Hepatic cirrhosis in young adults: association with adolescent onset of alcohol and parenteral heroin abuse.

Hepatic cirrhosis is infrequently diagnosed in young adults. In a hospital for addictive diseases in New York City, we found cirrhosis in 53 patients under age 35 within just 40 months. The cirrhosis was biopsy-proven in 37 patients (group I) and diagnosed clinically in 16 patients with severe liver disease (group II). Alcohol abuse was found in 51 patients (96%), and parenteral heroin abuse was seen in 52 (98%). The duration of alcohol abuse was seven or fewer years in 24 patients (45%) and 10 or fewer in 39 (74%). In 44 (83%), the substance abuse began in adolescence. Comparison of group I cirrhotic patients with 65 non-cirrhotic biopsied patients showed that cirrhosis was significantly associated with abuse of both alcohol and parenteral heroin (p less than 0.001). The distribution of 66 HLA antigens from A, B, C, and DR loci showed no differences when 42 patients were compared with 42 ethnically-matched control substance abusers. The early development of cirrhosis in these young patients may be related to multiple hepatic injuries induced by alcohol and parenteral heroin abuse and to the onset of addictive diseases during adolescence or early adult life.

Regulation of the in vitro early anamnestic antibody response by exogenous cholera enterotoxin and cyclic AMP.

Keyhole limpet hemocyanin was injected into the hind foot pads of rabbits. Six days later cell suspensions were prepared from the popliteal lymph nodes. Various amounts of hemocyanin (1 ng to 100 mug) were added to 1 times 10-7 cells to induce an anamnestic antibody response. Various amounts of cholera enterotoxin, which stimulates the enzyme adenylate cyclase, or dibutyryl cyclic adenosine 3'5'-monophosphate (AMP), were added to the cultures with or without hemocyanin. De novo synthesis of antibody, protein, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from radioactive precursors was assayed. The addition of cholera toxin or dibutyryl cyclic AMP for the first 24 hr with optimal (1 mug) or supraoptimal (100 mug) amounts of hemocyanin enhanced antibody synthesis by at least 100 to 200%. Addition of the toxin or dibutyryl cyclic AMP for the same period to cells minus hemocyanin or with suboptimal amounts (1 to 100 ng) of antigen failed to enhance antibody synthesis. Addition of these agents for 72 to 120 hr to hemocyanin-induced cultures consistently inhibited antibody synthesis. These agents slightly inhibited DNA and RNA synthesis. The increase in protein synthesis caused by the toxin or dibutyryl cyclic AMP was almost totally accounted for by the increase in antibody synthesis. Neither toxin nor cyclic nucleotide promoted the antibody response in the presence of antibody to rabbit thymus-derived lymphocytes; these lymphocytes as well as bursa-equivalent lymphocytes were required for potentiation of the response. Macrophages were not required either for induction of the anamnestic response or for enhancement of this synthesis by cyclic nucleotide or cholera toxin. Both IgM and IgG antibody synthesis were regulated by exogenous cholera toxin and dibutyryl cyclic AMP. A number of possible cellular mechanisms of regulation of the antibody response through the cyclic AMP pathway were discussed. These included the effects of modifications of this pathway on the activities of T lymphocytes early (0 to 24 hr) and B lymphocytes late (72 to 120 hr) in the response and on the apparent reversal of high zone tolerance.

Differentiation and functional expression of potential antibody-producing cells in the presence of chloramphenicol.

Rabbits were immunized with diphtheria toxoid combined with complete Freund's adjuvant. Half of the animals were started on intramuscular injections of chloramphenicol 24 hr before the injection of the antigens. There was a general depression of protein synthesis in the immune system in the presence of chloramphenicol, but a greater effect on the synthesis of antibody than on the synthesis of proteins necessary for reproduction and maturation. In contrast to the finding of antibody in cells of the spleen and in the circulation of the control animals, those animals receiving chloramphenicol did not have measurable circulating antibody, and their spleens contained only a few cells with intracytoplasmic antibody late in the course of the experiment. Cytologically there was maturation of potential antibody-producing cells in the red pulp and nonfollicular white pulp of the spleen while the animals were receiving chloramphenicol. These cells developed more slowly, and were fewer and smaller than those of the control animals. They had numerous small, electron-opaque particles in their cytoplasm early in development. Ribosomes were synthesized, though fewer in number. The endoplasmic reticulum formed more slowly.