Abstract-Circulating cholesterol oxidation products (ChOx) have long been implicated in the etiology of early atherosclerosis; however, direct in vivo evidence elucidating their role in atherogenesis is only recently becoming available. This study investigated ChOx effects on vascular lesion formation in New Zealand White rabbits under controlled hypercholesterolemic conditions. By closely monitoring plasma cholesterol levels and adjusting dietary cholesterol intake during a 78-day period, total plasma cholesterol exposures (cumulative plasma cholesterol levels over time) were controlled between 27 000 and 34 000 mg/dLϫday (final plasma cholesterol concentration, 467Ϯ77 mg/mL), representing a threshold range for sudanophilic lesion formation in the aorta. Twenty injections of a ChOx mixture (70 mg per injection) were made bearing an oxysterol composition similar to that found in circulating oxidatively modified low density lipoprotein. At sacrifice, the ChOx-injected rabbits (nϭ5) had (1) significantly higher plasma ChOx levels, (2) significantly increased cholesterol content in the aortas, mainly as esterified cholesterol, and (3) significantly greater sudanophilic lesion size and frequency in the aortas compared with vehicle-injected control rabbits (nϭ5). The aortic cholesterol content and extent of sudanophilic lesion area were correlated significantly with total plasma ChOx exposure (PϽ0.003 and PϽ0.0001, respectively) but not with total cholesterol exposure. The results indicate that for moderate experimental hypercholesterolemia, a situation more relevant to physiological hypercholesterolemia in humans, circulating ChOx may play an important role in inducing formation of early atherosclerotic lesions. Because ChOx are often present in cholesterol-containing diets, foam cell lesion formation induced by ChOx rather than cholesterol cannot be overlooked.

Surface immunoglobulins were determined on human lymph node lymphocytes by the use of immunofluorescence technique in 59 breast cancer patients undergoing radical mastectomy. In 10 of these cases, lymphocyte surface immunoglobulins were also studied on lymphocytes infiltrating the primary cancer mass. The most outstanding finding was a difference between the IgM lymphocyte populations in the lymph nodes of patients with and without lymph node metastases. When cancer tissue was present in one or more lymph nodes, the tumor‐free as well as the tumor‐positive nodes showed a higher percentage of IgM positive lymphocytes than did lymph nodes from patients without nodal metastases. The greatest difference was found when IgM lymphocytes from tumor‐bearing lymph nodes were compared with those from the lymph nodes of patients without nodal metastases (p < .005). The lymphocyte populations infiltrating 5 of the 10 primary cancer masses studied showed no surface immunoglobulins; in the remainder, both IgG and IgM positive lymphocytes were found but in variable proportions. While the findings are not definitive, this is the first study dealing with the quantitation of immunoglobulin specific lymphocytes in the lymph nodes and tumor tissue of patients with breast cancer.

An experimental model was designed where the frequency of blood-borne cancer cell metastases to the lungs of animals was used as an indicator to detect adverse effects of inhaled nitrogen dioxide (NO2). Animals were exposed to air containing 0.40 +/- 0.05 ppm or 0.80 +/- 0.05 ppm of NO2. After the appropriate exposure periods, the animals were infused intravenously with B16 mouse melanoma cells. At 3 wk post-infusion the animals were killed and the lungs were examined for melanoma nodule development. The lungs of the NO2-exposed animals contained a significantly higher number of melanoma nodules than the lungs of control animals (P less than .0025). These results indicate that inhalation of ambient or near ambient levels of NO2 influences the metastasis of blood-borne cancer cells. This raises the possibility that similar events may occur in the human population.

Semiquantitative measurements of chronic inflammation of the centriacinar region (proximal acinus of lung) were compared between 20 Miami and 18 Los Angeles residents (ages 11-30 years) for whom smoking histories were available. Mean extent and severity scores of four lung sites were higher for Los Angeles than Miami residents, with effect of city statistically significant for extent (P=0.02). Also, maximum scores for extent and severity by city were significantly greater for Los Angeles residents (P=0.02, each), but not by smoking history. Smokers did have higher scores for mean extent and severity (by lung site and smoking history), but neither this nor inclusion of smoking and city in the model reached significance. With respect to maximum extent and maximum severity scores, a stratified comparison of cities by smoking history showed a trend (not significant) toward higher scores for Los Angeles residents. Mean extent and severity scores for the lower lobe were higher for basilar sections than for apical sections (each P<0.001). Cumulative data indicate that expanded pathologic studies are essential for efforts to complete a convergence of epidemiological and experimental data implicating exceedences of the Federal ozone standard as a contributor to human lung injury.