Relationship of aging and nutritional status to innate immunity in tube-fed bedridden patients.

BACKGROUND AND OBJECTIVES: Aging and malnutrition are known to influence immune functions. The aim of this study was to investigate the relationship of aging and malnutrition to innate immune functions in tube-fed bedridden patients. METHODS AND STUDY DESIGN: A cross-sectional survey was performed in 71 tube-fed bedridden patients aged 50-95 years (mean age±SD, 80.2±8.5 years) with serum albumin concentrations between 2.5 and 3.5 g/dL. We evaluated associations of age and nutritional variables with natural-killer cell activity, neutrophilphagocytic activity, and neutrophil-sterilizing activity. Nutritional variables included body mass index, weightadjusted energy intake, total lymphocyte count, and serum concentrations of albumin, transferrin, prealbumin, total cholesterol, C-reactive protein, and zinc. RESULTS: Natural-killer cell activity, neutrophil-phagocytic activity, and neutrophil-sterilizing activity were normal or increased in 67 (94%), 63 (89%), and 69 (97%) patients, respectively. Multiple linear regression analysis with a backward elimination method showed that natural-killer cell activity correlated negatively with aging and lymphocyte counts (p<0.01 for both) but positively with body mass index and transferrin (p<0.01 for both). Neutrophil-phagocytic and neutrophil-sterilizing activities were not associated with any variables. CONCLUSIONS: In tube-fed bedridden patients with hypo-albuminemia, natural-killer cell activity may be associated with aging, body mass index, transferrin, and lymphocyte counts.

Long-term enteral immunonutrition containing lactoferrin in tube-fed bedridden patients: immunological and nutritional status.

OBJECTIVE: The aim of this study was to examine the efficacy and safety of a novel immune-enhancing enteral formula, Prem-8, which contains lactoferrin as an immunonutrient. DESIGN, SETTING, PATIENTS: A multicenter, randomized controlled trial was conducted in 5 hospitals in Japan, and 71 tube-fed bedridden patients with serum albumin concentrations between 2.5 and 3.5 g/dL were allocated to Prem-8 (n = 38) or control formula (n = 33) groups for an observation period of 12 weeks. MEASURES OF OUTCOME: Efficacy was evaluated by comparing immunological (natural killer cell activity, neutrophil-phagocytic activity, neutrophil-sterilizing activity, and C-reactive protein), and nutritional (anthropometric measurements and serum levels of nutritional assessment proteins and total cholesterol) variables. Safety was assessed by comparing the incidence of adverse events. In a secondary analysis, patients were subgrouped according to the amount of protein supplemented (1 g/kg/d) so that immunological and nutritional variables and safety could be further compared. RESULTS: Natural killer activity and neutrophil functions were normal for both groups throughout the study period, without significant between-group differences at any point. Nutritional status was stably maintained in both groups, although the body mass index at 12 weeks was marginally lower in the Prem-8 group than in the control group (p < 0.01). The incidence of adverse events were comparable between both groups, but the incidence of fever in the Prem-8 group (7/14) was significantly lower than in the control group (10/11) in a subgroup of patients whose supplemented protein was less than 1 g/kg/d (p < 0.05). CONCLUSION: Prem-8 did not demonstrate superiority to the control formula with respect to immunological and nutritional variables, whereas the body mass index of patients in the Prem-8 group marginally decreased. However, Prem-8 had a favorable effect on the incidence of fever in a subgroup of patients with low protein intake.

Co-expression of urokinase with haptoglobin in human carcinomas.

BACKGROUND: We have shown that colon and breast cancer contains large amounts of urokinase (uPA), and that these cells are the actual sites of its synthesis. We isolated a large complex molecule consisting of the beta-chain of uPA, both chains of haptoglobin (Hp), and part or all of an NCAM-like molecule. The question arose whether it would be possible to show the presence of Hp in the same cells where uPA was found. MATERIALS AND METHODS: Human colon and breast adenocarcinomas were investigated for expression of Hp and uPA by immunohistochemistry. Fluorescence in situ hybridization was used to identify the cells of origin of these antigens. RESULTS: Hp was expressed in 8 of 11 colon adenocarcinomas, and in 10 of 12 breast tumors. uPA was demonstrable on the cell membrane and in the cytoplasm of all 11 colon adenocarcinomas studied, and cytoplasmic uPA-mRNA was found in all cases. While uPA was also detected in some stromal and inflammatory cells, Hp was present abundantly in such cells, as well as in capillary endothelial cells. Hp-mRNA was also found in both colon and breast tumors wherever the antigens were expressed. CONCLUSIONS: uPA and Hp are produced by the cancer cells and are not taken up by stromal elements. While the role of uPA in the malignant process is well documented, that of Hp is largely unexplored. Its ubiquity, shown here, suggests that it is also involved in some aspects of that process.

Plasminogen activator system localization in 60 cases of ductal carcinoma in situ.

BACKGROUND: The lack of prognostic factors in ductal carcinoma in situ (DCIS) that reliably identifies biologically aggressive tumors adversely affects optimal management. The urokinase-type plasminogen activator (uPA) system, comprised of its receptor, uPAR, and its inhibitor (PAI-1), are critical elements for tumor invasion and their expression in invasive breast cancer can predict clinical outcome. Expression of the uPA system in DCIS may be relevant in defining histological subsets of DCIS with invasive potential. METHODS: Localization of uPA, uPAR, and PAI-1 was investigated immunohistochemically in 60 DCIS tumors. FISH experiments were performed to determine whether uPA was present in cancer cells themselves or derived from stromal elements. RESULTS: uPA was ubiquitously expressed in the malignant ductal epithelium of 95% (57/60) of DCIS tumors studied. uPA-mRNA was detected in the malignant ductal epithelium but not the adjacent normal ductal epithelium and stromal elements. uPAR was expressed in 27% (6/22) of high-grade and 24% (9/38) of non-high-grade DCIS. In comparing coexpression, uPA and uPAR were coexpressed in only 25% (15/60) of tumors. PAI-1 was infrequently expressed in high grade (3/22) and absent in non-high-grade DCIS. CONCLUSIONS: This study identifies the presence of uPA, uPAR, and PAI-1 in both high-grade and non-high-grade DCIS. It may be speculated that coexpression of uPA and its receptor may identify subsets of DCIS with an increased risk for progression to invasive disease. If so, then expression of uPA system components may have prognostic and therapeutic significance in DCIS.