ABSTRACT
The treatment with infliximab is employed successfully in Crohn's disease (CD) but predictors of efficacy are lacking. Activation of the transcription factor NF-kB has been demonstrated in CD and its inhibition is one of the mechanisms by which anti-inflammatory agents exert their effects. We evaluated the production of TNFalpha by peripheral blood mononuclear cells (PBMC) and the levels of NF-kappaB family molecules in the intestinal mucosa during infliximab therapy in 12 patients. TNFalpha was assayed on supernatants of PBMC culture stimulated with PHA or LPS. Immunohistochemistry was also done on intestinal biopsies. In six patients, Western blot analysis of the NF-kappaB subunit Rel-A, and its inhibitors IkappaBalpha and IkappaBgamma was performed on intestinal biopsies and PBMC. The TNFalpha production by LPS stimulated PBMC showed mild changes, while it was increased by PHA-stimulated PBMC after treatment. The number of inflammatory cells in the intestinal mucosa was reduced (p<0.002) by the treatment. In five out of six cases we detected an increase of the IkappaBalpha and IkappaBgamma)inhibitor levels in intestinal biopsies after treatment. An increase of IkappaB inhibitors levels could be one of the mechanisms by which infliximab decreases NF-kappaB activity and exerts its anti-inflammatory effects.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Crohn Disease/drug therapy , Crohn Disease/metabolism , Gastrointestinal Agents/therapeutic use , I-kappa B Proteins/metabolism , Intestinal Mucosa/metabolism , NF-kappa B/antagonists & inhibitors , Peptide Fragments/metabolism , Transcription Factors/metabolism , Adult , Aged , Blotting, Western , Female , Humans , Immunohistochemistry , Infliximab , Male , Middle Aged , Monocytes/immunology , NF-KappaB Inhibitor alpha , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The authors describe a case of amyloidosis associated with an electrophoretic picture, characterized by a monoclonal band with an M component in the alpha 2 and beta regions, in presence of para IgA-lambda. The case casually discovered in the course of a cerebral vascular manifestation and confirmed by bioptic exams, had negative results after four years due to an extremely progressive course involving intestine, liver and kidney, as a consequence of the extension of amyloidosis deposits.
Subject(s)
Amyloidosis/complications , Cerebrovascular Disorders/etiology , Immunoglobulin A/blood , Immunoglobulin lambda-Chains/blood , Liver Diseases/complications , Nephrotic Syndrome/complications , Paraproteinemias/etiology , Amyloidosis/blood , Cerebrovascular Disorders/blood , Female , Humans , Liver Diseases/blood , Middle Aged , Nephrotic Syndrome/blood , Paraproteinemias/bloodSubject(s)
Liver Neoplasms/pathology , Mesonephroma/pathology , Adult , Female , Humans , Immunohistochemistry , Liver Neoplasms/metabolism , Liver Neoplasms/ultrastructure , Mesonephroma/metabolism , Mesonephroma/ultrastructure , Microscopy, Electron , Microscopy, Electron, Scanning , alpha 1-Antitrypsin/metabolism , alpha-Fetoproteins/metabolismABSTRACT
Three cases of peritoneal cystic mesothelioma are reported. All patients were women who had undergone previous abdominal surgery for unrelated conditions. Tumors consisted of solitary and multiple cystic masses involving the abdominal and pelvic peritoneum. The cysts focally infiltrated the muscularis externa of the small intestine in case 1, the outer muscular layer of the uterus in case 2, and the omental tissue in case 3. These findings give morphologic support to the borderline clinical behavior of this tumor that often recurs and support the hypothesis that previous surgery may play a role in its pathogenesis.
