Search PubMed⌕ Search

Biomedical subjects

A Noble

Publications and source records attributed to A Noble.

At least 55 records · Page 3Linked to original sources
PubMed1993

Elimination of IgE regulatory rat CD8+ T cells in vivo increases the co-ordinate expression of Th2 cytokines IL-4, IL-5 and IL-10.

Immunization of rats with soluble antigen (ovalbumin) and the castor bean toxin, ricin, eliminates a subpopulation of CD8+ T cells which suppress IgE responses in vivo. This treatment also reduces the ability of splenic T cells to produce interferon-gamma (IFN-gamma) and enhances their capacity to make interleukin-4 (IL-4). In this report we describe the effect of immunization with ricin and antigen on the expression of mRNA for other T-helper type 2 (Th2) cytokines--IL-5 and IL-10--and their relationship to serum IgE and IL-4 mRNA expression. Splenocytes were taken from rats at different times after immunization with antigen or ricin and antigen and activated in vitro with phorbol myristate acetate (PMA) and ionomycin for 6 hr and total RNA extracted and reverse transcribed. Cytokine gene expression was detected using a quantitative polymerase chain reaction (PCR). Expression of IL-4, IL-5, and IL-10 was increased 7-20-fold 11 days after immunization with ricin and antigen (from 0.107% to 0.769% beta-actin for IL-4, from 0.0167% to 0.381% beta-actin for IL-5, and from 0.0581% to 0.954% beta-actin for IL-10), and preceded maximum serum IgE levels by 4-5 days. There was no increase in IgE or mRNA for these cytokines in rats immunized with antigen alone. The level of IL-4, IL-5, and IL-10 expression declined rapidly after 12 days. Our results suggest that immunization with antigen and ricin preferentially induces a Th2 response, and that CD8+ T cells may play a part in down-regulating the development of Th2 T cells.

Animals↗
PubMed1993

Generation of rat Th2-like cells in vitro is interleukin-4-dependent and inhibited by interferon-gamma.

Differentiation of naive T cells into effector cells producing T helper type 1 (Th1) and Th2 cytokines is regulated by the presence of specific cytokines in the T-cell microenvironment. The effect of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) on Th1- and Th2-like cell development was investigated in cultures of mixed rat spleen cells. These cells were cultured for 4 days in medium containing concanavalin A (Con A) with or without additional IL-2, IFN-gamma or IL-4. The cells were then washed and their capacity to produce IL-4, IL-5 and IFN-gamma determined following stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. Freshly isolated cells stimulated with PMA and ionomycin expressed detectable levels of IL-4 and IL-5 mRNA as measured by a quantitative polymerase chain reaction (PCR) procedure and much higher levels of IFN-gamma mRNA. Cells cultured with Con A for 4 days, washed, and restimulated with PMA + ionomycin were unable to express detectable levels of IL-4 and IL-5 mRNA, but produced high levels of IFN-gamma mRNA. Addition of IL-4, or anti-IFN-gamma antibody, to Con A-driven splenocyte cultures restored the ability of restimulated cells to express IL-4 and IL-5. CD4+ T cells isolated from these cultures also showed an increased capacity to secrete IL-4 and IL-5 when anti-IFN-gamma and IL-4 were present in the culture medium. When cultured for 4 days with Con-A, IL-4 and anti-IFN-gamma splenocytes showed an increased capacity to proliferate in response to recombinant IL-2 and proliferated in response to IL-4 alone. IL-2 had no effect on cytokine production by cultured splenocytes. These results indicate that: (1) IL-4 is essential for the generation of Th2-like cells; (2) IFN-gamma inhibits IL-4 production by mixed spleen cells and suppresses generation of IL-4 responsive T cells; (3) in mixed spleen cell cultures mitogenic stimulation favours differentiation of naive rat T cells into effector cells expressing a Th1, and not Th2, cytokine profile.

Animals↗
PubMed1993

Elimination of IgE regulatory rat CD8+ T cells in vivo differentially modulates interleukin-4 and interferon-gamma but not interleukin-2 production by splenic T cells.

Intraperitoneal immunization of Hooded Lister rats with a soluble antigen such as bee venom phospholipase A2 (PLA2), or ovalbumin (OVA) together with the toxic lectin, ricin, eliminates a population of early-activated CD8+ T cells which regulate IgE production. These early-activated CD8+ T cells are eliminated because they bear increased ricin-binding glycoproteins on their surface. This immunization regimen produces a vigorous and long-lived IgE response. The effect of this treatment on the capacity of splenic T cells to secrete interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and to generate IL-4 RNA message was assessed. IFN-gamma production by phytohaemagglutinin (PHA)- or ionomycin and phorbol myristate acetate (PMA)-stimulated splenocytes or purified splenic T cells from animals immunized with antigen and ricin was substantially reduced as compared with animals which were given saline or antigen alone (P < 0.001 Student's t-test). At the height of the primary IgE response IFN-gamma production by PHA-stimulated splenocytes was positively correlated with the number of CD8+ T cells (r = 0.90, P < 0.001) and inversely related to the level of serum IgE (r = -0.77, P < 0.020); serum IgE was inversely related to the number of CD8+ T cells (r = -0.92, P < 0.001). The reduced capacity of spleen cells from ricin and antigen immunized rats to produce IFN-gamma was first seen 7 days after immunization. The fall in the ability of splenocytes to secrete IFN-gamma closely paralleled the rise in serum IgE. IL-2 was assayed using an IL-2-dependent cell line which responded to rat IL-2 but not IL-4. Production of IL-2 by splenocytes taken from rats immunized with ricin+antigen was not significantly different to that produced by comparable cells obtained from animals immunized with antigen alone or saline. However, the levels of IL-4 mRNA, detected in ionomycin and PMA-stimulated splenocytes using a quantitative polymerase chain reaction (PCR) procedure, were three- to fourfold higher in ricin and antigen immunized animals as compared with control animals. Following boosting with antigen and ricin the levels of IL-4 message detected increased a further three- to fourfold. These data show that the potentiated IgE response produced by immunization with antigen+ricin is associated with a decreased ability of splenocytes to produce IFN-gamma and an increased capacity to make IL-4.

Animals↗
PubMed1991

Behavioural and biochemical evidence of the interaction of the putative antipsychotic agent, BMY 14802 with the 5-HT1A receptor.

The behavioural and biochemical profile of the sigma ligand and putative antipsychotic agent, BMY 14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2- pyrimidinyl)-1-piperazine butanol) has been determined in the mouse and rat. In mice, pretreatment with BMY 14802 attenuated both amphetamine-induced hyperactivity and conditioned avoidance responding, consistent with its previously reported antipsychotic potential. In common with 5-HT1A receptor agonists or partial agonists, BMY 14802 induced (a) a dose-dependent hypothermia in mice; (b) aspects of the 5-HT behavioural syndrome in rats, (c) antagonised mescaline-induced head twitches in mice and (d) generalised to the 8-hydroxy-2-(di-n-propylamino)tetralin discriminative stimulus over the dose range of 3-15 mg/kg. BMY 14802 had appreciable affinity for the 5-HT1A receptor (pIC50 = 6.7 compared to 7.3 for sigma binding) and antagonised forskolin-stimulated adenylate cyclase activity with a pEC50 of 6.2, consistent with an agonist action at this receptor. The results support the involvement of 5-HT1A receptors, but not the sigma binding site, in the behavioural profile of BMY 14802.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Performance of cryptococcus antigen latex agglutination kits on serum and cerebrospinal fluid specimens of AIDS patients before and after pronase treatment.

Cryptococcal antigen titers in 97 serum and 42 cerebrospinal fluid (CSF) specimens from 37 AIDS patients with culture-proven cryptococcal infection were determined with the Meridian kit (Meridian Diagnostics Inc., Cincinnati, Ohio) before and after treatment with pronase. The geometric mean titers before and after pronase treatment were 1:45 and 1:588 in serum and 1:97 and 1:79 in CSF, respectively. Only on serum (but not CSF) specimens after pronase treatment were (i) titers increased by 2 to 13 dilutions on 57% of the specimens, all of which had titers of less than or equal to 1:128 before pronase treatment, (ii) false-negative reactions on 27% of specimens before pronase treatment eliminated, all of which had titers from 1:4 to 1:4,096, (iii) prozone-like reactions (titer, less than or equal to 1:256) on 9% of the specimens before pronase treatment eliminated, and (iv) agglutination reactions on all specimens stronger and easier to interpret. Antifungal agents added to serum as well as freeze-thaw cycles did not change antigen titers in serum. After two separate tests, the same titers were obtained on 94% of 35 serum specimens that were treated with pronase and on 96% of 53 CSF specimens that were not treated with pronase. A total of 26 serum specimens and 28 CSF specimens from patients with no cryptococcal disease were negative before and after pronase treatment. The IBL kit (International Biological Labs Inc., Cranbury, N.J.) was compared with the Meridian kit on 41 serum specimens and 14 CSF specimens. Results from the two kits agreed on 54 and 68% of serum specimens and 86 and 93% of CSF specimens before and after pronase treatment, respectively. The IBL kit generally produced higher titers on specimens in disagreement and produced no prozone-like reactions. Routine pronase treatment of serum is recommended with the Meridian kit in order to eliminate false-negative and unclear agglutination reactions by producing a consistent interpretation of agglutination reactions. CSF specimens do not require pronase treatment. Titer results produced by the kits from the two different manufacturers varied considerably: the kits should not be used interchangeably for determining antigen titers in serum specimens.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Regulation of inactive renin secretion: studies with aprotinin.

The kidney and plasma of many species contain both an active form of renin and an inactive, but activatable, form. The kallikrein inhibitor aprotinin suppressed acid-activation of rabbit plasma inactive renin but not activation of the form of inactive renin released by rabbit kidney cortex slices incubated in vitro. This suggests that inactive renin is structurally modified after secretion. An aprotinin-sensitive step appears to regulate inactive renin secretion. Aprotinin inhibited inactive, but not active, renin secretion by rabbit kidney cortex slices and selectively suppressed the elevated release of inactive renin produced in sheep by the converting enzyme inhibitor enalapril. In anaesthetised rats, aprotinin potentiated the increase in plasma renin produced by captopril.

Animals↗