To elucidate the autoregulation of androgen receptor (AR) by androgen and antiandrogen, Western blot analysis and immunohistochemical study were performed. Castration reduced the immunodetected AR content, and nuclear staining was lost without cytoplasmic staining. Testosterone (T) supplement restored AR content. Quick response of AR content restoring following single administration of T was observed 48 hours after castration. The recovery of AR content detected by Western blot under each condition was accompanied by recovery of the reduced unclear staining intensities in the epithelia. Neither steroidal nor non-steroidal antiandrogens, cholormadinone acetate and flutamide, altered the AR content in normal rat ventral prostate 5, 12, 24 or 48 hours after single administration. Furthermore, neither of the drugs at various doses altered AR levels 12 hours after single administration. In summary, the rat AR is upregulated by androgen. Single administration of antiandrogens have no effect on immunodetected AR content.
We evaluated the effect of pioglitazone, a thiazolidinedione compound, on insulin-stimulated glucose disposal (Rd) and its efficacy on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty NIDDM subjects (mean age 58.2±9.4 year, body mass index [BMI] 23.9±3.4 kg/m2 [mean±S.D.], three with diet alone, 17 with sulfonylureas [SU]) participated in this trial from five diabetes clinics. Euglycemic (5.3 mmol/liter) hyperinsulinemic (insulin infusion rate 9 μmoles·kg−1·min−1) clamp studies were performed before and after oral administration of pioglitazone (30 mg/day) for 87±10 days. The Rd significantly improved from 5.5±2.5 to 8.3±3.1 mg·kg−1·min−1. Fasting plasma glucose (FPG) level significantly decreased from 11.0±2.0 mmol/liter to 8.9±1.1 mmol/liter with a significant improvement in the hemoglobin A1C level from 9.2±1.8% to 8.3±1.5%. Fasting serum insulin and C peptide levels decreased from 83±36 pmol/liter and 0.62±0.21 nmol/liter to 66±29 pmol/liter and 0.58±0.25 nmol/liter, respectively. Fasting serum triglyceride and free fatty acids levels significantly decreased with concomitant increase of fasting serum HDL-cholesterol levels from 1.2±0.2 to 1.5±0.3 mmol/liter. The change in Rd between before and after pioglitazone administration correlated with baseline values of FPG (ρ=0.633), serum insulin (ρ=0.653), BMI (ρ=0.456), Rd (ρ=−0.558) and 1,5-AG (ρ=−0.522). These data indicate that pioglitazone enhances the insulin action in NIDDM patients on diet alone or SU, and thereby improves both plasma glucose level and lipid profiles.
Granulocyte macrophage-colony stimulating factor (GM-CSF) regulates the growth and differentiation of hematopoietic cells and is also involved in angiogenesis. The induction of protein tyrosine phosphorylation is critical for cytokines and growth factor-mediated signal transduction. The protein tyrosine kinase (PTK), JAK2 is involved in signaling through a number of cytokine receptors, including GM-CSF receptors. In the present study, we investigated the effect of GM-CSF on the cell cycle and protein tyrosine phosphorylation in a human endothelial cell-derived cell line, EA.hy 926 cells. GM-CSF induced the cell cycle progression and tyrosine phosphorylation of cellular proteins including JAK2 kinase in EA.hy 926 cells. Herbimycin A, a PTK inhibitor, completely blocked the GM-CSF-induced cell cycle progession, protein tyrosine phosphorylation and JAK2 kinase activation in EA.hy 926 cells. Our results demonstrate that protein tyrosine phosphorylation and JAK2 kinase activation are closely related to the GM-CSF-mediated signal transduction and growth in vascular endothelial cells, and suggest the efficacy of herbimycin A in controlling angiogenesis.
The frequency of genetic homology of hepatitis C virus (HCV) E2 gene in 8 child-mother pairs was investigated. The route of HCV infection of all children suggested mother-to-child infection by their past history. In this study, we analyzed at least 5 complementary DNA (cDNA) clones for each case. In 6 of the 8 (75%) child-mother pairs, for the region between hypervariable region (HVR)-1 and HVR-2, the similarity of the nucleotide sequence of all 5 cDNA clones between each child and the mother was higher than that between the child and the other children, the other mothers and the sequences from GenBank. One of the 8 (13%) child-mother pairs showed a great similarity in parts of all cDNA clones. This was also confirmed by phylogenetic analyses of the sequences of cDNA clones from families and that from GenBank. These results suggested that the homology search of nucleotide sequence of this region was useful to confirm mother-to-child transmission of HCV.
In October, 1996, 24-hour food duplicate samples were collected from two groups of 50 adult women each; one group was in Jinan, the capital city of Shandong Province in China, and the other in a farming village of Baiquan in Zhangqiu area some 30 km away from the city. Perusal of food menus showed that wheat, rice, foxtail millet and maize were major cereals for the two groups. Nutritional analysis of the food duplicate samples were conducted taking advantage of weight of each food item and the standard food composition tables for Chinese populations. Whereas wheat was the leading source in both groups (73% of cereal-based energy in the city and 64% in the village), further urban-rural comparison showed that women in the village took substantial amounts of millet (19%) and maize (12%) in contrast to small consumption by the city people (millet by 5% and maize by 2%). Rice consumption was larger in the city (20%) than in the village (5%). The differences between the two groups were all significant for each of the four cereals. Nutritional significance of consumption of maize in particular and also that of millet were discussed.
To determine whether mechanically stimulated leukocytes increase pulmonary vascular permeability and resistance and, if so, whether cyclooxygenase metabolites mediate the increase, we assessed the effects of stimulated and unstimulated leukocytes, and of a cyclooxygenase inhibitor on pulmonary vascular permeability and resistance in isolated perfused lungs from Sprague-Dawley rats. Leukocytes were stimulated by gentle agitation in a glass container for 10 seconds. After baseline measurements were made, stimulated or unstimulated leukocytes were added to the perfusate. The effects of the cyclooxygenase inhibitor, meclofenamate, on the pulmonary vascular filtration coefficient and pulmonary vascular resistance were measured. In the rats that received stimulated leukocytes, the pulmonary vascular filtration coefficient and the vascular resistance were about 2.5 times and 3.3 times higher, respectively, than those in the rats that received unstimulated leukocytes. These increases were completely and partly blocked by meclofenamate. Histological examination indicated that meclofenamate did not prevent the adhesion of leukocytes to the pulmonary vascular endothelium. These findings suggest that mechanically stimulated leukocytes increase pulmonary vascular permeability and that cyclooxygenase metabolites produced by endothelial cells may injure the cells.
We present a 65-year-old man with an enlarged mass in the right parotid gland. A fine-needle aspiration cytology suspected Warthin's tumor. The ill-defined margin of the tumor in diagnostic imaging and unexpected clinical course of the occurrence of facial nerve paralysis suggested malignant neoplasm. The patient was treated with surgical resection of the primary site and neck following radiation therapy. Pathologic diagnosis was a salivary duct carcinoma. Difficulty in early diagnosis of this tumor may result in local extension, early metastasis to regional lymph nodes and distant sites, and death.