bluuebunny/crossref_metadata_2025 huggingface dataset:
The G-Immunoglobulins in Acute Leukemia in Children Hematologic and Immunologic Relationships
Authors: KIRAN OZDEN , GROSS SAMUEL
Published: October 2019

Serial IgG determinations were carried out on 29 children with acute leukemia. With the exception of the pretreatment assays, all determinations were performed during the course of specific antileukemic therapy. Following the initial introduction to cytotoxic agents, a significant, although temporary, reduction in IgG level occurred. The continuous use of antileukemic agents did not alter the IgG levels. Relapses, responsive to changes in therapy, were usually associated with moderate reductions in the IgG levels. Greater reductions in IgG levels occurred following the institution of changes in therapy. In both instances the declines were followed by a return in IgG to the normal range. Declines of significantly greater magnitude and rate occurred in those patients no longer capable of responding to therapy changes. In such patients, levels below 3.8 to 3.5 mg./ml. signified impending death, a lack of response to infection and inability to evoke an IgG response. An example of the interrelationships between clinical and immunologic responsiveness is shown by the patient in complete relapse with a normal IgG assay, who went into remission and had an impressive IgG response following a rubeola infection. Shortly thereafter, her disease process entered an irreversible relapse stage with an IgG level of 2.9 mg./ml., and death occurred within 30 days following a bacterial septicemia.

The relationship between hematologic and immunologic responsiveness raises the provocative question of paradoxically maintaining an immunologically responsive state as a means of prolonging the survival time in the face of persistent immunosuppressive therapy.
Paroxysmal Nocturnal Hemoglobinuria Terminating in Acute Granulocytic Leukemia
Authors: KAUFMANN RETO W. , SCHECHTER GERALDINE P. , MCFARLAND WILLIAM
Published: October 2019

A 58 year old male who developed paroxysmal nocturnal hemoglobinuria and acute granulocytic leukemia is described. This rare occurrence is pertinent in view of recent concepts suggesting common etiologic mechanisms for these diseases.
Brief Report: A Note on Hypertonic Saline Hemolysis of Red Cells
Authors: NESER MADELEINE L.
Published: October 2019

Fine dendritic crystals loaded at their ends with hemoglobin were found to be growing at the evaporating edges of an open hanging-drop preparation of blood diluted with normal saline. In another area dendritic crystals were growing direct from red cells. This phenomenon was found to be reproducible, as also the growth of larger crystals made with stronger NaCl solutions. These structures were identified as atypical NaCl crystals. Large as well as fine dendritic crystals were found still to form after removal of the red cell membranes and stroma and after the removal of plasma together with the remnants of hemolyzed red cells. It was concluded that hemoglobin was the sole agent responsible for modifying the form of the NaCl crystals. It was further apparent that NaCl has a strong affinity even for intracellular hemoglobin, and that hypertonic saline hemolysis of red cells can take place without any shrivelling of the cell membrane, occurring at the site of "membrane defects" located on the cell surface.
The Dense Bodies of Human Platelets: Inherent Electron Opacity of the Serotonin Storage Particles
Authors: WHITE JAMES G.
Published: October 2019

Platelets fixed in glutaraldehyde and then in osmic acid or potassium dichromate contain dense bodies which are known to be rich in serotonin. Opacity of the particles is believed to be due to a highly specific reaction between glutaraldehyde, serotonin and osmic acid. The present study has examined dense bodies of platelets in negatively stained whole mount preparations, unstained whole mounts, and glutaraldehyde fixed, plastic embedded cells not exposed to osmium or dichromate. The results demonstrate that dense bodies in platelet hyaloplasm are innately electron opaque. Osmic acid and potassium dichromate may deposit in dense bodies, but the metal containing oxidizing fixatives are not the primary cause of opacity to the electron beam. It is suggested that the inherent electron opacity may be due to a nucleation of heavy metals in the matrix of dense bodies.
The Chediak-Higashi Syndrome: Continuous Suspension Cultures Derived From Peripheral Blood
Authors: BLUME RALPH S. , GLADE PHILIP R. , GRALNICK HARVEY R. , CHESSIN LAWRENCE N. , HAASE ASHLEY T. , WOLFF SHELDON M.
Published: October 2019

Long-term suspension cultures have been established from peripheral blood of a patient with the Chediak-Higashi syndrome and his father (a heterozygote). The cells in these lines were principally lymphoblastoid in appearance, synthesized immunoglobulins and interferon, and demonstrated a modest phagocytic capacity. Giant abnormal granules characteristic of the Chediak-Higashi syndrome were present in the Homozygous Lines, and abnormally large granules were also present in the Heterozygous Line. Histochemical and euchrysine supravital staining demonstrated the lysosomal nature of these granules. Striking Golgi zone prominence was present in the Heterozygous Line, and to a lesser extent, in the Homozygous Lines. The potential significance of the establishment of these unique lines for investigations of the Chediak-Higashi syndrome, the nature of the heterozygous state, and role of lysosomes in general is discussed.
Experimental Induction of Myelofibrosis with Myeloid Metaplasia
Authors: ARGANO SALVATORE A. P. , TOBIN MARK S. , SPAIN DAVID M.
Published: October 2019

A simple and reproducible model for inducing a form of myelofibrosis with myeloid metaplasia by the injection of saponin intravenously is described. The histologic lesions produced resembled those of agnogenic MMM in man.
Haptoglobin Metabolism in Polycythemia Vera
Authors: KRAUSS STEPHEN
Published: October 2019

1. Turnover studies with 125I-labeled haptoglobin (Hp) were performed in 7 patients with polycythemia vera, 2 patients with erythrocytosis of unknown etiology, and 2 control subjects.

2. The T½ of plasma radioactivity was shortened in 6 of the 7 patients with polycythemia vera; 3 of these had diminished plasma Hp levels but lacked other evidence of hemolysis.

3. The fractional catabolic rate exceeded 40 per cent/day in all subjects with a shortened half-time of plasma radioactivity.

4. Increases in the fractional catabolic rate were not accompanied by increases in Hp turnover (mg./kg./day), suggesting that accelerated Hp catabolism per se does not provide a stimulus to Hp production.

5. It is concluded that patients with polycythemia vera catabolize Hp more rapidly than nonpolycythemic subjects, possibly because of increased formation and removal of the haptoglobin-hemoglobin complex.
Brief Report: Transplantation of Allogeneic Canine Bone Marrow Stored at -80 C. in Dimethyl Sulfoxide
Authors: STORB R. , EPSTEIN R. B. , LE BLOND R. F. , RUDOLPH R. H. , THOMAS E. D.
Published: October 2019

Prompt initial bone marrow engraftment was observed in 10 lethally irradiated dogs receiving infusions of 9.8 to 30.0 x 109 allogeneic marrow cells stored at -80 C. in dimethyl sulfoxide. The 3 recipients of bone marrow from unrelated donors, mismatched by canine histocompatibility testing, subsequently rejected their grafts and died within 16 days with marrow hypoplasia. The 3 dogs with matched unrelated donors and the 4 with matched litter mate donors all showed sustained marrow engraftment. Evidence of marrow repopulation by allogeneic cells was obtained by cytogenetic studies in one and by change to donor red cell type in 3 instances.
Studies on Erythropoiesis II. A Method of Segregating Immature From Mature Adult Rabbit Erythroblasts
Authors: BORSOOK HENRY , RATNER KAREN , TATTRIE BRENDA
Published: October 2019

A method is described of assessing the degree of maturation of erythroblasts in the marrow of adult rabbits. It has advantages over the conventional system of classification into pronormoblasts, basophilic, polychromatic and orthochromatic erythroblasts. Examples are given of the normal and two different extreme pictures: severe anemia (phenylhydrazine) and the early recovery stage after a nearly lethal injection of nitrogen mustard.

A method is described for segregating erythroblasts from adult normal rabbit marrow according to their degree of maturation. The erythroblasts are fractionated by centrifugation is a bovine serum albumin density gradient. A useful adjuvant procedure was prior lysis of the initial marrow cell suspension by an antiserum (goat) to rabbit erythrocytes. The appropriate concerntration of antiserum, with complement, lysed nearly all the acidophilic erythroblasts, reticulocytes and erythrocytes; basophilic erythroblasts remained, fewer, but more immature, the higher the concentration of antiserum used. Erythroblasts of the severely anemic (phenylhydrazine) rabbit were not fractionated as well as those of the normal by the centrifugation and not at all by the immune hemolysis procedure.
Immunologic Studies in Pernicious Anemia
Authors: TAI CHIAKI , MCGUIGAN JAMES E.
Published: October 2019

Experiments were directed to the investigation of evidence of a possible role of cellular immunity in patients with pernicious anemia. Lymphocyte-rich peripheral leucocyte preparations from 29 patients with pernicious anemia were cultured in the presence of a variety of preparations containing potential antigens: these included human gastric juice, human intrinsic factor (IF) preparations, and human gastric mucosal homogenates. Lymphocyte transformation was determined by measurement of the uptake of tritiated thymidine into DNA. Lymphocyte transformation occurred when lymphocytes from a portion of the patients with pernicious anemia (3.4 per cent to 37.5 per cent) were cultured in the presence of these antigen preparations. Lymphocyte transformation was noted in none of the patients whose sera contained blocking antibodies to intrinsic factor. There was no correlation between the presence or absence of lymphocyte transformation and the presence or absence of serum antibodies to the gastric parietal cell cytoplasmic antigen. These data on lymphocyte transformation permit the consideration that cellular immunity may participate in the pathogenesis of pernicious anemia.
Immunologic Characterization of 12 Factor VIII Inhibitors
Authors: FEINSTEIN DONALD I. , RAPAPORT SAMUEL I. , CHONG MAY N. Y.
Published: October 2019

Twelve Factor VIII inhibitors were characterized as immunoglobulins by highly specific antisera. All 12 inhibitors were characterized as belonging to the γG class of immunoglobulins. Ten inhibitors contained only K type light chain determinants and two contained only γ chain determinants. Therefore, these inhibitors were homogeneous by these criteria. Homogeneity cannot be established, however, until H-chain subtyping can be carried out.
Studies of the Delayed Response of Phytohemagglutinin (PHA) Stimulated Lymphocytes in 25 Chronic Lymphatic Leukemia Patients Before and During Therapy
Authors: BOURONCLE BERTHA A. , CLAUSEN KATHRYN P. , ASCHENBRAND JOAN F.
Published: October 2019

Comparative studies of in vitro responses to PHA stimulation between normal lymphoctyes and lymphocytes of CLL have shown significant functional differences.

Lymphocytes from 25 normal subjects showed maximum response at three days, while the leukemic cells did not reach a maximum degree of transformation until seven days. Moreover, the maximum transformation of the leukemic lymphocytes was significantly less than that of the normal lymphocytes.

After therapy, the lymphoctyes of the leukemic patients showed a gradual return to the levels and rates of lymphocyte transformation of the normal controls. This generally followed hematologic and clinical remission by several months.

This in vitro system demonstrates functional differences between normal lymphocytes and the lymphoctyes of CLL. It could also be used as one method for judging the therapeutic efficacy of agents used in the treatment of CLL.
Absorption of Physiologic Doses of Folic Acid in Subjects with Tropical Sprue Responding to Tetracycline Therapy
Authors: KLIPSTEIN FREDERICK A.
Published: October 2019

The response to therapy with oral tetracycline has been assessed in three subjects with tropical sprue, all of whom presented with a megaloblastic anemia due to combined folate and vitamin B12 deficiency, and all of whom were shown to have normal absorption prior to treatment of a physiologic dose of 25 µg. of folic acid, as tested by assay of the fecal excretion of a tritium-labeled test dose.

Treatment was associated with clinical and intestinal improvement and a hematologic response in all three subjects. The serum folate concentration rose to normal in one subject and the absorption of a pharmacologic dose of folic acid was normal when tested by microbiologic assay at the termination of the 20 day treatment period in all three. In contrast, both the absorption and serum concentrations of vitamin B12 remained subnormal.

These observations confirm the fact that folate deficiency can be present in some subjects with tropical sprue in whom the absorption of a physiologic dose of folic acid is normal. They suggest that in this circumstance folate repletion and the hematologic response secondary to tetracycline therapy in tropical sprue is mediated by a factor other than the absorption of crystalline folic acid; it is likely that this factor is increased absorption of dietary polyglutamate forms of folate.
Bone Marrow Reactions to Trauma Stimulation of Erythropoietic Marrow by Mechanical Disruption, Fracture or Endosteal Curettage
Authors: VAN DYKE DONALD , HARRIS NORMAN
Published: October 2019

The present series of studies were designed to examine the effect of artificially altered bone blood flow on activity of the contained marrow. In normal animals bone blood flow was increased locally by fracture, endosteal curettage, and following mechanical disruption of the marow. Local stimulation of erythropoietic marrow was demonstrated following each procedure. Local injury to bone circulation followed high doses of radiation and resulted in permanent marrow aplasia.

Attempts to apply the implications of these studies to therapy of two patients with marrow failure produced inconclusive results. One patient with severe anemia due to idiopathic myelofibrosis improved abruptly and significantly following endosteal curettage of one femur. Unexpectedly there was no demonstrable increase in blood flow in the operated bone and improvement in marrow occurred in skeletal areas other than the operative site.

In a second patient with severe anemia and Fanconi’s syndrome, endosteal curettage of one femur resulted in a marked local increase in bone blood flow with no evidence of stimulation of marrow locally or at other sites and no improvement in clinical condition until institution of androgen therapy.

Further clinical trials of endosteal curettage as a therapeutic measure would appear to be justified.
The Analysis of Blood Diseases with the Electron Microprobe
Authors: BEAMAN D. R. , NISHIYAMA R. H. , PENNER J. A.
Published: October 2019

Abnormal and normal blood smears were examined with an electron microprobe for their metallic Zn and Ti content in an attempt to confirm and extend the earlier work of Carroll and Tullis1 who had reported the simultaneous occurrence of Ti and Zn in up to 17 per cent of the examined leucocytes in various hematologic diseases. It was concluded that the earlier results1 were seriously affected by the presence of contaminants which, for the most part, were probably derived from materials present on the Si discs used as substrate material, from room dust or from improper handling. A thorough study of the possible sources of contamination revealed that Zn and particularly Ti were present on or in many of the materials used in these experiments. Only if external sources of Ti and Zn were avoided by careful sample preparation and handling were unambiguous results forthcoming. Twenty-three abnormal blood samples studied herein failed to show Ti and/or Zn in any leucocyte: nine of these which were collected on clean substrates in dust-free areas were, in addition, virtually free of contaminants or other noncellular materials. The examination of two samples provided by K. Carroll1 revealed that the simultaneous presence of Ti and Zn occurred primarily in noncellular material. Considerable information concerning blood and blood chemistry will be derived from electron microprobe examination, but, as discussed herein, careful consideration of probe operating variables and sample preparation will be essential.
Immunofluorescence Studies in Human Leukemia
Authors: BATES HENRY A. , BANKOLE RUFUS O. , SWAIM WILLIAM R.
Published: October 2019

Plasma obtained from patients with leukemia, was concentrated by high speed centrifugation and used to prepare antisera in rabbits. Unabsorbed, anti-human leukemia plasma and anti-murine leukemia virus (Rauscher) anti-sera showed similar immunofluorescence with normal and leukemia leukocytes. After absorption of these antisera with normal human antigens, normal cells were non-reactive and leukemia cells still reactive. Each antisera was shown to contain antibodies capable of cross reacting with and/or blocking the immunofluorescent reaction of cells from acute myelogenous, stem cell, or lymphatic leukemia cases. Pre-immunization rabbit serum and anti-human normal plasma antisera failed to show these reactions. These and antisera to other antigens (human globulin, Herpesvirus, adenovirus) were also non-reactive with acute phase leukemia cells. Such findings indicated a specificity for human leukemia cells by the described antisera and that human leukemia cells and Rauscher murine leukemia virus may have common antigens.

Serial studies on leukemia patients showed that the number and intensity of fluorescing cells varied with the clinical state of the patient. The three antisera gave similar reactions in acute leukemia. Differences were noted in remission. It was postulated that these differences were due to other cellular antigens, masked during the acute phase reaction. Leukocytes from patients with Hodgkin’s disease, lymphoma(s) and multiple myeloma also showed fluorescence when reacted with anti-murine leukemia. (Rauscher) virus anti-serum. Whether this common antigenicity with leukemia cells indicates similar altered cell growth and/or related etiology remains unresolved.
Delayed Clearance of Chloramphenicol from Serum in Patients with Hematologic Toxicity
Authors: SUHRLAND LEIF G. , WEISBERGER AUSTIN S.
Published: October 2019

The clearance of chloramphenicol from serum was studied in 18 patients. A significantly impaired clearance was found in all patients who manifested erythropoietic toxicity. Seven of the 18 patients were tested before chloramphenicol therapy was started. From these results it was possible to predict the patients who would subsequently develop hematologic toxicity. Therefore, prior testing with chloramphenicol may be valuable in screening adults susceptible to hematologic toxicity when the use of this drug is contemplated.
Studies in Iron Absorption IV. Effect of Humoral Factors on Iron Absorption
Authors: HÖGLUND S. , REIZENSTEIN P.
Published: October 2019

1. In a group of blood donors the mean serum iron concentration, and plasma clearance of iron did not differ significantly from normal means whereas the mean TIBC was increased. No statistically significant correlation existed between these values and the amount of blood donated in the year preceding the study.

2. The iron absorption was significantly correlated with the amount of blood donated during the year preceding the study, and the mean absorption value was significantly higher than in normal controls.

3. Compared to healthy men higher absorption values were likewise found in a group of healthy young women, without pathologic menstruations, and with essentially normal serum iron and TIBC values.

4. In order to discover how the intestine is instructed to increase iron absorption the correlations were studied between iron absorption and hemoglobin, serum iron, TIBC and plasma clearance of iron. No significant correlations were found. It is suggested that absorption is not primarily regulated by these factors. The finding of increased absorption in persons with essentially normal serum iron, TIBC and iron clearance supports this suggestion.

5. To determine whether the high absorption observed in women was a sign of iron deficiency, absorption was again studied after combined oral and parenteral iron treatment. It decreased in each case, except one where absorption remained unchanged.

6. Parenteral treatment alone, increased the serum iron but no statistically significant difference was found in TIBC, plasma clearance of iron, or iron absorption. Absorption after parenteral treatment was correlated mainly with pretreatment absorption.

7. After oral treatment on the other hand, absorption decreased significantly. No substantial changes were noted in serum iron or plasma clearance of iron, while TIBC unexpectedly increased. The findings support the view that no change in serum iron, TIBC or the plasma iron clearance is required to bring about a decrease in iron absorption.
Studies in Iron Absorption VI. Transitory Effect of Oral Administration of Iron on Iron Absorption
Authors: HÖGLUND S.
Published: October 2019

Iron absorption was studied before and after oral iron treatment in 5 groups of blood donors where the post-treatment absorption tests were performed at varying times after the end of therapy. The normalizing effect of oral iron on iron absorption is considerable 1 to 3 days after treatment has ended. Later, it rapidly diminishes. This correlates well with the short life span of the intestinal mucosal cells, and it is assumed that the transitory effect is caused by the iron content of these cells. When the cells loaded with iron by oral treatment die, the effect decreases. The iron content of the mucosal cells thus seems to play a part in the regulation of iron absorption.
Brief Report: Plasma Activity of Antihemophilic Globulin (AHG) and Other Coagulation Factors in Swiss Type of Agammaglobulinemia
Authors: MAURER HAROLD M. , VALDES ORESTES , SHUMWAY CLARE N. , MASSIE F. STANFORD
Published: October 2019

Although the site of synthesis and storage of antihemophilic globulin (AHG, Factor VIII) is unknown, available evidence suggests that these processes occur in the reticuloendothelial system. We studied the plasma activity of AHG and other coagulation factors in a patient with Swiss type of agammaglobulinemia. Except for increased fibrinogen concentration probably related to chronic infection, the activity of all coagulation factors including AHG was within the normal range. These studies suggest that the lymphocyte and plasma cell are unlikely sites of AHG synthesis or storage.
Chromosomal Aberrations in Polycythemia Vera
Authors: MODAN B. , PADEH B. , KALLNER H. , AKSTEIN E. , MEYTES D. , CZERNIAK P. , RAMOT B. , PINKHAS J. , MODAN M.
Published: October 2019

A number of chromosomal aberrations, occurring in polycythemia vera patients are presented, with an emphasis on their nonspecific nature. Among radiophosphorus-treated patients the frequency of these aberrations was moderately higher. The one finding typical to P32 treated patients was the presence of dicentric chromosomes, and a dose response curve to the last P32 dose was demonstrated. A Philadelphia-like chromosome was observed in two patients with polycythemia vera and in one with benign erythrocytosis, all post P32 therapy.

A question is raised whether it is possible that the future course of the polycythemic patient is dependent upon the type and location of chromosomal damage, and in turn, on the establishment of a clone of cells with a selective developmental advantage.
A Closed System for Large-Scale Lymphocyte Purification
Authors: WOODS A. H.
Published: October 2019

A method for lymphocyte purification is described. This is a closed system in which lightly heparinized blood is sedimented with Plasmagel in a plastic blood bag. The plasma layer is transferred to a second bag containing nylon powder and clotting is induced by agitation. Platelets, polymorphonuclear granulocytes, and monocytes are removed and trapped in the clot, together with the nylon powder. Lymphocyte suspension of 96 per cent purity and 61 per cent overall yield are produced. Viability of the lymphocytes is excellent and they are shown to be suitable for tissue culture. Comparison with other methods for lymphocyte isolation show this method to give higher yields and to be simpler in performance. It is particularly adaptable for large volumes of blood.
The Pattern of Stem Cell Repopulation in Heavily Irradiated Mice Receiving Transplants of Fetal Liver
Authors: KUBANEK BERNHARD , RENCRICCA NICHOLAS , PORCELLINI ADOLFO , HOWARD DONALD , STOHLMAN FREDERICK
Published: October 2019

Pluripotential cells derived from fetal liver had a lower plating efficiency than adult marrow cells, but estimates of the generation time derived from the growth curve are significantly shorter and may account for the earlier erythroid population.
A Possible Mechanism for the Erythrocytosis Associated with Hepatocellular Carcinoma in Man
Authors: GORDON ALBERT S. , ZANJANI ESMAIL D. , ZALUSKY RALPH
Published: October 2019

A case of hepatoma associated with erythrocytosis and increased levels of plasma ESF is described. Normal or tumorous liver tissue from this patient possessed neither erythropoiesis-stimulating activity nor a capacity to generate the ESF when incubated with normal human serum. Homogenates of tumor tissue served effectively as substrate for hypoxic rat REF in the generation of the ESF. Homogenates of nontumorous liver exhibited no substrate activity, but inactivated human urinary ESF when incubated with it. Homogenates of tumorous liver tissue lacked the capacity to inactivate the ESF.

It is suggested that the increased production or availability of substrate for the REF by the tumor significantly contributed to the increased levels of plasma ESF in this patient.
Prevalence of Precipitating Antibody to Antigens Derived from Burkitt Lymphoma Cultures Infected with Herpes-Type Virus (EB Virus)
Authors: STEVENS DAVID A. , PRY THOMAS W. , BLACKHAM ELIZABETH A.
Published: October 2019

The development of a sensitive immunodiffusion test for precipitating antibodies to antigens derived from herpes-type virus (HTV) infected Burkitt lymphoma cells in tissue culture is described. Seroepidemiologic observations with 517 sera were made. Precipitating antibody was found in a majority of the normal adult population, in contrast to some previous reports. The number of precipitin bands obtained was directly related to the titer of antibody reacting in indirect immunofluorescence. Antibody activity appears markedly increased in the sera of patients with Burkitt’s lymphoma, as shown by percent positive and number of precipitin bands. Studies of the antigens suggest that the precipitins are virus-specific, and may be virion protein antigens.
The Use of Homogenized Human Leukocytes for the Preparation of Anti-Lymphocyte Serum
Authors: JEHN ULRICH W. , RENNER HELMUT H.
Published: October 2019

This is the first report of the preparation of a potent antileukocyte serum produced by immunization with homogenates of human leukocytes. High titers of antibody activity were found against nuclei and a number of other intracellular materials, including several leukocyte enzymes. This antiserum, prepared in rabbits, also had marked in vitro lymphocyte stimulating activity that compared favorable with the activity of antilymphocyte serum prepared with intact cells. Cytotoxicity was enhanced in the presence of complement.
Immunologic Aspects of the Biogenesis of Erythropoietin
Authors: SCHOOLEY JOHN C. , ZANJANI ESMAIL D. , GORDON ALBERT S.
Published: October 2019

Immunologic evidence is presented that the interaction of Renal Erythropoietic Factor (REF) and a serum substrate results in the production in vitro of erythropoietin. Antibody capable of neutralizing erythropoietin (ESF) does not combine with either the REF or the serum substrate. Immune serum against the crude REF extract has been produced. This immune serum does not prevent the in vitro action or in vivo production of REF. This failure, however, may result from the diversity of antibodies produced.
Uracil Mustard in the Treatment of Thrombocythemia
Authors: ROBERTSON JEFFREY H.
Published: October 2019

Five patients with thrombocythemia are described. All were successfully treated with uracil mustard including two who were resistant to busulphan or radioactive phosphorus. Uracil mustard reduced the platelet count quickly and a single course of the drug produced a satisfactory remission without undue marrow depression. The results are compared with those which have been obtained with busulphan and radioactive phosphorus. It is concluded that uracil mustard may prove to be the most effective, convenient and possibly the safest, means of treating thrombocythemia.
Ultrastructural Aspects of Antibody Plaque-Forming Cells from Clinically Normal and Overtly Autoimmune NZB Mice
Authors: SIEGEL B. V. , BROOKS R. E. , MORTON JANE I.
Published: October 2019

Quantitative differences, in terms of antibody plaque-forming cells per mg. spleen, were observed in young and old animals of the BALB/c and NZB mouse strains. Ultrastructurally, antibody-producing cells from spleens of immunologically hyperactive young NZB mice appeared relatively similar to those from overtly autoimmune old NZB mice showing depressed immune responsiveness. There was more extensive dilatation of endoplasmic reticulum in cells of older mice, with some of these cells manifesting increased fragility. Viruslike particles, observed to be located intracisternally, lacked an electron dense nucleoid and were not seen budding from plasma membranes; they were thus unlike the murine leukemia type-C particles reported to be found in organs of NZB mice. Additionally, since these viruslike particles were observed in antibody-producing cells of young and old nonautoimmune BALB/c mice as well as in those of the NZB strain, it is probable that they do not represent the agent responsible for development of autoimmune disease or malignancy.
Waldenström’s Macroglobulinemia: Correlation Between Expanded Plasma Volume and Increased Serum Viscosity
Authors: MACKENZIE MALCOM R. , BROWN ELLEN , FUDENBERG H. H. , GOODENDAY LUCY S.
Published: October 2019

In 17 patients with Waldenström’s Macroglobulinemia, total chromium space, red cell mass, plasma volume and relative serum viscosities were determined; aldosterone excretion was determined in 12. Ten of the 15 patients who manifested elevated serum viscosity at some time during the course of study presented signs and symptoms of hyperviscosity syndrome. All patients had increased total blood volume. Fifteen had moderate decreases in red cell mass but all had elevations of plasma volume far in excess of that required to compensate for the lowered cell mass. The degree of the increase in plasma volume correlated (r = 0.74) with the degree of abnormality in relative serum viscosity. Aldosterone excretion in such patients was normal to low. It is concluded that the plasma volume increase is correlated with serum viscosity and is mediated by sodium retention mechanisms not involving modification of aldosterone secretion.
Morphology of Normal Erythrocyte and Acanthocyte Using Nomarski Optics and the Scanning Electron Microscope
Authors: KAYDEN HERBERT J. , BESSIS MARCEL
Published: October 2019

The morphology of normal erythrocytes and of acanthocytes from five patients with abetalipoproteinemia was studied by two relatively new technics. Interference microscopy with Nomarski optics was used to study the red blood cells in the living state; the scanning electron microscope was utilized to give a three dimensional appearance of the fixed red blood cells.

Isotonic saline washing of normal red blood cells produces multiple small uniform projections on the surface of the cell: the crenated red cell. Acanthocytes after saline washings also develop similar projections: the crenated acanthocyte. Crenation of both the normal red blood cell and the acanthocyte is reversed by restitution of a plasma environment and by chemical fixation by glutaraldehyde or osmic acid but the characteristic shape of the acanthocyte is preserved.

A comparison was made of the changes in the shape of the normal red blood cells and acanthocytes induced by alterations in the tonicity of the surrounding medium.
Effects of Hypertonic Stress on The Fine Structure of Sickled Erythrocytes
Authors: WHITE JAMES G.
Published: October 2019

The tendency of polymers of sickled hemoglobin (HbS) to align parallel and equidistant to each other has been pointed out in many investigations, and is considered a characteristic feature of erythrocyte sickling. A previous study on stroma-free solutions of sickled hemoglobin, however, suggested that polymers of HbS preferentially assumed radial rather than parallel relationships. Sickled erythrocytes were exposed to hypertonic stress in the present study in order to observe whether parallel bundles of polymers remained intact after removal of the cell membrane. Bundles of polymers in salicylate damaged sickled cells regularly developed branching and radial configurations similar to those found in stroma-free gels. Rotational stress appears to be the dominant factor influencing the relationship of HbS polymers, and the force generated by that tension may be an important factor in erythrocyte sickling.
Rare Variant of Lipid Storage Disorders
Authors: SAIDI PARVIN , AZIZI SADEGH P. , SARLATI REYHANALLAH , SAYAR NASROLAH
Published: October 2019

A 16-year-old boy with brownish pigmentation of the skin, bilateral pingueculae, macular degeneration, hepatosplenomegaly, suggested mental retardation, and abnormal histiocytes in the bone marrow and liver is presented. The morphologic appearance of the histiocytes is unique and specific, and so far only six similar cases have been reported in the literature. The contents of these histiocytes are thought to be phospholipids and glycolipids of sphingomyelin and cerebroside variety, respectively. The significance of the clinical and laboratory findings of these cases and the possible relationship to the lipid storage disorders are discussed.
The Effect of Chromium on Platelet Function In Vitro
Authors: KATTLOVE HERMAN E. , SPAET THEODORE H.
Published: October 2019

Sodium chromate inhibits platelet function in vitro. The primary effect is inhibition of connective tissue-induced aggregation. In addition, the primary wave of epinephrine-induced aggregation is moderately inhibited and adenosine diphosphate-induced aggregation is mildly inhibited. The effect on connective tissue-induced aggregation is due to inhibition of the platelet "release reaction"; chromate inhibited the release of adenine nucleotides, 14C labeled serotonin and the activation of platelet factor III normally caused by connective tissue. The amount of chromium which must be bound to platelets to inhibit aggregation is 10-100 times the amount of radioactive chromium bound to platelets under the usual conditions of labeling for survival studies. However, this does not imply that chromium labeled platelets function normally.
Bi-Directional Transport of Ferritin in Guinea Pig Erythroblasts In Vitro
Authors: TANAKA YASUKAZU
Published: October 2019

Direct morphologic evidence has been presented for a bi-directional flow of ferritin in guinea pig erythroblasts and reticulocytes both in vitro and in vivo. Ferritin intake by means of micropinocytotic vesicles is followed by their confluence and rupture of the large vesicles to the outside within 60 minutes. The origin of ferritin on the red cell surface prior to its uptake by the micropinocytosis (rhopheocytosis) is yet to be determined.
A Possible Subclass of the Hereditary Persistence of Fetal Hemoglobin
Authors: HUISMAN T. H. J. , SCHROEDER W. A. , ADAMS H. R. , SHELTON J. ROGER , SHELTON JOAN BALOG , APELL GERALD
Published: October 2019

Four individuals in two generations of a Caucasian family have about 5 per cent of Hb-F in which the sole type of γ chain is that with alanine in position 136. It is suggested that these heterozygotes may constitute a subclass of the hereditary persistence of fetal hemoglobin.
Hemoglobin-Seattle (α2Aβ276 Glu): An Unstable Hemoglobin Causing Chronic Hemolytic Anemia
Authors: HUEHNS E. R. , HECHT F. , YOSHIDA A. , STAMATOYANNOPOULOS G. , HARTMAN J. , MOTULSKY A. G.
Published: October 2019

Mild to moderate chronic hemolytic anemia in a mother and her two sons was found to be associated with the presence of about 40 per cent abnormal hemoglobin of rapid electrophoretic mobility: Hb-Seattle. Hb-Seattle was found to be unstable in vitro. It was shown to be due to a replacement of alanine by glutamic acid at position 76 of the β hemoglobin chain. The substitution occurs at the surface of the β hemoglobin chain. The hemoglobin instability was attributed to an abnormal interaction between the substituted glutamic acid and histidine at position β77.
Computer Simulation of Granulopoiesis: Normal and Impaired Granulopoiesis
Authors: KING-SMITH ERIC A. , MORLEY ALEC
Published: October 2019

A computer model simulating granulopoiesis has been constructed on the basis of two feedback loops, one controlling the rate of production of granulocytes at the stem cell level, the other controlling the rate of release of granulocytes into the blood. This model reproduced the low-amplitude neutrophil oscillation reported in normal individuals and, when mild and severe marrow failure were simulated, resulted in states resembling cyclical and severe noncyclical neutropenia, respectively. The results provide evidence that a number of the periodic features shown by normal and abnormal granulopoiesis occur because granulopoiesis is a feedback-controlled system and suggest that the main assumptions of the model have physical reality.
The Effect of Chronic Iron Deficiency on Some Biochemical Functions of the Human Hemopoietic Tissue
Authors: HERSHKO CH. , KARSAI A. , EYLON L. , IZAK G.
Published: October 2019

In view of the erythroid hyperplasia found in the bone marrow of subjects with chronic iron deficiency anemia, the delayed appearance of reticulocytosis following iron therapy is unexplained. Profound disturbances were observed in some biochemical functions of the bone marrow cells isolated from such patients. There was a substantial decrease in the cellular nucleic acid content, associated with a marked drop in the rate of 3H-thymidine incorporation into DNA. The utilization of 59iron and of glycine-2-14C for heme production, and of the latter compound for protein synthesis was also reduced, as compared to the findings in bone marrow cells from normal subjects. These metabolic alterations returned to the normal pattern in the bone marrow cell suspensions obtained from the patients following recovery after iron therapy.

The possible implications of these findings are discussed in the light of available information.
Lymphocyte Transformation Induced by Autologous Platelets in a Case of Thrombocytopenic Purpura
Authors: PIESSENS WILLY F. , WYBRAN JOSEPH , MANASTER JOSEPH , STRIJCKMANS PIERRE A.
Published: October 2019

In a case of chronic thrombocytopenic purpura, significant lymphocyte transformation could be induced with autologous platelets as a stimulant. The reaction was not due to serum factors since it occurred when culture medium was supplemented either with autologous or pooled human serum. Controls excluded nonspecific lymphocyte transformation. Modulation of normal platelet antigens by viral or chemical factors or adsorption of such factors on the platelet membrane could account for the observed reactions. However, since other auto-antibodies were demonstrated, the hypothesis of altered cellular "self-recognition" mechanisms is tentatively proposed as an alternative explanation for this observation.
Paroxysmal Nocturnal Hemoglobinuria in Myelofibrosis
Authors: HANSEN NIELS EBBE , KILLMANN S.-AA.
Published: October 2019

Ten consecutive patients with myelofibrosis were examined for the following signs of PNH: Ham’s test, the sucrose hemolysis test, low red cell acetylcholinesterase (ACHE) activity and intravascular hemolysis. Two of the patients displayed all these signs and also had clinical symptoms of PNH. Two patients had positive sucrose hemolysis tests, low red cell ACHE and intravascular hemolysis. One patient had a positive sucrose hemolysis test and low red cell ACHE. The remaining patients had no signs of PNH. In two of the patients, the PNH signs disappeared after splenectomy. The concurrence of myelofibrosis and PNH supports the hypothesis that PNH is a disease of the common hemopoietic stem cell.
Correlation of Lymphocyte Transformation and Morphology in the Human Fetal Thymus
Authors: PAPIERNIK MARTINE
Published: October 2019

A study was made of PHA-stimulated thymic lymphocyte transformation in 10 human fetuses ranging from 12 to 22 weeks of gestation. The results were compared with those obtained using circulating blood lymphocytes of the corresponding fetuses in seven cases. The degree of transformation of blood lymphocytes is independent of fetal age. On the other hand, thymic lymphocyte transformation is age-related. Until the 18th week of gestation, the per cent of transformed thymic lymphocytes is comparable to that of blood lymphocytes. After the 18th week of gestation, the per cent of transformed thymic lymphocytes diminishes to the level of adult thymic lymphocytes. The significance of these findings is discussed.
Congenital Agranulocytosis: Prolonged Survival and Terminal Acute Leukemia
Authors: GILMAN PRISCILLA A. , JACKSON DUDLEY P. , GUILD HARRIET G.
Published: October 2019

Three unrelated, Caucasian patients with a disorder resembling infantile genetic agranulocytosis have been studied. There was no history of consanguinity. Parents and siblings were normal. Onset occurred before 3 weeks of age and persisted throughout life. All had severe neutropenia, myeloid arrest pattern of the bone marrow, eosinophilia, monocytosis and hyperglobulinemia. Other congenital anomalies were not present. Their clinical courses were characterized by recurrent, severe bacterial infections particularly of the skin, mouth and lungs but without bacteremia. The infections responded to, but were not prevented by antibiotics, which were administered almost continuously. Fungal infections did not occur and viral infections were not severe. Splenectomy and corticosteroids were without apparent benefit. Relative, though transient, neutrophilia occurred during a few episodes of infection. Chromosome analysis was normal in two of the patients. In one, maturation of neutrophilic leukocytes was not observed in cultures of bone marrow to which normal serum or cysteine was added. One boy is living at 14 10/12 years of age, and one died at 13¾ years of disseminated infection. A unique occurrence was the development of terminal acute leukemia (monocytic) in the third patient, a girl at the age of 14¼ years.
A Technique for the Morphological Examination of Hemopoietic Cells Grown in Agar
Authors: TESTA NYDIA G. , LORD BRIAN I.
Published: October 2019

Histological preparations of hemopoietic cells growing in colonies in soft agar were made using a modified squash technique. Colonies were fixed in the Petri dish with 3:1 acetic-alcohol mixture for 1 hour. Individual colonies were pricked out with a microhematocrit tube and placed on a slide. Squash preparations of the cells were then made by the standard method. Preparation for staining the cells was made by immersing the slides in methyl alcohol for 10 minutes. The slides were finally treated with phosphate buffer at pH 6.4 for 45 minutes before staining with MacNeal’s tetrachrome. This technique allowed the recovery and cytological examination of most of the cells growing in a single colony.
The Potentiality of Out-of-cycle Acute Leukemic Cells to Synthesize DNA
Authors: STRYCKMANS P. , DELALIEUX G. , MANASTER J. , SOCQUET M.
Published: October 2019

The blood of 18 patients with acute leukemia was exposed to UV light. Within 2 hours, in all the patients (except one under chemotherapy), nearly 100 per cent of the leukemic blasts showed uptake of 3HTdR as a result of DNA repair replication. Similar exposures of CML blood white cells and chicken blood red cells to UV indicated that myeloid and erythroid cells have no capacity to repair DNA after they have stopped dividing as a result of maturation. This suggests that nonproliferating leukemia blasts are resting cells rather than "end cells."
Feedback Regulation by Red Cell Mass of the Sensitivity of the Erythropoietin-producing Organ to Hypoxia
Authors: NECčAS E. , NEUWIRT J.
Published: October 2019

The effects of short intervals of anemic, hypoxic and CO hypoxia of various degrees on erythropoietin production have been compared in anemic, normal and polycythemic rats. The anemic and CO hypoxia were terminated by the exposure of rats to hyperbaric oxygen. The duration of hypoxic periods of different types of hypoxia ranged from 15 to 120 minutes. The decreased response of erythropoietin production to hypoxia was observed in rats having higher hematocrit. It is assumed that there is feedback inhibition, by the circulating red cell mass, of the sensitivity of the erythropoietin-producing organ to hypoxia.
Reaction of Cold Agglutinins with I Antigen Solubilized From Human Red Cells
Authors: ROSSE WENDELL F. , LAUF PETER K.
Published: October 2019

The antigens reacting with cold-agglutinin antibodies and present in the red cell membranes of human red cells were found in the water-phase when the washed membranes were extracted with n-butanol. The presence of these antigens was demonstrated by agglutination inhibition, complement fixation, and antibody inhibition as determined by the C1 fixation and transfer test. Although antigen and antibody were not able to react at 37°C when the antigen was present in the intact cell, after solubilization, antigen and antibody reacted equally well at 37°C and at 0°C. The amount of anti-I inhibiting activity present in extracts from adult and cord cells was roughly the same, although the amount of antibody fixed to the intact cord cells was less with cord cells.
Glucose-6-Phosphate Dehydrogenase Deficiency in Egypt: With a Note on the Methemoglobin Reduction Test
Authors: MCCAFFREY RONALD P. , AWNY AMMHED Y.
Published: October 2019

Six hundred and fifty Egyptian males were screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency. The ascorbate-cyanide test and methemoglobin reduction test were used. An incidence of 4.9 per cent G6PD deficiency was found, in contrast to the previously reported incidence of 26.4 per cent. Good agreement was found between the ascorbate-cyanide test and methemoglobin reduction test. Unreliable results were obtained when previously prepared air-dried reagent tubes (modified methemoglobin reduction test) were used.
Studies on the Regulation of Granulopoiesis. IV. Possible Humoral Regulation
Authors: MORLEY ALEC , RICKARD KEVIN A. , HOWARD DONALD , STOHLMAN FREDERICK
Published: October 2019

Serum obtained from mice after irradiation shows an enhanced ability to stimulate growth of granulocytic colonies in vitro. This enhanced stimulatory ability of serum is related in both time and magnitude to the neutropenia developing after irradiation and in time to the granulopoietic response of the marrow to the neutropenia. The relationship suggests that the active factor in postirradiation serum might be granulopoietin, the physiological regulator of granulopoiesis.