No abstract available.
Animals ; Rats*

PURPOSE: The objective of our study was to evaluate the immunohistochemical expression of p53 and bax proteins as prognostic markers in FIGO stage IIb invasive squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: Sixty-five cases of squamous cell carcinoma of the cervix (stage IIb) that were diagnosed from October 1996 to December 2003 were analyzed retrospectively for the bax and p53 expression. These expressions were determined immunohistochemically and they were correlated to the patients' overall survival and disease-free survival. RESULTS: The overall 5-year survival (OS) rate and the disease-free survival (DFS) rate were 65.1% and 62.9%, respectively. p53 and bax immunoreactivity was seen in 26.2% and 52.3% of cases, respectively, with variable levels of expression. On the univariate analysis, only p53 positivity correlated with poor survival in DFS (log-rank test p=0.027), but this significance was not maintained on multivariated analysis by Cox's regression. The nine cases with the immunophenotype p53+/bax- had the poorest survival. CONCLUSION: Neither p53 nor bax expression are independent predictors of the prognosis for stage IIb cervical squamous cancers. Evaluation of p53 and bax co-expression may affect the clinical outcome and further investigation is needed.
bcl-2-Associated X Protein ; Carcinoma, Squamous Cell ; Cervix Uteri ; Disease-Free Survival ; Female ; Humans ; Prognosis ; Retrospective Studies

Lithium is the drug of choice for treating bipolar affective disorders. However, it has a narrow therapeutic index and acute and chronic toxicity can occur in patients with chronic ingestion. Chronic toxicity commonly presents as nephrogenic diabetes insipidus or thyroid dysfunction. Neurologic symptoms such as apathy, hyperreflexia, or clonus can also occur in acute toxicity. However, it rarely causes peripheral neuropathy. We experienced a case of lithium-induced peripheral polyneuropathy who had already nephrogenic diabetes insipidus and chronic kidney disease during 25 years of lithium ingestion due to bipolar disorder.
Apathy ; Bipolar Disorder ; Diabetes Insipidus ; Diabetes Insipidus, Nephrogenic* ; Eating ; Humans ; Lithium ; Mood Disorders ; Neurologic Manifestations ; Peripheral Nervous System Diseases ; Polyneuropathies* ; Reflex, Abnormal ; Renal Insufficiency, Chronic ; Thyroid Gland ; Upper Extremity*

PURPOSE: Thiazolidinediones (TZDs) are known to inhibit the proliferation of vascular smooth muscle cell (VSMC) by increasing the activity of p27(Kip1) and retinoblastoma protein (RB). However, the upstream signaling mechanisms associated with this pathway have not been elucidated. The Akt-mTOR-P70S6 kinase pathway is the central regulator of cell growth and proliferation, and increases cell proliferation by inhibiting the activities of p27(Kip1) and retinoblastoma protein (RB). Therefore, we hypothesized in this study that rosiglitazone inhibits VSMC proliferation through the inhibition of the Akt-TOR-P70S6K signaling pathway. MATERIALS and METHODS: Rat aortic smooth muscle cells (RAoSMCs) were treated with 10microM of rosiglitazone 24 hours before the addition of insulin as a mitogenic stimulus. Western blot analysis was performed to determine the inhibitory effect of rosiglitazone treatment on the Akt-mTOR-P70S6K signaling pathway. Carotid balloon injury was also performed in Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats that were pretreated with 3 mg/kg of rosiglitazone. RESULTS: Western blot analysis demonstrated significant inhibition of activation of p-Akt, p-m-TOR, and p-p70S6K in cells treated with rosiglitazone. The inhibition of the activation of the p-mTOR-p-p70S6K pathway seemed to be mediated by both the upstream PI3K pathway and MEK-ERK complex. CONCLUSION: The inhibitory effect of rosiglitazone on RAoSMC proliferation in vitro and in vivo is mediated by the inhibition of the Akt-mTOR-P70S6K pathway.
Animals ; Cell Proliferation/drug effects ; Cells, Cultured ; Cytoprotection/drug effects ; Enzyme Activation/drug effects ; Insulin/*pharmacology ; Male ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Muscle, Smooth, Vascular/drug effects/*metabolism ; Myocytes, Smooth Muscle/drug effects/*metabolism ; Phosphorylation ; Protein Kinase Inhibitors/pharmacology ; Protein Kinases/*metabolism ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism ; Rats ; Ribosomal Protein S6 Kinases, 70-kDa/*metabolism ; Signal Transduction/drug effects ; Thiazolidinediones/*pharmacology