bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fetal Hemoglobin with Abnormal γ-Polypeptide Chains: Hemoglobin Warren
Authors: HUISMAN T. H. J. , DOZY A. M. , HORTON B. E. , WILSON J. B.
Published: October 2019

The discovery of a variant of fetal hemoglobin in the cord blood of a Negro newborn is reported. The abnormal hemoglobin, designated as Hb-Warren, was studied by different analytic procedures, such as starch gel electrophoresis, anion exchange chromatography, ultraviolet spectral absorption, immunologic reactivity with various antisera, hybridization with canine hemoglobin and the determination of the total amino acid composition. It was concluded that Hb-Warren was composed of normal α-polypeptide chains and abnormal γ-polypeptide chains.
The Sites of Hemoglobin Catabolism
Authors: KEENE WILLIS R. , JANDL JAMES H. , Files Nancye M.
Published: October 2019

Hemoglobin is cleared from plasma principally by the liver, moderately by the marrow, and relatively little by the spleen or other organs. Haptoglobin binding has no effect on this relative distribution, its only discernible role in hemoglobin clearance or catabolism being that of preventing the renal loss of hemoglobin.

When bone marrow is depleted of parenchymal cells, as by cytotoxic chemicals or protein deprivation, its ability to take up hemoglobin from plasma is markedly enhanced.
Brief Report: The Early Loss of Radioactivity in Cr51 Survival Curves: Destruction of Cells or Loss of the Label?
Authors: KLEINE N. , HEIMPEL H.
Published: October 2019

Using human erythrocytes labeled simultaneously with DFP32 and Cr51, studies of specific red cell activities within the first 24 hours after infusion of labeled cells were carried out. The results obtained suggest that the early loss of Cr51 specific red cell activity which has been observed in radiochromium survival curves is due to rapid elution of a portion of the label.
Antigenic Behavior of the S-63 Mouse Leukemia Virus
Authors: BROWN ERIC R. , GREENSPAN IRVING , SCHWARTZ STEVEN O.
Published: October 2019

The present studies are an extension of earlier reports on the antibody response of mice to a leukemogenic virus (S-63). These investigations were designed to show whether a correlation exists between in vivo and in vitro determinations, and whether protective antibodies against the virus could be produced in immune-tolerant animals. Viral neutralization and protection studies in mice were compared with passive cutaneous anaphylaxis (PCA), immunodiffusion, microprecipitin, and immunofluorescent tests using similar antigens and antibodies. As shown in tables 1, 2 and 3, antibody could be demonstrated by both in vivo and in vitro methods, and these studies showed (table 2) that the antibody was protective.

The S-63 leukemia virus was isolated in 1963 from a mouse ascites cell leukemia line. That cell line had been carried in the laboratory for over 3 years. The virus has been carried in ICR mice since its isolation. Immunologic studies were carried out to determine the relation between the virus and the originating ascites cell. Studies of antibodies produced in normal rabbits against the S-63 virus were unsatisfactory for purposes of these experiments because of cross reaction with normal mouse tissue. Immune-tolerant animals have yielded valuable information:

Antibodies produced in immune-tolerant rabbits injected with the S-63 virus do not cross react against intact ascites cells from which the virus was originally isolated. Conversely, antibodies similarly produced against the ascites cells do not react against the virus antigen.

Antibodies produced in immune-tolerant rabbits against ascites cells protect mice against ascites cell-induced leukemia, but not against the disease induced by S-63 virus. Mice challenged with ascites cells and treated with antiascites cell gamma globulin are protected against the disease. The best therapeutic advantage is obtained when treatment is started either at the time of cell inoculation or in the early stages of the disease.

Antibodies which protect newborn animals from infection develop in adult ICR mice recovering from S-63 virus leukemia. These antibodies produced by convalescent mice are similar, from the standpoint of protection, to those produced in immune-tolerant rabbits.
Congenital Nonspherocytic Hemolytic Anemia, Associated with Glutathione Deficiency of the Erythrocytes
Authors: PRINS H. K. , OORT M. , LOOS J. A. , ZÜRCHER C. , BECKERS T.
Published: October 2019

1. A new biochemical defect of erythrocytes is described: glutathione deficiency (reduced glutathione less than 10 per cent of the amount of reduced glutathione in normal erythrocytes).

2. The defect is associated with a clinical picture of congenital nonspherocytic hemolytic anemia which is fairly well compensated.

3. The results of a family study are consistent with an autosomal recessive pattern of inheritance.

4. Labeling with Na2Cr51O4 has a damaging effect on glutathione-deficient erythrocytes. The erythrocyte life span, as estimated by a serological method (Ashby), was markedly shortened (30 days instead of 100-120 days).

5. Red cell destruction could be increased by the administration of primaquine.

6. Secondary to the glutathione deficiency, low glyoxalase activity was observed. The glutathione-reducing capacity, glycolytic activity, and the ATP level of the abnormal red cells were found to be within the normal range.

7. On incubation of the glutathione-deficient erythrocytes in vitro with glycine-C14 and glutamine-C14, no formation of labeled glutathione could be demonstrated.
Pyridoxine-Responsive Anemia Conditioned by Isonicotinic Acid Hydrazide
Authors: McCURDY PAUL R. , DONOHOE ROBERT F.
Published: October 2019

Three patients are described who had a pyridoxine-responsive anemia while under treatment for pulmonary tuberculosis with INH and PAS. The red cells were hypochromic and target cells were common. Two cases also had microcytosis and one had ringed sideroblasts in the bone marrow. None became hematologically normal with therapy. A somnolent reaction occurred in two of the patients following the parenteral administration of large amounts of pyridoxine, and seemed related to it. The concentration of erythrocyte glutamic oxaloacetic transaminase was less than 25 per cent of the normal mean in two of the patients at the time of relapse.
Multiple Cases of Leukemia in a Sibship
Authors: GUNZ F. W. , FITZGERALD P. H. , CROSSEN P. E. , MACKENZIE I. S. , POWLES C. P. , JENSEN G. R.
Published: October 2019

In a New Zealand Maori sibship of 9 (one a half-sib), 4 definite cases and 1 possible case of acute leukemia occurred in a space of 5 years. The children, 2 of whom were fraternal twins, developed symptoms at ages between 10 months and 6 years. One child had a marrow picture suspicious of leukemia nearly 2 years before the onset of symptoms.

Cytogenetic studies showed no major chromosome changes in either the parents or the 3 affected siblings examined. No linkage was found between the leukemias and any blood or serum group.

The nature of the factors causing the disease in this family is discussed.
The Activation of Proaccelerin by Bovine Thrombokinase (with Notes on the Antithrombic Activity of Phenylmethyl Sulfonylfluoride)
Authors: BRECKENRIDGE ROBERT T. , RATNOFF OSCAR D.
Published: October 2019

Through the kindness of Dr. J. H. Milstone we were able to perform clotting studies with purified bovine thrombokinase. Phenylmethyl sulfonylfluoride was found to inactivate bovine thrombin. Bovine thrombokinase, freed of traces of contaminating thrombin by treatment with phenylmethyl sulfonylfluoride, behaved in a manner similar to activated Stuart factor. Kinetic studies with this purified clotting factor and partially purified bovine proaccelerin supported the hypothesis that bovine proaccelerin is changed by the enzymatic action of thrombokinase to an agent which converts prothrombin to thrombin. The reaction between thrombokinase and bovine proaccelerin requires phospholipid and calcium and is blocked by soybean trypsin inhibitor. The similarities between human activated Stuart factor and bovine thrombokinase are apparent.
Sternberg-Reed Cells in the Peripheral Blood of Patients with Hodgkin’s Disease
Authors: BOURONCLE BERTHA A. , Mann Rosemary
Published: October 2019

Our observations of 135 patients indicate that 37 per cent of those suffering from Hodgkin’s disease exhibit abnormal cells in the leukocyte concentrates of the peripheral blood during the course of their illness. Typical Sternberg-Reed cells were found in 18.5 per cent of patients and were present only in the advanced stages of generalized Hodgkin’s disease.

The presence of Sternberg-Reed cells in the peripheral blood indicates an advanced stage of the disease but does not necessarily predict an immediately fatal outcome.

Comparative studies, searching for Sternberg-Reed cells in the splenic circulation, showed no Sternberg-Reed cells to be present in the splenic arteries of patients with Hodgkin’s disease; but numerous Sternberg-Reed cells were present in the splenic vein, particularly after mechanical squeezing of the spleen. A possible hypothesis is given to support the evidence for the circulation of Sternberg-Reed cells and an explanation for their lower incidence in the peripheral blood.

Our observations support the hematogenous metastasis of Hodgkin’s disease.
Roentgenographic Bone Changes in Chronic Iron Deficiency Anemia
Authors: AKSOY MUZAFFER , ÇAMLI NECDET , ERDEM SAKIR
Published: October 2019

Radiologic bone changes of the skull and long and short bones similar to those of thalassemia are described in 12 patients with chronic iron deficiency anemia. Certain differences between the roentgen findings of the present study and those of the cases reported by other investigators are discussed.
Normal Human Lymph Node Cells: An Electron Microscopic Study
Authors: BROOKS ROBERT E. , SIEGEL BENJAMIN V.
Published: October 2019

Lymph nodes, from 15 patients undergoing surgery for conditions not related to lymphoid tissue disease, have been examined with the electron microscope. The human lymph node cell types—including lymphocytic, reticular and plasma cells—have been described at low and medium electron microscopic magnifications, and the criteria for their identification are discussed. The characteristic features outlined for identification of these cell types provide a basis for comparison with pathologically altered lymph node cells.
Trisomy of Group C in a Myeloproliferative Disorder
Authors: WINKELSTEIN ALAN , SPARKES ROBERT S. , CRADDOCK CHARLES G.
Published: October 2019

A patient with an atypical myeloproliferative syndrome characterized by leukocytosis with myeloid immaturity, ineffective extramedullary erythropoiesis, overt hemolysis and low leukocyte alkaline phosphatase activity demonstrated a trisomy in the C group of bone marrow metaphase chromosomes.
Fetomaternal Passage of Leukocytes and Platelets in Erythroblastosis Fetalis
Authors: DESAI R. G. , MCCUTCHEON E. , LITTLE B. , DRISCOLL S. G.
Published: October 2019

Leukocytes and platelets labeled by the atabrine fluorescent technic have been demonstrated in the maternal circulation from ½ to 4 hours following intraperitoneal transfusion of the fetus in utero. The peak concentration of labeled cells was observed 2 hours after transfusion. The fetomaternal transfer of cells has been demonstrated in cases of erythroblastosis fetalis. It is not known whether this occurs in normal fetuses and the mechanism is not understood.
Promyelocytic-Myelocytic Leukemia as a Terminal Manifestation of Chronic Granulocytic Leukemia
Authors: BEN-ZEEV DAN , SCHWARTZ STEVEN O. , FRIEDMAN IRVING A.
Published: October 2019

1. A case of promyelocytic-myelocytic leukemia is reported as the terminal phase of chronic granulocytic leukemia. We believe that this is the first such case reported.

2. The terminal phase of this case is compared with acute promyelocytic-myelocytic leukemia; the course and laboratory data appear almost identical.

3. The nature of the abnormal granules in the promyelocytoid-myelocytoid cells and their relation to the fibrinogenopenia incite speculation.
Studies in the Pathogenesis of Autoerythrocyte Sensitization Syndrome
Authors: GROCH GEORGE S. , FINCH STUART C. , ROGOWAY WILLIAM , FISCHER DAVID S.
Published: October 2019

1. Two of three female patients with the autoerythrocyte syndrome were tested for sensitivity to various components of the erythrocyte membrane. One was consistently sensitive to purified phosphatidyl serine.

2. It is suggested that in at least one patient with autoerythrocyte purpura the phosphatidyl serine of the red cell membrane may play a role in the pathogenesis of the purpuric lesions.

3. It is likely that a broad spectrum of autosensitivity-type purpuric disorders exists in women with complex emotional problems. The threshold of reactivity may be modified by the psyche.
Ribonucleic Acid Biosynthesis in Human Leukocytes
Authors: CLINE MARTIN J.
Published: October 2019

Phagocytosis has profound effects on several aspects of the RNA metabolism of human leukocytes. The major changes induced by particle ingestion appear to be (1) an increased uptake of pyrimidine precursors from the suspending medium, (2) a contraction in the size of the nucleotide pool, (3) an accelerated rate of destruction of preexisting RNA, and (4) an increased rate of RNA synthesis. Sucrose density gradient analysis of the newly synthesized RNA suggests that several classes of RNA are involved in this process. The increased turnover rate of the nucleotide pool and of the cellular RNA of the leukocyte is proportional, within limits, to the total load of ingested particles.
Interaction of Influenza Virus with Blood Platelets
Authors: TERADA HIDEO , BALDINI MARIO , EBBE SHIRLEY , MADOFF MORTON A.
Published: October 2019

The interaction of human blood platelets with influenza virus (PR-8) was studied in vitro and in vivo.

It was found that "live" influenza virus was rapidly adsorbed onto human blood platelets at 4 C. and completely eluted at 37 C. "Dead" virus was adsorbed at 4 C. but not eluted at 37 C. unless the platelets were treated with RDE (receptor destroying enzyme). Adorption of virus also occurred at tem peratures above 4 C. (from 20 to 37 C.). However, while adsorption was maintained throughout incubation at 4 C., slow elution occurred after 30 to 90 minutes incubation at 26 to 37 C. Storage of the platelets for lengthy intervals at 4 C. or coating of the platelets with macromolecules did not interfere with virus adsorption. After one cycle of adsorption-elution, blood platelets could not adsorb virus again. Treatment with RDE greatly reduced virus adsorption. During the process of virus adsorption, prominent platelet clumping occurred. During elution, clumping remained unchanged, and gross alterations in morphology of the platelets were observed. In the process of virus adsorption-elution, large numbers of platelets were lysed.

Comparative experiments were performed simultaneously with human red blood cells (RBC) and identical results were obtained as with blood platelets. However, the extent of adsorption of live virus was equal for platelets and RBC only when the relationship between platelet number and RBC number in the preparations used was 6:1. This suggested a direct proportion between the surface area of both platelet and RBC and the number of available virus receptors.

Virus suspensions infused into rabbits produced a sharp and sustained drop of the platelet count. Survival of radioactively labeled platelets treated with virus prior to infusion was markedly shortened with live virus and was only slightly reduced with dead virus.

It is suggested from these experiments that blood platelets, as other blood cells, may serve as carriers of viruses in the circulation and that in this process the platelets are damaged and partially destroyed.
The Effect of Ellagic Acid on the Thrombin-Induced Hemorrhagic Syndrome in the Rat
Authors: CLIFFTON E. E. , GIROLAMI A. , AGOSTINO D.
Published: October 2019

The intraperitoneal administration of thrombin increased the bleeding due to the amputation of the tail in the rat (average blood loss 4.6 ml.). The intravenous administration of ellagic acid in thrombin-injected rats reduced the average blood loss to 0.6 ml. This value was slightly more than the average blood loss noted in animals given only ellagic acid (0.2 ml.). Both these figures were much less than the average blood loss observed in control animals (3.2 ml.).
Jordans’ Anomaly in White Blood Cells
Authors: ROZENSZAJN L. , KLAJMAN A. , YAFFE D. , EFRATI P.
Published: October 2019

Persistent vacuoles were seen in the protoplasm of granulocytes, monocytes and occasional lymphocytes of 2 sisters suffering from ichthyosis. In the bone marrow these vacuoles were found in the cytoplasm of promyelocytes, myelocytes, metamyelocytes and rarely in plasma cells. They were not observed in blasts or in red cells and thrombocytes and their precursors.

With the help of cytochemical staining technics and fluorescence microscopy studies, it was determined that the vacuoles contained lipids. A similar abnormality of leukocytes was described previously by Jordans in 2 brothers suffering from muscular dystrophy.

Ichthyosis was transmitted in this family in an autosomal recessive way.
Tabular and Ultrastructural Studies of Agranulocytes of the Thoracic Duct of Calves
Authors: WEBER ALVIN F. , JOEL DARREL , Smith Joyce , Frommes Stephen
Published: October 2019

1. Ultrastructural studies were made of 400 agranulocytes, each from the thoracic duct effluent of 12 normal Holstein calves of both sexes.

2. Tabular electron microscopic evaluation of the agranulocytes present demonstrated that 89 per cent were lymphocytes, 4.8 per cent plasmacytes, 1.3 per cent reticular lymphocytes, 4 per cent proplasmacytes, and 0.7 per cent mitotic forms of the various cell types enumerated.

3. Mitochondrial tabular studies demonstrated that profile numbers (6.2-8.2) and profile sizes (0.15-0.25 µ2) were similar among cell sections of the five designated cell groups in the calf and the lymphocyte of the human. Monocyte mitochondrial profiles of the human were highly significantly smaller (0.05 µ2) than those of other cells studied. These studies provided added proof that monocytes probably are not present in the thoracic effluent of the calf.

4. Nuclear bodies were found to be present only in lymphocytes. They were present on the average in 12 per cent of thin sections of cells in this class. In contrast to nuclear bodies of other nonblood cells,20 in lymphocytes they were not associated with the nucleolus, were smaller in overall diameter, and often contained practically no electron opaque central portion.
Mechanism of the Hereditary Anemia of Slm Mutant Mice
Authors: KALES A. N. , FRIED W. , GURNEY C. W.
Published: October 2019

The anemia of mutant homozygote C57BL/6SlmSlm mice is due to a gastrointestinal bleeding defect and to an erythropoietic defect. The anemic animals lose approximately 3.5 per cent of their blood volume into the gastrointestinal tract daily. The cause of this blood loss has not been established. The anemic animals also have an erythropoietic defect which renders them unable to respond normally to erythropoietin or to hypoxia. Although the homozygotes appear refractory to erythropoietin in moderately large single doses, they do respond if sufficiently large doses are given repeatedly.

The erythropoietic defect detected in the homozygote is also evident in the heterozygote. However, the defect remains latent in the heterozygote, for although this animal is subnormally responsive to erythropoietin and to hypoxia, it is not anemic.
Stilbestrol-Induced Porphyria: Increase in Hepatic δ-Aminolevulinic Acid Synthetase
Authors: LEVERE RICHARD D.
Published: October 2019

An increase in hepatic δ-aminolevulinic acid synthetase is demonstrated in a patient with cutaneous porphyria induced by stilbestrol. A genetically determined increase in this rate-limiting enzyme appears to be the basic abnormality in all of the hepatic porphyrias.
Ribonucleic Acid Biosynthesis in Human Leukocytes: The Fate of Rapidly Labeled RNA in Normal and Abnormal Leukocytes
Authors: CLINE MARTIN J.
Published: October 2019

Ribonucleic acid (RNA) was isolated from a variety of human leukocyte populations exposed to tritiated uridine in vitro. Several species of RNA were extractable from leukocytes in a phenol-water system. With mild conditions of extraction a pH 7.6 fraction was obtained, which contained 60 to 75 per cent of total cellular RNA. After removal of this RNA component reextraction at elevated temperature and pH yielded a pH 9 fraction which contained 25 to 40 per cent of total cellular RNA. The pH 7.6 fraction contained 28 and 18 S ribosomal RNA and 4 S RNA. The pH 9 RNA fraction was heterogeneously distributed in a sucrose density gradient. The 28 and 18 S components were slowly labeled by H3-uridine and were relatively stable. The 4 S component was rapidly labeled and was unstable. The pH 9 RNA fraction contained most of the rapidly labeled RNA, which was either of high molecular weight or heterogeneous as to molecular size.

The pattern of incorporation of H3-uridine into the various components of RNA was similar in normal and neoplastic granulocytes and lymphocytes.

Rapidly labeled leukocyte RNA had the following characteristics: (1) its synthesis was actinomycin sensitive; (2) it was unstable, having a half-life in the range of 16 to 225 minutes; and (3) it was in part a precursor of ribosomal RNA.

The sensitivity of granulocyte protein synthesis to inhibition of RNA synthesis suggests that granulocytes have both stable and unstable templates.
Staining of Blood Cells with Periodic Acid/Salicyloyl Hydrazide (PA-SH)
Authors: BURNS J. , NEAME P. B.
Published: October 2019

Stoward1 conjugated acidified solutions of salicyloyl hydrazide with the dialdehydes formed from the periodic acid oxidation of vicinal glycols in guinea pig tissue sections. The method has now been utilized, with minor modification, to demonstrate glycogen in blood and marrow cells, and it has been compared with the periodic acid-Schiff reaction and with a fluorescent acriflavine Schiff-type method. It is felt that the PA-SH method will replace the existing Schiff-type fluorescent methods and that it will prove to be a useful technic to aid in the diagnosis of blood conditions, such as acute leukemia, where PAS positivity is known to occur.
Human Leukocyte Metabolism in Vitro
Authors: SCOTT JAMES L. , MARINO JOSEPH V. , GABOR E. PETER
Published: October 2019

1. The effects of added 6-mercaptopurine (6-MP) on the in vitro incorporation of radioformate (C14) into the leukocyte nucleic acid purines and thymine of six cases of acute myeloblastic leukemia (AML) and four cases of acute lymphoblastic leukemia (ALL) have been compared with the patients’ clinical response to 6-MP.

2. In seven cases subsequent therapy with 6-MP produced leukopenia. Of these, in vitro 6-MP diminished leukocyte C14 incorporation into the nucleic acid purines in three cases of AML, had no effect in two cases of AML and one case of ALL, and enhanced C14 incorporation into the leukocyte purines of a second case of ALL. Thymine synthesis was slightly diminished by 6-MP in the AML leukocytes in which purine synthesis was inhibited, and in one drugsensitive ALL leukocyte population in which purine synthesis was slightly increased by the analog. Thus, no regular and consistent relationship between the antileukemic effect of the drug and suppression of purine or thymine synthesis by 6-MP in vitro could be demonstrated.

3. Studies of the leukocytes of two cases of drug-resistant ALL yielded results similar to those observed in presumably drug-sensitive ALL cells.

4. The leukocytes of two cases of AML with acquired drug-resistance showed an increased capacity for in vitro RNA purine synthesis; in the one case in which studies before and after the development of resistance were possible, this property was apparently acquired during therapy. This suggests that an increase in purine biosynthetic enzyme reserves may be a mechanism of 6-MP-resistance in some human leukemias.
DNA Replication Patterns of Normal Human Leukocyte Cultures
Authors: RIBAS-MUNDÓ MANUEL
Published: October 2019

Three patterns of DNA replication in the interphase nuclei of short-term leukocyte cultures are described: (1) light, homogenous labeling on the whole nucleus and no labeling over the nucleolus (nucleolus-negative phase), (2) heavy labeling equally distributed over the whole nucleus and nucleoli (intermediate phase), (3) heavy labeling over the nucleoli and moderate labeling at the periphery of the nucleus (nucleolus-positive phase).

These three patterns of labeling appear consecutively during the process of DNA synthesis. Thus, the nuclear and nucleolar associated chromatin replicates during the late stage of DNA synthesis. The existence of nucleolar chromatin is discussed. Study of H3-thymidine incorporation in the nucleoli of leukemic and neoplastic cells may develop data regarding the possible metabolic disturbances of these cells.
The Effects of Two Alkaloids Derived from Vinca Rosea on the Malignant Cells of Hodgkin’s Disease, Lymphosarcoma and Acute Leukemia in Vivo
Authors: MARMONT ALBERTO M. , DAMASIO EUGENIO E.
Published: October 2019

Hodgkin’s disease, lymphosarcoma, and acute leukemia have been studied after treatment with the Vinca rosea alkaloids (vinblastine and vincristine), in order to demonstrate and evaluate the mitosis-arresting effects of the two drugs on the malignant cells. Histologic sections, lymph node and bone marrow aspirations were performed immediately before and 24 hours after the intravenous administration of the drugs in 15 cases of Hodgkin’s disease, 12 of lymphoblastic lymphosarcoma, and 12 of acute leukemia, besides other miscellaneous cases.

In Hodgkin’s disease aspirates and sections showed a clear-cut metaphase arrest in the post-VLB specimens, chiefly affecting the pre-Sternberg or Hodgkin cells. This effect, besides corroborating the fundamentally stathmokinetic mechanism of VLB in Hodgkin’s disease, was considered an additional factor in confirming the widely proposed conception that these cells represent the fundamentally proliferating and malignant tissue of this disease.

In the acute leukemias and lymphoblastosarcomas, cytomorphologic and quantitative studies demonstrated that the oncolytic effects correlated well with the magnitude of metaphasic blockade. It is postulated that only actively proliferating cells—the so-called "growth fraction"—are the target for these alkaloids.
Brief Report: Coated Charcoal Assay of Erythrocyte Vitamin B12 Levels
Authors: KELLY ALAN , HERBERT VICTOR
Published: October 2019

A rapid, reproducible coated charcoal assay for vitamin B12 in erythrocytes is described. Results are almost identical to those of microbiologic assay.
The Size and Transit Time of Nondividing Subpool of Precursor Cells in Acute Leukemia
Authors: LIN MAX SHIUMING , BOURONCLE BERTHA A.
Published: October 2019

1. In order to elucidate the postulation and to quantitate the size and transit time of the nondividing subpool of precursor cells in acute leukemia, mathematical formulas based on a prolonged-labeling model were derived for the following kinetic parameters: (1) DNA synthesis time and generation time of dividing precursor cells in normal hemopoiesis and in acute leukemia. (2) size and transit time of the nondividing subpool of precursor cells in acute leukemia. The validity of the assumptions made in the model was discussed.

2. In vitro experimental estimation of the above kinetic parameters was done for the myeloid precursor pool in four cases: two with normal hemopoiesis; one, acute myeloid leukemia; one, subacute myeloid leukemia.

3. Variable decrease with time in availability of tritiated thymidine given initially in single dose to the in vitro system was observed and discussed.

4. DNA synthesis time and generation time of the dividing myeloid precursor cells in the two leukemic patients were not significantly different from, and were no shorter than, the corresponding values for normal myeloid precursor cells in the two nonleukemic patients. Thus it allows the prediction that as much as 86 per cent of the myeloid precursor cells in the marrow may be nondividing in acute myeloid leukemia.

5. In a case of acute myeloid leukemia about 87 per cent of the myeloid precursor cells in the marrow were estimated as nondividing with nondividing subpool transit time of about 32 days in closed in vitro system. The probable meanings of these in vitro estimates in vivo were discussed.

6. The result and analytical review of literature support the postulation of heterogeneous acute leukemia precursor cells with the nondividing fraction consisting of end cells being maintained by the dividing fraction. It is also suggested that a small fraction of nondividing cells may be capable of DNA synthesis and thus be initially-labeling. More definitive approaches to the problems await future investigation.
The Effect of Splenic X-Irradiation on the Ferrokinetics of Chronic Leukemia with a Clinical Study
Authors: AWWAD H. K. , BADEEB A. O. , MASSOUD G. E. , SALAH M.
Published: October 2019

The usefulness of splenic x-irradiation in the palliative treatment of chronic leukemia is illustrated by the results obtained in the treatment of 18 patients. This form of therapy was generally followed by reduction in organ size, improvement in blood levels, and control of associated anemia.

Abnormalities of iron kinetics were defined in nearly all patients prior to therapy. A second ferrokinetic study was performed after remissions were induced by splenic irradiation.

In the majority of patients, some evidence of increased red cell sequestration in the spleen could be demonstrated before therapy. The reaction of the erythropoietic tissue to this hemolytic process varied. In a number of patients with chronic lymphatic leukemia, there was an absolute hypoactivity. In the chronic myeloid group, erythropoiesis was either normal or slightly increased. In three cases of CLL with marked hemolytic activity, the erythropoietic activity was increased approximately twofold. However, in none of the anemic cases was erythropoiesis adequate to maintain a normal red cell mass. Extramedullary erythropoiesis was demonstrated in all patients of the myeloid group.
Analytical Review: Multiple Differentiation in Megakaryocytes and Platelets
Authors: PAULUS JEAN-MICHEL
Published: October 2019

The properties of the megakaryocyte and the platelet may be briefly summarized as follows: a polyploid cell secretes, by an apocrine type mechanism, an anucleate element, endowed with strong autolytic and endocytic properties, and capable of performing contractile work. The latter element, specialized in this way, is prepared to play a major role in hemostatic reactions.

The relationships between the five properties considered for these elements are still largely unknown. A certain degree of polyploidy may conceivably be necessary for the megakaryocyte to secrete platelets, but the importance of polyploidy in its cytoplasmic maturation has recently been questioned.6 The influence of the absence of a nucleus on platelet metabolism, as well as on the endocytic properties of cells, is still a matter of controversy.97,98 Finally, there remains to be established the possible role of contraction in the release of platelet material,84 and molecular material degraded by lysosome action.
Hydrogen Peroxide Toxicity and Detoxification in the Erythrocytes of Newborn Infants
Authors: GROSS RUTH T. , BRACCI RODOLFO , RUDOLPH NATHAN , SCHROEDER ELEANOR , KOCHEN JOSEPH A.
Published: October 2019

The deleterious effects on erythrocytes of low steady-state concentrations of H2O2 in vitro have been compared in samples from full-term and premature infants and adults. Methemoglobin and Heinz bodies were formed to a greater degree in the intact erythrocytes of the young subjects. In the absence of protective enzymes, however, the extent of oxidation was similar in hemoglobin prepared from cord blood and from adult blood, respectively.

Activity of the enzymes involved in the detoxification of H2O2 has been measured in the red blood cells of the aforementioned groups of subjects. Of note was the finding of significantly decreased activity of glutathione peroxidase in the full-term newborn and premature infants.

These findings of increased toxicity from H2O2 and decreased efficiency of the detoxification mechanisms are considered to have bearing on the susceptibility of young subjects to drug-induced hemolytic anemia.
Fine Structural Demonstration of Acid Phosphatase Activity in Auer Bodies
Authors: WHITE JAMES G.
Published: October 2019

The peripheral leukocytes of three patients with acute myelogenous leukemia have been studied by combined electron microscopy and ultrastructural cytochemistry. Auer bodies present in immature granulocytes were found to contain specific evidence of acid phosphatase activity, indicating that Auer rods are lysosomes. A number of observations were made which support the origin of Auer rod lysosomes from azurophilic granules which are known to be lysosomes. The nature of the stimulus causing transformation or fusion of azure granules to form Auer bodies, however, remains obscure.
Leukocytosis, Bone Marrow Hyperplasia and Leukemia in Chronic Magnesium Deficiency in the Rat
Authors: MCCREARY PATRICIA A. , BATTIFORA HECTOR A. , HAHNEMAN BETTY M. , LAING GRANT H. , HASS GEORGE M. , Singh Katherine
Published: October 2019

Hematologic studies, including bone marrow examinations, have been done on a series of rats which were on a magnesium-deficient diet, with or without 2-AAF supplementation. Leukocytosis and granulocytosis could be maintained in these deficient rats by decreasing their intake of magnesium and could be reversed by the addition of magnesium. The bone marrows of the magnesium-deficient group showed granulocytic hyperplasia; the bone marrows of the deficient 2-AAF supplemented rats showed erythrocytic hyperplasia, as well as granulocytic hyperplasia. Chronic granulocytic leukemia developed in two magnesium deficient rats and persisted after magnesium supplements were given. This leukemia has been successfully transplanted into newborn rats.
Brief Report: A Plasma Factor in Chronic Lymphocytic Leukemia which Stimulates DNA Synthesis and Blastogenesis in Leukocyte Cultures
Authors: KASAKURA SHINPEI , LOWENSTEIN LOUIS
Published: October 2019

Plasmas from each of three patients with CLL and from one patient with plasma cell leukemia were added to normal leukocyte cultures and were found to stimulate DNA synthesis and blastogenesis. The stimulatory material present in plasma from one of the CLL patients was nondialyzable and could be passed through a Millipore filter of 0.22 microns pore size. It retained all or most of its activity after exposure to 60 C. for 1 hour, repeated freezing and thawing, and treatment with RNAse and DNAse.
Studies on Erythropoietic Action of Angiotensin II
Authors: NAKAO KIKU , SHIRAKURA TAKUO , AZUMA MASAMI , MAEKAWA TADASHI
Published: October 2019

The effects of synthetic Angiotensin II on erythropoiesis were investigated.

1. Two daily intravenous injections of Angiotensin II, 100 µg./Kg. of body weight, revealed no acceleration of Fe59 incorporation into erythrocytes of either normal rabbits or hypophysectomized rats.

2. When given by intravenous drip, 100 µg./Kg. of Angiotensin II significantly accelerated the radioiron incorporation.

3. The renal blood flow was markedly reduced throughout the period of the dropwise injection; the same effect was transitory after single intravenous injection. The elevation of plasma erythropoietin activity was observed in hypertransfused polycythemic rabbits following the dropwise injection of Angiotensin II.

From these results, it is concluded that erythropoietic activity of Angiotensin II results from an increased erythropoietin production. The increased production may have been induced by a renal ischemia through administration of Angiotensin II.
THE SCHOENLEIN-HENOCH SYNDROME OF VASCULAR PURPURA
Authors: DAVIS ELI
Published: October 2019

The Schoenlein-Henoch syndrome is described on the basis of 44 personally observed cases. It is defined as a condition in which nontraumatic hemorrhage with or without edema may occur in the skin, or subcutaneous tissue, or joints, or viscera, or in any combination of them, and in which the blood platelets are normally abundant. The causes of the syndrome are varied, but streptococcal infection is important, and "anaphylactoid" causes rare. The prognosis is good, and the 4 cases with renal involvement also did well. Schoenlein-Henoch purpura and purpura simplex overlap, but in contrast with the latter, Schoenlein-Henoch purpura is not familial, and is common in males and children.
A MODIFICATION OF THE WAUGH-RUDDICK TEST FOR INCREASED COAGULABILITY OF THE BLOOD, AND ITS APPLICATION TO THE STUDY OF POSTOPERATIVE CASES
Authors: SILVERMAN SEYMOUR B.
Published: October 2019

1. A modification of the Waugh-Ruddick test for increased coagulability of the blood is described, which employs the use of recalcifled plasma in the place of whole blood.

2. Using this modification, studies were carried out on a series of patients undergoing operation. It was found that there was an increased coagulability of the blood present within 24 hours following operation, and that this condition lasted for a week or so. In all cases, the coagulability had returned to normal by the end of two weeks.

3. It is felt that the change is due to an increase in the circulating thromboplastin, presumably derived from damaged tissue in the operative area.
PRIMARY NONFAMILIAL HEMOLYTIC ANEMIA
Authors: STICKNEY J. M. , HECK FRANK J.
Published: October 2019

In our experience, in half of the cases of primary hemolytic anemia in which there is no family history of anemia, jaundice or splenomegaly, examination of the blood disclosed microspherocytic erythrocytes and increased fragility of erythrocytes. The results of splenectomy in these cases are better than in those in which microspherocytosis is absent. True macrocytosis was observed in only one instance. Females predominated in both groups of cases. Agglutinins and hemolysins have not appeared to play any significant role in the production of the hemolytic syndrome in our cases. We do not feel justified in expressing an opinion as to whether the microspherocytosis indicates a familial or congenital blood disorder. From a practical standpoint, it makes no great difference since splenectomy should be considered seriously in any case of chronic primary hemolytic anemia. It may be of value in some cases of secondary or symptomatic hemolytic anemia.
THE GENETIC RELATION AND CLINICAL DIFFERENTIATION OF COOLEY’S ANEMIA AND COOLEY’S TRAIT
Authors: DALAND GENEVA A. , STRAUSS MAURICE B.
Published: October 2019

1. Four additional families illustrating the clinical and genetic relationships of Cooley’s anemia and Cooley’s trait have been presented.

2. Blood findings in an offspring of a patient with Cooley’s anemia are recorded.

3. The asymptomatic nature of Cooley’s trait and its differentiation from Cooley’s anemia has been emphasized.

4. The inheritance of Cooley’s trait and Cooley’s anemia may be best explained in terms of an incomplete dominant or of the simultaneous appearance of two nonallelomorphic genes.
A Study of Thrombocytopenia
Authors: BRECKENRIDGE ROBERT T. , MOORE RICHARD D. , RATNOFF OSCAR D.
Published: October 2019

Sixty-nine cases of thrombocytopenia in which splenectomy had been performed have been reviewed. New cytological criteria are described for the diagnosis of disseminated lupus erythematosus by the examination of the splenic tissue.

Six cases of thrombocytopenia associated with the ingestion of drugs and eight with infectious diseases responded promptly and permanently to splenectomy. The thrombocytopenia associated with disseminated lupus erythematosus (in 16 cases) and idiopathic thrombocytopenic purpura (in 39 cases) had a much more variable response. Approximately three-fifths of patients in each group had a remission sustained for at least 12 months following splenectomy. In general those patients who had thrombocytopenia for more than one year before surgery were less likely to respond to splenectomy.
Tissue Distribution of Radio-B12 after Intravenous Injection of Gastric Juice, Saliva and Plasma-Bound Co57 B12
Authors: ROSENTHAL WILLIAM S. , WEISBERG HERBERT , GLASS GEORGE B. JERZY
Published: October 2019

Hepatic uptake of unbound radio-B12 and radio-B12 bound to various B12 binders was studied in 48 rats using a method of in situ liver perfusion of homologous whole blood without recirculation. Compared with unbound radio-B12, radio-B12 bound to pernicious anemia gastric juice, human saliva, hog intrinsic factor concentrate, and boiled hog intrinsic factor concentrate increased uptake of B12 by rat liver. B12 bound to normal human gastric juice, however, was removed in a manner quantitatively similar to that observed with unbound B12.

Depression of reticuloendothelial system activity by india ink injection prior to perfusion of hog intrinsic factor concentrate-bound B12 did not significantly alter hepatic B12 removal rates. Comparison with results obtained in similar experiments, but without prior reticuloendothelial system depression, suggests that the removal process was accomplished by hepatic parenchymal cells rather than reticuloendothelial cells of the liver.

These results suggest that B12 binders of hog intrinsic factor concentrate, pernicious anemia gastric juice, and saliva may function in the membrane transport of B12 in the liver in a manner both quantitatively and qualitatively different from those of serum. This transport function is obviously not limited to intrinsic factor, since materials with and without intrinsic factor activity can produce this effect.
Activation of Glycogen Phosphorylase in Blood Platelets
Authors: SCOTT ROBERT B. , Cooper LaVerne W.
Published: October 2019

1. In platelets incubated in vitro, glycogen phosphorylase was activated, and the degree of activation roughly corresponds to the degree of manipulation of the platelets and is greatest in the least physiologic incubation medium.

2. Activation proceeds with an increasing proportion of enzyme which is active in the absence of AMP, suggesting the action of the phosphorylase-activating enzyme, phosphorylase kinase, in platelets.

3. Total enzyme activity (activity with AMP) likewise increases and continues to increase while the AMP-independent fraction begins to decrease again, suggesting more than one activating mechanism.

4. During glycogen breakdown, and during coagulation and clot retraction induced by thrombin, glycogen synthesis was shown to continue in vitro. Clot retraction was found to be more dependent on adequate glycogen stores than was coagulation.
Brief Report: Correction of the Hemostatic Defects in Von Willebrand’s Disease
Authors: PERKINS HERBERT A.
Published: October 2019

The Pool cryoprecipitate provides an effective source of the factor lacking in the plasma of patients with von Willebrand’s disease which is necessary for a normal bleeding time. Correction of the bleeding time appears to be necessary for control of bleeding in some instances of severe spontaneous hemorrhage. None of the commercially prepared antihemophilic factor concentrates prepared in this country contain adequate amounts of the extremely labile bleeding time factor.
Mechanism of the Anemia of Pyridoxine Deficiency in the Rat
Authors: SHEN SHU CHU , KO RU LIN
Published: October 2019

Rats were fed a diet deficient in pyridoxine until they developed a microcytic, hypochromic, pyridoxine-responsive anemia. Studies of red cell survival time demonstrated that there was a hemolytic factor involved in this anemia; and the more severe the anemia, the more rapid the destruction of red cells. It also demonstrated that the defect was intracorpuscular. Blood regeneration studies confirmed findings by others that erythropoiesis was impaired in pyridoxine deficiency, particularly when the accompanying anemia was severe. These studies indicate that a dual mechanism may be operating in these anemic rats.
Induction of Autoimmune Hemolytic Disease by Diffusible Substances from the Thymus of NZB/Bl Mice
Authors: MASTERS JASON M. , SPURLING CARROLL L.
Published: October 2019

Mice of four strains were thymectomized neonatally and implanted with Millipore diffusion chambers containing thymic tissue from newborn mice of the NZB/Bl strain. Of a total of 60 surviving animals, 50 developed a positive Coombs’ test and other evidences of autoimmune hemolytic disease. Controls remained negative.

Various possibilities concerning the nature of the membrane-passing factor or agent are considered.
Biochemical Lesion in Dilantin-Induced Erythroid Aplasia
Authors: YUNIS A. A. , ARIMURA G. K. , LUTCHER C. L. , BLASQUEZ J. , HALLORAN M.
Published: October 2019

Clinical and biochemical studies are reported in a patient who developed pure red cell aplasia after 2 years therapy with Dilantin but in whom aplasia could subsequently be induced with 4-5 Gm. of the drug. Recovery occurred regularly when the drug was discontinued.

The administration of 1500 ml. of patient’s plasma obtained during the aplastic phase to a normal volunteer with Dilantin had no effect on the recipient’s reticulocyte count, number of nucleated red cells in his bone marrow, or Fe59 clearance. Attempts to demonstrate binding of gamma globulin to the patient’s nucleated red cells in the presence of Dilantin by immunofluorescence technic were unsuccessful.

Dilantin, in a concentration of 20 µg./ml. in vitro, caused significant inhibition of the uptake of C14 formate, glycine, adenine, orotic acid, and uridine into DNA but not into RNA of patient’s bone marrow studied when fully recovered. There was no effect on the uptake of deoxyuridine or thymidine.

The Dilantin effect was specific to the erythroid cells as shown by radioautographic studies and by the absence of inhibition when these cells were absent from the bone marrow.

Vitamin B12 and folinic aci dgiven to the patient in large doses did not reverse the hematologic effects of Dilantin. The daily intravenous administration of all four deoxyribonucleosides, deoxyadenosine, deoxyguanosine, deoxycytidine and thymidine had a suggestive, but not clear-cut, effect.

In an effort to examine a possible relationship of the pure red cell aplasia in this patient to riboflavin metabolism, the patient was started simultaneously on Dilantin and riboflavin. Dilantin was now without effect. However, the patient remains refractory to Dilantin a year after riboflavin was discontinued.

It is concluded that Dilantin exerted its toxic effect in this patient by specifically inhibiting DNA synthesis in erythroid cells probably at the step of deoxyribotide formation.

The role of riboflavin in the development of resistance to the toxic effect of Dilantin in this patient remains uncertain.
BRIEF REPORT: Defective Synthesis of IgM Antibodies in Macroglobulinemia
Authors: PITTS NEAL C. , MCDUFFIE FREDERIC C.
Published: October 2019

Four patients with macroglobulinemia demonstrated an impaired ability to produce IgM antibody when stimulated with a relatively weak antigen, sheep cell stroma, but not with a more potent antigen, Brucellin. The explanation of this defect is unknown. It may be in part the cause of the greater-than-normal infection rate seen in patients with macroglobulinemia.
Mechanisms of Isoimmunization
Authors: COHEN FLOSSIE , ZUELZER WOLF W. , Evans Margaret M. , Schmiedl Ruth E.
Published: October 2019

1. Fetal cells were demonstrated postpartum in approximately 20 per cent of Rh positive mothers with ABO incompatible infants and in only approximately 5 per cent of Rh negative mothers with both ABO and Rh incompatible infants in the absence of sensitization or presensitization.

2. When the prenatal findings were combined with those postpartum, the incidence was considerably greater in both groups (52 per cent and 32 per cent, respectively).

3. Two cases of massive transplacental hemorrhage in heterospecific pregnancies are reported with almost a normal survival of a few cells postpartum.

4. Observations on protective mechanisms bearing on isoimmunization in heterospecific pregnancies are made.