bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Maternal Isoagglutinins in ABO Hemolytic Disease of the Newborn
Authors: FONG SUSIE W. , NUCKTON ARLENE , FUDENBERG H. H.
Published: October 2019

Sera of group O mothers of infants with and without ABO hemolytic disease of the newborn were fractionated by diethylaminoethyl-cellulose chromatography and density gradient ultracentrifugation. Whole sera and serum fractions were evaluated for activity by various test systems currently used for the antenatal prediction of ABO hemolytic disease of the newborn. The results of these studies did not show any single serologic property that would unequivocally diflerentiate between the isoantibodies of mothers of affected infants and mothers of normal infants of incompatible blood group.
The Ultrastructural Localization and Release of Platelet Lipids
Authors: WHITE JAMES G. , KRIVIT WILLIAM
Published: October 2019

Investigation of the ultrastructure of platelets of carefully prepared, native platelet rich plasma fixed in gluteraldehyde-osmium has revealed a process not apparent by other technics. Platelet granules undergo transformation into lameller particles with the configuration of lipid micelles. The platelet micelles are released through the platelet cell membrane prior to aggregation. Comparison of the platelet micelles with micelles formed by aqueous dispersion of extracted platelet lipids and brain cephalin revealed similarities of particle size and miceller configuration. The origin of platelet micelles from platelet granules, their release from the cell in early clot development, and their similarity to other lipids active in coagulation are provocative. Platelet micelles may be the active lipid substance contributed by platelets to coagulation, and the lipoprotein complexes of platelet granules the "hidden form" of the platelet lipid in normal circulating cells.
"Intermediate" Cell Types and Mixed Cell Proliferation in Multiple Myeloma: Electron Microscopic Observations
Authors: MALDONADO JORGE E. , KYLE ROBERT A. , BROWN ARNOLD L. , BAYRD EDWIN D.
Published: October 2019

Bone marrow studies of multiple myeloma revealed, in some cases, a conspicuous proliferation of "lymphoid" cells, virtually indistinguishable by light microscopy from those seen in lympho-proliferative disorders.

Electron microscopy demonstrated a variety of cells ranging from typical lymphocytes to cells with plasmocytoid features. Between these two types of elements there were cells with intermediate characteristics.

In addition, in several cases of myeloma the presence of fixed reticuloendothelial cells and "reticular" plasma cells (or reticulum cells with plasmocytic features) was frequently noted.

The presence of reticulum cells and lymphocytes and of cells apparently "intermediate" between these cellular elements and plasma cells, as judged from electron microscopic observations, is suggestive morphologic evidence of a phenomenon of cell transformation and evidence of a mixed cell proliferation in certain cases of multiple myeloma.
Hydroxocobalamin
Authors: GLASS GEORGE B. JERZY , LEE DUK HO
Published: October 2019

The mean hepatic biological half-life of Co57-hydroxocobalamin injected to 5 normal human subjects was similar to that of Co60-cyanocobalamin, as shown by double-label hepatic surface counting during the first 30 weeks after intramuscular or intravenous injection of cobalamins. In 2 cases in whom the counting was extended over a year’s period, the clearance of hepatic radioactivity following the intramuscular injection of hydroxocobalamin has slowed down as compared to that of cyanocobalamin, between the 30th and 52nd week after injection.
Hydroxocobalamin
Authors: GLASS GEORGE B. JERZY , SKEGGS HELEN R. , LEE DUK HO
Published: October 2019

Administration of 6 intramuscular injections of 1000 µg. hydroxocobalamin every other day for 10 days enabled 15 individuals with initial vitamin B12 serum levels of 81 to 242 (mean 185 ± 44 µµg./ ml.) to maintain vitamin B12 concentration of the blood 6 months later at levels exceeding 3 times the pretreatment values. In 12 of these individuals who were studied for at least a 10-month period, vitamin B12 concentration in the serum 10 months after conclusion of injections was still double the initial pretreatment levels. This difference was highly significant statistically (p = 0.001). Of 11 patients followed for 15 months after conclusion of injections, in 7 the serum levels were still higher than before treatment.

No comparable results were ever reported with cyanocobalamin therapy.
Urticaria Pigmentosa Complicated by Polycythemia Vera
Authors: DIAMOND JOSEPH H. , GROSS LUDWIG
Published: October 2019

The coexistence of polycythemia vera with urticaria pigmentosa in a 62-year-old man is reported apparently for the second time. Review of literature indicates that mast cell disorder, manifested initially only in skin changes, may involve many systems. The possible mechanism responsible for the occurrence of the two disorders in the same individual is discussed. Administration of radioactive phosphorus had no effect on the mast cell infiltration of the skin, but resulted in a temporary suppression of erythropoiesis.
Studies on the Biochemical Alterations of the Protein Synthesizing Apparatus in Maturing Rabbit Reticulocytes
Authors: WILNER-ZEHAVI TOVA , IZAK G. , MAGER J.
Published: October 2019

The study of maturation of rabbit reticulocytes in vivo revealed an essential correlation between the degree of reticulocytosis, the RNA content of the circulating red blood cells and their ability to carry out amino acid incorporation into protein. The nevertheless frequent occurrence of considerable quantitative discrepancies between these parameters during the progress of maturation appears to be attributable to fluctuations in the reticulocyte population due to intrinsic difference in the life span of these cells and to release of young reticulocytes from the hyperplastic bone marrow into the circulation. The distortions in the pattern of maturation kinetics by the continued contribution of the bone marrow seem to be largely eliminated by blocking erythropoiesis at the height of reticulocytosis with the aid of actinomycin D treatment.
Bacterial Endotoxin: Effects on Erythropoiesis
Authors: FRUHMAN GEORGE J.
Published: October 2019

Mice injected with a single, large dose of a bacterial endotoxin displayed a significant shift in erythropoiesis from the bone marrow to the spleen. Splenic granulocytopoiesis also occurred. This finding may have some bearing on the observation that endotoxin pretreated mice make a better recovery following x-irradiation than do their controls.
The Increased Effectiveness of Platelet Concentrates Prepared in Acidified Plasma
Authors: FLATOW FREDERICK A. , FREIREICH EMIL J.
Published: October 2019

Platelet concentrates prepared in acidified plasma (pH 6.5-6.7) are superior to concentrates prepared by standard methods, and are 80-90 per cent as effective as platelet rich plasma (PRP). The use of excess citric acid to acidify plasma promotes resuspension of the concentrate by eliminating clumping, which is a major factor in the decreased effectiveness of standard concentrates. Analysis of posttransfusion recovery and survival of platelets reveals no evidence of platelet injury in an acid medium.

Acidification of PRP inhibits the aggregation of platelets by adenosine diphosphate (ADP). The presence of endogenous ADP may be an important factor in clumping during standard concentrate preparation.

A method of acidification of PRP using citric acid is described which allows preparation of an effective concentrate from fresh whole blood without subjecting the red cells to acid pH. Reconstitution of the acidified platelet poor plasma and its native red cells increases the citrate molarity by less than 6 per cent and results in minimal decrease in pH of the whole blood.
Tissue Culture of Bone Marrow
Authors: REISNER EDWARD H.
Published: October 2019

In cultures of normal human bone marrow in a medium of 20 per cent horse serum and balanced salt solution, estrone stimulated granulopoiesis; testosterone inhibited fibroblast formation markedly and stimulated erythropoiesis; prednisolone inhibited fibroblast formation completely and allowed continued differentiation of all blood elements in smaller numbers.
Measurement of the Amounts of the Individual Vitamin B12 Binding Proteins in Plasma
Authors: HALL CHARLES A. , FINKLER ALEXANDER E.
Published: October 2019

The findings of the present study, when combined with those of previous studies, support the following concept of binding of vitamin B12 by serum or plasma in vitro. There are primary binders of B12 which preferentially take B12 when small amounts are added and combine firmly with it. They include two already identified substances, TC I and TC II, which are of the seromucoid fraction of plasma. At concentrations of added B12 of the order of 1.0 ng./ml. of plasma, these proteins become saturated and secondary binders become important. The latter are relatively unimportant at lower concentrations of B12; they are weak binders of B12; they cannot be saturated by concentrations used to date, and they are not seromucoids.
Brief Report: In Vitro Effect of Erythropoietin on the Spleen of the Polycythemic Mouse. I
Authors: NAKAO KIKU , MIURA YASUSADA , TAKAKU FUMIMARO
Published: October 2019

1. Spleen explants of transfustion-induced polycythemic mice were incubated in vitro with and without erythropoietin.

2. After 24 hours incubation with the erythropoietin, immature large erythroblasts appeared, whereas the mature small erythroblasts were first observed after 48 hours incubation.

3. Marked radioiron incorporation into the heme was observed after 48 hours incubation with erythropoietin.

4. The control incubations without erythropoietin did not show these findings.

5. These data strongly suggest that erythropoietin induced the differentiation of erythroblasts from stem cells in vitro.
Chromosome Studies in Preleukemia
Authors: ROWLEY JANET D. , BLAISDELL RICHARD K. , JACOBSON LEON O. , Mikuta Judith , Byrne Rachel , Shepley Lona
Published: October 2019

Three patients with different obscure hematologic disorders are presented. All 3 patients had abnormalities of chromosome number confined to marrow cells. Case 1 is a 23-year-old man with aplastic anemia; most of his bone marrow cells contained 45 chromosomes, with one missing from group C. Case 2 is a 62-year-old man who died of idiopathic sideroachrestic anemia; most of his bone marrow cells contained 47 chromosomes with an extra C group chromosome which appeared to be an autosome. Case 3 is a 59-year-old woman with idiopathic thrombocythemia; while the majority of her bone marrow cells contained 46 chromosomes, a stable minority cell line had 48 chromosomes.

Although many of the reported patients with myelodysplastic-myeloproliferative disorders have normal chromosomes, 5 cases with some chromosomal aberration, previously reported by others, are summarized. None of these patients had clinical evidence of leukemia. In 4 of the patients, the chromosomal anomaly involved a chromosome in group C, which is the group in which aneuploidy occurred in all 3 of our patients.

It is postulated that a stable, aneuploid stem line does not of itself produce neoplasia, but rather that this alteration of the genome may provide a more favorable milieu for the action of some transforming agent. Because of the frequent occurrence of C group abnormalities in these cases of marrow disorders, it is further postulated that genes on one or more C chromosomes might be responsible for homeostatic control of hemopoiesis, and that a change in genetic balance involving a C group chromosome(s) coupled with a transforming agent might result in leukemia in a greater proportion of individuals than aneuploidy of some other chromosomal group.
Cytogenetic Observations in Vitamin B12 and Folate Deficiency
Authors: HEATH CLARK W. , Fliegelman Lila
Published: October 2019

Direct marrow cytogenetic preparations were examined in 14 cases of anemia associated with deficiency in vitamin B12 and/or folate. Seven cases showed distinct alterations in chromosome structure consisting of increased chromosome breakage, incomplete chromosome contraction and centromere spreading. These abnormalities were not present after vitamin replacement and were generally less distinct in cases with major medical complications or with only mild megaloblastic changes. No distinct aberrations in chromosome number or karyotype were found. The cytogenetic changes observed seem compatible with current concepts of megaloblastic cell division and with the role of folate and vitamin B12 in DNA metabolism.
The Action of Cytostatic Agents on the Chromosomes of Human Leukocytes in Vitro (Preliminary Communication)
Authors: HAMPEL KLAUS ERICH , KOBER BERNARD , RÖSCH DIETER , GERHARTZ HEINRICH , MEINIG KARL-HEINZ
Published: October 2019

Quantitative analysis of the chromosomal injuries following in vitro addition of various cytostatic agents to short-term human leukocyte cultures was carried out. The data obtained suggest that the cytogenic action of these various compounds in vitro follows a pattern similar to its action when administered therapeutically to man. The technics used may form the basis of further evaluation of the cytogenetic activity of these various compounds.
Hypothesis: On the Role of the Reticulum and Lymphoid Tissues in Water and Food Transport
Authors: SHIELDS JACK W.
Published: October 2019

The observations of many individuals are correlated to indicate that the myeloid and lymphoid derivatives of mesenchyme carry on important complementary roles in tissue nutrition. Whereas the myeloid tissues specialize to the internal transport of oxygen by producing erythrocyte hemoglobin, it is suggested that the lymphoid tissues and, to some extent, the reticulum become specialized to the transport of water and food by producing plasma containing a variety of low and high molecular weight proteins, and by producing lymphocytes which may carry nucleoproteins to the tissues. Fundamentally, the lymphoid tissues (and the reticulum elsewhere) appear to subserve this nutritive function by utilizing molecular substrate from multiple sources—including the arteries, the branchial pouch entoderm (in the embryo), the gastrointestinal mucosa (in the adult), and the peripheral lymphatics—to produce a variety of mononuclear cells which "give of themselves" by undergoing dissolution, by shedding soluble cytoplasmic droplets, or by migrating to other tissues and dissolving there. It is stressed that dissolution of the reticulum, the mononuclear cells, and the cytoplasmic droplets (essentially gels) will yield sols (plasmas) whose water makes possible the intravascular migration and flow of proteins and other nutritive elements, and whose proteins (colloids) osmotically enable the intravascular retention of water. While it is assumed that the parenchymal cells of the liver are the source of most of the plasma proteins, circumstantial evidence is presented to suggest that this assumption is incorrect, and that derivatives of mesenchyme are the direct source of the blood, its cells, its plasma, its water, and its diverse extracellular as well as intracellular proteins.
Effect of Thymus Enclosed in Millipore Diffusion Envelopes on Thymectomized Hamsters
Authors: WONG F. M. , TAUB R. N. , SHERMAN J. D. , DAMESHEK W.
Published: October 2019

Neonatally thymectomized hamsters implanted with diffusion envelopes containing thymus showed partial prevention of the effects of thymectomy. A normal humoral antibody response was maintained in these animals, although a significant lymphocytopenia remained. This suggests that the thymus participates in immunogenesis by a humoral mechanism and possibly by a cellular mechanism as well, which was blocked by the diffusion envelope. Thymectomized hamsters implanted with diffusion envelopes containing adult spleen, bone marrow or kidney were still impaired in their ability to produce humoral antibody, although these tissues appeared to enhance antibody production. The thymus humoral factor appeared to be specific to the thymus. Reimplanted diffusion envelopes, containing large thymic cells resembling epithelial-reticular cells, were used to show that these cells produced the thymus humoral factor.
Absence of Cis Delta Chain Synthesis in (δ β) Thalassemia (F-thalassemia)
Authors: COMINGS DAVID E. , MOTULSKY ARNO G.
Published: October 2019

(δ β) thalassemia or F-thalassemia is characterized by a thalassemic blood picture, elevated hemoglobin F, and normal hemoglobin A2.

A family with (δ β) thalassemia is reported in which the propositus was a mixed heterozygote for (δ β) thalassemia and hemoglobin B2. There was complete absence of hemoglobin A2, indicating that this (δ β) thalassemia mutation completely suppressed the cis delta gene. The remaining normal delta gene was capable of increasing delta chain synthesis sufficiently to bring the hemoglobin A2 to within normal range. These findings account for the absence of elevated hemoglobin A2 in this form of thalassemia and demonstrate that (δ β) thalassemia is an entity genetically distinct from A2 thalassemia. The possible genetic mechanisms of (δ β) thalassemia are discussed.
Respiration and Glycolysis of Normal Human Lymphocytes
Authors: HEDESKOV CARL J. , ESMANN VIGGO
Published: October 2019

The metabolism of intact, normal, human lymphocytes in vitro was studied from a total of 80 subjects. Corrected for the metabolism of contaminating red blood cells, the glucose uptake, lactic acid production, and oxygen consumption were 62, 95, and 117 µmoles per 1010 lymphocytes per hour, respectively, provided the cells were incubated at concentrations greater than 40 x 106 lymphocytes per ml. At lower lymphocyte concentrations the oxygen consumption per lymphocyte rose steeply with decreasing cell concentration (crowding effect). A similar but weaker crowding effect was noted for the lactic acid production, but not for the utilization of glucose.

The oxygen uptake was lower with 20 per cent than with 100 per cent oxygen as gas phase. Small Pasteur and Crabtree effects were demonstrated. The oxygen consumption and lactic acid production proceeded linear with time, while the glucose utilization was higher during the first 30 minutes of incubation than later on.

It is concluded that lymphocytes have a low aerobic glycolysis accounting for 75 per cent of the glucose utilization. The respiration is severely inhibited at high cell concentrations and it is suggested that this is caused by an insufficient availability of oxygen to the cells.
Selective Eradication of Erythropoiesis by Actinomycin D as the Result of Interference with Hormonally Controlled Effector Pathway of Cell Differentiation
Authors: REISSMANN KURT R. , ITO KENJIRO
Published: October 2019

Daily injections of 60 µg. actinomycin D per Kg. mouse caused cessation of erythropoiesis due to complete disappearance of erythroid marrow elements, and the mice were absolutely refractory to erythropoietin. No decrease in myelo-, lympho-, or megakaryocytopoiesis was found during more than 3 weeks of daily administration of the drug. Observations on the effect of the drug on a cohort of erythroid cells, induced by erythropoietin in polycythemic mice, gave no evidence of its destructive or inhibitory action on early or late normoblasts. A critical reduction in the number of integer stem cells was likewise ruled out as the cause of eradication of erythropoiesis. The latter is attributed to a specific interference of actinomycin D in the effector pathway of erythropoietin controlled transformation (differentiation) of stem cells into early pronormoblasts. The findings indicate this process to be contingent on formation of new types of mRNA rather than on activation of templates already present in erythropoietin-sensitive stem cells.
Urinary Excretion of Erythropoietin in Normal Men and Women
Authors: ALEXANIAN RAYMOND , Prewitt Brenda
Published: October 2019

The bioassay of erythropoietin in polycythemic mice was modified to include a protein-depletion diet and a divided erythropoietin injection schedule. Although less than 0.05 unit of standard erythropoietin was not detected, a more linear dose/response relationship resulted from increasing doses of erythropoietin in the 0.1 to 1.0 unit range. The amount of erythropoietin in concentrated specimens prepared from the 24-hour urinary excretion of 25 normal subjects was measured in comparison with known quantities of standard erythropoietin. A mean daily erythropoietin excretion in men of 2.8 ± 1.3 units, in women of 0.9 ± 0.4 unit and in prepubertal boys of 1.0 unit was calculated. The higher erythropoietin excretion in adult males may be secondary to a greater production of erythropoietin in this sex.
Erythropoietin Excretion in Normal Man
Authors: ADAMSON J. W. , ALEXANIAN R. , MARTINEZ C. , FINCH C. A.
Published: October 2019

Levels of erythropoietin have been consistently demonstrated in urine collections from healthy adult males using a modification of the polycythemic mouse assay. This method is stable and reproducible, and it provides assay animals with low background erythropoiesis. Six hour collections of urine can be concentrated without apparent loss of activity and the entire daily excretion can be used in the assay. Quantitation has been achieved by comparing the response to a concentrate of normal urine directly to a linear dose/response curve of erythropoietin standard B. Based on 6 hour urine collections, erythropoietin excretion in the subjects tested averaged 4.0 units of erythropoietin standard B (range 1.2-9.5). In addition to wide unexplained variations in results seen from day to day, the data indicate that a diurnal pattern of excretion of the hormone may exist.
Serum Anti-γG Globulin Factors in Paroxysmal Nocturnal Hemoglobinuria
Authors: KAPLAN MANUEL E. , KOCHWA SHAUL , WASSERMAN LOUIS B. , ROSENFIELD RICHARD E.
Published: October 2019

Sera from 16 of the 25 patients with PNH were found to exhibit anti-γC globulin activity as demonstrated by their ability to agglutinate human red cells sensitized with certain incomplete Rh antibodies. Of the 16 active sera, 9 agglutinated human FII-coated tanned sheep cells and 5 FII-coated latex particles in significant titer. Only one serum exhibited anti—Gm specificity. In 3 cases serum anti-γG globulin activity was found prior to transfusion of the patient, suggesting that isoimmunization is not in all cases responsible for this phenomenon. The chromatographic behavior of the serologically active substances and their inactivation by treatment with 2 ME suggest that they are γM globulins related to the rheumatoid factors. The possible role of these antiglobulin factors in the lysis of the PNH erythrocyte is discussed.
The Intravascular Lifespan of Monocytes
Authors: WHITELAW D. M. , Bell Maureen
Published: October 2019

Monocytes, defined as peroxidase positive mononuclear cells in the peripheral blood of healthy rats, were labeled by frequent intermittent injections of tritiated thymidine. About 25 per cent of the monocytes were labeled within 1 day and 82 per cent in 8 days. Both labeled and unlabeled monocytes disappeared from the circulation in accordance with an exponential function with a half-time of about 3 days. Mean grain counts increased asymptotically toward a limit reached in 4 or 5 days. The monocyte turnover rate in the rat is in the neighbourhood of 3.6 x 106 cells per day.

It is concluded that monocytes leave the circulation at random and not as a consequence of senescence. It is probable that they are the product of a cell lineage consisting of about 3 generations from the primitive precursor to the mature form, and that the average generation time is about 24 hours. Because of the rapid appearance of large numbers of labeled cells, it is unlikely that they are derived from lymphocytes which acquire label much more slowly.
Impairment of Red Cell Viability by Exposure to "Excess" Acid—Citrate Dextrose
Authors: MAYER KLAUS , LEY ALLYN B. , D’AMARO JOSEPH
Published: October 2019

Collection of blood in "excess" ACD leads to a loss of red cell viability when the blood is transfused back into the donor, even without any appreciable storage period. The mechanism of this loss of viability is not clear. The loss is accentuated by incubation at 37 C.; it is not affected by varying the dextrose concentration of the ACD; it cannot entirely be attributed to change in pH of the final suspension medium; and it is not related to the degree of swelling of the red cells. The loss of viability can completely be corrected by the addition of small amounts of chloride to the ACD.

This effect is presumably the same as the "lesion of collection" described by Gibson et al. in relation to viability studies after 28 days of storage.4
Brief Note Lymphocyte RNA Synthesis in Infectious Mononucleosis: The Response to Phytohemagglutinin in Vitro
Authors: RUBIN ARNOLD D.
Published: October 2019

Circulating lymphocytes were isolated from normal individuals and from patients with IM. IM lymphocytes synthesized RNA at 10 times the rate of normal lymphocytes. A 1-hour exposure to PHA did not result in the stimulation of 4 to 30S RNA synthesis which occurs in a similarly treated normal lymphocyte. RNA synthesis in IM lymphocytes actually appeared to be depressed by this short exposure to PHA.
The Detection of Iso-Antigens on Leukemic Cells Using the Cytotoxicity Test
Authors: PEACOCKE IVAN , AMOS BERNARD , LASZLO JOHN
Published: October 2019

The cytotoxicity test has been shown to give reproducible information concerning specific iso-antigens of human leukemic lymphoxytes. The distribution frequency of these antigens is at least as great in chronic lymphocytic leukemia antigens or of decreased cellular reactivity. The majority of patients were tested repeatedly and in most instances the cytotoxicity test remained constant, regardless of drug therapy and disease status. Cells from five patients having acute granulocytic leukemia were typed in a similar fashion and contained antigens in common with normal lymphocytes.
Allogeneic Marrow Engraftment by Cross Circulation in Lethally Irradiated Dogs
Authors: EPSTEIN R. B. , GRAHAM T. C. , BUCKNER C. D. , BRYANT J. , THOMAS E. D.
Published: October 2019

Dogs given 1200 r of total body irradiation were cross-circulated with dogs having normal marrow function. Irradiated controls died in from 4 to 11 days with marrow aplasia. Dogs cross-circulated daily for 6 to 9 days showed histologic evidence of bone marrow repopulation after 1 week. Male dogs cross-circulated with female partners showed typical female drumsticks on mature granulocytes after repopulation had occurred. Cytogenetic studies of an irradiated male dog cross-circulated with a female partner showed all mitotable cells from the bone marrow and peripheral blood to be of female donor type. Allogeneic bone marrow engraftment was associated with an early and severe secondary syndrome which resulted in the death of the animals in the second week. When methotrexate was given, survival was increased to 3 weeks.

It was concluded that (1) cross circulation provided leukocytes and platelets adequate for support during the period of radiation-induced marrow aplasia, (2) allogeneic marrow engraftment was produced consistently by cells transferred in the peripheral blood of the normal cross circulation partner, (3) the grafts were associated with an early and severe form of secondary disease, and (4) methotrexate given during the early period of engraftment reduced the severity of the secondary disease.
Iron-Deficient Diet: Effects in Rats and Humans
Authors: KAUFMAN RICHARD M. , POLLACK SIMEON , CROSBY WILLIAM H.
Published: October 2019

1. Iron absorption in rats is increased by dietary iron deprivation.

2. Erythropoiesis in the rat is unaffected by dietary iron deprivation that increases iron absorption by more than a factor of four.

3. Iron absorption is not increased in rats bled of an amount of iron equivalent to that lost in 5 days of iron deprivation.

4. These findings are compatible with the concept that iron-absorption is controlled by depletion of iron from a specific pool, separate from the hepatic and erythrocytic iron pools.

5. Iron absorption in human subjects was unaffected by dietary iron deprivation for 13 days. Reasons for differences between human and rat results are discussed.
A Radioautographic Study of Hemopoietic Repopulation Using Irradiated Parabiotic Rats
Authors: TYLER RUTH W. CAFFREY , EVERETT N. B.
Published: October 2019

These radioautographic studies using parabiotic rats and partial marrow shielding showed that cells responsible for recovery of irradiated bone marrow had their origin in the shielded marrow. Three morphologically distinct cell types appeared in the blood of these parabionts, mature granulocytes, small lymphocytes and monocytoid cells. The monocytoid was the major cell type which crossed from the shielded to nonshielded marrow, and the observations suggested that it is this cell which served as a stem cell for both the erythrocytic and granulocytic cell lines.

Labeled erythroblasts and myeloblasts were observed in the recovering marrow, and the labeling intensity of these cells indicated that they were the second or third division products of labeled immigrant cells.

The effect of marrow shielding upon the recovery of lymphopoiesis in spleen, thymus, lymph nodes and bone marrow is also discussed.
Observations on the Presence of Pteroyl Polyglutamates in Human Serum
Authors: BANERJEE D. K. , CHATTERJEA J. B.
Published: October 2019

Treatment of serum with folic acid conjugase obtained from fresh chicken pancreas indicated the presence therein of polyglutamyl derivatives of pteroic acid. The polyglutamyl derivatives appeared to belong to a group higher than the triglutamate.

Two groups of subjects, one with normal level and the other with low level of unconjugated folate, were studied. In the normal group, the level of unconjugated serum folate varied between 3.2 and 18.0 ng./ml., while that of total folate (unconjugated plus conjugated) varied between 14.0 and 47.0 ng./ml. In the other group, the level of unconjugated folate varied from 2.0 to 2.6 ng./ ml., while that of total folate varied from 14.5 to 31.0 ng./ml. No significant difference, either in the individual values or in their means, was noticed in the two groups of subjects.
The Effect of Plethora on Growth and Differentiation of Normal Hemopoietic Colony-Forming Cells Transplanted in Mice of Genotype W/Wv
Authors: TILL J. E. , SIMINOVITCH L. , McCULLOCH E. A.
Published: October 2019

Suppression of erythropoiesis by transfusion of animals of genotype W/Wv was found to prevent the development of macroscopic spleen colonies following injection of normal coisogenic marrow cells. This inhibition of colony-formation was not due to a failure of colony-forming cells to proliferate in the absence of erythropoietic stimulation, since the growth rate of normal colony-forming cells in plethoric animals did not differ significantly from that seen in anemic hosts. It is likely that, in plethoric hosts, insufficient differentiated erythroblasts were produced to permit the development of macroscopically visible spleen colonies. Evidence was obtained that granulocytic differentiation proceeded during the growth of the transplanted colony-forming cells, and that this mode of differentiation was not affected by the suppression of erythropoiesis. These results indicate that both granulocytic differentiation and the process of selfrenewal by which colony-forming cells increase in numbers are controlled independently of the control of erythropoiesis. These experiments provide additional support for the view that colony-forming cells differ from erythropoietin-sensitive cells.
Regulation of Fetal and Adult Hemoglobin Formation in Patients with Sickle Cell Disease Transfused to Normal Hematocrits
Authors: GABUZDA THOMAS G. , GARDNER FRANK H. ,   Anne Council
Published: October 2019

Two patients with sickle cell anemia and one patient with sickle thalassemia were acutely transfused to normal hemoglobin levels. The synthesis of fetal and adult (in this instance, Hb S) hemoglobins was assessed in cohorts of reticulocytes emerging during the period of erythroid suppression which followed. In two patients observations were also made during the period of recovery from the suppression. Hemoglobin synthesis in the reticulocytes was assessed by means of in vitro incorporation of C14-labeled leucine into the separate hemoglobins. The results in all three patients suggested that both fetal and adult hemoglobin synthesis are under similar physiologic control mechanisms during short-term alterations in the state of erythropoiesis; the formation of both was almost completely stopped soon after transfusion, and both were almost simultaneously reactivated as the patients returned to the anemic state.
Brief Report: Protease Content and Fibrinolytic Activity of Human Leukocytes
Authors: ASTRUP TAGE , HENRICHSEN JØRGEN , KWAAN HAU C.
Published: October 2019

The fibrinolytic activity of human leukocytes was studied by the fibrin plate method and by the histochemical fibrin slide method, using plasminogen-rich and plasminogen-free fibrin substrates. Lysis is caused by a protease. Plasminogen activator is absent. The slide method showed the effect of leukocytes to be weak in comparison to that produced by the plasminogen activator in capillary endothelial cells invading fibrin deposits in the body.
Composition and Structure of Cytoplasmic Globules in Leukemic Lymphocytes
Authors: LASZLO JOHN , GERBER HERBERT J. , SOMMER JOACHIM R.
Published: October 2019

Lymphocytes from a patient with lymphocytic leukemia were found to contain cytoplasmic globules. The globules varied in size, the largest appearing identical to Russell bodies. Histochemical staining was used to demonstrate the glycoprotein composition of these bodies. Electron microscopy revealed this material to be within dilated cisternae of rough endoplasmic reticulum. It is proposed that these globules are abnormal accumulations of glycoprotein which represent stages in the evolution of "Russell bodies." The generic description of these cytoplasmic globules would seem to be preferable to the continued use of eponyms.
Studies on the Macroglobulins of Human Serum
Authors: WOLLHEIM FRANK A. , WILLIAMS RALPH C. , POLESKY HERBERT F.
Published: October 2019

Eighteen sera containing cold hemagglutinins were examined. IgM levels were determined before and after absorption of this cold antibody. In 5 sera with M-components (immunologic type M kappa) 33 per cent, 93 per cent, 93 per cent, 95 per cent, and 75 per cent of the total IgM was serologically active—that is, lost after the absorption. In 12 sera with no M-component (polyclonal), 0-24 per cent of the IgM molecules had cold activity. One exception was noted in a serum from a patient with cold agglutinin disease containing no monoclonal M-component, but which lost 66 per cent of its IgM after absorption with stromata. No correlation existed between cold agglutinin titer, total IgM-concentration, or per cent active IgM molecules. The results indicate a general qualitative difference between polyclonal and monoclonal cold hemagglutinins.
A Marrow Chromosomal Abnormality Preceding Clinical Leukemia in Down’s Syndrome
Authors: DEMAYO ALAN P. , KIOSSOGLOU KOSMAS A. , ERLANDSON MARION E. , NOTTERMAN REBECCA F. , GERMAN JAMES
Published: October 2019

During a routine diagnostic cytogenetic study of the marrow of a child with Down’s syndrome, a minor line of cells with a complement of 50 chromosomes was discovered. The predominant cell in marrow and blood had 47 chromosomes with the standard trisomy in Group 21-22. Although anemia and thrombocytopenia were present, other diagnostic criteria of leukemia did not appear until several weeks later. It is proposed that careful cytogenetic studies combined with serial clinical evaluation may disclose important relationships between chromosomal mutation, aneuploid stemlines, and the production and evolution of neoplasms.
Brief Report: Nuclear Bodies of Normal and Pathological Human Lymph Node Cells: An Electron Microscopic Study
Authors: BROOKS ROBERT E. , SIEGEL BENJAMIN V.
Published: October 2019

Nuclear bodies in normal and pathologic human lymph node cells have been examined with the electron microscope and their structure has been illustrated and described. In normal lymph node cells, nuclear bodies are 0.3-0.5 microns in diameter, are slightly less electron dense than the nucleolus, and consist of peripheral fibrillar material with centrally located, dense granules, 200-400 Å in diameter. Morphologically abnormal nuclear bodies have been observed in a case of Hodgkin’s disease. The appearance of these atypical bodies would suggest either contact and fusion of two or more atypical bodies, or possibly the existence of single, large, irregular bodies.
The Regeneration of Reduced Glutathione in Normal and Glucose-6-Phosphate Dehydrogenase Deficient Human Red Blood Cells
Authors: KOSOWER NECHAMA S. , VANDERHOFF GRACE A. , LONDON IRVING M.
Published: October 2019

Reduced glutathione (GSH) was rapidly regenerated in normal human red blood cells treated with the GSH oxidizing agent, methyl phenylazoformate. Erythrocytes of G-6-PD deficient males regenerated little, if any, GSH under the same conditions. The rate of regeneration of GSH in erythrocytes of G-6-PD deficient heterozygote females was similar to that of a mixture of normal red blood cells and erythrocytes of G-6-PD deficient males. It was compatible with the assumption of mosaicism of the erythrocytes in the heterozygote females. The rapid rate at which the normal erythrocyte can regenerate its GSH may render it capable of continuously absorbing free radicals derived from drugs without harmful consequences to the cell.

Study of the rate of regeneration of GSH in erythrocytes treated with methyl phenylazoformate may be useful in the detection of deficiencies of G-6-PD, GSSG reductase, and hexokinase.
Treatment of Hereditary Spherocytosis in Peromyscus by Radiation and Allogeneic Bone Marrow Transplantation
Authors: STEINMULLER DAVID , MOTULSKY ARNO G.
Published: October 2019

An inherited disease of the bone marrow identical in its pathophysiology to human hereditary spherocytosis has been described in the deer mouse, Peromyscus maniculatus. As Peromyscus are not inbred and of distinct individually-specific histocompatibility, they provide an experimental model system for the use of hemopoietic allotransplantation in the treatment of hereditary diseases of the erythron. Ninety adult mice were exposed to otherwise 100 per cent lethal doses of x-rays and then inoculated intravenously with 20 to 60 million nucleated marrow cells. Marrow was transplanted on a one-to-one donor recipient basis in four combinations of phenotypes: normal to normal; spherocytic to normal; spherocytic to spherocytic; and normal to spherocytic. Mortality and pathology were similar in all groups. Thirty per cent of the hosts died as a direct result of the irradiation within 20 days. Another 30 per cent subsequently succumbed to secondary disease presumably of graft-against-host origin, bringing the overall mortality to 60 per cent at the end of 10 weeks. At 3 months, however, the hematologic status of the survivors, nearly without exception, was of donor phenotype: Genetically spherocytic recipients of normal marrow contained normal red cells; conversely, wild type recipients of spherocytic marrow had assumed the mutant phenotype. Evidence of chronic grafthost interaction was obtained. By 7 months, six mice in the spherocytic to normal transplant group had reassumed the host hematologic phenotype, but only one animal in the normal to spherocytic group reverted to the mutant phenotype.
Differential Consumption of Coagulation Factors Resulting from Activation of the Extrinsic (Tissue Thromboplastin) or the Intrinsic (Foreign Surface Contact) Pathways
Authors: NOSSEL H. L.
Published: October 2019

1. The consumption of coagulation Factors IX, X, and XI was studied in normal whole blood clotted with celite (intrinsic activation) or tissue thromboplastin (extrinsic activation).

2. During these studies an assay method for Factor XI was developed which was not influenced by the presence of tissue thromboplastin. The assay method is based on the thromboplastin generation principle.

3. When blood clotted in silicone treated tubes, the serum and plasma concentrations of Factors IX, X, and XI were almost identical, indicating that little consumption or activation of these factors had occurred.

4. In the presence of celite, coagulation Factors IX and XI are consumed, whereas Factor X is consumed only slightly.

5. In the presence of tissue thromboplastin, Factor X is consumed, whereas Factors IX and XI are not consumed.

6. In the presence of both celite and thromboplastin, the thromboplastin decreased the consumption of Factors IX and XI produced by celite.

7. The study of serum coagulation factor levels may provide evidence as to whether the coagulation process had been initiated by the intrinsic (foreign surface contact) or extrinsic (thromboplastin) pathways.
Studies of the Changes in Leukocyte Alkaline Phosphatase Following Pyrogen Stimulation in Chronic Granulocytic Leukemia
Authors: PERILLIE PASQUALE E.
Published: October 2019

Studies of changes in leukocyte alkaline phosphatase (LAP) in a patient with chronic granulocytic leukemia (CGL) following infection and pyrogenic stimulation revealed that increased LAP appeared in circulating mature neutrophilic forms 24 hours later than in similar cells of the marrow, suggesting that the cells containing increased LAP originated in the marrow. It was reasoned that the LAP responsiveness in CGL probably requires the presence of foci of normal myeloid tissue.
The Chediak-Higashi Syndrome: Cytoplasmic Sequestration in Circulating Leukocytes
Authors: WHITE JAMES G.
Published: October 2019

In the course of investigations into the nature of the giant granulation anomaly of leukocytes from patients with the Chediak-Higashi syndrome, an unusual process was observed in white cells from three patients with the disease. Small, normal-sized, lysosomal granules present in abundance in C.H. leukocytes were observed in the concentric arrangements around areas of cytoplasm. Apparent union of the small granules resulted in development of "doughnut-shaped" channels of fused granular material. Serial sections have indicated that the organelles formed in this manner are complete spheres or discs. Cytoplasmic constituents enclosed by the double-walled vacuoles were frequently observed in various stages of destruction. Ultrastructural cytochemical staining for acid phosphatase defined the presence of this lysosomal enzyme in the matrix between the unit membranes of the double-walled vacuoles, and associated with fragments of enclosed cytoplasm undergoing digestion. Sequestration and destruction of areas of C.H. cell cytoplasm within membrane-bound vacuoles is strikingly similar to the process of autophagy reported in other tissues. The possible relationship of the process of cytoplasmic sequestration to the giant lysosomes which characterize the leukocytes of patients with the C.H. syndrome is discussed.
Influence of Immunologic Hyperstimulation on Murine Viral Leukemogenesis
Authors: SIEGEL BENJAMIN V. , MORTON JANE I.
Published: October 2019

Mice inoculated with Rauscher leukemogenic virus, following a series of weekly injections of complete Freund’s adjuvant in combination with virus-unrelated antigens, showed increased survivals and delayed appearances of circulating nucleated erythrocytes characteristic of the leukemia. Virus-neutralizing serum antibody was not observed to be produced as a result of this hyperimmunization. The retardation of leukemogenesis was attributed to a transient diminution of numbers of host target cells available to viral infection as a consequence of their prior commitment along immunologic pathways.
Cytoplasmic Fibrils in Mixed Lymphocyte Cultures
Authors: PARKER JOHN W. , WAKASA HARUKI , LUKES ROBERT J.
Published: October 2019

Bundles of cytoplasmic fibrils are described in activated (increased cytoplasm and organelles) lymphocytes and blasts in human mixed lymphocyte cultures. Similar bundles were not observed in the transformed lymphocytes in PHA cultures. They were encountered in the activated lymphocytes in the control cultures, but with a lower incidence. The fibrils were usually perinuclear, were frequently in contact with the nuclear envelopes and occasionally penetrated through defects in the nuclear membrane into the nucleus. A less frequent and less convincing connection with mitochondria was also observed.

These morphologic observations seem to indicate that the transformed cells observed in mixed lymphocyte and PHA cultures are not identical.
Release of Histamine from Human Basophils
Authors: SAMPSON DIAN , ARCHER G. T.
Published: October 2019

A method is described for obtaining basophil-enriched preparations of white cells from normal donor blood and from the blood of patients with chronic myeloid leukemia. This histamine content of basophils obtained from normal donor blood was found to be equivalent to 2.4 ± 0.6 µg. histamine acid phosphate/106 basophils, and the histamine content of basophils obtained from patients with chronic myeloid leukemia was found to be equivalent to 1.8 ± 1.4 µg. histamine acid phosphate/106 basophils. The difference between the two mean values was significant (0.01 > p > 0.001).

Histamine was found to be present in the granule fraction of basophils and was released from basophils in conditions associated with granule lysis. Human basophils were shown to be capable of active movement and were able to phagocytose sensitized group A red cells. The basophils were less active as phagocytes than neutrophils and eosinophils. Granule lysis occurred independantly of phagocytosis in the A anti-A immune system, in human serum absorbed with zymosan, and following the addition to basophils of eosinophil peroxidase.
The Application of Freeze-Cleaving Technics to Studies on Red Blood Cell Fine Structure
Authors: WEINSTEIN RONALD S. , BULLIVANT STANLEY
Published: October 2019

A simplified freeze-cleave and replication method of tissue preparation for examination in the electron microscope is applied to studies on red blood cell fine structure. With this technic, the cytoplasm of red blood cells appears to have a uniform pattern of packed granularity, with individual particles approximating the dimensions anticipated for replicas of individual hemoglobin molecules. The cell surface is smooth and partially covered with small particles which may represent antigens, enzymes, or some structural proteins. The possibility that particles seen in cells and on cell membranes may represent an artifact is discussed. Pretreatment of cells prior to freezing influences the plane of cleavage through packed cells so that the plane of cleavage can be preferentially directed either through the cytoplasm or along red cell membranes. The freeze-cleave technic may be of particular value in applications where extensive areas of membrane must be surveyed, such as searching for leukemogenic viruses budding through cell membranes.
In Vitro Effect of Erythropoietin on the Spleen of The Polycythemic Mouse
Authors: MIURA YASUSADA , TAKAKU FUMIMARO , NAKAO KIKU
Published: October 2019

1. An in vitro method to observe radiosensitivity of stem cells was developed in the present study. In vivo and in vitro effect of 60Co irradiation on the erythropoietin-induced stem cell differentiation into erythroblasts was observed, using a tissue culture method of polycythemic mouse spleen. Response to erythropoietin was demonstrated by an appearance of heme synthesis and erythroblasts in spleen fragments.

2. A significant correlation between the rate of appearance of erythroblasts and heme synthesis of the spleen fragments was observed.

3. After irradiation, marked impairment of both heme synthesis and production of erythroblasts was observed, yielding D37 values in the vicinity of 70 r in vivo and 120 r in vitro irradiation, respectively.

4. Marked recovery of erythropoietin-induced heme synthesis in the polycythemic mouse spleen was observed 9 days after 300 r irradiation, with an "overshooting" phenomenon on the 12th day.