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Biomedical subjects

A C Allison

Publications and source records attributed to A C Allison.

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

Gingival crevicular fluid IL-8: correlation with local IL-1 beta levels and patient estrogen status.

Gingival crevicular fluid (GCF) IL-8 and IL-1 beta levels were determined by sandwich enzyme-linked immunosorbent assays. Associations between IL-8 and IL-1 beta GCF levels, and between these cytokines and patient estrogen status were evaluated. IL-8 and IL-1 beta were detected more frequently and in higher amounts/30 s GCF sample in estrogen-deficient patients than in estrogen-sufficient patients. IL-8 and IL-1 beta GCF levels were significantly correlated. These findings suggest that GCF IL-8 levels are associated with patient estrogen status and local IL-1 beta concentrations.

Adult↗
PubMed1993

Inhibition by glucocorticoids of the formation of interleukin-1 alpha, interleukin-1 beta, and interleukin-6: mediation by decreased mRNA stability.

The mechanism by which glucocorticoids inhibit interleukin (IL)-1 and IL-6 formation in human monocytes and a promonocytic cell line activated by Escherichia coli lipopolysaccharide was analyzed. Dexamethasone (DEX) decreased levels of IL-1 alpha and IL-1 beta mRNAs in a dose-related fashion. The DEX-induced decrease in levels of IL-1 alpha and IL-1 beta mRNAs was abolished by the steroid receptor antagonist RU486. The levels of IL-1 alpha and IL-1 beta proteins within the cells and of IL-1 beta in the culture medium were decreased by DEX to comparable extents, so that DEX had no detectable effect on cytokine secretion. DEX did not influence lipopolysaccharide-induced transcription of the IL-1 beta gene in monocytes. However, DEX markedly decreased the stability of IL-1 beta mRNA, as shown both by steady state measurements and by pulse-labeling. DEX-induced instability of IL-1 beta mRNA required protein synthesis. DEX was also found to be a potent inhibitor of IL-1-induced expression of the IL-6 gene in connective tissue-type cells from the synovium of patients with rheumatoid arthritis. Inhibition of the formation of proinflammatory cytokines, including IL-1 beta and tumor necrosis factor-alpha, is a mechanism by which glucocorticoids exert anti-inflammatory effects. Inhibition by glucocorticoids of the expression of IL-1 alpha in antigen-presenting cells could decrease the capacity of the cells to stimulate the proliferation of T lymphocytes. This activity, as well as inhibition of the production and effects of IL-1 beta, including induced formation of IL-6 and of certain lymphokines, could explain the immunosuppressive effects of glucocorticoids.

Cell Line↗
PubMed1992

High levels of "complexed" interleukin-6 in human blood.

The biochemical nature of endogenous interleukin-6 (IL-6) as it exists in human serum or plasma was investigated. Serum from a patient following bone marrow (BM) transplantation and fresh plasma samples from patients with epidermolysis bullosa or psoriasis, as well as from normal volunteers, were fractionated through G-200 columns and each of the eluted fractions assayed for IL (interleukin)-6 content using enzyme-linked immunosorbent assays (ELISAs) based on the monoclonal antibody (mAb) pairs IG61/5IL6 or 4IL6/5IL6 and in the B9 hybridoma growth factor bioassay. The IG61/5IL6 ELISA and the B9 assay detected IL-6 in BM serum almost exclusively of molecular mass approximately 20 kDa. In contrast, the 4IL6/5IL6 ELISA detected strong IL-6 immunoreactivity in complexes of size 100-150 and 400-500 kDa. IL-6 present in the 100-150- and 400-500-kDa complexes was purified by immunoaffinity chromatography through a 5IL6 mAb column. The 5IL6 mAb immunoaffinity column eluate of the respective pools from BM serum contained IL-6 at concentrations approaching 1 microgram/ml as characterized by Western blotting. Sufficient IL-6 and associated proteins were purified by 5IL6 mAb immunoaffinity column chromatography of the 100-150-kDa complex from 0.8 ml of BM serum to allow (i) verification of three of the polypeptides as IL-6 by amino-terminal sequencing (estimate of IL-6 in original serum sample: 5-10 micrograms/ml), (ii) identification by amino acid sequencing of the "associated" proteins as complement factor C3b (carboxyl-terminal of the alpha-chain), complement factor C4b (gamma-chain), C-reactive protein, and albumin, and (iii) detection of an "associated" polypeptide consistent with the soluble IL-6 receptor. Taken together, these data establish that IL-6 is present at unexpectedly high concentrations in human blood in novel biochemical complexes that include other plasma proteins, which in turn, can camouflage IL-6 immunoreactivity and bioactivity as measured in conventional assays.

Amino Acid Sequence↗
PubMed1992

Interleukin 6 determination in the detection of microbial invasion of the amniotic cavity.

A growing body of evidence suggests a role for cytokines in the mechanisms responsible for preterm parturition associated with intrauterine infection. Interleukin 6, a polyfunctional cytokine that is secreted by tissues in the feto-maternal interface in response to microbial products, has been implicated in the host response to intrauterine infection. The purpose of this study was to establish whether measurement of amniotic fluid concentrations of interleukin 6 could be of value in the diagnosis of microbial invasion of the amniotic cavity. Fluid was obtained by transabdominal amniocentesis from patients with preterm labour and intact chorioamniotic membranes and cultured for aerobic and anaerobic bacteria and mycoplasmas. Interleukin 6 concentrations were determined by an ELISA validated for human amniotic fluid. An interleukin 6 concentration above 11.2 ng/ml had a 93.7% sensitivity and a 92.3% specificity in the diagnosis of intra-amniotic infection. Moreover, patients with an amniotic fluid interleukin 6 level above 11.2 ng/ml and a negative amniotic fluid culture failed to respond to tocolysis, delivered a preterm infant and showed histological evidence of chorioamnionitis, and their neonates were at risk for congenital infections.

Amniotic Fluid↗
PubMed1992

Prolongation of murine thyroid allografts by interleukin 2 (DAB486)-toxin and RS-61443.

We evaluated the efficacy of interleukin 2 (DAB486)-toxin (IL-2-diphtheria toxin fusion protein; IL-2-toxin) in combination with RS-61443 to prolong murine thyroid allograft survival. B10.BR thyroid allografts were transplanted beneath the renal subcapsule in recipient (C57BL/10 mice and graft survival determined 21 days later. Treatment with IL-2-toxin (25 microg/day for 14 days) was unable to prolong graft survival significantly. RS-61443 treatment (21 days) achieved significant graft prolongation only at doses of 300 mg/kg daily or greater. When both drugs were used in combination (IL-2-toxin, 25 microg/day for 14 days RS-61443 200 mg/kg daily for 21 days), statistically significant (P < 0.0001) graft prolongation was obtained. Our results suggest that IL-2-toxin in combination with subtherapeutic RS-61443 levels significantly prolongs murine thyroid allograft survival. IL-2-toxin and RS-61443, because of their unique and complementary mechanisms, hold promise for more selective immunosuppression.

Animals↗
PubMed1992

Characterization and applications of the disc angiogenesis system.

A model to study microvascular proliferation, the Disc Angiogenesis System (DAS), consists of a synthetic foam disc implanted subcutaneously in experimental animals. After a period of growth, usually 7 to 21 days, the disc is removed. Planar sections are used to measure and characterize the growth. Microvessels grow centripetally into the disc, together with fibroblasts. Concentric growth zones have been defined by light and electron microscopy. Moderate growth occurs spontaneously and is accelerated by angiogenic stimulants placed in the center of the disc. Morphometric analyses have shown that vessel growth is directly proportional to total fibrovascular growth, so the former can be quantified by procedures measuring the latter. These include manual projection of sections and computer-assisted digital image analysis, which is recommended for routine use. The proliferation of endothelial and other cells is determined by incorporation of tritiated thymidine, using scintillation counting and autoradiography. Using the DAS, well-established angiogenic agents such as basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and prostaglandin E1 were found to increase proliferation of endothelial cells (EC) and microvessels. Heparin augmented the effect of bFGF. When used by itself heparin increased angiogenesis but not EC proliferation, in keeping with in vitro observations indicating that it stimulates migration but not proliferation of EC. Locally applied hyperthermia and ionizing radiation decreased angiogenesis, even when applied after the angiogenic stimulus. Systemic prostaglandin synthetase inhibitors antagonized the angiogenic effects of bFGF and EGF, in accordance with a postulated role of prostaglandins in the transduction of proliferative signals in microvascular EC. The DAS is easy to assemble and implant in small animals, including mice, which tolerate it well. Hence multiple discs can be used for each time or dose point, which allows reproducible measurements of vascular growth and increases statistical accuracy. Another advantage of the system is the capability of discriminating between proliferation and migration of EC and fibroblasts. The DAS can be used to test putative agonists or antagonists of angiogenesis. More generally, the DAS provides a model of wound healing, either uncomplicated or complicated by inflammation, and of angiogenic responses to solid tumors.

Animals↗
PubMed1992

Facilitation of specific tolerance induction in adult mice by RS-61443.

RS-61443 is an immunosuppressive agent that facilitates pancreatic islet allograft acceptance in two mouse strain combinations (BALB/c----CBA and C57Bl/6J----BALB/c). A remarkable feature of this agent is its ability to facilitate long-term graft acceptance after a short (30 days) period of treatment; following withdrawal of the agent 40-70% of islet allografts are maintained for an indefinite period. This long-term graft acceptance has been shown to result from specific tolerance induction in the recipient animal. The state of specific tolerance is an active rather than a passive form of tolerance, such as clonal deletion or anergy. Active tolerance induction is cyclosporine-sensitive, although cyclosporine enhances graft acceptance when used in combination therapy with RS-61443, this agent inhibits tolerance development under the influence of RS-61443.

Animals↗