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1.
Respirology ; 8(1): 91-4, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12856748

ABSTRACT

Langerhans cell histiocytosis (LCH) is a rare disorder which frequently involves the lungs of affected adults. Recent evidence suggests it is a clonal neoplastic disorder. Prognosis in this disease is variable, but in its multisystem form or when associated with progressive respiratory dysfunction, prognosis is poor. Recent case reports and a phase II trial of the antimonocyte drug 2-chlorodeoxy-adenosine (2CDA) have described success in treating LCH. We used 2CDA to treat a young Australian man with LCH involving lungs and bone. A complete symptomatic remission was achieved with no evidence of recurrence some 5 years after completion of chemotherapy.


Subject(s)
Antineoplastic Agents/administration & dosage , Cladribine/administration & dosage , Histiocytosis, Langerhans-Cell/drug therapy , Histiocytosis, Langerhans-Cell/pathology , Lung Diseases/drug therapy , Lung Diseases/pathology , Adult , Biopsy, Needle , Drug Administration Schedule , Follow-Up Studies , Humans , Immunohistochemistry , Infusions, Intravenous , Male , Respiratory Function Tests , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome
2.
Cardiovasc Res ; 57(1): 139-46, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12504823

ABSTRACT

OBJECTIVE: Members of the protein kinase C (PKC) family are important mediators of cell signaling underlying multiple aspects of myocardial function. Activation of the betaII isoform of PKC is thought to be involved in the development of congestive heart failure. To investigate the biological effect of PKC-betaII, we measured gene expression of angiotensin converting enzyme (ACE) and angiotensin II (AngII) receptors AT(1A) and AT(1B) in cardiomyocytes overexpressing PKC-betaII. METHODS: An adenovirus construct expressing PKC-betaII was introduced into cultured neonatal rat ventricular myocytes (NRVMs). Western blot and in situ kinase assay was used to measure PKC-betaII level and activity in NRVMs. Real time quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to measure the mRNA levels of several genes following PMA stimulation of either un-infected or ad-PKC-betaII infected cells. RESULTS: Our data show that activation of PKC-betaII in cardiomyocytes leads to elevated expression of angiotensin-converting enzyme (ACE) gene. Treatment of adeno-PKC-betaII infected cardiomyocytes with phorbol 12-myristate 13-acetate (PMA) resulted in an 8-fold increase of ACE mRNA expression, whereas ACE mRNA levels only increased around 2-fold in uninfected or adeno-GFP (green fluorescent protein) infected cardiomyocytes with similar PMA treatment. The induction of ACE mRNA was blocked by the PKC-beta-specific antagonist LY379196. No significant change of angiotensin II receptors AT1a and AT1b could be detected in the cardiomyocytes expressing PKC-betaII. CONCLUSION: These data indicate that ACE is a transcription target of PKC-betaII activation in cardiomyocytes, and also suggest a mechanism for the involvement of PKC in cardiac hypertrophy and fibrosis through increased activity of angiotensin converting enzyme in the myocardium.


Subject(s)
Isoenzymes/metabolism , Myocytes, Cardiac/enzymology , Peptidyl-Dipeptidase A/metabolism , Protein Kinase C/metabolism , Angiotensin I , Animals , Cells, Cultured , Enzyme Activation , Enzyme Inhibitors/pharmacology , Gene Expression , Isoenzymes/antagonists & inhibitors , Isoenzymes/genetics , Mesylates/pharmacology , Peptidyl-Dipeptidase A/genetics , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/genetics , Protein Kinase C beta , Pyrroles/pharmacology , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Receptors, Angiotensin/genetics , Tetradecanoylphorbol Acetate/pharmacology , Transduction, Genetic/methods
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