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Biomedical subjects

K Connor

Publications and source records attributed to K Connor.

At least 19 recordsLinked to original sources
PubMed1995

Naringenin: a weakly estrogenic bioflavonoid that exhibits antiestrogenic activity.

Treatment of immature 21-day-old female Sprague-Dawley rats with 17 beta-estradiol (E2) (0.5 microgram/rat) caused a significant increase in uterine wet weight, DNA synthesis, progesterone receptor (PR) binding, and peroxidase activity. At doses as high as 40 mg/rat, the bioflavonoid naringenin did not cause a significant increase in any of these E2-induced responses. However, in rats cotreated with E2 (0.5 microgram/rat) plus naringenin (30 mg/rat); there was a significant decrease in E2-induced uterine wet weight, DNA synthesis, PR binding, and peroxidase activity, indicating that naringenin exhibits antiestrogenic activity in the immature rodent uterus. The binding of uterine nuclear extracts to a 32P-labeled estrogen responsive element (ERE) or progesterone responsive element (PRE) was determined using gel electrophoretic band shift assays. Incubation of [32P]ERE with uterine nuclear extracts from rats treated with naringenin or E2 resulted in the formation of estrogen receptor (ER):ERE complexes; a higher mobility complex was prominent in the extracts from E2-treated rats, whereas a lower mobility complex was observed using nuclear extracts from naringenin-treated animals. There was a significant decrease in the intensity of the E2-induced complex using nuclear extracts from rats treated with E2 plus naringenin. In contrast, transformed cytosol from control rats gave an intense ER:ERE complex, whereas the intensity of the band was decreased markedly using transformed uterine cytosol from treated rats. Formation of a PR:PRE complex was also determined using transformed uterine cytosol. Cytosol from E2-treated rats gave an intense retarded band, whereas only weak bands were observed using cytosols from DMSO- (solvent), naringenin-, or naringenin plus E2-treated cells. The results of in vitro studies showed that 1 nM E2 increased (3- to 4-fold) the growth of MCF-7 human breast cancer cells, whereas 1-1000 nM naringenin had no effect on cell proliferation. In cells cotreated with 1 nM E2 plus 1000 nM naringenin, there was a significant decrease in E2-induced cell growth. In MCF-7 cells transiently transfected with a pS2 promoter-regulated luciferase reporter gene, naringenin exhibited weak estrogenic activity. In cells cotreated with 0.1 or 1.0 microM naringenin plus 1 nM E2, naringenin inhibited E2-induced luciferase activity. The results of these studies confirmed that naringenin is a weak estrogen that also exhibits partial antiestrogenic activity in the female rat uterus and MCF-7 human breast cancer cells.

Animals↗
PubMed1995

Characterisation of ovine Bordetella parapertussis isolates by analysis of specific endotoxin (lipopolysaccharide) epitopes, filamentous haemagglutinin production, cellular fatty acid composition and antibiotic sensitivity.

Isolates of Bordetella parapertussis, recovered from sheep or man, were characterised by reaction with specific anti-Bordetella lipopolysaccharide monoclonal antibodies, production of filamentous haemagglutinin, fatty acid patterns, and antibiotic sensitivity. Generally, the isolates lay within one of four groups, with separation of the ovine isolates into two groups. Reactions with specific monoclonal antibodies against lipopolysaccharide separated the ovine isolates into these two groupings. Analysis of the cellular fatty acid compositions by cluster analysis differentiated between the human and the ovine strains and also showed variation within the ovine isolates. When the production of filamentous haemagglutinin was analysed in an ELISA system, a similar pattern emerged. Varying concentrations of filamentous haemagglutinin (11-429 ng (mg total protein)-1) were extracted from the human isolates and the one group of ovine isolates with no significant protein detected in the other ovine group. These studies demonstrate variation between and within B. parapertussis isolates recovered from two mammalian sources.

Adhesins, Bacterial↗
PubMed1995

Phorbol ester and diacylglycerol activation of native protein kinase C species from various tissues.

The characteristics of PKC activation induced by a number of compounds were investigated using PKCs, partially-purified from sources with a naturally high abundance of certain Ca2+ dependent PKC isoforms. Native isoforms were used rather than PKC isoforms expressed from a baculovirus system to assess the effect of tissue specific factors on activity. However, some data using recombinant PKC alpha were included for comparison. The presence of specific PKC isoforms in different tissues was determined using Western blot analysis. Protein kinase C alpha, beta 1, delta, epsilon, and zeta/iota were all present in rat midbrain cytosolic extract, PKC alpha, beta 1, delta, and zeta/iota were present in spleen cytosol, and PKC alpha and zeta/iota were present in COS 7 cell cytosol. The predominance of alpha and beta activities in COS 7 and spleen extracts respectively was confirmed by enzymic assay. The PKC activity assay was configured such that the Ca2+ dependence of the PKC activity induced by different PKC activators could be determined. Phorbol 12,13-dibutyrate (PDBu) was virtually equipotent on the Ca(2+)-dependent PKC activity from midbrain and spleen and slightly less potent on that from COS 7 cells. In the absence of Ca2+, PDBu was considerably less potent overall (as, indeed, were the other PKC activators) and was less potent on COS 7 cell PKC than on those from midbrain or spleen. Mezerein was more potent than PDBu at inducing PKC activity in COS 7 cell extracts in either the absence or presence of Ca2+ whereas in the presence of Ca2+, mezerein was slightly less potent on midbrain and spleen than PDBu and equipotent in the absence of Ca2+. Maximum values for Ca(2+)-independent activation by mezerein indicated that this activator was particularly effective in recruiting Ca(2+)-dependent PKC isoform activity in a Ca2+ free environment. The greater potency of mezerein on PKC alpha was confirmed using PKC alpha and beta further purified from rat spleen by hydroxylapatite (HAP) chromatography. The effects of both PDBu and mezerein were investigated using anterior pituitary tissue where a particularly high potency of mezerein in the absence of Ca2+ was noted. The diacylglycerol, 1,2-dioctanoyl-sn-glycerol (DOG), appeared to cause little or no activation of native Ca(2+)-dependent isoforms in Ca2+ free conditions unlike another longer chain diacylglycerol, 1,2-dioleoyl-sn-glycerol. Also DOG activated midbrain PKCs more potently than PKCs from spleen or COS 7 cells (or lung and pituitary tissue) in the presence of Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Immunosuppressive activity of polychlorinated biphenyl mixtures and congeners: nonadditive (antagonistic) interactions.

The dose-response inhibition of the splenic plaque-forming cell (PFC) response and serum IgM units to the antigen, trinitrophenyl-lipopolysaccharide, was determined for several polychlorinated biphenyl (PCB) mixtures and congeners in female B3C3F1 mice. The ED50 values for Aroclor 1260-, 1254-, 1248-, and 1242-induced immunotoxicity varied by less than twofold from 355 to 699 mg/kg. The range of ED50 values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4'-tetrachlorobiphenyl, 3,3',4,4',5-pentaCB, 3,3',4,4',5,5'-hexaCB, 2,3,3',4,4'-pentaCB, 2,3',4,4',5-pentaCB, 2,3,3',4,4',5-hexaCB, 2,3,3',4,4',5,5'-heptaCB, 2,2',3,3',4,4',5-heptaCB, and 2,2',3,4,4',5,5'-heptaCB were 4.6 to 4.9, 134 to 245, 4.7 to 7.0, 6.9 to 11.1, 88,000 to 121,000, 122,000 to 132,000, 99,000 to 157,000, 89,000 to 129,000, 117,000 to 240,000, and 132,000 to 238,000 micrograms/kg, respectively. The immunotoxicity-derived toxic equivalency factors (TEFs) for these congeners could be calculated from the ED50 (TCDD)/ED50 (congener) ratios and the TEF values were within the range of those previously determined for other aryl hydrocarbon receptor-mediated responses. Based on the known concentrations of these congeners in the PCB mixtures, TCDD or toxic equivalents (TEQs) in the mixture were calculated [i.e., TEQ = sigma (PCBcongener x TEF)] using the immunotoxicity-derived TEFs (plaque-forming cells/10(6) viable cells). TEQ values for Aroclors 1260, 1254, 1248, and 1242 were 16.0, 54.4, 260.4, and 197 ppm, respectively. Based on the ED50 value for the immunosuppressive activity of TCDD (4.8 micrograms/kg), the calculated ED50 values for immune suppression by Aroclors 1260, 1254, 1248, and 1242 were 300, 88, 18, and 24 mg/kg, respectively. The ED50 (observed)/ED50 (calculated) ratios were 1.2, 5.9, 21, and 22.0 for Aroclors 1260, 1254, 1248 and 1242, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗
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↗
PubMed1987

Effects of age and diet on the lipid content and composition of gallbladder bile, liver and serum in laying strains of hen.

1. Changes in lipid content and composition of liver and bile during pre- and post-laying periods were investigated in hens of a laying strain. 2. The large increase in liver lipid concentration, particularly triacylglycerols, at the onset of laying was accompanied by the appearance of triacylglycerols in the bile. 3. Accumulation of triacylglycerol in the liver was increased by a diet containing maize and soyabean meal. This was associated with increases in the triacylglycerol concentration in both serum and bile. 4. Liver microsomal phosphatidate phosphohydrolase activity was positively correlated with liver triacylglycerol content in birds given the maize/soyabean meal diet. 5. The time course of triacylglycerol accumulation in the liver and associated changes in the bile triacylglycerol concentration in laying strain hens were different to those previously observed in broiler hens. 6. Over the lifetime of the bird, secretion of triacylglycerols into bile may play an important role in the prevention of fatty liver syndromes.

Aging↗
PubMed1986

Changes in the lipid metabolism of the chick embryo with parental age.

A study has been made on the distribution and composition of the lipids associated with the yolk contents, yolk sac membrane, liver, and extrahepatic tissues of chick embryos at Days 15 and 19 of incubation from 25- and 41-week-old broiler-breeder stock. The higher embryo mortality displayed by the eggs from the young breeders was associated with an abnormal distribution of lipid between the tissue pools. The amount of lipid associated with the total yolk, i.e., yolk contents plus yolk sac membrane, of the embryos from the 25-week-old parents at Day 19 of incubation was greater than that of the embryos from the 41-week-old parents, and there was a much higher proportion of lipid still remaining in association with the yolk contents. In the embryos from the young parents, a smaller proportion of embryonic lipid was associated with the extra-hepatic tissues at Day 19 of incubation. Differences were observed in the relative proportions of the major lipid fractions within the yolk and embryonic tissues between the eggs from the two sets of parents. The higher mortality of the embryos from the young parents was associated with a malfunction of yolk lipid assimilation and mobilization from the yolk contents thereby denying access to the major nutrient associated with development during the last week of incubation.

Age Factors↗
PubMed1986

The role of defensiveness in cognitive impulsivity.

The role of anxiety in reflection-impulsivity has been a source of controversy, with impulsives portrayed as unanxious by some researchers and as extremely anxious by others. Defensiveness may account for these seemingly contradictory results. Impulsives may present a facade of unconcern to mask underlying anxiety. The impulsive response itself may occur in part because impulsives are defensive about appearing incompetent. Equating rapidity of response with competence, they respond quickly to appear competent. 120 children, with a mean age of 9 years, 7 months, served as subjects. Measurements of defensiveness and impulsivity were examined. Correlations were examined separately by sex since previous research showed that defensiveness correlated negatively with problem-solving success for boys only. Defensiveness and impulsivity were positively correlated for boys only. Unlike previous studies, test anxiety correlated positively with impulsivity for girls.

Anxiety↗
PubMed1984

A unique lipid pattern associated with the gall bladder bile of the chick embryo.

A study has been made of the lipid and fatty acid composition of the gall bladder bile of the chick embryo during the last week of incubation. The lipids and their fatty acid composition showed a unique pattern when compared to other animal species. Of the total lipid present, phospholipid accounted for less than half, and there were substantial proportions of both cholesteryl ester and triglyceride. In the cholesteryl ester, the proportion of which increased significantly over the last week of incubation, there was a very high level of oleic acid. The phospholipid contained a high level of arachidonic acid. The results are discussed in relation to observations on the biliary lipids of other animal species and the major features of the lipid metabolism of the chick embryo during the last week of incubation.

Animals↗