No abstract

While blood transfusion is increasingly implicated in the aetiology of tumour recurrence, the mechanism of this effect is unclear. Cancer-bearing patients are known to have factors in their sera which depress the function of normal lymphocytes. It is possible that blood transfusion accentuates this natural suppression. An animal model was therefore developed to study the effect of blood transfusion on humoral immunosuppressive activity and its possible relationship to red cell clearance. WAG rats given a transfusion of chromium-labelled allogeneic but blood-group compatible DA rat blood, developed significantly increased (P < 0.001) levels of lymphocyte suppressive factors in plasma (maximum at 7 days) which coincided with accelerated red cell clearance (t1/2 = 7 days). A transfusion of syngeneic WAG blood caused only a small transient increase in plasma suppression and red cells were cleared at a normal rate (t1/2 = 13 days) consistent with previous studies. However, when syngeneic WAG red cells were lysed and the red cell membranes infused there was a rapid increase in plasma suppression (P < 0.001), similar to but less prolonged than that achieved with allogeneic blood. The immunosuppressive effect of blood transfusion may result from accelerated clearance of allogeneic or damaged syngeneic red blood cells.

Transition from a normal to a cancerous state is marked by alterations in the cytoskeletal structure of those cells involved. We have examined such changes to determine if these transitions are markers of disease progression. Cytokeratin (CK) protein and messenger RNA (mRNA) expression were examined in malignant and benign breast tissues. Flow cytometric results demonstrated a significant correlation between cytokeratin protein expression detected by 5D3 antibody, specific for cytokeratins 8, 18, and 19 and axillary node metastasis (P = 0.01). A threshold of positivity of 338,000 molecules/cell was determined and reflected the wide range in cytokeratin levels expressed by normal or benign tissues. Examination of cytokeratins 8, 18, and 19 revealed a consistent pattern of expression with respect to tumor grade. Only cytokeratin 19 showed significant correlation with increasing tumor size (P = 0.006). mRNA expression for cytokeratin 8 was significantly higher in node-positive compared with node-negative disease (P = 0.02). Cytokeratin 18 mRNA levels were significantly lower in both node-negative (P = 0.03) and node-positive (P = 0.02) patients when compared with benign samples. Increased levels of cytokeratin 18 mRNA showed an inverse relationship with protein expression (P = 0.05). The results indicate that cytokeratin expression in breast cancer may be associated with tumor progression. Furthermore, the alteration in the expression of individual cytokeratins deserves further investigation to determine the consequences of these changes with respect to cellular function.

Although nutritional repletion of malnourished individuals may improve tests of cell‐mediated immunity, the effects of intravenous nutrient solutions themselves on the immune system are largely unknown. This study examined the effects of five parented nutrition solutions on in vitro lymphocyte reactivity and measured lymphocyte responsiveness in patients receiving parenteral nutrition. Normal human lymphocytes were incubated with dilutions of (a) an amino acid/dextrose solution, (b) an amino acid/dextrose/fat solution, (c) an amino acid solution, (d) dextrose, and (e) a fat emulsion, and lymphocyte responsiveness to antigenic (ppd) and mitogenic (pha) stimulation was measured using an in vitro electrophoretic test of cell‐mediated immunity. Lymphocyte reactivity was measured in 15 postoperative patients allocated randomly to receive either simple electrolyte solutions or isocaloric parenteral regimes with or without a fat emulsion. in vitro lymphocyte responses were significantly depressed (p < 0.001) by the fat emulsion at concentrations similar to those achieved in clinical practice but were unaffected by dextrose or amino acid solutions. Lymphocyte reactivity was significantly depressed in patients during infusion of the fat emulsion in comparison with controls (p < 0.05). The results show that fat emulsion impairs lymphocyte reactivity and suggest that careful consideration should be given before using fat emulsions in patients in whom cell‐mediated immunity is impaired already.