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Biomedical subjects

A C Allison

Publications and source records attributed to A C Allison.

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

Inhibition of experimental autoimmune uveoretinitis by mycophenolate mofetil, an inhibitor of purine metabolism.

Mycophenolate mofetil (MM), an inhibitor of purine metabolism, was found to effectively inhibit the development of experimental autoimmune uveoretinitis (EAU) induced by S-antigen (SAg) in Lewis rats. MM completely inhibited EAU development in the majority of rats when administered daily, on days 0-13, at a dose of 30 mg kg-1 day-1. The drug was less effective, however, when given on days 7-20: minimal disease inhibition was achieved with the drug at 30 mg kg-1 day-1, although at 60 mg kg-1 day-1 the drug inhibited EAU development in most treated rats during the period of its administration. MM also completely inhibited in most treated rats the development of EAU adoptively transferred by SAg-sensitized lymphocytes, thus depicting its capacity to inhibit the efferent limb of the immune response. Treatment with MM also suppressed the cellular and humoral immune responses against SAg, with a good correlation being observed between the inhibition of these responses and suppression of EAU in the different groups of rats. MM is currently being examined for its immunosuppressive effects in humans and the data recorded here thus suggest this compound may be useful in treatment of immune-mediated uveitic conditions.

Animals↗
PubMed1994

Extraction of intraerythrocytic malarial parasites by phagocytic cells.

Phagocytosis is an intricate process adopted by some unicellular organisms as a feeding behaviour. It has developed in the tissues of multicellular organisms, both vertebrates and invertebrates, as a defence system to confine and eliminate foreign matter and, in this manner, protect the host against infection. During evolutionary development, phagocytic cells have evolved to show greater specificity. Lakshmi Kumaratilake, Antonio Ferrante, Jaliya Kumaratilake and Anthony Allison here describe a unique mechanism used by phogocytic leukocytes to engulf intra-erythrocytic malarial parasites.

Journal Article↗
PubMed1994

Vaccinating guinea pigs with recombinant glycoprotein D of herpes simplex virus in an efficacious adjuvant formulation elicits protection against vaginal infection.

Guinea pigs were immunized with glycoprotein gD-2t in SAF-m or saline, then challenged with herpes simplex virus, type 2 (HSV-2). Animals given gD-2t in SAF-m had higher anti-gD-2t antibodies, fewer and less severe vaginal lesions, and decreased ganglionic latency compared to animals given gD-2t in saline. Leucocytes from animals vaccinated with gD-2t in SAF-m had greater proliferative responses to gD-2t in vitro than cells from control animals. MHC II-restricted, gD-2t-specific cytotoxic T cells were induced in guinea pigs vaccinated with gD-2t in SAF-m. Thus, immunization of guinea pigs with gD-2t in SAF-m markedly reduced the incidence and severity of primary HSV-2 by eliciting both humoral and cell-mediated responses.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1994

Adjuvants and immune enhancement.

Adjuvants increase cell-mediated and humoral immune responses to specific antigens. Used with recombinant viral antigens, they can elicit the production of T lymphocytes that lyse target cells, expressing the antigen in a genetically restricted fashion. Adjuvants can augment the production of interferon-gamma, thereby favoring the production of protective antibody isotopes, such as immunoglobulin G2a in the mouse. Modern adjuvants display the efficacy of Freund's complete adjuvant without its side effects. One such adjuvant is Syntex adjuvant formulation, a synthetic analogue of muramyl dipeptide in a microfluidized squalane/squalene-in-water emulsion. Monophosphoryl lipid A in a similar lipid emulsion is also effective. Immune-stimulating complexes of saponin and antigens elicit potent cell-mediated and humoral responses. A purified saponin component has adjuvant activity with reduced side effects; liposomes also can have adjuvant activity. Administering antigens in adjuvants can overcome low responsiveness in very young and old experimental animals and in those that are genetically low responders. Adjuvants are likely components of a new generation of recombinant and subunit vaccines.

Adjuvants, Immunologic↗
PubMed1994

Some antioxidants inhibit, in a co-ordinate fashion, the production of tumor necrosis factor-alpha, IL-beta, and IL-6 by human peripheral blood mononuclear cells.

Some antioxidants, including butylated hydroxyanisole (BHA), tetrahydropapaveroline (THP), nordihydroguiauretic acid, and 10,11-dihydroxyaporphine (DHA), were found to be potent inhibitors of the production of tumor necrosis factor (TNF)-alpha, IL-1 beta, and IL-6 by human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS) (IC50s in the low micromolar range). Inhibition of cytokine production was gene selective and not due to general effects on protein synthesis. Inhibition of cytokine production by PBMC was observed also when other inducers were used (staphylococci, silica, zymosan). Much higher concentrations of other antioxidants--including ascorbic acid, trolox, alpha-tocopherol, butylated hydroxytoluene, and the 5-lipoxygenase inhibitor zileuton--did not affect the production of these cytokines. The active compounds did not inhibit IL-1-induced production of IL-6 in fibroblasts, showing the cell selectivity of the effect. Antioxidant-mediated inhibition of cytokine production was correlated with low levels of the corresponding messenger RNAs. Nuclear run-on experiments showed that THP inhibited transcription of the IL-1 beta gene. THP decreased the concentration of the transcription factors NF-kappa B and AP-1 detected in nuclear extracts of PBMC cultured in the presence or absence of LPS. THP and DHA markedly decreased the levels of TNF-alpha and IL-1 beta in the circulation of mice following LPS injection. Thus antioxidants vary widely in potency as inhibitors of the activation of transcription factors and of the transcription of genes for pro-inflammatory cytokines. Coordinate inhibition of the transcription of genes for inflammatory cytokines could provide a strategy for therapy of diseases with inflammatory pathogenesis and for septic shock.

Antioxidants↗
PubMed1994

Gingival fluid IL-1 beta and IL-6 levels in menopause.

Menopause and oophorectomy without estrogen therapy (ED) have been associated with increased production of bone-active cytokines by peripheral blood mononuclear cells. The current study extended evaluation to gingival crevicular fluid (GCF) levels of interleukin (IL)-1 beta and IL-6 in such subjects compared to premenopausal and postmenopausal estrogen-treated females (ES). 13 ED and 13 ES Caucasians with a history of moderate-severe adult periodontitis provided GCF from 1-3 clinically identical sites each (5-6 mm probing depth, 5-7 mm clinical attachment loss, bleeding on probing). 30 s GCF samples were obtained and evaluated for IL-1 beta and IL-6 levels using two-site enzyme-linked immunosorbent assays (ELISAs). The frequency of GCF IL-1 beta-positive subjects was elevated in ED versus ES (92% versus 23%; p < 0.0004, chi 2 analysis). IL-6 was detected more frequently in ED subjects (23% versus 8%; not significant); however, the frequency of IL-6 detection was low in both groups due to short sampling times. These data support the concept that clinical conditions causing low estrogen environments allow increased local production of the bone-active cytokine IL-1 beta, and perhaps IL-6.

Adult↗
PubMed1994

Effect of mycophenolic acid on Epstein-Barr virus infection of human B lymphocytes.

The effect of mycophenolic acid (MPA) on the growth of Epstein-Barr virus (EBV)-transformed B cells and on EBV lytic-cycle gene expression was investigated. MPA inhibited the proliferation of newly infected or established EBV-transformed B-cell lines but was not able to block cell growth transformation or the viral lytic cycle. These results suggest that MPA might reduce transformed-cell proliferation in transplant patients and possibly decrease the risk of development of EBV-related lymphoproliferative disorders.

B-Lymphocytes↗
PubMed1993

Novel immunosuppressive and antiinflammatory drugs. A 1993 perspective.

Research on immunosuppressive and antiinflammatory drugs is progressing rapidly. Several new drugs are in development, and learning how to combine them optimally, for treatment of different diseases and prolonging graft survival, will be a major task for the next few years. Decreasing the incidence of complications following transplantation will reduce patient anxiety and cost, and the shortage of donor organs is an additional reason for wishing to prolong graft acceptance. Many clinical findings with the new drug combinations should be published by the end of the century. We can begin the next millennium with improved immunosuppressive and antiinflammatory drugs discussed at the Orlando conference.

Animals↗
PubMed1993

Gingival fluid IL-1 and IL-6 levels in refractory periodontitis.

Selected gingival bacteria and cytokine profiles associated with patients who did not respond to conventional periodontal therapy (refractory) were evaluated. 10 subjects with a high incidence of post-active treatment clinical attachment loss (> 2% sites/year lost > or = 3 mm) were compared to 10 age-, race-, and supragingival plaque-matched patients with low post-treatment clinical attachment loss (< 0.5% sites/year) relative to the following parameters at 2 sites/patient with the deepest probing depths: (1) presence of 3 selected periodontal pathogens (Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Eikenella corrodens) in subgingival plaque as determined by selective culturing, and (2) gingival crevicular fluid (GCF) levels of 3 cytokines associated with bone resorption (IL-1 alpha, IL-1 beta, IL-6) as determined by two-site ELISA. Results indicated no significant differences in any clinical measurement (except incidence of clinical attachment loss), in the presence of any bacterial pathogen, or in GCF cytokine levels between refractory subject sites versus stable subject sites. However, when sites producing the greatest total GCF cytokine/patient were compared, sites from refractory patient produced significantly more IL-6 (30.1 +/- 4.0 versus 15.4 +/- 2.8 nM, p < 0.01). The subgingival presence of each of the 3 bacterial pathogens was associated with elevated GCF IL-1 concentrations. These data suggest that gingival IL-1 and IL-6 production is different in response to local and systemic factors associated with periodontitis, and that IL-6 may play a role in the identification and mechanisms of refractory periodontitis.

Adult↗
PubMed1993

IL-1 in gingival crevicular fluid following closed root planing and papillary flap debridement.

Interleukin (IL)-1 alpha and beta are cytokines which can mediate inflammatory, bone resorbing, and reparative effects in the periodontium, but few longitudinal data exist exploring their role following periodontal therapy. This study examined gingival crevicular fluid (GCF) concentrations of IL-1 alpha and IL-1 beta at sites with shallow sulci (SS) or inflamed moderate/advanced pockets (M/AP) before and 6 months after treatment with closed scaling/root planing (SC/RP) or papillary flap debridement (PFD), all in the same subject (n = 14 patients). No significant differences were noted in IL-1 alpha or beta concentrations (determined with two-site enzyme-linked immunosorbent assays) between SS and M/AP sites at baseline. While both therapies improved clinical parameters of periodontal disease, IL-1 alpha concentration increased significantly (p < 0.05) in M/AP-PFD sites 6 months after treatment, but were unchanged in other groups. IL-1 beta concentrations were numerically lower after therapy, except for a significant increase (p < 0.05) in M/AP-PFD sites. These data suggest that surgical wound healing in an inflamed, plaque-infected site (M/AP-PFD) results in prolonged production of IL-1, which may be a reflection of the extent of tissue trauma and delayed wound healing. In spite of increased IL-1 levels, these sites demonstrated significant short-term improvement in clinical attachment level (+ 1.8 mm, p < or = 0.001) postoperatively.

Adult↗