GM-CSF secretion in primary cultures of normal and cancerous human renal cells.

Rates of secretion of granulocyte-macrophage colony stimulating factor (GM-CSF) were measured in 50 primary cell cultures derived from cancerous and normal human kidneys. Mean rates of GM-CSF secretion measured by TF-1 cell proliferation assay (N = 21) and by ELISA (N = 31) were 2.5 and 7.8 ng/10(6) cells/24 hr, respectively. There was no significant difference between the mean rates of GM-CSF secretion by cancerous and normal renal cells. GM-CSF was also secreted by primary renal cell cultures grown in serum-free medium and by renal cell lines. GM-CSF mRNA was detected by RT-PCR in cultured renal cells, but not in undissociated kidney tissue. Rates of GM-CSF secretion were reduced up to 99% under conditions where the cellular density or substratum more closely resembled the in vivo environment. Some cultured human renal carcinoma cells (RCC) secreted GM-CSF at levels that occasionally overlapped the levels produced by the GM-CSF gene-modified human RCC vaccine now in phase I trial. The data indicate that GM-CSF is not expressed in vivo, and that stable GM-CSF secretion is induced by the dissociation and culture of human renal cells.

The role of ozone in tracheal cell transformation.

This project examined the potential role of ozone as a respiratory carcinogen by characterizing its ability to induce or modulate the preneoplastic transformation of rat tracheal epithelial cells. The chemical reactivity of ozone and the types of damage it can cause suggest that it may have a role in environmental carcinogenesis. Previous reports have described an increase in the incidence and number of lung tumors per animal in strain A mice exposed to ozone. However, the role of ozone in the development of the tumors has not been clear. Ozone also has been reported to act alone and synergistically with ionizing radiation to induce changes related to neoplasia in primary hamster embryo cells and in the mouse C3H/10T1/2 cell line in culture. Few other studies have examined the direct cytotoxic or transforming effects of ozone after in vivo or in vitro exposure of cells, and no studies have been reported on the comparative effects of ozone on respiratory cells exposed in vivo or in vitro. The induction of early preneoplastic changes in populations of rat tracheal epithelial cells by carcinogens can be detected and quantified in vitro after exposures in vivo or in vitro of tracheal epithelial cells. This cell culture and transformation system was used to characterize the transforming potency of ozone. Tracheal epithelial cells were isolated from Fischer-344/N rats that had been exposed for six hours per day, five days per week for one, two, or four weeks to 0, 0.12, 0.5, or 1.0 parts per million (ppm)* ozone (sea-level equivalents). Cell populations were examined in culture for increases in the frequency of preneoplastic variants. Rats exposed to ozone did not exhibit an increase in the frequency of preneoplastic tracheal cells, although exposed tracheas did exhibit dose-dependent morphological changes. Rat tracheal epithelial cells were given single, 40-minute in vitro exposures to concentrations of ozone that did not result in any detectable decrease in colony-forming efficiency (approximately 0.7 ppm) and to concentrations that resulted in approximately a 40% decrease (approximately 10 ppm). Exposed cultures were examined for increases in the frequency of preneoplastic variants. The results of these experiments, like those for the in vivo experiments described above, suggest that a single ozone exposure does not induce preneoplastic variants of rat tracheal epithelial cells. In contrast, cultures of rat tracheal cells exposed to 0.7 ppm ozone twice weekly for about five weeks exhibited approximately a twofold increase in the frequency of preneoplastic variants compared with control cultures.(ABSTRACT TRUNCATED AT 400 WORDS)

Preneoplastic transformation of rat tracheal epithelial cells by ozone.

The transforming potency of ozone for rat tracheal epithelial (RTE) cells exposed in vivo or in vitro was determined. RTE cells isolated from rats exposed to ozone (0, 0.14, 0.6, or 1.2 ppm, 6 hr/day, 5 days/week for 1, 2, or 4 weeks) showed no increase in the frequency of preneoplastic transformation compared to cells isolated from unexposed rats, although ozone-induced morphologic changes were observed in exposed tracheas. In contrast, preneoplastic variants of RTE cells were induced by multiple, but not single, exposures of RTE cells to ozone in culture. RTE cells exposed biweekly to ozone (approximately 0.7 ppm for 40 min, nine total exposures) had approximately twofold increases in the frequency of preneoplastic transformation compared to that of concurrent controls exposed to air. Single, 40-min exposures to ozone (approximately 1 or approximately 10 ppm) did not induce preneoplastic variants. However, single, 40-min exposures of RTE cells to approximately 10 ppm ozone did result in approximately 40% decreases in colony-forming efficiency. In addition, single, 40-min exposures of RTE cells to approximately 1 ppm ozone reduced the transforming potency of a subsequent exposure to the direct-acting chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). When multiple ozone exposures followed exposure to MNNG (approximately 0.7 ppm ozone for 40 min, nine biweekly exposures), an additive (or possibly a multiplicative) effect of ozone on MNNG-induced preneoplastic transformation was seen. These results demonstrate that ozone can, under some conditions, induce preneoplastic variants of RTE cells. In addition, depending on the sequence or combinations of exposures, ozone can reduce or, possibly, increase, the transforming potency of the carcinogen MNNG for rat tracheal cells in culture.

Association of malnutrition with nosocomial infection.

To study the association of malnutrition with nosocomial infection in a general medical and surgical inpatient population, we retrospectively compared 45 patients with nosocomial infection to 45 uninfected control patients, matched using several nonnutritional variables known to predispose to nosocomial infection. Univariate and multivariate analyses were done. Poor nutritional score (derived from serum albumin, total lymphocyte count, and unintentional body weight loss), unintentional body weight loss, low serum albumin level at both time of admission and the first nosocomial infection, and worsening in the nutritional score and serum albumin from admission to the first nosocomial infection were associated with the development of nosocomial infection. Nutritional factors were more abnormal in subgroups of patients with nosocomial pneumonia, urinary tract infection, wound infection, and bacteremia than in controls. The findings suggest that further study of correlations between nutritional factors and nosocomial infections is needed.

Prospective sensory evaluation of preparatory methods of elemental diets.

Palatability of elemental diets has been the greatest obstacle to their successful long-term oral administration. Two elemental diet products, A and B, were evaluated in four preparatory methods for acceptability in a prospective double-blind study. The elemental diets evaluated were most acceptable when prepared in the form of Jello (57% receiving acceptable scores) followed by frozen Tang (27% receiving acceptable scores) and those prepared with Flavor Packets (18% receiving acceptable scores). The Kool-Aid method of preparation was not accepted well (6% receiving acceptable scores). Product B was more acceptable than A in palatability and overall acceptability in the methods tested. To successfully administer elemental diets when a nasogastric tube is not employed, we recommend that these diets include formulations with Jello, frozen Tang, or Flavor Packets and that they be prepared by the dietary department. It is recognized that alterations in the composition of elemental diets result from the addition of flavoring agents. The significance of these alterations should be considered for each patient.