are effective systemic adjuvants but the relatively little data on their potential as oral adjuvants is inconclusive. Liposomes containing ovalbumin (OA) were effective adjuvants when administered intraperitoneally to mice. Feeding mice with OA or keyhole limpet haemocyanin in liposomes in a series of priming and boosting regimes failed to elicit any significant increase in serum or intestinal antibody response compared with feeding the free antigen. Oral tolerance induction to systemic challenge was also unaffected by OA entrapment in liposomes. In vitro liposome stability assays at 37 degrees C demonstrated a substantial resistance to disruption in the presence of acidic stomach contents. However, the addition of bile caused a rapid and profound release of protein marker from the liposomes. The rate and degree of disruption was influenced by the type of phospholipid used. These results suggest that liposomes may be useful as carriers for orally administered compounds but they are ineffective as adjuvants for the non-particulate, naturally weak immunogens used in this study.

Adjuvants, Immunologic↗
PubMed1992

The intestinal and serum humoral immune response of mice to orally administered antigens in liposomes: II. The response to liposome-entrapped bacterial proteins.

Effective oral adjuvants are needed to improve the intestinal immune responses to oral vaccines that are based on relatively low molecular weight antigens refined from veterinary pathogens. Liposomes prepared by different methods and composed of phospholipids of varying transition temperature were used to entrap cholera toxin (CT) and fed to mice. No significant increase in the intestinal antibody nor the serum IgA antibody response was detected but levels of serum IgG anti-CT antibody were significantly elevated in the group fed CT in phosphatidylcholine-based liposomes. Levels of antibody were significantly reduced in the groups fed CT in dipalmitoylphosphatidylcholine liposomes. Escherichia coli wall extract (ECWE) entrapped in certain liposome types and fed to mice elicited significantly increased serum anti-ECWE antibody responses but intestinal antibody responses were insignificantly different from the controls. These results suggest that orally administered liposomes fail to act as potent intestinal adjuvants for the entrapped antigens of bacterial origin used in this study.

Adjuvants, Immunologic↗
PubMed1992

Depressed potential for interleukin-2 production following early weaning of piglets.

Spleen cells, but not mesenteric lymph node cells, from 3-week-old piglets abruptly weaned onto a soya-based diet, produced less interleukin-2 (IL-2) following non-specific activation with concanavalin A (Con A) than did cells from age- and litter-matched, unweaned controls. In contrast, the ability to express receptors for IL-2 was only marginally reduced. The effect on IL-2 production was most marked in animals weaned for as little as 24-48 h. Variation within groups increased with time after weaning, indicating differences between individuals in the longer-term effects of weaning. This finding may be due to endogenous production of steroids resulting in generalised impaired immune function or to retention of cells within intestinal sites owing to an active local immune response.

Animals↗
PubMed1992

Living arrangements of the elderly: an examination of differences according to ancestry and generation.

Using data from the November 1979 Current Population Survey, the pattern of living with relatives among American elderly of European origin was examined. The data show that, in general, the elderly with Southern, Central, and Eastern European ancestries were more likely to live with relatives than were their Northwestern European counterparts. There were exceptions, most notably those elderly with a Russian background. There was no decreased likelihood of living with relatives among those with more generations in the United States.

Acculturation↗