Granulocyte function in human allogenic marrow graft recipients.

Granulocyte chemotaxis and iodination were studied in 87 allogeneic marrow transplant recipients and in 25 normal individuals. Chemotactic responses of marrow transplant recipients as a group were depressed during the first 4 months after transplantation and normal in patients studied as long-term survivors (days 175--2202 post-transplantation). Patients with moderate to severe acute or chronic graft-versus-host disease (GVHD) or infections had lower chemotactic responses than those without. Granulocyte iodination and the ability of patient serum to support iodination were normal. Thus, depressed granulocyte chemotaxis recovered slowly with time following allogeneic marrow transplantation. Both acute and chronic GVHD, however, were associated with impairment of granulocyte chemotaxis, a defect which may contribute to the high risk of infection among allogeneic marrow graft recipients with GVHD.

Intestinal permeability to large particles in normal and protein-deficient adult rats.

Intestinal absorption of ferritin and virus particles was assessed in control and protein-deficient rats using light and electron microscopic procedures. Rats weighing 100 to 130 grams were divided into two groups and fed either a 0.5% of 18% lactalbumin diet. At monthly intervals following diet initiation, three rats from each group were administered ferritin (MW-650,000) or adenovirus Type 5 (MW is greater than 1,000,000) via ligated jejunal loops either 15 or 30 minutes prior to loop excision and processing for electron microscopy. Morphological evaluation of jejunal tissues revealed that both control and protein-deficient rats absorbed ferritin and virus particles via pinocytosis and in both situations the exogenous particles were believed to be present in lysosmal bodies of typical absorptive cells. Neither ferritin molecules nor virus particles were identified elsewhere in the jejunal mucosa of control rats. Rats deprived of sufficient dietary protein for four months or longer, however, demonstrated exogenous tracer materials in intercellular spaces of the epithelium and lamina propria. Since these severely protein-deprived rats also demonstrated deterioration of apical intercellular junctions, the possibility exists that large particles moved directly between cells of the epithelial lining and subsequently into underlying connective tissue and vascular compartments for conveyance (as antigens) to other body regions.

Effect of daily ethanol ingestion on intestinal permeability to macromolecules.

The effects of regular ethyl alcohol ingestion on morphological and permeability characteristics of the small intestine were assessed in mature rats using the tracer protein, horseradish peroxidase. Thirty adult rats were divided into two groups and provided a standard commercial diet in pellet form. Each morning, after an overnight fast, every animal in the experimental group was administered by gavage an aliquot of 20% ethanol; animals in the control group were provided aliquots of 20% sucrose in water by the same method. After 4 and 8 weeks on the gavage routine (and 10 days and 4 weeks after gavage cessation), jejunal permeability to horseradish peroxidase was examined in animals from each group. Using a routine ligated-loop procedure and light and electron microscopy, ethanol-exposed rats demonstrated increased intestinal permeability to horseradish peroxidase by 4 weeks; sucrose-exposed animals revealed little alteration in mucosal integrity. It is proposed that regular ingestion of sizable amounts of alcohol alters morphological characteristics of the gut and increase the permeability of the mucosa to "undigested" macromolecules.

Effects of essential amino acid deficiencies on syngeneic tumor immunity and carcinogenesis in mice.

The present study was designed to evaluate in a syngeneic system the longterm effect of dietary reduction of each of three essential amino acids on carcinogenesis with methylcholanthrene (MCA) and immunity to a transplanted MCA tumor. Inbred mice were provided a standard amino acid diet or a diet deficient in isoleucine, leucine, or phenylalanine-tyrosine. In the carcinogenesis experiment, MCA pellets were implanted in each mouse and weekly records were maintained of body weight, tumor incidence, tumor size, and death rate. Mice in the immunity study were inoculated with syngeneic tumor cells; tumors were excised when the largest tumor in the control group reached 12 mm and each animal then received a second challenge of tumor cells. The available data suggest that (1) restriction of the selected amino acids does not inhibit chemical carcinogenesis with MCA, (2) phenylalanine-tyrosine deficiency may actually enhance chemical carcinogenesis with MCA, and (3) selected essential amino acid deficiencies do not enhance immunity to a transplanted MCA tumor.