Paul Heller

Clinical Implications of Sickle-Cell Trait and Glucose-6-Phosphate Dehydrogenase Deficiency in Hospitalized Black Male Patients

To determine whether sickle-cell trait and glucose-6-phosphate dehydrogenase deficiency influence the course and fatality rates of certain diseases requiring hospitalization, especially those associated with thrombotic phenomena, we conducted a co-operative study of 65,154 consecutively admitted, black male patients in 13 Veterans Administration hospitals. The overall frequency of sickle-cell trait was 7.8 per cent and of glucose-6-phosphate dehydrogenase dificiency 11.2 per cent. Both conditions were present in 0.9 per cent of those examined. There were regional, but no age-dependent, differences in the frequency of sickle-cell trait. Sickle-cell trait had no effect on average age at hospitalization or death, overall mortality, length of hospitalization on medical and surgical wards and frequency of any diagnosis, except essential hematuria and pulmonary embolism. Although statistically significant (P less than 0.001), the differences for the latter were small (1.5 per cent of all patients with normal hemoglobin and 2.2 per cent of patients with sickle-cell trait). Glucose-6-phosphate dehydrogenase deficiency had no adverse effect.

Hepatic involvement in extrapulmonary tuberculosis; histologic and functional characteristics.

Abstract Hepatic function was studied in fifty patients with extrapulmonary tuberculosis. Abnormalities of one or more of the liver function and/or serum protein tests were found in all patients. The most frequent changes were impaired bromsulfalein excretion and hyperglobulinemia. Analysis of these results revealed several patterns of hepatic dysfunction which have been described previously with other diseases. These patterns are (1) the elevated serum alkaline phosphatase and bromsulfalein retention associated with space-occupying lesions (granulomas), (2) the abnormal flocculation tests and hyperglobulinemia associated with certain chronic infections and inflammatory diseases and (3) combinations of (1) and (2) which may simulate intrinsic hepatic disease except for the relatively lower levels of serum bilirubin. Liver biopsy specimens were obtained in thirty of these patients. Granulomas were demonstrated in twenty-four or 80 per cent of the specimens. Fourteen of the fifteen patients with elevated alkaline phosphatase levels had hepatic granulomas. Ten of the fifteen patients without alkaline phosphatase elevations also had granulomas. Microgranulomas were described and were considered significant. Focal Kupffer cell hyperplasia and diffuse sinusoidal inflammatory reaction were sufficiently frequent to be characteristic of hepatic involvement in tuberculosis. Abnormality of the hepatic parenchymal cells was commonly observed and in three patients free hyaline bodies were present.

Changes in Lymphocyte Surface Immunoglobulins in Myeloma and the Effect of an RNA-Containing Plasma Factor

Patients with multiple myeloma have a reduced number of B lymphocytes with normal surface immunoglobulin. When, however, anti-idiotypic antiserums to the respective myeloma globulins were used for the visualization of surface immunoglobulin by indirect immunofluorescence, a large number of surface immunoglobulin carrying lymphocytes were detected. The possibility of absorption of these monoclonal surface immunoglobulins from the surrounding plasma was excluded by showing their resynthesis after removal from the cells by trypsinization. The change in the character of surface immunoglobulin was reproduced on normal lymphocytes with an RNA-rich extract from the plasma of patients with myeloma; this effect was inhibited by RNase and cycloheximide. These findings suggest the possibility that an RNA-containing plasma factor transmits information for synthesis of surface immunoglobulins between myeloma cells and normal lymphocytes. This mechanism may contribute to the dysfunction of B lymphocytes in patients with myeloma, leading to immunologic deficiency.

ENZYMES IN ANEMIA: A STUDY OF ABNORMALITIES OF SEVERAL ENZYMES OF CARBOHYDRATE METABOLISM IN THE PLASMA AND ERYTHOCYTES IN PATIENTS WITH ANEMIA, WITH PRELIMINARY OBSERVATIONS OF BONE MARROW ENZYMES

Excerpt Several published studies1, 2, 3, 4have shown that patients with megaloblastic anemia have markedly elevated serum levels of lactic dehydrogenase. The sera of patients with sickle cell anem...

Two myeloma globulins (IgG and IgA) in one subject and one cell line.

Abstract This paper describes the clinical history of a patient who produced two distinct myeloma globulins (IgG and IgA). Immunofluorescent studies revealed the presence of the two myeloma globulins in single plasma cells.

Light-Chain Heterogeneity of Cold Agglutinins

Cold agglutinins with specificity to I or to i antigens of humanadult or cord-blood erythrocytes produced during the course of Mycoplasma pneumoniae infection and infectious mononucleosis contain light chains of K and L types. However, cold agglutinin isolated from the serums of patients with chronic cold-agglutinin hemolytic anemia contains only type K light chains. The experimental evidence suggests that some cold agglutinins contain both types of light chains in the same molecule.

THE DISTRIBUTION OF HEMOGLOBIN A1

Genetic and biochemical considerations, namely the low concentration of hemoglobin A2 in cord blood hemolysates, its absence in the homozygote individual with persistent fetal hemoglobin’ and the primary structure of hemoglobin Lepore’ have produced the generally accepted hypothesis of close linkage of the genes for the delta and beta polypeptide chains. Although there is indirect ~ u p p o r t ~ ’ ~ for the assumption that hemoglobin A2 is present in all cells containing hemoglobin A, direct proof of this distribution pattern of H b A2 has still been missing from the total evidence. It is also not definitely known whether the high F cells of patients with 0-thalassemia minor and of normal infants also contain H b A2, Matioli’s‘ admirable attempts of microelectrophoresis of single red cells of normal adults suggest that this minor fraction might not be present in each cell, but the technique is so formidably difficult that the results are questionable. Distribution patterns on blood films have been studied for hemoglobin F,6 hemoglobin S,7 hemoglobin H8 and hemoglobin M.9’’0 The techniques for such studies are based on abnormal solubility characteristics of these hemoglobins under varying conditions. To our knowledge, no such differences exist between hemoglobin A and Az. However, the immunologic specificity of the &chain, which has been amply confirmed since our original report, can be utilized for the production of immunofluorescent sera which react only with hemoglobin A2 and permit its visualization in single cells. The same is, of course, true of hemoglobin F which is highly antigenic in rabbits. 11

Antigenicity of connective tissue extracts.

Summary 1. Antibodies to rabbit connective tissue have been induced in the guinea pig. 2. Connective tissue extracts from aged rabbits had greater antigenicity than from young animals. 3. Anticonnective tissue serum crossreacted with the cytoplasmic fraction of rabbit leukocytes. 4. Chemical characteristics of the antigenic component of connective tissue remain incompletely explored.

Vitamin B12 binding capacity of serum in B12 deficiency.

Summary 1. Human serum has been found to have a limited binding capacity for Vit. B12. The B12 binding protein, a seromucoid fraction, appears to be normally only approximately 30-40% saturated. In Vit. B12 deficiency the unsaturated binding capacity is normal but total binding capacity is diminished. 2. It is postulated that; the slower than normal disappearance of Co57-B12 from the plasma of B12 deficient individuals is caused by diminished binding capacity in the tissues. The authors wish to express their appreciation to Medical Illustration Service, VA West Side Hospital and to Mr. Lemuel Hall for technical assistance.

Passive Immunity to Murine Plasmacytoma by Rabbit Antiidiotypic Antibody to Myeloma Protein

Summary Antiidiotypic antisera to LPC-1 and MOPC-300 plasmacytoma globulins were produced in rabbits by immunization with the corresponding antigen and exhaustive immunoabsorption with normal BALB/c plasma and other myeloma globulins. IgG fractions of these antisera when given intraperitoneally on three consecutive days after tumor implantation, protected the animal specifically from the grafting of the corresponding plasmacytoma or induced regression of the tumors after their initial grafting and growth. In vitro cytotoxicity of the antisera to plasmacytoma cells was not demonstrated. Plasma of the antisera-treated normal BALB/c mice, though containing antiidiotypic antibody in high titers (320-640), was not cytotoxic to tumor cells. The inhibitory effect on tumor growth can be considered the result of passive immunization against plasmacytoma with xenogeneic humoral antibody.