ABSTRACT
Sodium nitroprusside (SNP) induces apoptosis in H9C2 cardiac muscle cells. Treatment with an exogenous NO donor SNP (2 mM) to H9C2 cells resulted in apoptotic morphological changes; a bright blue-fluorescent condensed nuclei and chromatin fragmentation by fluorescence microscope of Hoechst 33258-staining. The activity of caspase-3 like protease was increased during SNP-induced cell death. However, the activity of caspase-1 like protease was not affected by SNP. Pretreatment with Z-VAD-FMK (a pan-caspase inhibitor) or Ac-DEVD-CHO (a specific caspase-3 inhibitor) abrogated the SNP-induced cell death. SNP markedly activated three MAP kinases (JNK/SAPK, ERK and p38 MAP kinase) in the cardiac muscle cells. In this study, selective inhibition of the ERK or p38 MAPK pathway (by PD98059 or SB203580, respectively) had no effect on the extent of SNP-induced apoptosis in cardiac muscle cells. In contrast, inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK markedly reduced the extent of SNP-induced cell death. Taken together, we suggest that JNK/SAPK will be related to SNP-induced apoptosis of H9C2 cardiac muscle cells.
Subject(s)
Apoptosis/drug effects , Mitogen-Activated Protein Kinases/metabolism , Myocardium/cytology , Myocardium/enzymology , Nitroprusside/pharmacology , Amino Acid Chloromethyl Ketones/pharmacology , Animals , Caspase 1/metabolism , Caspase 3 , Caspase Inhibitors , Caspases/metabolism , Cell Line , Cysteine Proteinase Inhibitors/pharmacology , Cytochrome c Group/metabolism , Enzyme Activation/drug effects , JNK Mitogen-Activated Protein Kinases , Mitogen-Activated Protein Kinases/genetics , Mutation , Nitric Oxide Donors/pharmacology , Oligopeptides/pharmacology , Rats , TransfectionABSTRACT
We describe a 19-year-old female patient who developed recurrent ulcerations limited to the orogenital mucosa for the last 3 years. She also developed dyspnoea 5 months after the onset of the orogenital lesions. Castleman's tumour of the retroperitoneum was found incidentally during routine physical examination. The diagnosis of paraneoplastic pemphigus (PNP) was made by pathological and immunological studies. The orogenital ulceration responded well to corticosteroid therapy, but severe bronchiolitis obliterans progressed despite intensive care. The patient eventually died from respiratory failure. This case demonstrates the diversity of clinical features of paraneoplastic pemphigus.
Subject(s)
Bronchiolitis Obliterans/etiology , Castleman Disease/complications , Pemphigus/etiology , Ulcer/etiology , Adult , Bronchiolitis Obliterans/pathology , Female , Genital Diseases, Female/etiology , Humans , Oral Ulcer/etiology , Oral Ulcer/pathology , Ulcer/pathologyABSTRACT
Flow cytometrically determined nuclear DNA content has been measured on 74 formalin-fixed, paraffin embedded specimens of non-small cell carcinoma of the lung. Of the 60 tumors that were successfully analyzed, 32 (53%) were diploid and 28 (47%) were aneuploid. The mean DNA index of aneuploid tumor was 1.5 +/- 0.25, ranging from 1.1 to 2.0. There was no significant correlation between DNA ploidy and the patient's clinical characteristics, histology of tumor, nodal status or tumor stage. Tumor ploidy was not found as a prognostic determinant in non-small cell carcinoma of the lung in this study.
