Cell adhesion molecules--update.

Cell adhesion molecules are glycoproteins expressed on the cell surface and play an important role in inflammatory as well as neoplastic diseases. There are four main groups: the integrin family, the immunoglobulin superfamily, selectins, and cadherins. The integrin family has eight subfamilies, designated as beta 1 through beta 8. The most widely studied subfamilies are beta 1 (CD29, very late activation [VLA] members), beta 2 (leukocyte integrins such as CD11a/CD18, CD11b/CD18, CD11c/CD18, and alpha d beta 2), beta 3 (CD61, cytoadhesions), and beta 7 (alpha 4 beta 7 and alpha E beta 7). The immunoglobulin superfamily includes leukocyte function antigen-2 (LFA-2 or CD2), leukocyte function antigen-3 (LFA-3 or CD58), intercellular adhesion molecules (ICAMs), vascular adhesion molecule-1 (VCAM-1), platelet-endothelial cell adhesion molecule-1 (PE-CAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). The selectin family includes E-selectin (CD62E), P-selectin (CD62P), and L-selectin (CD62L). Cadherins are major cell-cell adhesion molecules and include epithelial (E), placental (P), and neural (N) subclasses. The binding sites (ligands/receptors) are different for each of these cell adhesion molecules (e.g., ICAM binds to CD11/CD18; VCAM-1 binds to VLA-4). The specific cell adhesion molecules and their ligands that may be involved in pathologic conditions and potential therapeutic strategies by modulating the expression of these molecules will be discussed.

Topical treatments for hydrofluoric acid dermal burns. Further assessment of efficacy using an experimental piq model.

Several topical treatments for hydrofluoric acid dermal burns (Zephiran, calcium acetate and magnesium hydroxide antacid soaks, and calcium gluconate gel) were assessed for efficacy in a pig model. Gross appearance and histopathology of treated and untreated burn sites were evaluated. For superficial burns, Zephiran was most effective; calcium acetate, magnesium hydroxide antacid, and calcium gluconate gel were less effective. For deep burns, gross observations showed that calcium acetate and Zephiran were most efficacious, whereas histopathology indicated comparable efficacy of Zephiran, calcium acetate, and calcium gluconate gel for all skin layers. Magnesium hydroxide antacid demonstrated efficacy only for the subdermis. The clinically beneficial effects of both Zephiran and calcium gluconate gel were affirmed. Although results suggest that calcium acetate and magnesium-containing antacids may be beneficial for human hydrofluoric acid dermal burns, these are not established clinical treatments.

Hydrofluoric acid dermal burns. An assessment of treatment efficacy using an experimental pig model.

There currently exist various opinions concerning the best therapy for managing hydrogen fluoride (HF) dermal burns. Previously reported animal studies designed to evaluate the efficacy of certain therapies are not completely convincing. Studies initially were conducted to develop a reliable animal model for assessing efficacy of treatment. Evaluation of several animal species, dosing regimens (HF concentrations, exposure periods), and application techniques showed that the most consistent and reproducible dermal lesions were produced with 38% HF applied to the skin of anesthetized pigs for exposures of 9, 12, or 15 minutes using Hill Top Chamber patches. Using this model, the efficacy of six clinically applicable treatments was assessed by subjectively scoring and statistically analyzing photographic and histopathological data obtained from treated and untreated control lesions. Photographic data analysis ranked treatments with respect to effectiveness as follows: iced Zephiran and 10% calcium acetate soaks--highly effective; 2.5% calcium gluconate gel, 5.0% calcium gluconate injection and iced Hyamine soaks--effective; 10% calcium gluconate injection--ineffective. Histopathological data analysis showed the topical treatments (2.5% calcium gluconate gel, iced Hyamine, or iced Zephiran soaks) to be most effective in reducing superficial epidermal damage, and the 5% calcium gluconate injection or 10% calcium acetate soaks to be beneficial to deeper tissues of the dermis and subdermis. Injection of 10% calcium gluconate was ineffective. This study suggests that the anesthetized pig model has good applicability for assessing efficacy of HF dermal burn therapies. In addition, it indicates that further experimentation with 10% calcium acetate soaks is warranted.

Effect of soy fiber and soy protein on cholesterol metabolism and atherosclerosis in rabbits.

The effect of dietary fiber isolated from dehulled, defatted soybean seeds on cholesterol (CHOL) metabolism and atherosclerosis in rabbits was studied alone and in combination with isolated soy protein (ISP). Soy fiber (SF) contains both cellulosic and non-cellulosic dietary fiber. Based on the official AOAC method, soy fibers contains 75% total dietary fiber. Rabbits at 6 months of age were randomly assigned to 1 of 4 dietary treatments. All rabbits received either a casein or ISP-based diet with cellulose or SF as the only dietary fiber source for 36 weeks. Fasting blood samples and feces were collected and analyzed for lipids from individual rabbits. The entire aorta was removed and fixed, and sudanophilic stained lesions were examined visually. Rabbits consuming the SF and/or ISP diets had lower plasma CHOL levels and lower incidence of atherosclerotic lesions relative to the rabbits fed the casein-based cellulose diets. Rabbits consuming the SF and/or ISP diets also had a lower CHOL content in their liver and heart. Rabbits fed ISP-based diets had consistently increased fecal bile acid excretion, whereas rabbits fed diets containing SF had increased fecal and cholesterol concentration. These results suggest a complementary role for SF and ISP in preventing atherosclerosis in rabbits.

Eosinophilic myositis and muscular sarcocystosis in the carcasses of slaughtered cattle and lambs.

Fifty-three bovine and 7 ovine carcasses condemned for having eosinophilic myositis were evaluated. Four (7.3%) of the bovine carcasses had a few, large local lesions in skeletal muscles (category A), and 49 (92.7%) of the bovine carcasses and 7 (100%) of the ovine carcasses had multiple, small, disseminated lesions in tongue, esophagus, heart, diaphragm, or skeletal muscles (category B). Tissue from carcasses of category B were evaluated for bacteria, viruses, selenium, and pathologic changes. Pathogenic bacteria and viruses were not isolated and selenium concentrations were normal. In category B, all carcasses had granulomas; of the 49 bovine carcasses and 7 ovine carcasses, 38 (77.6%) and 7 (100%), respectively, had one or more granulomas with opened dead sarcocysts. The data indicated that opened sarcocysts killed the host myocyte and adjacent myocytes and stroma, thereby initiating granuloma formation.

Pancreatic beta-cell carcinoma with renal metastasis in a dog.

Severe hypoglycemia associated with a metastatic pancreatic beta-cell carcinoma was found in an adult female American Eskimo dog. Metastatic tumor was found in the renal glomeruli as opposed to the more common hepatic metastatic site.

Effects on the monkey, pig and rat pancreas of soy products with varying levels of trypsin inhibitor and comparison with the administration of cholecystokinin.

Raw and heated soy flour and casein diets were compared in rats, pigs, and monkeys with respect to growth, pancreatic changes, fecal trypsin, and nitrogen digestibility. Cholecystokinin injection was compared to feeding raw soy flour and casein in rats and casein in pigs. Several soy protein preparations were fed to rats and monkeys. Neither raw soy flour nor any other soy product produced pancreatic enlargement in pigs or monkeys. Casein and heated soy flour performed similarly. By comparison, other effects of raw soy flour were as follows. Growth was depressed 60% in rats and 84% in pigs, but not at all in monkeys. Nitrogen digestibility was depressed 5, 45, and 9% in rats, pigs, and monkeys, respectively. Pancreatic DNA, RNA, and protein levels were unchanged in monkeys fed raw soy flour. In rats, RNA per milligram pancreas was increased 40%, in pigs 20%. Pancreatic protein was decreased 7% in pigs and increased 47% in rats. Changes in pancreatic trypsin, chymotrypsin, lipase, and amylase were dissimilar in the three species. Fecal trypsin was elevated 300-400% in rats, and decreased approximately 50% in pigs and monkeys. Cholecystokinin injections in pigs and rats produced changes both quantitatively and qualitatively different from those seen with raw soy flour. Feeding of heated soy flour or soy protein isolates was comparable to feeding casein in all three species, and produced no deleterious effects.

Excretion and tissue distribution of radioactive lysinoalanine, N epsilon-DL-(2-amino-2-carboxyethyl)-U-14C-L-lysine (LAL) in Sprague-Dawley rats.

Rats were fed either a control soybean protein diet or a diet containing 3,000 ppm soybean protein-bound lysinoalanine (LAL) for 4 or 6 weeks, at which time all rats were dosed by stomach tube with 14C-LAL labeled in the lysine moiety. Urinary and fecal excretion and tissue distribution were followed in one experiment at 6, 12, 18, 24, 48 and 72 hours. Excretion in urine, feces and expired air was followed in the other metabolic experiment at 2-hour intervals for 48 hours, and at 24-hour intervals for the next 7 days. Tissue samples were counted and LAL determination was made by amino acid analysis in both experiments. The group of rats fed LAL excreted slightly more LAL than the group fed the control diet. Very little LAL remained in the rat tissues after either experiment, and the largest remaining quantity of radioactivity was found as lysine. Quantitation of 14C-lysine in the original material and in the material from rat organs showed that the rat has some capacity for converting LAL to lysine. Less than 0.5% of the original 14C remained in any organ examined 9 days after dosing in the either control or LAL-fed rats. Autoradiographs of the kidneys 24 hours after dosing showed that the radioactive material had accumulated in the proximal convoluted tubules of the corticomedullary junction.

Effect of protein-bound lysinoalanine, N epsilon-DL-(2-amino-2-carboxyethyl)-L-lysine on fetal and neonatal rats.

Diets containing 5% to 30% of an alkali-treated isolated soybean protein (ATSP) containing 1% lysinoalanine (LAL) were fed to female Sprague-Dawley rats during gestation and lactation to provide 500, 1,000, 2,000, or 3,000 ppm LAL in the diet. An isolated soybean protein containing no LAL was used as control. No teratological effects were observed. No significant differences in birth weight, mortality, live births/litter, or number of pups/litter was found at any LAL level fed. However, significantly decreased weight gains were observed in pups from dams fed either 2,000 or 3,000 ppm LAL. No LAL was found in the milk, and protein content of all milks was similar. The decreased weight gains appeared to be due to reduced milk production in dams fed high levels of ATSP.