Identification and characterization of the rat intestinal epithelial cell (IEC-18) interleukin-1 receptor.

Interleukin-1 (IL-1), an important mediator of inflammation, may act in chronic inflammatory disorders of the intestine such as idiopathic inflammatory bowel diseases. Although the IL-1 receptor (IL-1R) has been studied extensively in many cell lines, including T cells, B cells, and fibroblasts, it has not been demonstrated on intestinal epithelial cells. IL-1 affects intestinal epithelial cell proliferation in vitro, suggesting the presence of IL-1Rs on intestinal epithelium. This paper demonstrates and further characterizes an IL-1R in a rat intestinal epithelial cell. Cells from rat intestinal epithelial cell line IEC-18 were grown to confluence in six-well plates, and association studies with 125I-labeled IL-1 beta to determine specific binding and equilibrium conditions were performed. A competitive-inhibition curve verified the IL-1 concentration required to saturate the IL-1R, and a Scatchard plot revealed a dissociation constant (Kd) of 1.2 x 10(-10) M, with 1,000 receptors per epithelial cell. Binding studies using increasing concentrations of 125I IL-1 beta alone confirmed the receptor density. Cross-linking 125I-IL-1 beta to the IEC-18 IL-1R demonstrated an IL-1R of approximately 80.5 kDa. cDNA transcribed from IEC-18 mRNA was used as a template for amplification of a segment of the IL-1R using complementary oligonucleotides. The resulting sequence of the IL-1R demonstrated a high degree of homology with both the human and mouse type I IL-1R.(ABSTRACT TRUNCATED AT 250 WORDS)

Eosinophilic cholecystitis, appendiceal inflammation, pericarditis, and cephalosporin-associated eosinophilia.

A patient with eosinophilic cholecystitis and accompanying eosinophilic appendiceal inflammation, eosinophilic pericarditis, and peripheral eosinophilia is described. Review of the nine previously reported cases of eosinophilic cholecystitis suggests that this is the first case with closely associated eosinophilic appendiceal inflammation and pericarditis as manifestations of a systemic hypereosinophilic syndrome. The possible etiologic role of cephalosporin hypersensitivity is discussed.

2-Phenyl-3H-imidazo[4,5-b]pyridine-3-acetamides as non-benzodiazepine anticonvulsants and anxiolytics.

A series of 2-phenyl-3H-imidazo[4,5-b]pyridine-3-acetamides were designed and synthesized as non-benzodiazepine anxiolytics based on a molecular disconnection of a typical 1,4-benzodiazepine (BZD). A number of these compounds showed submicromolar potency in a [3H]benzodiazepine binding assay in vitro and good potency in protecting rodents against pentylenetetrazole-induced seizures. Compound 84 appears to be a selective anticonvulsant (pentylenetetrazole) agent when tested against a profile of chemically and electrically induced seizures in mice. In addition, compound 148 appears to be a selective anxiolytic/hypnotic agent on the basis of biochemical and pharmacological characterization. It appears to be a full BZD agonist as assessed by GABA shift ratio and to be effective in punishment and nonpunishment animal models of anxiety. In addition, it shows a lower side-effect profile than diazepam as assessed by rotorod neurotoxicity and potentiation of ethanol-induced sleep time in mice. The chemistry and structure-activity relationships of this series is discussed.

Elution of the catalytic subunits of the type I and type II forms of cyclic AMP-dependent protein kinase within the type I chromatographic peak.

The purpose of this investigation was to determine the elution location upon ion-exchange chromatography of the catalytic subunits of both the type I and type II isozyme forms of cAMP-dependent protein kinase. We show that ion-exchange chromatography with DEAE-Sepharose CL-6B yields an apparent type I chromatographic peak of cAMP-dependent protein kinase which can represent not only type I holoenzyme activity but also catalytic activity derived from either the type I or type II enzyme forms. Such knowledge of the elution location of the dissociated catalytic subunits can prevent incorrect identification of the distribution of cAMP-dependent protein kinase isozymes in studies which estimate the isozyme concentrations based on the relative proportions of the kinase activity peaks.