Synthesis of 5'-amino-3,5'-dideoxybutirosin A.

The titled compound was prepared by condensation of 3'-deoxyparomamine derivative (5) with 2,3-O-bis(p-nitrobenzoyl)-5-O-tosyl-D-xylofuranosyl bromide followed by 1-N-acylation with the active ester of (S)-4-benzyloxycarbonylamino-2-hydroxybutyric acid. The compound was slightly more active than 3'-deoxybutirosin A against Pseudomonas.     

Subculture of chondrocytes on a collagen type I-coated substrate with suppressed cellular dedifferentiation

To evaluate the degree of cellular dedifferentiation, subculture of chondrocytes was conducted on a surface coated with collagen type I at a density of 1.05 mg/cm(2). In the primary culture, most of the cells were round in shape on the collagen (CL) substrate, whereas fibroblastic and partially extended cells were dominant on the polystyrene plastic (PS) substrate. Stereoscopic observation revealed that the round-shaped cells on the CL substrate were hemispherical with nebulous and punctuated F-actin filaments, whereas the fibroblastic cells on the PS substrate were flattened with fully developed stress fibers. This suggested that cell polarization was suppressed during culture on the former substrate. Although serial passages of chondrocytes through subcultures on the CL and PS substrates caused a decrease in the number of round-shaped cells, the morphological change was appreciably suppressed on the CL substrate, as compared with that on the PS substrate. It was found that only round-shaped cells formed collagen type II, which supports the view that cellular dedifferentiation can be suppressed to some extent on the CL substrate. Three-dimensional cultures in collagen gel were performed with cells isolated freshly and passaged on the CL or PS substrate. Cell density at 21 days in the culture of cells passaged on the CL substrate was comparable to that in the culture of freshly isolated cells, in spite of a significant reduction in cell density observed in the culture of cells passaged on the PS substrate. In addition, histological analysis revealed that the expression of glycosaminoglycans and collagen type II was of significance in the collagen gel with cells passaged on the CL substrate, and likewise in the gel with freshly isolated cells. This indicated that the CL substrate could offer a monolayer culture system for expanding chondrocyte cells.     

Clinicopathologic features of villoglandular papillary adenocarcinoma of the uterine cervix

OBJECTIVES: The objectives of this study are to analyze the clinicopathologic features of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix and to discuss the management thereof. We examined 13 patients with VGPA. METHODS: Clinical profiles, including patient age, clinical stage, surgical procedure, and outcome, were recorded. Pathologically, macroscopic features, polypoid tumor size, horizontal spread and depth of endophytic tumor, nuclear atypicality, mitotic count, lymph capillary space invasion, and lymph node metastasis were investigated. RESULTS: The median age of 13 patients was 45 years, with 10 and 3 patients staged Ib and IIb, respectively. All the patients underwent hysterectomy and pelvic lymphadenectomy and are alive without recurrence. Macroscopically, the tumor showed a polypoid pattern in 8 patients and a flat pattern in the remaining 5 patients. Polypoid tumor size ranged between 4 x 2 and 20 x 15 mm. Horizontal spread and depth of endophytic tumor ranged between 8 and 30 mm and between 3 and 11 mm, respectively. The tumor in all the 13 patients except 1 showed moderate nuclear atypicality. The mean mitotic count was 43/10 high-power fields. Lymph capillary space invasion was present in 4 patients, 1 of whom also had bulky lymph node metastases. CONCLUSIONS: VGPA has been reported to rarely involve lymph capillary space invasion or lymph node metastasis, leading some surgeons to conduct less radical surgeries such as conization. Nevertheless, we encountered patients with these pathologic risk factors. Much caution should be exercised in managing patients with VGPA.     

Promotion of beta-cell differentiation by conophylline in fetal and neonatal rat pancreas

Conophylline is a vinca alkaloid extracted from the tropical plant Ervatamia microphylla and has been shown to induce differentiation of pancreatic AR42J cells. In the present study, we investigated the effect of conophylline on the differentiation of pancreatic precursor cells. In the rat pancreatic rudiment in organ culture, conophylline inhibited the formation of cystic structure and increased the number of insulin-positive cells. Conophylline also markedly increased the expression of mRNA for insulin and the number of pancreatic duodenal homeobox-1-positive cells. These effects of conophylline were similar to those of activin A. We also examined the effect of conophylline on neonatal rats treated with streptozotocin, a model of type 2 diabetes. Treatment with conophylline significantly reduced the plasma glucose concentration and improved glucose tolerance in response to glucose loading. The insulin content and the beta-cell mass at 2 months were significantly increased by conophylline. The number of islet-like cell clusters and pancreatic duodenal homeobox-1-positive ductal cells was greater in conophylline-treated rats. These results suggest that conophylline induces differentiation of pancreatic precursor cells and increases the formation of beta-cells.