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Biomedical subjects

K Connor

Publications and source records attributed to K Connor.

At least 37 records · Page 2Linked to original sources
PubMed1995

Bronchopneumonia in mice caused by Pasteurella haemolytica A2 after predisposition by ovine Bordetella parapertussis.

Initial intranasal inoculation of four to eight-week-old Swiss White mice with 7.5 x 10(6) colony forming units (cfu) of ovine B. parapertussis followed 30 min, three or five days, by intranasal inoculation with 1.4 x 10(5) cfu of Pasteurella haemolytica A2 resulted in a more severe infection pattern than when either agent was administered alone. Histopathological examination showed that inoculation with B. parapertussis alone caused a bronchopneumonia the severity of which was dependant upon the infecting dose. Bacteria were recovered up to 10 days after inoculation. P. haemolytica alone had no apparant pathogenic effect and was cleared from the lungs within 24 h. When both agents were given in combination the lesions were most severe when P. haemolytica was administered three days after B. parapertussis infection. These findings suggest that B. parapertussis predisposes mice to subsequent infection with P. haemolytica and that the timing of the P. haemolytica administration influences the severity of the lung lesions.

Animals↗
PubMed1995

Predisposition of specific pathogen-free lambs to Pasteurella haemolytica pneumonia by Bordetella parapertussis infection.

Three groups of specific pathogen-free (SPF) lambs were inoculated intratracheally with an ovine isolate of Bordetella parapertussis (5.5 x 10(9) colony-forming units) or with B. parapertussis followed 2 or 5 days later with Pasteurella haemolytica serotype A2 (120-180 million colony-forming units). When P. haemolytica A2 was administered 2 days after infection with B. parapertussis all lambs became febrile for at least 72 h. At necropsy their lungs were discoloured, congested and showed large areas of collapse and consolidation which, in one case, covered the entire lung. Histopathological examination confirmed that the combined infection produced a severe acute bronchopneumonia in four of seven lambs. B. parapertussis and P. haemolytica were recovered from all of the lambs in this group. Seven lambs challenged with P. haemolytica 5 days after B. parapertussis and six lambs infected with B. parapertussis alone showed no clinical signs of disease other than mild pyrexia and only mild histopathological changes. B. parapertussis, but not P. haemolytica, was recovered from these lambs. The findings indicated that B. parapertussis predisposed the SPF lambs to P. haemolytica pneumonia. This effect appeared to be dependent upon the time interval between the administration of the two agents.

Animals↗
PubMed1994

An enzyme-linked immunosorbent assay (ELISA) specific for antibodies to TNP-LPS detects alterations in serum immunoglobulins and isotype switching in C57BL/6 and DBA/2 mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.

An enzyme-linked immunosorbent assay (ELISA) was developed to detect IgM and IgG antibodies specific for trinitrophenyl-lipopolysaccharide (TNP-LPS). Treatment of C57BL/6 and DBA/2 mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon (Ah) receptor agonists followed by immunization with TNP-LPS resulted in a dose-dependent decrease in serum IgM which paralleled the decrease in the splenic PFC response. The ED50 values for the IgM and splenic PFCs in C57BL/6 mice for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (pentaCB) and 3,3',4,4',5,5'-hexaCB were 2.8 and 1.6, 11 and 14, and 25 and 20 micrograms/kg, respectively; in the less Ah-responsive DBA/2 mice, the ED50 values were 8.5 and 10, 61 and 69, and 73 and 71 micrograms/kg, respectively. In addition, treatment of C57BL/6 mice with TCDD resulted in alterations of serum IgG relative to IgM and a delay of isotype switching was observed after immunization and boosting with TNP-LPS. This ELISA may prove to be a useful tool in monitoring immune function during long-term exposure of mice to TCDD and related compounds and exploring the mechanism of Ah receptor-mediated immunosuppression.

Animals↗
PubMed1994

Isolation and characterization of Bordetella parapertussis-like bacteria from ovine lungs.

Bacteria resembling two Bordetella species were isolated from both normal and pneumonic ovine lungs using a selective charcoal agar. Twenty-eight of the 33 isolates showed similarities to stock NCTC B. parapertussis strains in their SDS-PAGE gel protein profiles, in their biochemical reactions and in causing browning on tyrosine agar. Five isolates behaved similarly to stock B. bronchiseptica strains, in being actively motile, in giving identical positive reactions in three out of four biochemical tests and in causing no colour change in tyrosine agar. Multilocus enzyme electrophoresis separated the isolates into two electrophoretic types distinguishable from those of stock B. parapertussis and stock B. bronchiseptica strains.

Animals↗
PubMed1993

Immunosuppressive effects of highly chlorinated biphenyls and diphenyl ethers on T-cell dependent and independent antigens in mice.

The dose-dependent effects of 2,2',3,3',4,4',5,5',6-nonachlorobiphenyl (nonaCB), 2,2',3,3',4,4',5,6,6'-nonaCB, 2,2',3,3',4,5,5',6,6'-nonaCB and decaCB on the suppression of the splenic plaque-forming cell (PFC) response to the T-cell-dependent antigen, sheep red blood cells (SRBCs) and the T-cell-independent antigen, trinitrophenyl-lipopolysaccharide (TNP-LPS), were determined in genetically inbred mice. In addition, the induction of hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity was also measured. The highly chlorinated biphenyls suppressed the splenic PFC response to SRBCs in C57BL/6 and DBA/2 mice and were relatively more active in the former strain. The C57BL/6 mice are more responsive to aryl hydrocarbon (Ah) receptor agonists than DBA/2 mice and these data support a possible role for the Ah receptor in mediating this response. However, previous studies with polychlorinated biphenyls (PCBs) indicate that congeners with 3 or 4 ortho-chloro substituents are inactive as Ah receptor agonists and this was consistent with the minimal induction of hepatic microsomal EROD activity by the highly chlorinated biphenyls in both strains of mice. Thus, the results suggest that the inhibition of the splenic PFC response to SRBCs observed in this study was primarily an Ah receptor-independent response. Some of the highly chlorinated diphyenyl ethers namely decachlorodiphenyl ether and 2,2',3,3',4,4',5,6,6'-nonachlorodiphenyl ether, inhibited the antigenic response to TNP-LPS in C57 BL/6 mice. The results indicate that the suppression of the TNP-LPS-mediated immune response may be a more reliable indicator of the Ah receptor-dependent immunotoxicity of halogenated hydrocarbons.

Animals↗
PubMed1993

Evidence for a distinct H7-resistant form of protein kinase C in rat anterior pituitary gland.

Inhibition of phorbol 12,13-dibutyrate-induced protein kinase C (PKC) activity from rat midbrain, anterior pituitary and a number of other tissues, as well as COS 7 cells, was studied in vitro. In anterior pituitary, Ca(2+)-independent activity was notably resistant to H7 but sensitive to staurosporine and Ro 31-8220. All Ca(2+)-dependent activity was sensitive to these three inhibitors. Mezerein and 1,2-dioctanoyl-sn-glycerol also activated this H7-insensitive PKC from anterior pituitary. The distribution of this activity, prominently expressed in pituitary and perhaps also lung, and its characteristic resistance to H7 but not other inhibitors, does not obviously correlate with that of any of the well-characterised PKCs, and may reflect either a novel or a modified isoform.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Evidence that protein kinase C alpha has reduced affinity towards 1,2-dioctanoyl-sn-glycerol: the effects of lipid activators on phorbol ester binding and kinase activity.

The effect of 1,2-diacylglycerols on specific binding of [3H]phorbol 12,13-dibutyrate to cytosolic protein kinase C (PKC) was investigated in tissues reported to contain different proportions of PKC isoforms. In lung, frontal cerebral cortex and cerebellum cytosols (enriched in PKC alpha, beta and gamma, respectively) displacement of specific binding by phorbol 12,13-dibutyrate or diacylglycerols containing unsaturated acyl chains was of similar potency for each tissue. A range of 1,2-diacylglycerols containing saturated acyl chains exhibited varying affinities for [3H]phorbol 12,13-dibutyrate binding sites in each tissue; defining an optimal acyl chain length of around 14 carbons in each case. However, the affinities of saturated diglycerides were consistently lower in lung cytosol than in frontal cerebral cortex and cerebellum cytosols, with the greatest differences occurring at lower acyl chain lengths, especially with 1,2-dioctanoyl-sn-glycerol. Furthermore, a mixed micelle assay of PKC activity showed that 1,2-dioctanoyl-sn-glycerol displayed reduced potency at PKC alpha partially-purified from COS 7 cell cytosol compared to the mixture of PKC isoforms present in rat midbrain cytosol. Both low potency of 1,2-dioctanoyl-sn-glycerol as a displacer of [3H]phorbol 12,13 dibutyrate binding and the ability of arachidonic acid to act as an allosteric enhancer of binding, correlated with the proportional PKC alpha content of a range of tissues reported in the literature. In PKC enzyme activity assays, 1,2-dioctanoyl-sn-glycerol, but not phorbol 12,13-dibutyrate, was correspondingly a much poorer activator of PKC alpha from COS 7 cells than of the broad consensus of isoforms in rat midbrain. When alpha and beta isoforms were extensively-purified on DEAE-cellulose then hydroxyapatite, both the low affinity of 1,2-dioctanoyl-sn-glycerol for [3H]phorbol 12,13-dibutyrate binding sites and their allosteric regulation by arachidonic acid were confirmed to be characteristic of the alpha rather than the beta isoforms.

Amino Acid Sequence↗
PubMed1993

Immunotoxic potencies of polychlorinated biphenyl (PCB), dibenzofuran (PCDF) and dibenzo-p-dioxin (PCDD) congeners in C57BL/6 and DBA/2 mice.

The dose-dependent effects of a single acute exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 1,2,3,7,9-PeCDF, 1,3,6,8-tetrachlorodibenzofuran (TCDF), 3,3',4,4',5-pentachlorobiphenyl (pentaCB), and 3,3,',4,4',5,5'-hexaCB on the suppression of the splenic plaque-forming cell (PFC) response to the T-cell-independent antigen trinitrophenyl-lipopolysaccharide were determined in C57BL/6 and DBA/2 mice. In addition, the induction of hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity was also measured in these animals. 2,3,7,8-TCDD and 2,3,4,7,8-PeCDF were the most immunotoxic congeners in both strains of mice and with the exception of the latter congener, the ED50 values for each compound were lower in the C57BL/6 than the DBA/2 mice. 2,3,7,8-TCDD induced hepatic microsomal EROD activity in both strains of mice whereas the other congeners were considerably less active or inactive as inducers. The results of this study demonstrated that for the halogenated aromatic hydrocarbons the immunotoxic response was a more sensitive indicator of exposure than the induction of CYP1A1 activity. The rank order for the immunotoxic potencies of the chlorinated aromatic compounds used in this study was 2,3,7,8-TCDD approximately 2,3,4,7,8-PeCDF > 3,3',4,4',5-pentaCB approximately 3,3',4,4',5,5'-hexaCB > 1,2,3,7,9-PeCDF > 1,3,6,8-TCDF. The order of activity for these congeners was similar for other Ah receptor-mediated responses and these results coupled with the differential responsiveness of the C57BL/6 and DBA/2 mice confirms the role of aryl hydrocarbon (Ah) receptor in mediating the suppression of this T-cell-independent response.

Animals↗
PubMed1993

Isoenzymes of protein kinase C in rat mammary tissue: changes in properties and relative amounts during pregnancy and lactation.

Protein kinase isoenzymes belonging to the protein kinase C (PK-C) family present in rat mammary tissue have been resolved from one another by chromatography on hydroxyapatite, and characterized. PK-C alpha is the predominant isoenzyme and is present at a constant level of activity throughout mammary-gland development and differentiation. In contrast, marked changes in the relative abundance of other mammary PK-C isoenzymes accompany the transition from pregnancy to lactation. The sensitivity of mammary PK-C alpha to Ca2+ is greater in tissue from pregnant than from lactating rats. This isoenzyme has other atypical properties consistent with its being more highly phosphorylated than PK-C alpha in rat brain and spleen. One of the protein kinase isoenzymes resolved from mammary tissue recognizes the peptide substrate used to assay AMP-activated kinase and may thus interfere in the determination of this activity. Another is fully active in the absence of Ca2+ and is more than 80% active in the absence of added lipid effectors. A 'housekeeping' role is proposed for PK-C alpha in mammary tissue, whereas the less abundant PK-C isoenzymes may be involved in mammary cell proliferation and differentiation.

Animals↗
PubMed1993

Immunosuppressive and monooxygenase induction activities of highly chlorinated diphenyl ether congeners in C57BL/6 and DBA/2 mice.

The dose-response effects of 2,2',3,3',4,5,5',6,6'-2,2',3,3',4,4',5,6,6'- and 2,2',3,3',4,4',5,5',6- nonachlorodiphenyl ether (non-aCDE) and decachlorodiphenyl ether (decaCDE) on the splenic plaque-forming cell (PFC) response to sheep red blood cells (SRBCs) and the induction of hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity was determined in aryl hydrocarbon (Ah)-responsive C57BL/6 and less Ah-responsive DBA/2 mice. All the congeners exhibited immunotoxicity at doses between 2.5 and 10 mumol/kg in C57BL/6 mice whereas in DBA/2 mice doses > or = 25 mumol/kg were required to cause inhibition of the PFC response to SRBCs. The results also showed that the nonaCDE isomers and decaCDE were more active as inducers of hepatic EROD activity in C57BL/6 than DBA/2 mice; however, there was not a correlation between the induced EROD activity and the CYP1A1 and CYP1A2 mRNA levels in the C57BL/6 mice. These data suggested that the immunotoxicity of these compounds was mediated through the Ah receptor. However, the results showed that the immunotoxicity of the nonaCDE isomers and decaCDE was unexpectedly high compared to that of lower chlorinated diphenyl ethers and there were no apparent structure-activity relationships among the higher chlorinated congeners. This suggests that some of the immunosuppressive effects observed for the nonaCDE isomers and decaCDE may be Ah receptor-independent.

Animals↗
PubMed1991

Cyclic AMP-dependent protein kinase in mammary epithelial cells; activity and subcellular distribution are acutely modulated by isoprenaline.

Brief incubation of a mammary epithelial cellular preparation from lactating rats with isoprenaline is shown to result in major re-distribution of the activity of cyclic AMP-dependent protein kinase (measured in the presence of saturating cyclic AMP) within the cell. Activity in the soluble fraction was halved and a corresponding increase in the sedimentable activity occurred. Similar effects were observed when cell-free extracts were treated with cyclic AMP in the presence of inhibitors of phosphodiesterase and subsequently fractionated by a simple one-step centrifugation procedure. The concentration of the catalytic subunit of cyclic AMP-dependent protein kinase, assessed by quantitative Western blot analysis, did not reflect these activity changes. Quantitation of the regulatory subunits (R-I plus R-II) of A-kinase enabled independent assessment of the possible total A-kinase holoenzyme in mammary epithelial cells and was in reasonable agreement with the measured total A-kinase activity. Isoprenaline selectively increased the apparent mean specific catalytic activity of the C-subunit in the particulate fraction.

Animals↗
PubMed1988

Comparative study of the lipid composition of the liver and bile from broiler birds during growth and egg laying.

A comparative study was made of biliary and liver lipid compositions during the growth and egg laying periods of the broiler bird. The liver lipids showed high concentrations of triacylglycerols at seven weeks old which increased when egg laying proceeded. At seven weeks old the lipids of the bile also showed high levels of triacylglycerols which decreased with the onset of egg laying but increased slightly as egg laying proceeded. At seven weeks old the fatty acid composition of the bile triacylglycerols differed from that of the liver which in turn was different from that of the liver at the onset of egg laying. In particular the bile triacylglycerols had lower levels of oleic but higher levels of arachidonic and docosahexaenoic acids. By the late egg laying period, the fatty acid compositions of the bile and liver triacylglycerols were similar. The unique bile lipid composition and its changes are discussed in relationship to the major features of liver lipid metabolism in the broiler bird and the mechanism of lipid deposition during egg laying.

Animals↗