Antioxidant enzymes levels were determined in monocytes during phorbol myristate acetate (PMA)-induced differentiation. PMA induced the differentiation of a human monocytic leukemia cell line THP-1 into macrophage-like cells as indicated by activity of acid phosphatase and morphological changes. The level of Mn-superoxide dismutase (SOD) was selectively increased in PMA-treated THP-1 cells after one day of culture, while the levels of Cu/Zn-SOD and catalase were progressively decreased by Western blot analysis. In contrast, levels of Cu/Zn-SOD and catalase protein and enzyme activitiy remained unchanged in THP-1 cells after transforming growth factor-p, treatment. Cu/Zn-SOD is oxidatively inactivated by exposure to H,O, which is produced by PMA-treated THP-1 cells, and then the inactivated enzyme undergoes proteolysis and fragmentation as analyzed by radiolabeled method. Thus monocytes have a coordinated system for synthesis and degradation of antioxidant enzymes during PMA-induced differentiation.
Acid Phosphatase ; Blotting, Western ; Catalase ; Cell Line ; Humans ; Leukemia ; Monocytes* ; Proteolysis ; Superoxide Dismutase ; Tetradecanoylphorbol Acetate

PURPOSE: With the process of neoangiogenesis being linked to the growth and metastasis of various tumors, anticancer therapeutics with a basis in the suppression of neoangiogenesis has recently been receiving attention. In this study, we tried to clarify the immunoreactivities of vascular endothelial growth factor (VEGF), major angiogenic inducer and thrombospondin-1 (TSP-1), major angiogenic inhibitor in human Wilms' tumor and its clinicopathological significance. MATERAILS AND METHODS: Utilizing immunohistochemical staining, we assessed the immunoreactivities of VEGF and TSP-1 in archival tissues of 29 Wilms' tumors and 25 normal kidneys. Also, we assessed the relationship between expression of each factor and clinicopathological parameters in 29 cases of Wilms' tumors. RESULTS: Immunoreactivities of VEGF and TSP-1 were detected mainly in the cytoplasm of the tubular cells in normal kidneys. In Wilms' tumors, whereas VEGF was detected in the cytoplasm of the tumor cells and peritumoral stromal tissues, but TSP-1 only in the peritumoral stromal tissues. Immunohistochemical expression patterns of each factor were divided into two groups according to the area of immunoreactivity (negative:<10%, positive: > OR =10%). VEGF immunoreactivity was detected in 25 (100%) normal kidneys and in 20 (69%) Wilms' tumors. However, TSP-1 immunoreactivity was detected in 24 (97%) normal kidneys and in 3 (10%) Wilms' tumors. Therefore, although no significant difference was observed between the expressions of VEGF and TSP-1 in normal kidney, the TSP-1 immunoreactivity was significantly lower than VEGF immunoreactivity in Wilms' tumors. A relatively higher rate of positive expression of TSP-1 was observed in the patients with no demonstrable lymph node metastasis. Also, as for the VEGF, maximal diameter of the tumor was larger in the positive expression group. However, it proved otherwise for TSP-1 as the negative expression group demonstrated tumors with larger maximal diameters. CONCLUSIONS: Our study demonstrated that the TSP-1 immunoreactivity was significantly lower than VEGF immunoreactivity in Wilms' tumors, and disease progression has a tendency to be found in the VEGF-positive cases and TSP-1 negative cases. We suggest that the growth and metastasis of Wilms' tumor may be influenced mainly by TSP-1 decrease rather than VEGF increase.
Cytoplasm ; Disease Progression ; Humans ; Kidney ; Lymph Nodes ; Neoplasm Metastasis ; Thrombospondin 1 ; Vascular Endothelial Growth Factor A* ; Wilms Tumor*

No abstract available.
Ulcer*

No abstract available.
Child* ; Humans ; Peak Expiratory Flow Rate

PURPOSE: To evaluate the antitumor effect of the proapoptotic Bax gene in prostate cancer cells, in vitro, using a plasmid vector expressing the human Bax gene. MATERIALS AND METHODS: cDNA of the human Bax gene, amplified by RT-PCR, was cloned to pCR@3.1. The expression of the cloned Bax (pCR3.1-Bax) was observed by RT-PCR and Western blot analyses. The efficacy of growth inhibition by the cloned Bax gene was tested, in vitro, on PC-3 and DU145 human prostate cancer cell lines using the MTT assay. Immunoblot analysis for the expressions of Bcl-2 and Bcl-xL were performed. Assays were also performed to evaluate the apoptosis, DNA fragmentation and CPP32. RESULTS: The Bax protein was expressed in the parental PC-3 cells, but not in the DU-145 cells. The expressions of Bax mRNA in the transfected PC-3 and DU-145 cells had increased by 24 hr, and those of Bax protein in the transfected PC-3 and DU-145 cells had increased by 48 and 24 hr, respectively, compared with the control cell lines. The cytotoxicity of pCR3.1-Bax on PC-3 and DU-145 cells increased significantly compared with an empty vector, pCR3.1 (p<0.05, respectively). An increased cytotoxicity of the Bax-transfected cell lines was associated with enhanced apoptosis. The Bcl-2 protein was not expressed in the transfected cells, and the levels of Bcl-xL protein expression in transfected cells were no different to those in the parenteral cells. The Bax/Bcl-xL ratio was increased by the transfection of the Bax expression vector. CONCLUSIONS: Our results show that the cloned Bax-expression plasmid vector efficiently inhibits the growth of PC-3 and DU145 human prostate cancer cell lines. These data suggest that exogenous Bax expression may have therapeutic applications in prostate cancer.
Apoptosis* ; bcl-2-Associated X Protein ; bcl-X Protein ; Blotting, Western ; Cell Line ; Clone Cells ; DNA Fragmentation ; DNA, Complementary ; Gene Expression* ; Genetic Therapy ; Humans ; Parents ; Plasmids ; Prostate* ; Prostatic Neoplasms* ; RNA, Messenger ; Transfection

PURPOSE: We tried to find out whether the nadir PSA level after hormone therapy affected the progression into hormone-refractory prostate cancer (HRPC). MATERIALS AND METHODS: We reviewed the progressive status and the survival of the 177 patients with stage C or D prostate cancer who had received hormone therapies. The relative efficacy of the nadir PSA level for predicting the progression into HRPC was evaluated by the receiver operating characteristic (ROC) analysis. RESULTS: 85.4% of patients responded to the treatment and 78% of responders progressed into HRPC. Median time to nadir PSA level after hormone therapy and to HRPC were 8.1 and 24.0 months, respectively. The nadir PSA levels were under 0.2ng/ml in 31%, 0.2-1.0ng/ml in 23%, 1.1-10ng/ml in 42%, and over 10ng/ml in 5% of the responders (n=151). As the nadir PSA levels were lower, pretreatment PSA levels, Gleason score and the number of cases progressing into HRPC were significantly lower (p<0.05). In addition, the nadir PSA level was inversely correlated with the interval to the establishment of HRPC (r= 0.465, p<0.05). By univariate analysis, the bone metastasis, the nadir PSA level, PSA level at six months after treatment and pretreatment PSA level were associated with the progression into HRPC. Only the nadir PSA level was an independent factor by multivariate analysis. ROC analysis disclosed an accuracy of 86.2% for the nadir PSA level to predict the progression into HRPC after two years. By setting the lower limit of the nadir PSA level to 1.1ng/ml, the sensitivity was 80.3% and the specificity was 83.8%, being most adequate. CONCLUSIONS: The nadir PSA level after hormone therapy may be the most important factor that can predict the progression into HRPC. Also, in consideration of sensitivity and specificity, it would be adequate to set the lower limit of the nadir PSA level to 1.1ng/ml.
Humans ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Metastasis ; Prognosis ; Prostate* ; Prostate-Specific Antigen* ; Prostatic Neoplasms* ; ROC Curve ; Sensitivity and Specificity

PURPOSE: Conventional pathologic classifications of human renal cell carcinoma give little insight into oncogenesis and little assistance in predicting the clinical behavior of this disease. For genetic classification, deletion of the short arm of chromosome 3(3p), the hallmark of nonpapillary/clear cell RCC, is a major diagnostic criterion. Because of the limited routine applicability of cytogenetics and molecular genetic techniques we investigated fluorescence in situ hybridization(FISH) for the detection of this aberration in RCC. MATERIALS AND METHODS: Isolated nuclei from 8 human RCC paraffin embedded tissue sections were examined with a dual color FISH technique for loss of chromosome 3p. Telomeric DNA probe from 3p and an internal ploidy control probe, centromeric probe of chromosome 2, were applied to the isolated nuclei of RCC. RESULTS: 87.5% of the patients(7) lost chromosome 3p. The loss of 3p in the samples tested was unrelated to patient age, gender, tumor stage, and grade. CONCLUSIONS: FISH for the detection of loss in 3p from paraffin embedded tissue sections provides a sensitive and feasible methods for the genetic classification of kidney tumors and FISH is a very useful diagnostic tool for detection of the genetic aberrations of the tumors.
Arm ; Carcinogenesis ; Carcinoma, Renal Cell* ; Chromosomes, Human, Pair 2 ; Classification ; Cytogenetics ; DNA ; Fluorescence* ; Humans ; In Situ Hybridization* ; In Situ Hybridization, Fluorescence ; Kidney ; Molecular Biology ; Paraffin ; Ploidies

We report a case of methimazole-induced acute hepatic failure, which occurred 4 days after initiation of drug in a 51-year-old man with hyperthyroidism. Liver function was evaluated before taking methimazole, total bilirubin was 14.2 mg/dL. This finding suggested toxic hepatitis d/t herbal medication or unknown liver disease. He was treated with methimazole with increasing doses from 15 to 45 mg/day, he developed liver failure gradually, despite of suspending methimazole. From the time of admission, his liver function test was abnormal and liver cirrhosis was suspected by liver sonography. With aggravated liver function, he died of renal failure, sepsis of unknown origin and respiratory failure. Fulminant hepatitis rarely occurs in methimazole users, and spontaneous recovery is expected. But this case shows that methimazole-induced hepatotoxicity with possible underlying liver disease could increase the risk of poor outcomes. And in case of continued deterioration of liver function, prompt liver transplatation should be considered.
Bilirubin ; Drug-Induced Liver Injury ; Graves Disease ; Hepatitis ; Humans ; Hyperthyroidism ; Liver ; Liver Cirrhosis ; Liver Diseases* ; Liver Failure ; Liver Failure, Acute* ; Liver Function Tests ; Liver Transplantation ; Methimazole* ; Middle Aged ; Renal Insufficiency ; Respiratory Insufficiency ; Sepsis

An eleven-year-old spayed female Yorkshire Terrier presented with a sublumbar mass and upon ultrasonographic examination, was revealed to have a mammary gland tumor. Black to reddish colored masses, located in the visceral peritoneum of the sublumbar region was observed on laparotomy with masectomy of the right side. In the laparotomy, we observed reddish masses multifocally located in the serosal membrane of the large intestine. Histopathologic examination of the intestinal and abdominal mass showed highly invasiveness into the muscle and metastasis of melanocytic tumor cells through the blood vessels. The mammary glands showed abnormal hyperplasia of melanocytes, destruction of the normal glands by tumor cells and infiltration of some lymphocytes in the pool of melanocytic cells. We have identified a malignant melanoma containing an angiotumoral complex in which tumor cells occupied a pericytic location along the microvessels with intravasation determined by immunohistochemistry for S100 protein and protein kinase C-alpha. Histologic findings in this dog lead to a diagnosis of an angiotropic metastatic malignant melanoma.
Animals ; Blood Vessels ; Dogs ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Intestine, Large ; Laparotomy ; Lymphocytes ; Mammary Glands, Human ; Melanocytes ; Melanoma ; Membranes ; Microvessels ; Muscles ; Neoplasm Metastasis ; Peritoneum ; Protein Kinase C-alpha

Relapsing polychondritis (RP) is an uncommon disease that is characterized by inflammation and destruction of cartilaginous structures. When tracheobronchial tree is involved, respiratory obstructive symptoms can occur. A 35-year-old man, with a previous diagnosis of RP, was scheduled for rigid bronchoscopy to relieve dyspnea, caused by subglottic stenosis. After laser splitting of the subglottic web, the spontaneous respiration of the patient was insufficient, and hypercarbia developed progressively even with assisted ventilation. After 20 minutes of aggressive hyperventilation to reduce end-tidal CO2 level, sudden extreme tachycardia and hypotension developed. Ventilation rate was reduced and prolonged expiration time was allowed to alleviate a near-tampon status from dynamic hyperinflation. After the hemodynamic status was stabilized, the patient was transferred to the ICU for mechanical ventilation. He received ICU care for 30 days, and now, he was on supportive care on a ward, considering Y stent insertion to prevent luminal collapse from tracheobronchomalacia.
Adult ; Bronchoscopy* ; Constriction, Pathologic ; Diagnosis ; Dyspnea ; Hemodynamics ; Humans ; Hyperventilation ; Hypotension ; Inflammation ; Laryngostenosis ; Phenobarbital ; Polychondritis, Relapsing* ; Respiration ; Respiration, Artificial ; Respiratory Insufficiency* ; Stents ; Tachycardia ; Tracheobronchomalacia ; Ventilation