The red cell in hereditary spherocytosis (HS) is unusually susceptible to the damaging effects of erythrostasis. The spleen is the primary site of erythrostasis in vivo, and it is a feature of HS that splenectomy corrects the hemolytic anemia, although the intrinsic red cell defect persists. The characteristic laboratory findings in HS of an increase in osmotic fragility and in autohemolysis are enhanced by in vitro incubation that simulates in vivo erythrostasis. Since these in vitro abnormalities are partially corrected by the addition of glucose (2), efforts have been made to detect a defect in the carbohydrate metabolism of the HS erythrocyte. As yet no definite abnormality in glycolysis has been demonstrated (3-5).In 1953 Harris and Prankerd (6) showed that there was an increased rate of extrusion of Na by the HS red cell, and in 1957 Bertles (7) demonstrated an increased rate of influx of Na into the HS erythrocyte. Jacob and Jandl (8) have confirmed this earlier work and have observed an increased turnover of Na by the HS red cell that is approximately twice normal. Based on these observations, they have postulated that the primary defect in HS is an abnormal permeability of the red cell to the passive influx of Na with secondary changes in glycolysis. To maintain a high concentration of K and a low concentration of Na within the red cell with respect to the concentration of these cations in the plasma, active transport against a gradient must take place. In the HS * Submitted for publication December 15, 1964; accepted May 10, 1965. This investigation was supported by grant HE-06239 from the National Heart Institute.Part of this work was presented at the national meeting of the American Federation for Clinical Research, Atlantic City, N. J., May 3, 1964 (1). red cell there is an increased passive influx of Na (7, 8) that must be compensated by increased active efflux of Na if osmotic hemolysis is to be prevented. Jacob and Jandl (8) have demonstrated that maneuvers which interfere with this compensatory increase in active Na transport lead to an increased rate of destruction of HS red cells in vivo. Since the energy necessary for the active transport of Na is derived from glycolysis in the form of adenosine triphosphate (ATP) (9-12), increased utilization of ATP and glucose by the HS red cell would be anticipated. Furthermore, ouabain, which blocks the utilization of ATP by the Na-K pump (11-13), should nullify increased rates of ATP and glucose utilization by HS red cells if the increase is caused by hyperactivity of cation transport. The data presented in this paper indicate an increased rate of ATP and glucose utilization by the HS erythrocyte that is only partially abolished by ouabain. The results suggest that in addition to increased utilization of ATP for active cation transport, the HS erythrocyte has an increased requirement of ATP for other metabolic processes as well. MethodsSubjects studied. HS red cells were obtained from eight patients. These patients were from three families, and all but...
To test the hypothesis that methyldopa induces red-cell autoantibodies by inhibiting the activity of suppressor lymphocytes, we studied its effect on several immune functions. Methyldopa inhibited T-lymphocyte suppression of IgG production by peripheral-blood mononuclear cells stimulated by poke-weed mitogens. This effect occurred in isolated T cells incubated with methyldopa and in T cells obtained from patients taking methyldopa. In addition, the drug caused a 30 to 80 per cent reduction in the proliferative response of peripheral-blood mononuclear cells to mitogens in vitro, and this reduction primarily involved the activation of T lymphocytes. Methyldopa also caused a persistent elevation of intracellular lymphocyte cyclic AMP in vitro and in vivo. We postulate that methyldopa alters the immune system by causing a persistent increase in lymphocyte cyclic AMP, which inhibits suppressor T-cell function. These effects may lead to unregulated autoantibody production by B cells in some patients.
A patient with paroxysmal nocturnal hemoglobinuria of 14 years duration presented with severe abdominal pain and fever. On admission, his hematocrit had fallen to 19% from his usual level of approximately 30%, and stools were positive for occult blood. Dilated loops of small bowel with air fluid levels were noted on radiographs, and sonography revealed free intraperitoneal fluid. Several sections of gangrenous jejunum and ileum were resected at exploratory laparotomy, and mesenteric venous thromboses were present. This is the second report of pathologically proven intestinal infarction in a patient with paroxysmal nocturnal hemoglobinuria who has survived this abdominal emergency with surgical intervention. Although abdominal pain in patients with paroxysmal nocturnal hemoglobinuria has frequently been attributed to mesenteric venous thromboses, this has rarely been documented either during life or at autopsy.
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