Ultrastructural autoradiographic analysis of RNA in isolated human lung mast cells during secretion and recovery from secretion

BACKGROUND: Previous work has implicated isolated, control human lung mast cell granules in RNA metabolism using multiple methods of high-magnification imaging based on different mechanistic principles. These methods have demonstrated ribosomes, RNA, U1snRNP and uridine in, around and attached to secretory granules. METHODS: Here, we have extended these studies using ultrastructural autoradiography of radiolabeled uridine incorporation in degranulating and recovering mast cells. RESULTS: We found that control cells incorporated uridine into granules, with values that decreased dramatically in conjunction with stimulated histamine secretion and granule extrusion, and that granule stores of tritiated uridine increased together with the reconstitution of secretory granules in recovering mast cells. CONCLUSION: These findings support a possible new role for secretory granules in RNA metabolism in mast cell biology.     

Randomized controlled trial to determine the safety and efficacy of a multi-cell pulsating dynamic mattress system in the prevention of pressure ulcers in patients undergoing cardiovascular surgery

The purpose of this study was to determine the efficacy and safety of a multi-cell pulsating dynamic mattress system in comparison with conventional management for the prevention of pressure ulcers in the operative and postoperative period in patients having cardiovascular surgery. The study was a single center, prospective, randomized, controlled trial. Patients who were having cardiovascular surgery for a duration of at least 4 hours were randomly assigned, prior to surgery, to dynamic mattress system or conventional management--both of which were initiated in the operating room and continued for up to 7 days postoperatively. Patients were assessed daily using a standardized scoring system. The results of the study showed that 198 patients in the dynamic pressure system (n = 98) or conventional management group (n = 100) were similar at baseline. A strong trend of decreased pressure ulcers existed in the dynamic pressure system group (n = 2) compared to the conventional management group (n = 7). The study concluded that a multi-cell pulsating dynamic mattress system is safe and mitigates risks for and decreases incidence of pressure ulcers in patients who undergo cardiovascular surgery.     

Differential effects of cisplatin in proximal and distal renal tubule epithelial cell lines

Pathological studies suggest that cisplatin injures different portions of the nephron to different extents. To investigate this issue further, we examined the cytotoxicity and uptake of cisplatin in cell lines derived from S₁ and S₃ proximal tubule and distal convoluted tubule segments isolated from a mouse carrying the SV40 large T-antigen transgene. S₁ cells displayed the highest sensitivity to cisplatin cytotoxicity, followed by S₃ and distal convuluted tubule (DCT) cells. These differences in cytotoxicity did not correlate with differences in cisplatin uptake. Cytotoxic concentrations of cisplatin triggered apoptosis in all three cell lines. Although BAX and BCL-2 expression was similar among the three cell lines, the expression of the anti-apoptotic protein, BCL-X_L, was significantly lower in S₁ cells than in S₃ and DCT cells, and this may have contributed to the heightened sensitivity of S₁ cells. Cisplatin transport characteristics demonstrated a saturable component of cisplatin uptake and differences in apparent K_M and V_max values among the three cell lines. The three cell lines were 43- to 176-fold more sensitive to cisplatin than to carboplatin. This distinction between the two drugs could not be fully explained by differences in the uptake rates of carboplatin and cisplatin. We conclude that cells from different portions of the nephron display different sensitivities to cisplatin, different transport characteristics for cisplatin and different levels of expression of BCL-X_L. In addition, the relative resistance of renal cells to carboplatin vs cisplatin is mostly due to the differential effects that follow internalization. © 1999 Cancer Research Campaign     

Heritability of cervical tumours

Development of cervical cancer is strongly associated with genital infection of oncogenic types of human papillomavirus (HPV). However, the majority of women infected with HPV never develop cancer; thus, additional factors appear to be necessary. The relative importance of genetic and environmental factors to the development of cervical tumours is not known. Therefore, we have estimated the heritability of liability to this disease. The Swedish Cancer Register and the National Family Register were used to identify biological and adoptive mothers and full, half- and adoptive sisters of cases with cervical tumours, as well as age-matched controls. Tetrachoric correlations were calculated and model fitting techniques used to estimate the relative importance of shared genes and shared familial environment. Shared genes (heritability) explain 27% (95% CI 26%-29%) of the total variation in liability to the disease. A significant effect of shared familial environment was seen among sisters but not among mother/daughter relations. Sister-specific shared environment accounts for 2% (95% CI 1%-4%) of the variance. Our results indicate that development of cervical tumours depends, to a significant extent, on inherited genetic factors. Genetic predisposing factors may influence the likelihood of, sensitivity to or persistence of HPV infection, as well as the rate of tumour development.     

VI. Somatic pubertal development.

The pubertal development of 212 randomly selected Swedish urban children has been investigated as part of a prospective longitudinal study of growth and development. The timing and pattern of pubertal changes were in agreement with the findings in other contemporary studies. The good agreement with data on pubertal development reported in other investigations of Swedish children indicates that the present sample was representative of contemporary Swedish children. Two procedures of assessment of secondary sex characters - clinical examination and whole-body photography - have been compared and contrasted. A clinical examination is less laborious and resource-consuming and also has psychological advantages but should be supplemented in boys by the estimation of testicular volume (orchidometry). In girls the two methods have similar precision and reliability. The first pubertal changes may be observed before 9 years in girls (breast development) and before 10 years in boys (genital development). On average the first change takes place about one year earlier in girls than in boys. Peak height velocity (PHV) is an early event during puberty in girls and a relatively late event during puberty in girls and a relatively late one in boys, the sex difference in mean age being about two years. In girls, menarche is a late event, always occurring after PHV. At the age of 13-14 years some boys and girls have not yet begun theri pubertal development, while others have reached the adult stage.