bluuebunny/crossref_metadata_2025 huggingface dataset:
Micropinocytotic Ferritin in Erythroid Cells: Species Dependency and Relation to Serum Iron Levels
Authors: TANAKA YASUKAZU , BRECHER GEORGE
Published: October 2019

Effect of SI level and saturation of TIBC on the induction of ferritin in erythroid cells was investigated in rats, guinea pigs, and rabbits. Evidence presented indicates that species difference and serum iron level are important factors in induction of micropinocytotic ferritin in developing erythroid cells: (1) Micropinocytotic ferritin was occasionally seen in erythroblasts of control guinea pigs. Erythroblasts of control rats and rabbits were negative. (2) Elevated SI and high saturation of TIBC increased micropinocytotic ferritin in developing erythroid cells in guinea pigs. Iron administration to rats and rabbits did not affect the accumulation of micropinocytotic ferritin. In guinea pigs, disappearance of stromal ferritin during erythroid maturation was demonstrated. High SI level did not affect the stromal ferritin of erythroid cells. Dissociation of ferritin increase in micropinocytotic vesicles of erythroblasts on the one hand and in macrophage cytoplasm on the other was seen when iron-sorbitol was injected. The results emphasize the biologically dissimilar nature and kinetics of morphologically different types of ferritin in erythroblasts.
2,3-Diphosphoglycerate Content and Oxygen Affinity as a Function of Red Cell Age in Normal Individuals
Authors: HAIDAS STAVROS , LABIE DOMINIQUE , KAPLAN JEAN-CLAUDE
Published: October 2019

A parallel decline of 2,3-diphosphoglycerate (2,3-DPG) and P50 of intracorpuscular hemoglobin is found in red blood cells during their in vivo aging. After 2,3-DPG depletion due to in vitro storage, the capacity to restore, 2,3-DPG in the presence of inosine is significantly impaired in senescent cells as compared with young cells.
Spherocytic Hemolytic Disease During Magnesium Deprivation in the Rat
Authors: OKEN MARTIN M. , LICHTMAN MARSHALL A. , MILLER DENIS R. , LEBLOND PIERRE
Published: October 2019

Young male rats (115 g) were maintained on diets containing 4-8 mg of magnesium per 100 g of diet for 12 wk. By 3 wk the characteristic features of magnesium deprivation developed, including decreased plasma and tissue magnesium concentration, growth retardation, ruffled fur, patchy dermatitis, irritability, hyperemia of acral parts, onychymegaly, and in the most severely restricted, premature death. By 7 wk of deprivation, evidence of a hemolytic state existed and thereafter reticulocytosis, spherocytosis, shortened 51Cr red cell survival, erythroid hyperplasia of the bone marrow, and mild anemia were present. Erythrocytes during magnesium deficiency were characterized by decreased intracellular magnesium, glucose utilization, lactate production, ATP and 2,3-DPG concentration. A progressive decrease in red cell deformability as measured by cell elastimetry occurred. The reduction in lactate production and in ATP concentration due to magnesium deficiency may be causal in the development of rigid spherocytes with shortened survival in vivo. In addition, the shape and deformability alteration of the red cell may be due to defective membrane construction in a magnesium-deficient environment.
Attempts at Identification of Hemopoietic Stem Cell in Mouse
Authors: VAN BEKKUM D. W. , VAN NOORD M. J. , MAAT B. , DICKE K. A.
Published: October 2019

Stem cell concentrates were prepared from mouse bone marrow by treating the marrow donors with a vinblastinenitrogen mustard regimen and subjecting the marrow suspensions to repeated density separation over albumin gradients. An enrichment of the colony-forming units (CFU) content by a factor of up to 30 as compared to normal mouse bone marrow was obtained, which corresponds to a calculated stem cell content of over 20%. Using an adapted May-Grünwald-Giemsa staining method and electron microscopic techniques, the morphologic characteristics of a candidate stem cell have been defined in these enriched cell populations. These criteria have been applied to count candidate stem cells in preparations varying over a 100-fold range in their CFU content, and a fair correlation between the two entities was found. The candidate stem cell is shown to be quite distinct from the so-called "small lymphocyte."
Hemoglobin Hirose: α2β237(C3) Tryptophan Yielding Serine
Authors: YAMAOKA KOTARO
Published: October 2019

During an electrophoretic screening survey for hemoglobinopathies in western Japan, a slow-moving variant of hemoglobin A, to be designated hemoglobin Hirose, was found in a family of Japanese origin. Chemical characterization of hemoglobin Hirose revealed that tryptophan at the 37th position of the β-chain was replaced by serine, the third residue of C-helix of the β-chain involving contacts between αl and β2 subunits. Even though the oxygen equilibrium of this hemoglobin was abnormal, none of the family members showed any clinically significant symptoms.
Fetal Lymphocytes in the Maternal Blood
Authors: Schröder Jim , de la Chapelle Albert
Published: October 2019

The fluorescence of the human Y chromosome after staining with quinacrine derivatives was used in an attempt to determine the prevalence of XY lymphocytes presumptively emanating from male fetuses in the blood of pregnant women. Seven women who subsequently gave birth to male infants had 0.03%-0.20% lymphocytes with a Y body. In two women pregnant with male fetuses, no Y bodies were detected. Of 12 women who gave birth to girls, eight had no Y bodies. In the remaining four, fluorescent spots were interpreted as Y bodies. One of those women had previously had an abortion. In the remaining three cases, it was found in retrospect that the fluorescent spots emanated from exceptionally brightly fluorescent autosomal regions in the maternal or paternal chromosomes, or both. Phytohemagglutinin-stimulated and unstimulated lymphocytes showed similar frequencies of Y body. Based on determinations of the incidence of Y body-containing lymphocytes in males (35%-66.5%), it was estimated that approximately 0.1%-0.5% of lymphocytes in the blood of most women pregnant with a male fetus are of fetal origin. This figure is remarkably high, since it exceeds in relative terms that of fetal erythrocytes (which mostly appear in the mother’s blood at the time of delivery) by several orders of magnitude. It is suggested that fetal lymphocytes actively cross the feto-maternal barriers. This phenomenon may have a profound influence on the immunologic interactions between fetus and mother. The method described may not turn out to be profitable in the assessment of the fetal sex, since its accuracy may be of the order of only 80%-95%. Moreover, several limitations prevail.
Radioautographic Study of Cellular Migration Using Parabiotic Rats
Authors: Tyler Ruth W. , Everett N. B.
Published: October 2019

Leukocyte exchange between the hemopoietic tissues of parabiotic rats was studied subsequent to giving multiple injections of 3H-thymidine to one member of each pair while arresting the cross-circulation. Cell types that migrated from one parabiont to the other were segmented granulocytes, small, medium and large lymphocytes, immunoblasts, monocytoid cells, macrophages or their immediate precursors, and plasma cells. Evidence for the transformation of circulating cells to other cell types was rarely seen. The long-lived small lymphocytes were equilibrated between parabionts, suggesting that this is a single pool of cells with respect to kinetic behavior and recirculation. There was no evidence for a trephocytic function of lymphocytes. A small number of bone marrow lymphocytes coursed directly to lymph nodes and spleen. Evidence is given for a limited recirculation of short-lived lymphocytes of thoracic duct lymph (TDL), as well as for long-lived cells. Only a few immunoblasts of TDL recirculated. The majority of cells that entered the white pulp of the spleen were long-lived small lymphocytes, while the majority of immigrant cells to the red pulp were monocytoid cells and granulocytes. Many small lymphocytes originated in splenic red pulp and entered the blood. No immigrant cells to the thymic cortex were noted, although some small lymphocytes and monocytoid cells entered the medullary areas. Immigrant cells to the bone marrow (less than 2% of the cells in marrow) included monocytoid cells, small lymphocytes, and plasma cells. Evidence for the direct transformation of a circulating cell into a committed blast, based on reduction in grain count, was noted only in bone marrow.
Hereditary Nonspherocytic Hemolysis With Erythrocyte Phosphofructokinase Deficiency
Authors: Waterbury Larry , Frenkel Eugene P.
Published: October 2019

Hereditary nonspherocytic hemolysis associated with abnormal erythrocyte phosphofructokinase activity was demonstrated in a young man. Enzyme activity in the propositus, his mother, and maternal grandmother was approximately 60% of normal controls. There was markedly increased lability of enzyme activity on in vitro storage. Kinetic studies revealed increased sensitivity to adenosine triphosphate inhibition. Erythrocyte adenosine triphosphate levels were depressed. The absence of muscle disease and the presence of normal in vivo lactate production following ischemic exercise differentiated this kindred from those with Type VII glycogen storage disease.
Separation of Immunocompetent Cells From Human and Mouse Hemopoietic Cell Suspensions by Velocity Sedimentation
Authors: Amato D. , Cowan D. H. , McCulloch E. A.
Published: October 2019

Cell suspensions from human and mouse bone marrow, heterogeneous with respect to size, were physically separated by a technique of velocity sedimentation at unit gravity. Fractions were collected, cell counts performed, and a sedimentation "profile" obtained. Fractions were assayed in culture for response to phytohemagglutinin and to allogeneic irradiated leukocytes. The peak activity in these assays occurred in fractions taken from the region of small, slowly sedimenting, nucleated cells, which in humans have an average sedimentation velocity at 4°C of approximately 3.5 mm/hr. The results suggest that velocity sedimentation can be used to separate human stem cells from cells that cause graft-vs.-host disease.
Experimentally Induced Alterations in the Affinity of Hemoglobin for Oxygen. I. In Vitro Restoration of Erythrocyte 2,3-Diphosphoglycerate and Its Relationship to Erythrocyte Purine Nucleoside Phosphorylase Activity in a Variety of Species
Authors: Oski Frank A. , Sugerman Harvey J. , Miller Leonard D.
Published: October 2019

The relationship between red cell purine nucleoside phosphorylase activity and the ability of stored erythrocytes to regenerate the organic phosphate 2,3-diphosphoglycerate was evaluated in man, monkey, rabbit, dog, cat, and rat. A linear relationship was observed between the activity of this enzyme and the in vitro regeneration of 2,3-diphosphoglycerate from a solution of inosine, pyruvate, and inorganic phosphate. These studies suggest that rabbit and monkey erythrocytes respond in a manner similar to that of human erythrocytes and, therefore, might be useful experimental models for the evaluation of pharmacologic methods for the in vivo alteration of the oxygen-hemoglobin equilibrium curve.
Experimentally Induced Alterations in Affinity of Hemoglobin for Oxygen. II. In Vivo Effect of Inosine, Pyruvate, and Phosphate on Oxygen-Hemoglobin Affinity in Rhesus Monkey
Authors: Sugerman Harvey J. , Pollock Thomas W. , Rosato Ernest F. , Delivoria-Papadopoulos Maria , Miller Leonard D. , Oski Frank A.
Published: October 2019

In an attempt to produce in vivo alterations in the affinity of hemoglobin for oxygen by pharmacologic means, rhesus monkeys were infused with 20 ml/kg of a 0.1 M solution of inosine, pyruvate, and bisodium phosphate. Control monkeys received equal volumes of isotonic saline. The monkeys given the inosine-pyruvate-phosphate mixture demonstrated a mean rise in P50 from 33.5 to 36.1 mm Hg and an increase in mean red cell 2, 3-diphosphoglycerate levels from 5.1 to 7.6 µmoles/ml RBC. The changes were maximal 6 hr postinfusion, remained elevated for 24 hr, and then gradually returned to normal over a 4-day period. Inosine alone, or pyruvate and phosphate together failed to produce the same results. This finding indicates that intravenous administration of inosine, pyruvate and phosphate can alter oxygen affinity in vivo and may be of value in diseases associated with poor oxygen delivery to tissues.
Granulocyte Collection by Continuous-flow Filtration Leukapheresis
Authors: Herzig Geoffrey P. , Root Richard K. , Graw Robert G.
Published: October 2019

A safe and simple technique for the collection of large numbers of granulocytes from normal donors, based on the reversible adhesion of granulocytes to nylon wool filters, is described. The procedure is well tolerated by donors, and the granulocytes obtained show nearly normal bactericidal and phagocytic capacity in vitro. However, a surprisingly small median 1-hr posttransfusion increment of 233/cu mm was observed in leukopenic recipients lacking preformed leukocyte antibodies, as compared to the median increment of 850/cu mm reported following transfusion of leukocytes obtained by differential centrifugation. The safety and effectiveness of these granulocytes for the treatment or prevention of bacterial infections in granulocytopenic patients remains to be proven, however our initial experience with such transfusions has been encouraging.
Bone Marrow and Peripheral Blood Globin Synthesis in an American Black Family With Beta Thalassemia
Authors: Friedman Shlomo , Oski Frank A. , Schwartz Elias
Published: October 2019

Synthesis of globin chains in bone marrow and peripheral blood samples from a black family with mild beta thalassemia was compared with similar studies in white people. Blood and bone marrow were incubated with 14C-leucine, globin chains were isolated, and β/α and γ/α ratios were calculated. The results of studies of globin synthesis in homozygotes of different races were similar, despite the differences in severity of clinical disease. In the heterozygotes, there was a significant defect in beta synthesis in the peripheral blood of white subjects, while in two of three black patients the β/α ratio was in the normal range. Although there was no evidence of segregation of an alpha thalassemia gene in this black family to explain the unusual β/α ratios, the presence of such a gene in the heterozygotes could not be excluded.
The Effect of Erythropoietin on Synchronized Rabbit Hemopoietic Tissue in Culture
Authors: Izak G. , Karsai A.
Published: October 2019

Synchronized erythroid cell cohorts were cultured for up to 6 days with and without added erythropoietin. The presence of erythropoietin in the medium was found indispensable for the synchronized differentiation and maturation of those cell populations. The appearance, during maturation in vitro, of a soluble cell component that is capable of inducing hemoglobin producation by polysomes isolated from undifferentiated blast cells is described. The same polysomes with their isologous soluble cell component were unable to produce this protein. These results confirm earlier observations made on synchronized rabbit cell populations in vivo.
THE DISTRIBUTION OF HISTOCHEMICALLY DEMONSTRABLE GLYCOGEN IN HUMAN BLOOD AND BONE MARROW CELLS
Authors: WACHSTEIN MAX
Published: October 2019

By applying Schiff’s reagent after periodic acid treatment to blood and bone marrow films, a cytoplasmic staining reaction is seen in some cells of the myeloid series, as well as in megakaryocytes and platelets. The intensity of the staining reaction in the myeloid cells increases with their maturation. The staining reaction can be prevented altogether in alcohol-fixed films by salivary digestion, but only incompletely in air-dried films. The staining reaction is due to the presence of glycogen in some chemical association, possibly with protein.
THE PROTHROMBIN CONSUMPTION TEST: ITS CLINICAL AND THEORETIC IMPLICATIONS
Authors: QUICK ARMAND J. , FAVRE-GILLY JEAN E.
Published: October 2019

The prothrombin consumption test, which originally was carried out on serum one hour after coagulation, is modified. Blood is distributed to several test tubes, and after fixed time intervals, the tubes are centrifuged. The prothrombin of the serum of each tube is determined immediately and every fifteen minutes within the limits of one hour from the time the blood is taken.

The prothrombin consumption shows considerable variations in normal individuals. In hemophilia and in thrombocytopenia it is very incomplete. In hypoprothrombinemia the prothrombin may be very complete as in congenital hypoprothrombinemia of the Component A deficiency type, or surprisingly incomplete as in dicumarol hypoprothrombinemia. The possible significance of prothrombin consumption in relation to hemostatasis is discussed.
HYPOPROTHROMBINEMIA: STUDIES OF A CASE OF THE IDIOPATHIC TYPE AND THE EFFECT OF SERUM ADMINISTRATION
Authors: CROCKETT CHARLES L. , SHOTTON DONALD , CRADDOCK CHARLES G. , LEAVELL BYRD S.
Published: October 2019

1. The reported cases of idiopathic hypoprothrombinemia are reviewed briefly, and a case observed for over three years is presented. Particular attention is called to the similar clinical pattern presented by the chronic cases.

2. Studies are presented indicating that in this patient the delay in prothrombin time was due, at least in part, to a deficiency of a factor necessary for rapid conversion of prothrombin. This factor, or factors, which we have called Ac-globulin, is contained in a highly active state in fresh normal serum.

3. After the in vitro demonstration of a deficiency of Ac-globulin in the patient’s blood, it was possible to bring about a marked reduction in the patient’s prothrombin time by the intravenous administration of relatively small amounts (15 to 45 cc.) of fresh normal (thrombin-free) serum. A further reduction of the prothrombin time to near normal values was brought about by combined whole blood and serum administration. The evidence suggests that partial correction of both prothrombin and Ac-globulin deficiency respectively resulted from such therapy.

4. The possible effects of serum and whole blood upon the delayed prothrombin conversion rate of dicoumarolization and liver disease are discussed and preliminary observations in the former type suggest that such therapy may be useful.
PERNICIOUS ANEMIA IN CHILDHOOD REPORT OF CASE IN SIX YEAR OLD GIRL RESPONDING TO REFINED LIVER EXTRACT, FOLIC ACID AND VITAMIN B12 IN SUCCESSIVE RELAPSES
Authors: DAVIS R. WENDELL , CHRISTIAN RICHARD M. , ERVIN DONALD M. , YOUNG LAWRENCE E.
Published: October 2019

A case of megaloblastic anemia without specific neurologic complications in a 6 year old girl is presented as an example of pernicious anemia in childhood despite the fact that a small amount of free hydrochloric acid was present in the gastric juice after injection of histamine. Prompt hematologic response was obtained following administration of refined liver extract, folic acid and vitamin B12 in successive relapses.
A CASE OF CYCLICAL AGRANULOCYTOSIS WITH MARKED IMPROVEMENT FOLLOWING SPLENECTOMY
Authors: FULLERTON H. W. , DUGUID H. L. D.
Published: October 2019

1. A case of cyclical agranulocytosis beginning in a man at the age of 62 years is described.

2. The course of the illness was greatly modified by splenectomy; neutropenia continued but phases of complete agranulocytosis and infection ceased.
A METHOD FOR ISOLATING LIVING POLYMORPHONUCLEAR LEUKOCYTES FROM PERIPHERAL BLOOD
Authors: MINOR ALLEN H. , BURNETT LEE
Published: October 2019

A simple method is described for isolating living polymorphonuclear leukocytes from peripheral blood. It is based on the selective adherence of these cells to a microscope slide, which permits all other blood components to be removed by washing. The reasons for considering this method useful in cell studies are discussed.
CHRONIC CONGENITAL AREGENERATIVE ANEMIA (PURE RED-CELL ANEMIA) ASSOCIATED WITH ISO-IMMUNIZATION BY THE BLOOD GROUP FACTOR "A"
Authors: SMITH CARL H.
Published: October 2019

Chronic congenital aregenerative anemia describes a "pure red-cell" anemia in which the failure of hematopoiesis is restricted entirely to the erythrocytes without simultaneous impairment of leukocyte or platelet production. The separation of this entity from the category of the increasing number of cases designated as hypoplastic anemia will facilitate a more direct examination of the factors involved in its pathogenesis.

In the case described in this paper illustrating this condition, the onset of the anemia dated to the newborn period with the clinical and hematologic features of a mild type of erythroblastosis fetalis. The mother’s blood group was O, Rh positive and that of the infant and father A, Rh positive. The anti-A serum titer in the mother reached a maximum of 1:128,000. The infant was shown to be a non-secretor. The patient, now 17 months of age, requires repeated transfusions to maintain normal blood levels. The bone marrow reveals a persistent depression of erythropoiesis but the platelet and granulocyte levels are entirely unaffected.

It is postulated that prolonged depression in red blood cell production may result from an antibody directed solely against the red cells in fetal life or from the early neonatal period. This concept finds substantiation in other cases of erythroblastosis in which temporary failure of erythropoiesis as confirmed by bone marrow studies is reflected in a state of protracted anemia.
A RAPID SLIDE TEST FOR HETEROPHILE ANTIBODY IN INFECTIOUS MONONUCLEOSIS
Authors: MOLONEY WILLIAM C. , MALZONE LUCY
Published: October 2019

The sera of 473 individuals were examined for sheep cell agglutinins both by the slide test and the Paul-Bunnell method. In this group there were 46 patients with positive slide tests and 35 of these individuals also had a diagnostic serum dilution test for heterophile antibody. In 11 cases the slide test was positive but the Paul-Bunnell test gave very low serum dilution values. However, when the slide test was carried out at 37 C, it was negative in 9 of the 11 cases. In the remaining 2 instances, one patient had a Forssman type of antibody which gave a 1:64 titer in saline and the slide test was positive at 37 C. In the other case no studies were made on the effect of temperature and the nature of the agglutination reaction was unfortunately not determined.

Using human and bovine albumen, sheep serum and human AB serum absorbed with sheep cells as a diluent no evidence for blocking or hyperimmune antibody was discovered in the cases of infectious mononucleosis studied in this series. Moreover, of the 6 patients with negative serology but with strong clinical and hematological evidence for the disease, no blocking or hyperimmune antibody was disclosed by the slide test or by the use of absorbed human AB serum. The conclusion seems justified that blocking, incomplete or hyperimmune heterophile antibody must be rather uncommon in infectious mononucleosis.

In the use of the rapid slide test it has been pointed out that cold agglutinins, (which may be abolished by warming to 37 C) and Forssman antibodies (which may be absorbed by guinea pig kidney) can give positive results. However, diseases in which cold agglutinins are strong enough to give a positive slide test are relatively rare and the occurrence of Forssman antibodies of a strength likely to give a positive slide test would be decidedly uncommon. In any event unless further experience reveals more serious discrepancies, the rapid slide test as described in this paper seems to offer a practical screening test to detect clinically significant amounts of heterophile antibody in cases of infectious mononucleosis.
COMPARISON OF VITAMIN B12 FROM LIVER AND FROM STREPTOMYCES GRISEUS IN THE TREATMENT OF PERNICIOUS ANEMIA
Authors: ERF LOWELL A. , WIMER BRUCE
Published: October 2019

1. A clinical remission in one case of pernicious anemia in relapse treated with 50 µg. of vitamin B12 from liver is reported; the patient was followed for 114 days after two doses of 25 µg. were given on successive days and a peak of 3,900,000 erythrocytes occurred on the eighty-sixth day.

2. Preliminary observations are reported in 2 patients with pernicious anemia in relapse treated with a vitamin B12 derived from Streptomyces griseus; the first patient who had no neurologic complaints received 32 µg. while the second was given two doses of 32 µg. each because of severe, subacute, combined degeneration. A good hematologic response and a satisfactory clinical remission occurred in both cases. There was definite improvement neurologically in the second case.

3. The administration of 32 µg. of vitamin B12 derived from Streptomyces griseus to each of 5 cases of pernicious anemia in remission resulted in minor subjective and objective improvement.
USE OF ANTIMONY IN MULTIPLE MYELOMA
Authors: RUBINSTEIN MICHAEL A.
Published: October 2019

The effect of antimony treatment (neostibosan) of multiple myeloma is described. The following observations are reported:

1. Control of bleeding. In one instance of multiple myeloma the presenting symptom was uncontrollable nosebleed of one and one-half years’ duration. The platelet count as well as the clotting and bleeding time were normal, the only abnormality was the failure of the clot to retract. It is possible that the latter abnormality was connected with the abnormal protein composition of the blood (hyperglobulinemia was found).2

Topical treatment, including repeated cauterizations and radium application to the nasal mucosa, remained without any effect, and constant packing and frequent transfusions were necessary. Following a course of neostibosan injections there was gradual diminution of the bleeding, and after one month complete cessation of bleeding was noted. Since that time (6 months at the time of writing) the bleeding did not recur, and the patient was discharged from the hospital. At the same time a moderate decrease of hyperglobulinemia was observed.

2. Reduction of hyperglobulinemia. In reviewing all other cases treated it was found that in all four instances with hyperglobulinemia there was reduction of the serum globulin content. When a few months later the hyperglobulinemia was rising, a repeated course of antimony was followed again by its reduction.

In three instances without hyperglobulinemia no change of serum globulin was noted following the antimony treatment. In four other cases the globulin changes were not followed.

3. Regression of palpable tumors. Three instances with visible tumors, a rather uncommon phenomenon in multiple myeloma, were observed.

Disappearance of the palpable tumors in two patients after combined antimony and radiotherapy was reported in a previous communication. In the present paper, almost complete disappearance of palpable tumors following antimony treatment alone without radiotherapy is reported.

With regard to these observations, the following reservations should be kept in mind:

1. In evaluating the influence of antimony on multiple myeloma it is necessary to realize the possibility of occasional spontaneous remissions in this disease, as well as of a prolonged course over a period of years with relative freedom from symptoms, and occasional sensitivity to radiation.

2. The number of observations is insufficient to warrant at this point conclusions as to the therapeutic value of antimony. They indicate merely a possible influence of antimony on the myeloma tissue and on the disturbed chemistry of myeloma.
Congenital Deficiency of Fibrin-stabilizing Factor (Factor XIII): A Report of Four Cases (Two Families) and Family Members
Authors: Aziz Mohammed A. , Siddiqui Azizur Rehman
Published: October 2019

Four patients with congenital deficiency of fibrin-stabilizing factor (factor XIII) from two families have been described. The mother and the sibs in one family and both parents in the other family were found to have varying degrees of factor XIII deficiency. The observations support the hypothesis of autosomal recessive inheritance of factor XIII deficiency.
Monocyte Function in Children With Neutropenia and Chronic Infections
Authors: Baehner Robert L. , Johnston Richard B.
Published: October 2019

The phagocytic, bactericidal, and metabolic activities of monocytes from patients with congenital neutropenia were not significantly different than the activities of monocytes from patients with cyclic neutropenia or chronic infections. However, significant differences in metabolic, phagocytic, and bactericidal functions were found between monocytes from any source and normal neutrophils. During phagocytosis, monocytes produced more of the bactericidal product hydrogen peroxide than did neutrophils. However, monocytes in suspension had decreased phagocytic capacity compared to neutrophils and killed staphylococci less well. Moreover, monocytes had a diminished capacity to iodinate ingested bacteria. Quantitation of granular myeloperoxidase activity revealed that monocytes had a relative deficiency of this enzyme, which could explain the decreased iodination and killing of ingested bacteria by monocytes when compared to neutrophils. These findings offer an explanation for the failure of compensatory monocytosis to protect the host from bacterial infection when neutrophil reserves are diminished.
Migration of Long-lived Lymphocytes to the Bone Marrow and to Other Lymphomyeloid Tissues in Normal Parabiotic Guinea Pigs
Authors: Rosse Cornelius
Published: October 2019

Guinea pigs, in which cells with long life span were selectively labeled (3H-thymidine), were joined in parabiosis to nonlabeled syngeneic litter mates at a time when label reutilization detectable by radioautography could be excluded. The distribution of labeled cells was investigated quantitatively using radioautography and liquid scintillation counting in the marrow and blood at the time of establishment of parabiosis and again at its termination 2 wk later, when the thoracic duct lymph, lymph nodes, spleen, and thymus were also examined. Single animals labeled in the same manner served as controls. Of all cells with a slow rate of turnover and long life span, only small lymphocytes entered the circulation and crossed the anastomosis in detectable numbers. As indicated by the similar percentages of labeling in respective tissues, a complete intermixing of long-lived lymphocytes occurred in the bone marrow, lymph, lymph nodes, and spleen of the parabionts. The sum of the per cent labeled lymphocytes in two parabionts was in agreement with the extent of labeling in respective tissues of single controls. The presence of a minor population of lymphocytes with a long life span was confirmed in the marrow. Ten to 30 times as many labeled long-lived lymphocytes migrated into the bone marrow of initially unlabeled animals as were found in an equal volume of blood. The majority, if not all long-lived lymphocytes migrate to the marrow from the blood, and they also reenter the blood. They have a similar life span and in parabionts equilibrate in a similar manner as recirculating long-lived lymphocytes.
Proliferation of Human Bone Marrow Cells in Diffusion Chambers Implanted Into Normal or Irradiated Mice
Authors: Boyum Arne , Boecker Werner , Carsten Arland L. , Cronkite Eugene P.
Published: October 2019

Diffusion chambers containing normal, human bone marrow cells were implanted in the abdominal cavity of normal and irradiated mice. Granulocytic cells and macrophages proliferated in the chambers. The number of cells in the granulocytic series recovered from the chambers dropped to 60% after 1 day; during the next 7 days it varied between 40% and 60% of the inoculated number of granulocytes, with no difference between irradiated and non-irradiated animals. From day 9 the yield of cells in granulocytic series increased in chambers from irradiated animals, and a higher percentage of cells were in the proliferating pool of the granulocytic series. Simultaneously, the cell yield in chambers from normal animals dropped markedly and consisted mostly of mature granulocytes. In both groups the percentage of eosinophilic cells increased significantly during the last part of the culture period. The enhanced growth in the irradiated mice suggests an increased self-renewal of granulocytic stem cells, leading to a larger yield of differentiated granulocytic cells later in the culture period. A shortened generation time and/or increased cloning efficiency of stem cells may also contribute to the enhanced granulocyte production. The suppression of the immune reactivity by irradiation of the host animals may allow better proliferation by delaying production of cytotoxic antibodies against the xenogenic human cells. The number of macrophages increased gradually, and there was no significant difference between irradiated and nonirradiated animals. The lymphocyte number decreased after implantation and varied between 30% and 50% of the inoculated number. From day 11, the lymphocyte number dropped more in normal animals than in irradiated animals.
Canine Hemophilia and Hemopoietic Grafting
Authors: Storb Rainer , Marchioro Thomas L. , Graham Theodore C. , Willemin Mary , Hougie Cecil , Thomas E. Donnall
Published: October 2019

Two hemophilic beagles were given 1200 R whole-body irradiation followed by a successful marrow graft from a normal sibling. During observation periods of 7 and 24 mo, there was no evidence of factor VIII synthesis.
Hemoglobin LeporeWASHINGTON in Two Jamaican Families: Interaction With Beta Chain Variants
Authors: Ahern E. J. , Ahern V. N. , Aarons G. H. , Jones R. T. , Brimhall B.
Published: October 2019

Hb Lepore Washington was found segregating in two unrelated families. In one family, three subjects doubly heterozygous for Hb Lepore and a beta-chain variant were observed. A woman, aged 76 yr, with the Hb Lepore-Hb S combination had two offspring with Hb Lepore-Hb C combinations. One Hb Lepore-Hb C subject married to a hematologically normal woman had eight offspring: seven living at the time of study, six with Hb Lepore trait, and one with Hb C trait. In the second family, only Hb Lepore trait was found. Interest centers on the first family: the mild symptomatology of the Hb Lepore-Hb S subject, and the absence of crossovers in the seven living offspring of one Hb Lepore-Hb C subject. The latter finding provides further genetic evidence for allelism or close linkage of the locus for Hb Lepore with the beta chain structural locus.
Quantitative Recovery of 14C-labeled Carbon Monoxide (14CO) From Viable Heme-labeled Red Blood Cells in the Rat
Authors: Landaw Stephen A.
Published: October 2019

Long-term recovery of 14C-labeled carbon monoxide (14CO) from labeled, transfused red blood cells (RBC) was studied in buffalo rats. Donor RBC (labeled with 14C-2-glycine) were transfused into host rats, and the 14CO formed from degradation of labeled hemoglobin heme was collected over the next 110+ days. The heme-equivalent 14CO recovery in 13 animals averaged 102.1 ± 2.1% (mean ± SE) of activity in hemoglobin heme of donor RBC. This confirms that heme of circulating RBC destroyed by random hemolysis and senescence is quantitatively converted to CO.
Leukocyte Labeling With 51Chromium. III. The Kinetics of Normal Lymphocytes
Authors: Scott James L. , Davidson J. Gary , Marino Joseph V. , McMillan Robert
Published: October 2019

The kinetics of radiochromate-labeled autologous blood lymphocytes were studied in normal subjects. The labeled cells equilibrated within hours with a recirculating lymphocyte pool (RLP) distributed between the blood, the spleen, and the bone marrow. The RLP was found to be about twice the size of the blood lymphocyte pool contained within it and turned over through the blood about 12 times daily. The labeled cells had an average half life in the RLP of 18 days.
Eosinophilic Fibrohistiocytic Lesion of Bone Marrow: A Distinctive New Morphologic Finding, Probably Related to Drug Hypersensitivity
Authors: Rywlin Arkadi M. , Hoffman Erwin P. , Ortega Rolando S.
Published: October 2019

A distinctive, hitherto undescribed lesion was found in histologic sections of aspirated bone marrow particles in five patients. The lesion occurred in close relation to lymphoid follicles, vessels, and sinusoids. It consisted of collections of cells with regular, spindle-shaped nuclei and poorly defined cytoplasmic borders. Among these cells, which were interpreted as histiocytic and/or fibroblastic elements, there were abundant eosinophils, often in aggregates (eosinophilic abscesses), plasma cells, and a few mast cells. Four of the patients were anemic, and all took numerous drugs including ampicillin, procainamide, and allopurinol. In four patients, the anemia remitted after the suspected drug was discontinued. Repeated bone marrow aspirates in three showed only an increased number of eosinophils around lymphoid follicles and blood vessels in two patients and complete disappearance of the lesion in one. Hodgkin’s disease, eosinophilic granuloma, Kaposi’s sarcoma, and lipid granuloma were considered in the differential diagnosis and were ruled out by histologic and clinical considerations.
The Splenic Platelet Reservoir in Sickle Cell Anemia
Authors: Schwartz Allen D.
Published: October 2019

The presence of hypersplenism and functional asplenia occurring concomitantly in a child with sickle cell anemia prompted a study of the splenic platelet reservoir in this hemoglobinopathy. The young child with sickle cell anemia and a large spleen, who is unable to remove Howell-Jolly bodies, concentrate 99mTc sulfur colloid in his spleen, or respond to intravenous particulate antigen, retains the splenic reservoir function to pool platelets. This reservoir function is lost in the older patient in whom the spleen has become autoinfarcted. Thus, an independence of certain splenic functions is present in young children with sickle cell anemia who have splenomegaly.
Reticulocyte Survival in Sickle Cell Anemia: Effect of Cyanate
Authors: Alter Blanche P. , Kan Yuet Wai , Nathan David G.
Published: October 2019

Cyanate prevents sickling in vitro and apparently prolongs the survival of 51Cr-tagged sickle erythrocytes in vivo. Cautious interpretation is required because the effects of cyanate on 51Cr binding to sickle and fetal hemoglobin-containing red cells are unknown, and comparison of the effect of cyanate on sickle red cell survival to control red cell survival must be performed sequentially. We have studied the survival of sickle reticulocytes utilizing radioactive amino acids that are incorporated into hemoglobin. Two informed adult patients with sickle cell disease were studied. In each study, two 50-ml samples of blood were incubated separately with 14C- and 3H-leucine for 2 hr, after which 50 mM cyanate was added to one aliquot for 1 hr. The cells were then washed and reinfused. Frequent venous samples were obtained, and the specific activities of 14C and 3H in the hemoglobin were followed. The t ½ of the carbamylated cells was tripled, but remained below normal. This method provides a generally useful measurement of the influence of drugs bound to red cells on reticulocyte lifespan. The labels are incorporated into the hemoglobin molecule of the reticulocyte, and simultaneous comparison of the survivals of the same cohort of drug-treated and control cells is achieved.
Vitamin B12 Malabsorption Due to Intrinsic Factor Deficiency in Indian Subjects
Authors: Desai H. G. , Antia F. P.
Published: October 2019

Sixteen patients (from Bombay) with severe vitamin B12 malabsorption due to intrinsic factor deficiency, presenting as subacute combined degeneration of the cord (7), tropical sprue (3), anemia (2), thyrotoxicosis (2), diabetes mellitus (1), and pain in the abdomen (1), are reported. The difficulties of establishing a definite diagnosis of pernicious anemia in Indian population are described. The lower incidence of circulating intrinsic factor antibody (IFA) in Indian patients with histamine-fast achlorhydria and poor vitamin B12 absorption is emphasized. The necessity of separating atrophic gastritis, with severely impaired vitamm B12 absorption, from pernicious anemia on the basis of absence or presence of IFA in serum and/or gastric juice cannot be overemphasized.
Surface Bound Immunoglobulins as a Cell Marker in Human Lymphoproliferative Diseases
Authors: Preud’homme J. L. , Seligmann M.
Published: October 2019

Membrane-bound Ig were studied by immunofluorescence methods in 116 patients with lymphoproliferative disorders. Surface Ig synthetized in vitro were studied in many patients. In 70 of 73 cases of chronic lymphocytic leukemia (49 without and 24 with monoclonal serum Ig), monoclonal surface Ig with a distribution for heavy and light chains similar to that of normal lymphocytes were found. In three cases, these surface Ig accumulated as crystals in the lymphocyte cytoplasm. Studies limited to staining of freshly drawn cells may lead to erroneous conclusions since serum antibodies may become bound to the cell surface and simultaneous positivity for µ, γ, κ, and λ, due either to the attachment of immune complexes at the lymphocyte surface or to anti-IgG antibody activity of the monoclonal surface IgM, was not rare. IgM with anti-IgG activity was found on the surface of both lymphocytes and lymphoblasts in a patient with acute transformation of chronic lymphocytic leukemia. In a single case, µ and γ chains were simultaneously found on some lymphocytes besides two single producer clones. A biclonal proliferation characterized by distinct surface Ig markers was demonstrated in three other cases of lymphocytic leukemia and in a patient with Waldenström’s macroglobulinemia. In this latter condition (31 cases), most marrow lymphoid cells including plasma cells and the majority of blood lymphocytes carried IgM determinants which had the same light chain type as the serum IgM and which shared its eventual antibody activity. Similar results were obtained in a few patients with the hematological features of macroglobulinemia but with serum monoclonal IgG or IgA or with unreleased IgM. Studies on cases of γ and α heavy chain diseases, cold agglutinin disease, leukemic reticuloendotheliosis, and Sezary’s reticulosis are also recorded. The value of surface Ig as B cell markers in lymphoproliferative diseases is outlined.
Effects of Plasmin on Human Factor VIII (AHF)
Authors: Pasquini R. , Hershgold E. J.
Published: October 2019

Highly purified, fibrinogen-free human factor VIII was incubated with plasmin, and the liberated split products of the factor VIII were analyzed by gel filtration, acrylamide gel electrophoresis, bioassay, and for immunologic reactivity. At least three fragments retaining different antigenic determinants are released from the factor VIII after prolonged digestion and at least three new fragments are seen in acrylamide gel electrophoresis. The split products were not anticoagulant in the factor VIII activity assay. In fact, the breakdown products in the hydrolysate increased the factor VIII activity of normal plasma mixed with it. Therefore, it is not likely that the factor VIII split products formed in fibrinolytic states contribute actively to the hemorrhagic diathesis.
Lymphocyte Plasma Membranes: Analysis of Proteins and Glycoproteins by SDS-Gel Electrophoresis
Authors: Lopes John , Nachbar Martin , Zucker-Franklin Dorothea , Silber Robert
Published: October 2019

A method is described for the preparation of plasma membranes from human tonsil lymphocytes. The membrane preparation has been characterized by electron microscopy and by the use of 5'-nucleotidase as an enzymatic marker. Acrylamide gel electrophoresis in sodium dodecyl sulfate yields a reproducible pattern for the membrane proteins and glycoproteins. A minimum of 26 polypeptide bands were identified with the Coomassie blue stain. The glycoprotein material was distributed into at least five bands. Similarities and differences between the lymphocyte and red cell membrane are discussed.
Refractory Anemia With Dysproteinemia: Long-term Therapy With Low-Dose Corticosteroids
Authors: Hume R. , Dagg J. H. , Goldberg A.
Published: October 2019

Nine elderly patients with a refractory anemia associated with a high blood sedimentation rate and with minor serum protein abnormalities, especially elevation of the alpha2 globulin fraction, have been studied. The anemia was characterized by red cell hypochromia, reduced serum iron, and normal or reduced iron binding capacity concentrations, elevated erythrocyte protoporphyrin levels, and normoblastic erythropoiesis with reticuloendothelial iron present on Prussian-blue staining of bone-marrow preparations; no evidence of hemolysis was elicited by radiochromium red cell survival measurements, and plasma clearance and red cell utilization of intravenously injected radioiron were normal. The mechanism of the anemia was thus compatible with a block in reticuloendothelial release of iron derived from hemoglobing catabolism. Five patients complained of musculoskeletal pains and could thus be classified as polymyalgia rheumatica. Four patients had no pain and anemia dominated the clinical presentation. Carcinoma, myelomatosis, lymphoid neoplasm, leukemia, chronic infection, renal and hepatic failure, and auto-immune disease were excluded by investigation, and prolonged follow-up for 3-11 years has failed to reveal underlying disease. All patients responded clinically and hematologically to prednisolone, with a rapid increase in general well-being, a fall in sedimentation rate, and a return of the hemoglobin level to normal; remission has been maintained for 3-11 yr on minimal steroid dosage. Steroid dependence was illustrated in two cases, where withdrawal of therapy resulted in a rapid relapse of symptoms, a rise in sedimentation rate, and a return of the anemia. While five patients had clinical manifestations suggestive of polymyalgia rheumatica, four had no pain. In view of the excellent therapeutic response to steroids, the recognition of this pain-free group is important.
Cyclic Neutropenia: The Relationship Between Urine Granulocyte Colony Stimulating Activity and Neutrophil Count
Authors: Mangalik Aroop , Robinson W. A.
Published: October 2019

Urinary colony stimulating activity (CSA) has been studied in a 70-yr-old female with chronic cyclic neutropenia of unknown cause. Changes in urinary CSA were correlated with absolute granulocyte counts and were found to be highest when the granulocyte count was high or falling. It is suggested, on the basis of this and other data, that granulopoiesis, at least in part, may be regulated by a positive feedback control mechanism.
Acute Leukemia With C-G Chromosome Translocation
Authors: Hinkes Elliott , Crandall Barbara F. , Weber Felice , Craddock Charles G.
Published: October 2019

The occurrence of acute lymphocytic leukemia in a young man with a C-G translocation is described. Two members of his family also show C-G translocations but have not as yet developed leukemia. A third member of the family, on whom no chromosomal information was available, died of acute lymphocytic leukemia.
Pernicious Anemia in Southwestern American Indians
Authors: Sievers Maurice L. , Metzger Allan L. , Goldberg Leonard S. , Fudenberg H. Hugh
Published: October 2019

Pernicious anemia (PA), previously considered rare among American Indians, was diagnosed in 18 Indians during a 16-yr period at the Phoenix Indian Medical Center. These patients, from ten different tribes, did not vary significantly from all adult hospital admissions in proportionate sex, tribe, or blood group distribution. The current minimum prevalence of PA for southwestern Indians is 1:514 beyond 50 yr of age and 1:293 after 60 yr of age. Despite a marked predominance of blood group 0 (81%), the Indians developed PA as frequently as other ethnic groups in which PA is strongly associated with blood group A. Their clinical and hematologic manifestations were similar to those of whites with PA. Of the 13 subjects tested immunologically, 11 demonstrated parietal cell antibodies, and six had blocking antibodies to intrinsic factor. During follow-up none developed gastric carcinoma, although this tumor— the most frequent malignancy among southwestern Indians-is correlated with PA in whites. The findings establish that PA in full-blooded south-western Indians is not rare and is clinically and immunologically similar to PA in whites.