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Biomedical subjects

I Kleiter

Publications and source records attributed to I Kleiter.

7 recordsLinked to original sources
PubMed2004

Targeting fibroblast growth factor-inducible-14 signaling protects from chronic relapsing experimental autoimmune encephalomyelitis.

The TNF-related weak inducer of apoptosis (TWEAK) is a TNF family member mediating proinflammatory effects by its receptor fibroblast growth factor-inducible-14 (Fn14). We studied the role of TWEAK/Fn14 in experimental autoimmune encephalomyelitis (EAE) by protein vaccination with TWEAK and Fn14 and recombinant TWEAK-DNA, respectively. TWEAK-DNA vaccination worsened the clinical course of EAE and increased central nervous system (CNS) inflammation. TWEAK increased the secretion of CCL2 [monocyte chemotactic protein-1 (MCP-1)] by CNS endothelial cells and astrocytes in vitro, suggesting CCL2 as a critical mediator of TWEAKs proinflammatory effects. Vaccination with the extracellular domain of TWEAK or with Fn14 resulted in the induction of specific inhibitory antibodies and an amelioration of EAE signs in two different models in rats and mice. Spinal cord inflammatory infiltrates were significantly diminished. Purified IgG from TWEAK- or Fn14-vaccinated rats prevented TWEAK-induced production of CCL2 by endothelial cells. Blocking Fn14 signaling represents a novel approach with potential for the treatment of CNS autoimmunity.

Animals↗
PubMed2004

Intraventricular cytarabine in a case of idiopathic hypertrophic pachymeningitis.

Idiopathic hypertrophic chronic pachymeningitis (IHCP) is characterised by inflammatory fibrotic thickening of the dura mater. Long term management is controversial. A 28 year old man with craniospinal IHCP and prominent lymphocytic meningitis is reported. Cerebrospinal fluid and histological examination suggested a CD4+ T cell driven process and B cell stimulation. After surgical, tuberculostatic, and immunosuppressive treatment failed to control the progressive meningeal hypertrophy, causing severe headache and neurological disability, the disease process eventually abated with intraventricular cytarabine treatment.

Adult↗
PubMed1999

NO-Evoked macrophage apoptosis is attenuated by cAMP-induced gene expression.

BACKGROUND: Previous work has suggested that an increase in expression of cyclooxygenase-2, concomitant formation of E-type prostanoids, and in turn intracellular cAMP conveys macrophage resistance against apoptosis. MATERIALS AND METHODS: We analyzed the effects of lipophilic cAMP analogs on nitric oxide (NO)-induced apoptosis in RAW 264.7 macrophages and human primary monocyte-derived macrophages. Parameters comprised DNA fragmentation (diphenylamine assay), annexin V staining of phosphatidylserine, caspase activity (quantitated by the cleavage of a fluorogenic caspase-3-like substrate Ac-DEVD-AMC), and mitochondrial membrane depolarization (DeltaPsi), analyzed using DiOC(6)(3). Western blots detected accumulation of the tumor suppressor protein p53, relocation of cytochrome c, and expression of the antiapoptotic protein Bcl-X(L). A cAMP response-element decoy approach confirmed cAMP-dependent gene induction. RESULTS: We verified resistance of murine and human macrophages against NO donors such as S-nitrosoglutathione or spermine-NO by pre-exposing cells to lipophilic cAMP analogs or by pretreatment with lipopolysaccaride, interferon-gamma, and N(G)-nitroarginine-methylester for 15 hr. Cellular prestimulation decreased NO-evoked apoptosis, as apoptotic parameters were basically absent. Macrophage protection was not achieved during a short period of preexposure, i.e., 1 hr. To verify gene induction as the underlying protective principle, we treated RAW cells with oligonucleotides containing a cAMP-responsive element in order to scavenge cAMP response element-binding protein prior to its promoter-activating ability. Decoy oligonucleotides, but not an unrelated control oligonucleotide, weakened cAMP-evoked protection and re-established a p53 response following NO addition. CONCLUSION: Gene induction by cAMP protects macrophages against apoptosis that occurs as a result of excessive NO formation. Decreasing programmed cell death of macrophages may perpetuate inflammatory conditions in humans when macrophages become activated in close association with innate immune responses.

Animals↗
PubMed1977

Efficacy of bufexamac (NFN) cream in skin diseases. A double-blind multicentre trial.

The effect of a new non-steroid anti-inflammatory substance (bufexamac) in a special constituent was compared with that of 0.1% triamcinolone acetonide, 1% hydrocortisone cream, and placebo during a double-blind multicentre trial. The clinical effect of these four creams was studied in 193 patients receiving treatment for the following skin disorders: atopic dermatitis, allergic contact dermatitis, and non-allergic contact dermatitis, as well as dermatitis seborrheica. After 2 and 4 weeks' treatment, when 193 and 157 patients, respectively, were re-examined, the effect of triamcinolone acetonide and hydrocortisone cream was significantly better, than that obtained with bufexamac in the cream basis employed. On the other hand, no statistically significant difference in effect between bufexamac and placebo cream was observed.

Administration, Topical↗