Peroxidase-catalysed metabolism of drugs and carcinogens.
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Acetaminophen↗
Biomedical subjects
B Andersson
Publications and source records attributed to B Andersson.
Monoclonal antibodies against the rat liver glucocorticoid receptor.
Splenic cells from one BALB/c mouse and one C57/BL mouse, immunized with purified rat liver glucocorticoid receptor (GR), were fused with the mouse myeloma cell line Sp 2/0-Ag 14. Screening for production of anti-GR-antibodies by the hybridomas was carried out with an enzyme-linked immunosorbent assay, using partially purified rat liver GR as antigen. Further screening was by a second-antibody immunoprecipitation assay using [3H]triamcinolone acetonide-GR complex from rat liver cytosol as tracer. Hybridomas from 10 different microplate wells, positive in both assays, were successfully cloned by the limiting dilution method to monoclonality. The different origins of the monoclonal antibodies were confirmed by their various isoelectric points when analyzed by isoelectric focusing. Four of the monoclonal hybridoma cell lines secreted IgM antibodies; two, IgG1; three, IgG2a; and one, IgG2b. The GR-antibody complex was identified in glycerol density gradients by a shift of the 4S GR to an 8.5S or 19S GR-antibody complex when incubated with monoclonal IgG or IgM antibody, respectively. The 10 monoclonal antibodies recognized different determinants on the GR, all situated on that domain of the receptor that is separate from the ligand and DNA-binding domains. Also, the cross-reactivity to the mouse liver GR varied among the monoclonal antibodies. No cross-reactivity was observed to the human lymphocytic GR. NaDodSO4 electrophoresis of a 0.5% pure GR preparation followed by immunoblotting using one of the monoclonal antibodies identified a single peptide with a molecular weight of 94,000, identical to the purified rat liver GR.
Animals↗
Prostaglandin synthase and horseradish peroxidase catalyzed DNA-binding of p-phenetidine.
The prostaglandin synthase and horseradish peroxidase catalyzed binding of p-phenetidine to DNA was investigated. The addition of arachidonic acid to an incubation containing ram seminal vesicle microsomes, [14C]p-phenetidine and DNA resulted in a rapid incorporation of radioactivity into DNA. This was inhibited by greater than 75% by indomethacin (0.1 mM) or butylated hydroxyanisole (0.5 mM). Hydrogen peroxide was as efficient as arachidonic acid in mediating the activation of p-phenetidine thus implicating the involvement of the hydroperoxidase activity of prostaglandin synthase in this reaction. Horseradish peroxidase and hydrogen peroxide also catalyzed the activation of p-phenetidine to DNA-binding metabolites. Reduced glutathione (GSH) stimulated the binding of p-phenetidine to DNA by greater than 3-fold in both the prostaglandin synthase and the horseradish peroxidase system, whereas cysteine and N-acetylcysteine reduced the DNA-binding in the prostaglandin synthase system by up to 62% under the conditions used. Furthermore, water-soluble metabolites formed in the presence of GSH also bound to DNA. Seventy-two hour dialysis of DNA samples from incubations with GSH present reduced the amount of bound material by 75%. In contrast, the radioactivity which associated with DNA in the absence of GSH was not decreased by dialysis.
Aminophenols↗
Renal excretion of prostaglandin metabolites, arginine vasopressin, and sodium during endotoxin and endogenous pyrogen induced fever in the goat.
Responses to intravenous injections of an endotoxin (E. coli-lipopolysaccharide, 1 microgram/kg b.wt.) and endogenous pyrogen were studied in euhydrated and hyperhydrated goats. The biphasic febrile response to the endotoxin was associated with a pronounced increase in the renal excretion of measured prostaglandin (PG) metabolites (11-ketotetranor PGF metabolites). This increase was time-correlated with the elevation of the rectal temperature, and (in hyperhydrated animals) with an inhibition of the water diuresis and an increase in renal excretion of arginine vasopressin (AVP). Other effects of the endotoxin were an immediate depression of renal Na and K excretion followed by the development of pronounced natriuresis, and a reduction of plasma Fe and Zn concentrations. The appearance of the febrile reactions (peripheral vasoconstriction and shivering) was accompanied by miosis. The maximum elevation of the rectal temperature was significantly greater during euhydration than during hyperhydration. Also endogenous pyrogen elicited miosis concomitant with febrile reactions, and an elevation of the renal excretion of PG metabolites which was closely correlated in time with the monophasic febrile response, and (during hyperhydration) with temporary inhibition of the water diuresis and an increase in the renal AVP excretion. However, the responses were much weaker than the corresponding endotoxin effects. No appreciable changes in renal excretion of Na and K were observed in response to the endogenous pyrogen. It is concluded that the observed effects on renal cation excretion were manifestations of direct endotoxin influences on kidney function.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Glycoconjugate receptors involved in the adhesion of Escherichia coli and Streptococcus pneumoniae to epithelial cells.
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Adhesiveness↗
Attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells in vitro--mechanism of binding.
To colonize mucosal surfaces and to invade underlying tissues, bacteria need to bind to components of the mucosa. Unattached bacteria are transported away from the surface with the fluid flow. By binding to the nasopharyngeal mucosa, Streptococcus pneumoniae causing otitis media may persist at the site of infection. High binding capacity of the bacterium and increased receptivity of the epithelial cells for attaching bacteria may both contribute to the susceptibility of patients prone to otitis. Thus, epithelial cells from children with frequent episodes of otitis bind attaching bacteria more readily than do cells from age-matched controls. The binding mechanism probably involves bacterial surface proteins and epithelial cell surface glycoconjugate receptors. Evidence is presented that phosphorylcholine, a component of the bacterial surface, as well as epithelial cell receptor analogues, that is, natural or synthetic saccharides analogous to the lactoneoseries of glycolipids, inhibits pneumococcal attachment. Inhibition of bacterial binding in vivo may be a new approach to prophylaxis against otitis media.
Adhesiveness↗
Changes in the expression of B cell surface markers on complement receptor-positive and complement receptor-negative B cells induced by phorbol myristate acetate.
The ability of phorbol myristate acetate (PMA) to induce changes in the expression of B cell surface markers on CR- and CR+ B cells from normal mice in an in vitro culture system was examined. The markers studied were CR, sIgM, sIgD, and sIa. CR- B cells acquired the CR after overnight incubation with PMA. A twofold increase in sIa expression on CR- and CR+ B cells was also noted, whereas the staining intensity of sIgM and sIgD decreased on both B cell populations. These changes in the expression of surface markers took place without detectable increases in cell proliferation, cell size, or RNA content. Furthermore, the same effects were observed when CR- and CR+ B cells were prepared from a small B cell population purified by elutriation. It therefore appears that PMA can exert its effect directly on small, resting B cells.
Animals↗
Avidities of hapten-specific antibodies when the responses are modulated by anti-carrier antibodies.
Either alone or in combination with antibodies having specificity for the carrier erythrocyte, TNP-ORBC were injected i.p. into CBA/J mice. Five days later, their spleens were removed and evaluated for TNP-specific PFC. The spleens from animals receiving 19S antibody (IgM) with carrier specificity displayed 3-4-fold more direct and indirect hapten-specific PFC than control animals receiving the TNP-erythrocyte conjugate only. Animals receiving 7S antibodies (IgG) with carrier specificity displayed very little change in their direct PFC response to the hapten. However, the indirect response to the hapten was suppressed as much as 16-fold by carrier specific IgG. Evaluation by haptenic inhibition of the relative avidity of the antibodies being secreted by these cells revealed the following: the relative avidity of antibodies secreted by indirect PFC in the spleens of animals receiving TNP-ORBC only was approximately 20-fold higher than antibodies secreted by the direct PFC. The 3-4-fold potentiation of the hapten-specific PFC response by carrier-specific IgM antibody did not result in a change in relative avidity of direct or indirect PFC. IgG with carrier specificity did not change the relative avidity of the antibodies secreted by direct PFC having specificity for the hapten. However, evaluation of the remaining PFC in spleens from animals whose indirect hapten-specific PFC response had been suppressed by carrier-specific IgG revealed that the remaining PFC had a lower avidity than indirect PFC from animals receiving TNP-ORBC only. In other words, carrier-specific IgG selectively induced suppression of high avidity hapten-specific IgG antibody secreting cells.
Animals↗
The immune response of the mammary gland and its significance for the neonate.
The immune response of the mammary gland is dominated by local production of secretory IgA antibodies (SIgA). These milk antibodies, amounting to about 0.5-1 g/day throughout lactation, are directed against food proteins and microorganisms often present in the intestine. This is presumably explained by the enteromammaric link: after antigenic exposure in the Peyer's patches of lymphoid cells they home to various exocrine glands, including the mammary gland. Similarly, lymphoid cells from the bronchial mucosa, may contribute to the antibody-producing cell population in the mammary gland. SIgA antibodies against common foods like cow's milk and soy proteins are regularly found in milk if such proteins are part of the mother's diet. It is possible, but unproven, that milk antibodies can decrease the exposure of the infant's intestinal mucosa to foreign food proteins introduced during continued breast-feeding. Milk SIgA antibodies do not prevent intestinal colonization by microorganisms, against which the milk antibodies are directed. The SIgA antibodies are thought to exert protection primarily by preventing contact between the microorganisms and the mucosal membranes. In this manner, human milk blocks attachment of otitis media-causing strains of pneumococci and H. influenzae to retropharyngeal cells, possibly explaining why breast-feeding may prevent otitis media. Milk antibodies have anti-attachment capacity, but there is also low molecular weight material in the milk with this capacity. It probably consists of analogues to the oligosaccharide receptor for pneumococci on the retropharyngeal cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Caries increment and progression in teenagers when using a prevention- rather than restoration-oriented treatment strategy.
In a group of young teenagers restorative treatment on approximal carious surfaces was postponed until carious lesions were radiographically detected in the dentine, permitting a reallocation of resources to preventive care. The development of new lesions and the rate of progression of unrestored lesions were studied by means of bitewing radiographs obtained at 13 and 16 years of age. Of the radiographically sound surfaces at age 13, 1.3% developed dentinal lesions within the three year period. Approximately 18% of outer enamel lesions and about 55% of inner enamel lesions progressed into the dentine. The number of new lesions as well as the rate of progression varied between groups of patients exhibiting different caries experience at age 13. A total of 1.2 surfaces per patient required restorative treatment according to the treatment strategy applied compared to 5.3 if all radiographically diagnosed lesions would have been restored.
Adolescent↗
Changes in the lateral distribution of the light-harvesting chlorophyll-a/b--protein complex induced by its phosphorylation.
The effect of protein phosphorylation on the distribution of chlorophyll-protein complexes between appressed and non-appressed thylakoid regions of spinach chloroplasts has been investigated. Stroma lamellae vesicles and inside-out vesicles, representative of non-appressed and appressed thylakoids, respectively, were isolated from thylakoid membranes before and after phosphorylation. The fractions were analyzed with respect to the yield of vesicles, incorporation of [32P]phosphate into the light-harvesting chlorophyll-a/b--protein complex, chlorophyll composition, and the relative content of the main chlorophyll-protein complexes. The yield of inside-out vesicles from phosphorylated thylakoids was 20% lower than that from control thylakoids, indicating a partial destacking. The specific incorporation of [32P]phosphate into the light-harvesting chlorophyll-a/b--protein complex was at least four times higher in stroma lamellae vesicles than in inside-out vesicles. The proportion of the light-harvesting chlorophyll-a/b--protein complex in stroma lamellae vesicles increased from 13% to 21% of their total chlorophyll after phosphorylation of the thylakoids. There was also a corresponding increase in the level of chlorophyll b. These observations strongly suggest that phosphorylated light-harvesting complexes migrate from appressed thylakoids rich in photosystem 2 to non-appressed thylakoids rich in photosystem 1. In contrast, there was no evidence for a lateral migration of the chlorophyll-a--protein complex of photosystem 2 after phosphorylation. Our results indicate that a lateral migration of phosphorylated light-harvesting complexes in combination with a lateral separation of photosystem 1 and 2 to the different thylakoid regions, is a basis for the regulation of excitation energy between the two photosystems.
Chemical Phenomena↗
Identification of an active disaccharide unit of a glycoconjugate receptor for pneumococci attaching to human pharyngeal epithelial cells.
Glycoconjugates containing the disaccharide unit GlcNAc beta 1 leads to 3Gal beta were suggested as receptors for pneumococci adhering to human pharyngeal epithelial cells. The receptor activity was detected both by inhibition of adhesion by an excess of free oligosaccharide and by induction or increase of adhesion after coating of target cells with glycolipid. Studies with free natural and synthetic oligosaccharides identified the disaccharide GlcNAc beta 1 leads to 3Gal beta as one critical binding site. The specificity of recognition was shown inter alia by the lack of inhibitory activity of GlcNAc beta 1 leads to 4Gal beta, which differs only in the linkage of the two sugars. Specific interference with pneumococcal adhesion by administration of soluble receptor sugar may improve our understanding of the role of adhesion in vivo.
Animals↗
Mucosal immunity.
Mucosal defense is provided by a number of host factors countering the specific virulence factors of the many microorganisms infecting the mucous membranes. Secretory IgA antibodies presumably play an important role. Increase of the sIgA antibodies may most advantageously be attained by parenteral immunization, following mucosal priming. This was demonstrated in a rat model, where it was also noted that antigen injection into PP induced high milk IgA antibody levels. In man, parenteral vaccination against polio increased the sIgA antibody levels in the milk of mothers previously exposed naturally to the poliovirus. The response was relatively short-lived. In the previously unexposed, there was little or no response. By contrast peroral immunization with live poliovirus vaccine did not increase, or even decrease, the milk sIgA poliovirus antibody levels. Although salivary sIgA antibodies against antigens of colonizing E. coli appear during the first days of life, they are slow to increase. This deficiency is richly compensated for by all the sIgA antibodies that are provided the baby through the milk. No transfer of dimeric IgA into the milk could be shown in lactating rats, in contrast to what has been reported in mice. There is no evidence for a contribution to milk sIgA from serum in man. Close to parturition, human milk often contains some 7S IgA and various sizes of free SC, in addition to the dominating 11S sIgA. A few days later there is almost exclusively monomeric SC and 11S sIgA. IgG antibodies also play a role at the mucosal level. IgG2 antibodies against the bacterial polysaccharide capsule are as slow to appear as sIgA in ontogeny, possibly explaining the prevalence of infections with encapsulated bacteria and the poor response to polysaccharide vaccines in early childhood. Other defense factors preventing infections by way of mucous membranes may be important. Thus, oligosaccharides present in human milk seem to specifically prevent pneumococcal attachment to retropharyngeal cells. This anti-attachment capacity, in addition to that provided by milk and salivary IgA antibodies, may explain why breast-fed babies have less otitis media than formula-fed ones.
Adult↗
Receptor analogues and anti-pili antibodies as inhibitors of bacterial attachment in vivo and in vitro.
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Adhesiveness↗
Reconstitution of oxygen evolution in high salt washed photosystem II particles.
Photosystem II thylakoid particles possessing high rates of oxygen evolution, were shown to have a very simple polypeptide composition. Upon washing of these particles with 250 mM NaCl the oxygen evolution was inhibited up to 80% concomitant with a release of two polypeptides of 23 and 16 kDa. Readdition of the pure 23 kDa protein to the depleted thylakoids under low ionic strength reconstituted more than half of the lost activity. No stimulation was obtained with the 16 kDa protein alone or in combination with glycerol. The results give further strong evidence that the 23 kDa protein is an essential component in the oxygen evolving complex. The possible involvement of other proteins in this complex is discussed in light of the demonstrated simple polypeptide pattern of the photosystem II particles.
Chloroplasts↗
Hydroperoxide-dependent activation of p-phenetidine catalyzed by prostaglandin synthase and other peroxidases.
p-Phenetidine is metabolized by ram seminal vesicle (RSV) microsomes, horseradish peroxidase (HRP) and rat liver microsomes to protein-binding products. These reactions are very rapid and depend on the presence of arachidonic acid (AA) or various hydroperoxidases. The RSV- and HRP-mediated binding was inhibited more than 80% by the addition of reduced glutathione (1 mM) or the antioxidant butylated hydroxyanisole (0.5 mM). Indomethacin (100 microM) and acetylsalicylic acid (1 mM) reduced the AA-dependent reaction in RSV microsomes to less than 5% of control values. When hydrogen peroxide replaced AA, the RSV/H2O2-supported binding in the presence of 50 microM p-phenetidine proceeded at rates similar to that observed with RSV/AA. Unlike the AA-dependent reaction, the H2O2-supported reaction showed no inhibition of protein binding at higher p-phenetidine concns. The data in this report are consistent with a peroxidatic activation of p-phenetidine possibly involving an amine radical catalyzed by prostaglandin synthase (PGS) present in RSV microsomes as well as by other peroxidases. The mechanism for this activation and physiological implications are discussed.
Aminophenols↗
[Long-lasting pain relief with rectal methadone therapy].
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Aged↗
Follicular fluid steroid levels and ovarian steroid secretion in polycystic ovarian disease.
Comparison of the plasma levels of steroids between ovarian and peripheral venous blood in polycystic ovarian disease revealed that polycystic ovaries secreted androstenedione, testosterone, dihydrotestosterone, dehydroepiandrosterone and 17-hydroxyprogesterone significantly more than healthy ovaries at the early follicular phase of the cycle, whereas the levels of estradiol and progesterone did not differ from the control values. Follicular cyst fluid from polycystic ovaries showed significantly higher concentrations of testosterone, androstenedione jand dehydroepiandrosterone and much lower levels of estrone, estradiol, progesterone and 17-hydroxyprogesterone than follicular fluid from healthy preovulatory follicles. Testosterone and estradiol did not, however, show any significant difference when follicles in polycystic ovaries were compared to those in healthy ovaries at early follicular phase of the cycle. According to these findings follicle development in polycystic ovaries is arrested at a stage corresponding to the early follicular phase of the cycle. Increased androgen and 17-hydroxyprogesterone secretion by polycystic ovaries seems to originate mainly from the hyperplastic theca interna cells.
Adult↗