Natural killer cell activity in patients with pernicious anemia.

Patients with pernicious anemia have an estimated risk of gastric adenocarcinoma that ranges from three- to fivefold greater than that of the general population. It has been reported that NK cells may be involved in immunosurveillance against tumor spread. The natural killer cell activity of peripheral blood mononuclear cells was analyzed in 22 patients with pernicious anemia and in 19 healthy controls. Levels of natural killer cell activity against K-562 target cells were similar in control subjects and patients, regardless of gastrin levels and time elapsed since diagnosis. According to quantitative flow cytometry analysis, similar percentages of phenotypically defined NK cells (CD16+) were found in peripheral blood mononuclear cells from patients and healthy controls. Our results show that in pernicious anemia patients, the percentage of NK cells present in peripheral blood mononuclear cells and their lytic activity are normal.

Functional defect of T cells in autoimmune gastritis.

The functional response and phenotypic characterisation of peripheral blood T cells were studied in 41 patients with autoimmune gastritis--nine patients with autoimmune gastritis alone, 11 with untreated pernicious anaemia, and 21 with resolved pernicious anaemia who were taking vitamin B-12. Phenotypic analysis showed no changes in the CD4/CD8 ratio in any group of patients. CD3+ cells were significantly decreased and CD16+ cells were significantly increased in patients with autoimmune gastritis alone. Phytohaemagglutinin induced T cell proliferation, with or without interleukin 2, was reduced in the three groups. T cell proliferation induced by phorbol myristate acetate was normal. Interleukin 2 production of phytohaemagglutinin-stimulated lymphocytes was normal in the three groups. Five patients with pernicious anaemia treated with vitamin B-12 were followed and persistent hypoproliferation of T cells in response to phytohaemagglutinin was observed. The follow up study of the phenotype of these patients showed a significant increase of the CD2+ CD3- lymphocyte population after six months' treatment. In conclusion, the three groups of autoimmune gastritis patients studied have a functional defect in T cells that is independent of B-12 treatment and of the presence of pernicious anaemia.

Deficient interleukin 2 dependent proliferation pathway in T lymphocytes from active and inactive ulcerative colitis patients.

There is increasing evidence that ulcerative colitis is associated with an abnormality of the immune system. Although the aetiology remains unknown, it has been suggested that the immune system of these patients is implicated in the pathogenesis of their disease. T cell function was investigated in ulcerative colitis patients and defective phytohaemagglutinin induced T cell mitogenesis was found. The DNA synthesis induced by stimulation with phorbol esters plus ionophore (ionomycin), however, was normal. These changes cannot be ascribed to either decreased interleukin 2 synthesis or to a defective interleukin 2 receptor expression after cellular activation. Moreover, this defective proliferative response of the T lymphocytes was observed even in the presence of saturated concentrations of exogenous interleukin 2. These results emphasise that the interleukin 2 dependent proliferation pathway is deficient in T lymphocytes from ulcerative colitis patients.

Natural killer cell activity in laryngeal carcinoma.

We studied the relationship of natural killer cell activity from peripheral blood mononuclear cells with the clinical and pathologic stage of disease in 23 male patients with previously untreated carcinoma of the larynx and 22 healthy male control subjects. Levels of natural killer cell activity against K-562 target cells were similar in control subjects and patients, regardless of stage, tumor size, and clinical cervical adenopathies. Natural killer cell activity, however, was significantly decreased in patients with pathologic cervical lymph node involvement. The number of natural killer cells, as estimated by CD16 and CD56 monoclonal antibodies, was similar in all groups of subjects. We conclude that in patients with laryngeal carcinoma, there is a correlation between deficient natural killer cell activity and nodal metastases, which may represent a prognostic indicator in these patients.

Sex differences in hepatic sulfation of taurolithocholate in the rat.

Metabolism of the bile salts by formation of sulfate esters is catalyzed by bile salt sulfotransferase, an enzyme isolated from rat liver and kidney. The activity of bile salt sulfotransferase was measured in liver and kidney of male and female rats and in oophorectomized rats with or without estrogen replacement. In vitro sulfotransferase activity was correlated with in vivo sulfation by measuring the percentage of an infused dose (0.03 micron per 100 g per min) of taurolithocholate, which was excreted in bile as the sulfate. The activity of sulfotransferase in liver was higher in females (26.3 +/- 3.0 pmoles per mg of protein per min) than in males (9.6 +/- 3.9) and was lower (12.1 +/- 3.8) after oophorectomy. The decrease in activity was prevented by replacement of estrogen. Renal sulfotransferase activity did not differ between the sexes and was unaffected by oophorectomy. Hepatic sulfotransferase activity measured in vitro correlated with in vivo sulfation of taurolithocholate. This study shows definite sex differences in hepatic bile salt sulfotransferase activity, which in females is affected by the presence of estrogen. The correlation between in vitro sulfotransferase activity and in vivo bile salt sulfation suggests that bile salt sulfotransferase is responsible for bile salt sulfation in vivo.