ALBERT

Description: 1. Porphyrin and hemoglobin metabolism have been studied in a case of photosensitive or congenital porphyria with the aid of glycine containing N15. The case was that of a 4 year old girl who also exhibited splenomegaly and hemolytic anemia. The reticulocytes and fecal urobilinogen were markedly increased and the bone marrow was hyperplastic-normoblastic. The urine contained large amounts of uroporphyrin I and lesser amounts of coproporphyrin I, while the reverse was true in the feces. Splenectomy resulted in disappearance of anemia, together with marked reduction of porphyrin excretion. 2. In two separate periods of study a rapid incorporation of glycine N15 was observed in the hemoglobin protoporphyrin, in both coproporphyrin isomers of the urine and in the type I isomer in the feces; also in the uroporphyrin I of the urine, and in the protoporphyrin and stercobilin of the feces. 3. The N15 data obtained for the urinary and fecal coproporphyrin and the urinary uroporphyrin, clearly reveal a synthesis similar in character to that of the hemoglobin protoporphyrin. The striking decline in formation of copro- and uroporphyrin after splenectomy is believed to be correlated directly with the reduced erythropoiesis incident to removal of the excessive hemolysis. 4. In both experiments the peak concentration of N15 was earlier and greater in the copro- than in the uroporphyrin. This, together with the closely similar slopes of decrease of the N15 curves for the two substances, does not appear to support a transition of uro- to coproporphyrin in the present case. The data are more consistent with the view that coproporphyrin I is a precursor of uroporphyrin I, or that both porphyrins are synthesized independently from common precursors. 5. The amount of coproporphyrin III in the excreta was too small to permit N15 analysis except in one period early in the first experiment; here the value was approximately the same as that of the copro- I for the same period, indicating a closely related synthesis.

Description: Through clinical, genetic and physicochemical studies a new inherited abnormality of hemoglobin has been recognized in American Negroes. The new hemoglobin, provisionally called hemoglobin III, can be separated from both normal and sickle cell hemoglobin by electrophoretic analysis. The structural anomaly of the hemoglobin molecule is determined by a gene inherited as a simple Mendelian dominant. A distinct hemolytic syndrome which is intermediate between the benign sickle cell trait and sickle cell anemia results from the combination of the new hemoglobin with sickle cell hemoglobin. A tentative characterization of the syndrome is presented. In contrast to classical sickle cell anemia this form of sickle cell disease is characterized by a mild hemolytic anemia with slowly progressive splenomegaly in the absence of cardiac or musculo-skeletal manifestations. In vitro, the erythrocytes sickle like those of sickle cell anemia. The bone marrow shows erythroid hyperplasia, fecal urobilinogen excretion is increased, and the survival time of the erythrocytes in normal recipients is shortened, but in the patients the red cell count and hemoglobin concentration are only slightly depressed. Reticulocytosis is slight and icterus is not observed. Whereas in sickle cell anemia both parents are expected to have the sickle trait, only one parent of these individuals shows sickling, while the nonsickling parent is a carrier of the hemoglobin III. The new syndrome does not appear to be identical with that resulting from the simultaneous presence of the sickling gene and the thalassemiagene. The presence of hemoglobin III when combined with structurally normal hemoglobin is expressed as an asymptomatic carrier state. The erythrocytes do not sickle but have a high incidence of target cell deformity and increased resistance to hypotonic saline. Although there is no evidence of hemolysis in such individuals their erythrocytes are eliminated with abnormal rapidity from the circulation of normal recipients. The homozygous state with respect to this new hemoglobin has not yet been identified but may well be some already recognized atypical form of chronic hemolytic anemia. Studies are now in progress to determine the incidence of this new molecular abnormality of hemoglobin.

Description: Types of non-wettable surfaces and their means of application are outlined and discussed.

Description: Exposure of rats and of human subjects to cold was associated with an elevation of the antifibrinolytic activity of blood. Administration of chymotrypsin to rats and rabbits caused a decrease in the antifibrinolytic activity of blood The possible significance of these and earlier observations on the fibrinolysis antifibrinolysis system in blood is discussed.

Description: Three families are described in which there occur one or more children with sickle cell-hemoglobin C disease. Additional data are presented concerning two previously described families.

Description: 1. The manner of inheritance of the sickling phenomenon has been investigated in 75 kindreds, with hematologic observations on 465 persons. 2. Data are presented to support the contention that with a possible rare exception, the differential diagnosis between the sickle cell trait and sickle cell anemia is readily made. 3. The hematologic findings pertinent to a decision as to the mode of heredity of the sickle cell trait and sickle cell disease are as follows: a. Out of a total of 94 parents of children with sickle cell disease, 93 have shown the sickle cell trait. b. The incidence of sickle cell disease in segregating sibships would appear to lie between 0.18 and 0.26. c. In sibships segregating for sickle cell disease, the ratio of sickle cell trait to normal is approximately 2:1, but in sibships resulting from the marriage of a normal person with an individual with the sickle cell trait, the ratio of sickle cell trait to normal is significantly less than 1:1. d. Of the 4 children in this series who have a parent with sickle cell disease, all have the sickle cell trait. 4. The most reasonable hypothesis which will render the above data intelligible is that the sickling phenomenon is due to a gene which in single dose (heterozygous condition) produces only the sickle cell trait, and in double dose (homozygous condition), sickle cell disease. The chief and only discrepancy between theory and fact at the present time appears to lie in a deficiency of individuals with the sickle cell trait in certain types of matings. 5. No clear cut differences between normal and sickle cell trait were observed with respect to erythrocyte number, hemoglobin level, hematocrit, the cell constants, the leukocyte number or the differential count. 6. Certain minor hematologic abnormalities encountered in the kindreds under study and not obviously related to the sickling phenomenon are described.

Description: A family of Greek derivation is described in which 2 out of 6 children examined exhibited a sickle cell type of anemia. The father of these children was found to have thalassemia minor and the mother the sickle cell trait. It is presumed that the anemia in the two children was due to simultaneous heterozygosity for the sickling and thalassemia genes. Biochemical studies with reference to the occurrence and amounts of normal, sickle cell, and fetal hemoglobin were carried out on the parents and the 6 children. The theoretic interpretation of the biochemical findings is discussed.

Description: 1. The clinical features, laboratory findings and special studies of a case of photosensitive (congenital) porphyria in a 4 year old girl have been presented. This case was of particular interest in view of severe hemolytic anemia with hepatosplenomegaly. 2. Copro- and uroporphyrin I were isolated from the urine and feces. The ratio of these porphyrins in the urine varied from 1:10, to 1:30 respectively, while in the feces the ratio was reversed at about 70:1. Coproporphyrin III was isolated in much smaller amount than the type I isomer, from both urine and feces. Isomer analyses of the coproporphyrins in the excreta indicated that approximately 98 per cent was type I. 3. Prior to splenectomy copro- and uroporphyrin I were isolated in crystalline form for the first time from circulating human erythrocytes. Coproporphyrin III was also isolated in lesser amount. Uroporphyrin I was crystallized from the plasma, which also contained coproporphyrin I. Microfluorospectrometry of the bone marrow revealed large amounts of porphyrin in the developing red cells. The porphyrin fluorescence spectra indicated that at least three porphyrins were present. 4. Splenectomy was followed by disappearance of uro- and coproporphyrins from the erythrocytes, and a marked decrease in plasma, urine and feces without any essential change in the type of porphyrins excreted. The metabolic defect porphyria, was still present, but now latent in character. Reduction in porphyrin excretion was apparently related to elimination of hypersplenic hemolysis and compensatory increase of erythropoiesis. Anemia and dermal photosensitivity to sunlight disappeared simultaneously with the reduction in porphyrin excretion. 5. Efforts to reproduce the skin lesions by artificial light were unsuccessful.

Description: 1. A method for the combined demonstration of erythrophagocytosis, agglutination, and hemolysis was developed and applied to the study of a series of antierythrocytic antibodies under varying conditions of temperature and pH, using normal, trypsinized, and PNH corpuscles. Erythrophagocytosis was observed supravitally and in fixed preparations. 2. Only those antibodies which were potentially or actually hemolytic produced phagocytosis under the experimental conditions employed. The conditions necessary for the production of the two phenomena were similar except in the case of anti-A. In titration experiments, erythrophagocytosis occurred in higher serum dilutions than did hemolysis. 3. All the antibodies producing opsonization required the presence of thermolabile components of fresh serum for optimal activity. Except with anti-A, appreciable erythrophagocytosis was not produced by heat-inactivated sera. Hemolysis produced by systems other than antibody and complement was unaccompanied by phagocytosis. 4. It is suggested that hemolysis and erythrophagocytosis may both result from the same type of alteration of the red cell surface.