Nasrollah T. Shahidi

Androgens and Erythropoiesis

SINCE early investigations exploring the role of sex hormones on the red cell, hemoglobin and hematocrit,1 , 2 numerous reports have now firmly established that androgens stimulate erythropoiesis. ...

Bone-Marrow Microenvironment Defect in Congenital Hypoplastic Anemia

An abnormal bone-marrow microenvironment has been thought to have an important role in the pathogenesis of aplastic and hypoplastic anemia in some patients, but direct evidence of such a defect has not been found. We have investigated the pathogenesis of chronic anemia in a young woman. Her bone-marrow cells, obtained by means of aspiration, showed exuberant erythroid growth in methylcellulose despite marked erythroid hypoplasia. The erythroid nature of the colony growth was further confirmed through measurement of heme synthesis and messenger RNA-globin accumulation in a liquid-culture system. In contrast, when whole bone fragments were similarly cultured, no appreciable hemoglobin synthesis was observed. The experimental evidence suggests that, in this patient, hypoplastic anemia resulted from an unfavorable microenvironment.

Immune Thrombocytopenia Due to a Drug Metabolite

Abstract A patient who developed thrombocytopenia while taking analgesics was found to have circulating antibody to a metabolic product of N-acetyl-p-aminophenol (NAPA), but not to the drug itself. The antibody reacted in vitro with an antigen present in the blood of a normal volunteer who had ingested NAPA. The antigenic material was purified from the urine of this volunteer and shown to be the sulfate conjugate of the drug. These findings demonstrate that a drug metabolite may be antigenically active in drug-induced thrombocytopenia when the drug itself is immunologically inert, representing a form of drug-induced thrombocytopenia.

Androgen-Induced Increase in Red-Cell 2,3-Diphosphoglycerate

Abstract The administration of testosterone enanthate to six patients with chronic renal failure on biweekly hemodialysis increased erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in all patients. Whereas the value was 5670 ± 550 (mean ± S.E.) nmoles per milliliter of red blood cells before treatment, it was 9097 ± 760 after 12 weeks of androgen therapy. This increase was statistically significant (p less than 0.01). None of a group of seven similarly affected patients who did not receive androgens and were followed within the same period showed any increase in red-cell 2,3-DPG. The shift in oxygen equilibrium curve to the right that results from testosterone enanthate should greatly enhance the unloading of oxygen to the tissues.

Anemia associated with protein deficiency: A study of 2 cases with cystic fibrosis

Summary Anemia, with diminished concentration of serum iron and total iron-binding capacity as the result of protein failure, has been described in two young male infants suffering from cystic fibrosis, who had been fed formulas based on soya bean protein. Hypocupremia was also present in one of the patients. In the absence of detectable protein loss or increased protein degradation the hypoproteinemia appeared to be the result of inadequate utilization of this vegetable protein by these infants with defective protein digestion. The age at onset of anemia, the normochromic, normocytic appearance of the erythrocytes, and the decreased erythroid activity in the bone marrow all made the possibility of iron deficiency unlikely. Rapid and sustained reticulocytosis following an adequate intake of high-quality protein without additional iron suggested that protein deficiency was responsible for the low hemoglobin concentrations. In this connection the role of inadequate protein intake in the quantitative disturbance of hemoglobin synthesis is discussed. While the hypoferremia is through to reflect a defect in the transport process, the mechanism whereby protein deficiency leads to hypocupremia remains less certain.

Lymphocyte dysfunction in congenital hypoplastic anemia.

Congenital hypoplastic anemia (Diamond-Blackfan syndrome) is thought to involve the erythropoietic cell line alone. In this study, the evaluation of lymphocyte function in five patients with this syndrome revealed a number of abnormalities. Peripheral blood T lymphocyte percentages as assessed by monoclonal antibodies were decreased in three patients. T-helper/T-suppressor cell (OKT4:OKT8) ratios were almost unity in four of the five patients. We usually find a ratio of 2:1 in normal populations. Studies of lymphocyte-mediated suppression of lymphoproliferation demonstrated an inability to generate concanavalin A-induced suppressor cells in the same four patients and impaired prostaglandin-mediated suppression in two patients. Co-culture studies revealed a T lymphocyte-mediated suppression of erythropoiesis in a single patient, who also showed suppression of the mixed lymphocyte reaction. The four remaining patients showed no excessive suppressor effects either upon erythropoiesis or lymphoproliferation. These studies demonstrate that in congenital hypoplastic anemia, the cellular defect is not restricted to the erythroid progenitor cells, but extends to the lymphocytes.

Erythrocyte 2,3-Diphosphoglycerate in Adaptive Red-Cell-Volume Deficiency

Abstract Measurement of red-cell volume, plasma volume and erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in five patients with panhypopituitarism and one patient with isolated growth-hormone deficie...

Erythrocyte Acid Phosphomonoesterase and Glucose-6-Phosphate Dehydrogenase Deficiency in Caucasians

Caucasian patients with erythrocyte glucose-6-phosphate dehydrogenase deficiency also have a deficiency in erythrocyte acid phosphomonoesterase. This acid phosphomonoesterase deficiency is not present in Negroes with the glucose-6-phosphate dehydrogenase deficiency.

Evaluation of growth and of endocrine systems in testosterone-corticosteroid-treated patients with aplastic anemia

The long-term follow-up of three children with acquired aplastic anemia who received combined testosterone-corticosteroid therapy in large doses over a long period revealed no significant discrepancy between the linear growth and skeletal maturation. The lack of great acceleration of skeletal maturation is thought to be the result of corticosteroids which were given in conjunction with testosterone. The endocrine exploration in two of the patients who were in the adolescent age group showed no abnormality, suggesting that the endocrine disturbances which may have occurred during therapy have been restored to normal.

Effect of hemodialysis on erythrocyte 2,3-diphosphoglycerate in patients with uremia.

The relationship between erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and changes in blood pH and serum inorganic phosphate was studied before and after 25 hemodialyses in 11 patients with chronic uremia. Despite a significant increase in mean pH from 7.33 to 7.44 after dialysis, the mean red cell 2,3-DPG decreased from 5,866 to 4,238 nmoles/ml erythrocytes. Serum inorganic phosphate decreased from a mean level of 7.2 mg/100 ml to 4.1 mg/100 ml. This study suggests that, although pH can be correlated with 2,3-DPG levels in the predialysis state, during dialysis the change in serum inorganic phosphate plays an important role in regulating 2,3-DPG concentration. The decreased red cell 2,3-DPG and increased pH after dialysis may significantly increase the affinity of hemoglobin for oxygen and consequently result in inadequate tissue oxygenation.