11beta-hydroxysteroid dehydrogenase and corticosteroid action in lyon hypertensive rats.
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Adrenocorticosteroid activity in Lyon hypertensive (LH) and low blood pressure (LL) rat strains differ in several respects. Abnormal activity of 11beta-hydroxysteroid dehydrogenase enzymes (11beta-HSD1 and 11beta-HSD2), which interconvert corticosterone and inactive 11-dehydrocorticosterone, might contribute to the LH phenotype by regulating corticosteroid hormone access to receptors. 11beta-HSD2 (expressed in kidney but not liver) prevents endogenous glucocorticoids from binding to mineralocorticoid receptors. 11beta-HSD1 (expressed in liver and kidney) favors active glucocorticoid formation from 11-dehydrocorticosterone. 11beta-HSD properties in LH and LL have been compared by several approaches: (1) 11betaHSD activities have been measured in vitro as corticosterone dehydrogenation and in vivo as interconversion of injected cortisol and cortisone; (2) the effects of cortisol and cortisone on urine electrolytes and volume have been measured; and (3) 11beta-HSD mRNA expression has been measured by in situ hybridization. 11beta-HSD2 enzyme activities in LH and LL rats were similar and urinary cortisone:cortisol ratios were not different after cortisol injection. Cortisol caused a natriuresis and kaliuresis in both strains, with a slightly reduced response in LH rats. Renal 11beta-HSD2 mRNA expression was slightly lower in LH rats. 11beta-HSD1 was less active in LH than LL rats: enzyme activities were lower in tissue extracts; urinary cortisone:cortisol was lower in LL rats after cortisone injections; cortisone increased urine volume in LL but not LH rats; and mRNA levels tended to be lower in LH tissues. We conclude that 11beta-HSD1 is impaired in LH rats. The LH phenotype of heavier adrenals, raised corticosterone, and reduced thymus weight is similar to that described for 11beta-HSD1 knockout mice. (+info)
Growth of Rickettsia typhi in irradiated L cells enhanced by lysosomal stabilization.
(10/508)
The growth of some obligate intracellular parasites is contingent upon avoidance of lysosomal activation during growth in their host cells. This is accomplished by the various parasites by different mechanisms and with different degrees of efficiency. The possibility was tested that the lysosomal stabilizer cortisone acetate might protect and thus enhance the growth of Rickettsia typhi in mouse L cells irradiated 6 days earlier. Beginning 2 days before infection of the L cells with a multiplicity of 10 rickettsiae, 20 microgram of cortisone per ml was added in medium 199 containing 5% fetal calf serum. This concentration of cortisone was below the cytotoxic level, as determined by viability staining, but was sufficient to significantly alter the ratios of cellular and released acid phosphatase and beta-glucuronidase in uninfected and infected cells, as shown by spectrophotometric analysis. Rickettsial replication, measured by hemolytic activity at 96 h and confirmed by microscopic observations at earlier stages of infection, was increased by the cortisone. Cortisone concentrations of 10 or 40 microgram/ml were less effective, and cortisone was ineffective when the rickettsial multiplicity per L cell was 2 or lower. These results indicate that amounts of cortisone that increase lysosomal stabilization in L cells favor rickettsial multiplication when the multiplicity of infection is relatively high. (+info)
Interferon treatment of mice: enhanced expression of histocompatibility antigens on lymphoid cells.
(11/508)
Treatment of young and mature mice with potent mouse interferon preparations results in a marked enhancement of the expression of histocompatibility antigens on the surface of thymocytes and splenic lymphocytes as measured by an enhanced absorption of alloantiserum. We postulate that such modifications of the cell surface may reflect an effect of interferon on lymphocyte maturation and may be relevant to the effect of interferon on lymphocyte function. (+info)
Glucocorticoids and dietary iron regulate postnatal intestinal heavy and light ferritin expression in rats.
(12/508)
To cope with increasing dietary iron exposure, the intestinal epithelium of weaning rats must control intracellular labile iron pools. Intestinal expression of heavy (H) and light (L) ferritin subunits during early weaning and after cortisone administration and/or iron feeding was investigated. Changes in H and L ferritin gene expression were determined by nuclear runoff transcriptional assay, Northern blot analysis, and metabolic labeling of protein synthesis. H ferritin mRNA levels did not change between days 12 and 15, doubled on day 18, and tripled on day 24. L ferritin mRNA was reduced by 50% on days 18 and 24. The protein level of the H and L subunits paralleled the change in mRNAs. Cortisone treatment on day 12 induced a precocious increase of H and decrease of L mRNA expression on day 15. Nuclear runoff assays showed that cortisone did not change H and reduced L ferritin gene transcription. The increased level of H mRNA by cortisone was not translated, unless the rats were fed an iron-fortified diet, which reduced iron regulatory protein activity and stimulated a three- to sixfold increase of ferritin synthesis. Thus changes in intestinal H and L ferritin expression in weaning rats are modulated by glucocorticoids and iron; the former stabilizes H mRNA and suppresses L ferritin gene transcription, and the latter derepresses translation of ferritin mRNA. (+info)
Efficacy of SCH27899 in an animal model of Legionnaires' disease using immunocompromised A/J mice.
(13/508)
The efficacy of SCH27899, a new everninomicin antibiotic, against replicative Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease. A/J mice were immunocompromised with cortisone acetate and inoculated intratracheally with L. pneumophila serogroup 1 (10(5) CFU per mouse). At 24 h postinoculation, mice were administered either SCH27899 (6 to 60 mg/kg [MPK] intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary growth of L. pneumophila were assessed. In the absence of SCH27899, there was 100% mortality in L. pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria. In contrast, administration of SCH27899 at a dose of > or =30 MPK resulted in > or =90% survival of infected mice, which was associated with inhibition of intrapulmonary growth of L. pneumophila. In subsequent studies, the efficacy of SCH27899 was compared to ofloxacin (OFX) and azithromycin (AZI). Administration of SCH27899, OFX, or AZI at a dose of > or =30 MPK once daily for 5 days resulted in > or =85% survival of infected mice and inhibition of intrapulmonary growth of the bacteria. However, L. pneumophila CFU were recovered in lung homogenates following cessation of therapy with all three antibiotics. These studies demonstrate that SCH27899 effectively prevents fatal replicative L. pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria. However, in this murine model of pulmonary legionellosis, SCH27899, like OFX and AZI, was bacteriostatic. (+info)
Mechanisms of corticosteroid action on lymphocyte subpopulations. I. Redistribution of circulating T and b lymphocytes to the bone marrow.
(14/508)
The effect of corticosteroid administration on the redistribution of sirculating lymphocytes was studied in the guinea-pig, since this species closely resembles man in its relative resistance to the lymphopenic effect of corticosteroids. A single intravenous injection of hydrocortisone (either 10 mg or 100 mg/kg) caused a profound but transient lymphocytopenia which was maximal at 4 hours following injection, with a returnto normal counts by 24 hours. There was a proportionately greater decrease in circulating T lymphocytes compared to B lymphocytes, although both populations were diminished. Chronic cortisone acetate treatment (100 mg/kg subcutaneously for 7 days) caused a similiar pattern of lymphocytopenia except that it was sustained during the period of chronically elevated plasma cortisol levels. The lymphocytes remaining inthe circulation during the period of lymphocytopenia responded normally in vitro to the mitogens phytohemagglutinin, concanavalin A, and pokeweek mitogen. There was very littleeffect of corticosteroid administration on the numbers, proportions, or mitogenic response of splenic lymphocytes. There was a dramatic increase in the bone marrow of proportions and absolute numbers of lymphocytes bearing surface T-and B-cell markers, as well as a marked increase in response of bone marrow lymphocytes to mitogenic stimulation during the period of maximal circulating lymphocytopenia caused by the administration of corticosteroids, especially chronic cortisone acetate. There was a preferential homing of reinfused -51Cr-labelled syngeneic peripheral blood lymphocytes to the bone marrow of corticosteroid-treated recipients. These studies demonstrate aredistribution of circulating lymphocytes to the bone marrow during corticosteroid treatment, resulting in an increase in immunocompetence of this compartment, while the peripheral blood lymphocyte compartment is quantitatively immunosuppressed due to a lymphocytopenia. (+info)
Changes in thymocyte reactivity to lectins induced by B-cell mitogens of the type of sulphated polyanions.
(15/508)
Dextran sulphate, polyvinyl sulphate and carrageenan (but not the other polyanions tested, such as poly I:poly C, poly-L-glutamic acid or E. coli lipopolysaccharide) act synergisticaly with PHA on mouse thymocyte stimulation, as measured by thymidine uptake and blast cell transformation. Furthermore the active compounds shift the dose response of thymocytes to Con A. The effect could be observed in four different strains of mice tested by using normal or cortisone-resistant thymocytes. Two possibilities are envisaged for explanation of these effects: (a) attachment of polyanions by their anionic groups to cell surface constituents and interaction of the sulphate groups of the polymers with plant lectins; and (b) modification of the cell membrane induced by sulphated polymers changing either the binding capacity or the effectiveness of the membrane-associated events leading to thymocyte stimulation by the lectins. (+info)
Effect of aprotinin on immunological resistance in tumour-bearing animals.
(16/508)
Previous studies suggested that aprotinin might enhance the host's immunological resistance to tumours. This possibility has now been further investigated by studying the behaviour of tumours in both hamsters and mice. A second tumour graft in tumour-bearing hamsters appeared more rapidly than the first. Prior administration of aprotinin abolished this effect. Pretreatment of non-cancerous mice with cortisone nullified the effectiveness of aprotinin in inhibiting the growth of a subsequent tumour graft. These results are interpreted as additional evidence that aprotinin enhances the immunological system against tumour cells. (+info)