bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Distribution of Red Cell Volumes
Authors: BULL BRIAN S.
Published: October 2019

A large number of red cell volume distribution curves can be generated on the same sample of blood by manipulating the length of the Coulter Counter aperture and the shape of the red cell. Curves derived from sphered red cells flowing through an aperture 70 x 98µ long, or longer appear to be relatively free from artefacts and therefore the most likely to be "real."

The use of long apertures to size sphered red cells will give a volume distribution curve that is approximately Gaussian and with a mean that is large relative to the variance. Whether red cells are Gaussian or log normal in their volume distribution is very difficult to determine. On a particle population where volumes are controlled as closely as on red cells (i.e. with such a low variance), the normal and the log normal distributions become practically indistinguishable. If in the future this decision can be reached by some independent means, then the volume distributions using the Coulter volume transducer can be easily and simply fitted to the shape desired by appropriate manipulation of aperture length. These ideal volume distribution curves are not likely to differ markedly from those obtained under the conditions suggested in this paper. For the present, use of a 70 x 98µ aperture to size red cells sphered by suspension in isotonic Sodium Potassium Tartrate will contribute to considerably greater accuracy in identification of red cell subpopulations in abnormal blood.
Erythrocytosis Secondary to Increased Oxygen Affinity of a Mutant Hemoglobin, Hemoglobin Kempsey
Authors: REED CON S. , HAMPSON ROGER , GORDON SUSAN , JONES RICHARD T. , NOVY MILES J. , BRIMHALL BERNADINE , EDWARDS MILES J. , KOLER ROBERT D.
Published: October 2019

An abnormal hemoglobin, termed hemoglobin Kempsey, was found in association with erythrocytosis in ten members of an Australian family. Genetic transmission fits an autosomal dominant pattern. Chemical characterization of hemoglobin Kempsey identified a single amino acid substitution, β99Asp→Asn. Properties of hemoglobin Kempsey include a marked increase in oxygen affinity, retention of the Bohr effect, and decreased heme-heme interaction. Possible structure-function relations of this and other abnormal hemoglobins associated with erythrocytosis are discussed.
The Occurrence of Hemoglobins Bart’s and F Associated With Carbonic Anhydrase Deficiency In A Patient With Alpha-thalassemia And Malignant Thymoma
Authors: IMAMURA TAKASHI , OHTA YOSHIRO , HANADA MOTOSUKE
Published: October 2019

A 17 year old Japanese girl is described with morphologic evidence of thalassemia characterized by an increase in fetal hemoglobin distributed heterogenously among the red cell population, a slight relative depression of α-chain synthesis, and an increase in γ-chain synthesis, as well as a significant depression in carbonic anhydrase activity.

The data suggest that some increase in the severity of these abnormalities took place with the development of a malignant thymoma. The combination of defects present here is not characteristic of the usual manifestations of α-thalassemia and might therefore be considered as an unusual variant of this condition.
Brief Note: Effect of Erythropoietin on Polycythemic Mouse Spleen in Vitro IV. Response of the Colony-forming Cells to Erythropoietin
Authors: MIZOGUCHI HIDEAKI , MIURA YASUSADA , TAKAKU FUMIMARO , NAKAO KIKU
Published: October 2019

It is shown that an in vitro system of assaying the size of an erythropoietin-responsive stem cell pool could be applied to the spleens of polycythemic mice after irradiation and bone marrow transplantation.

With this method, the presence of erythropoietin-responsive cells in the spleen was first detected on the second day after transplantation. Therefore, it is considered probable that colony-forming cells and erythropoietin-responsive cells are at different stages of maturation or cell cycle.

Furthermore, necessity of erythropoietin for further differentiation of transplanted stem cells into erythroblasts is also suggested.
Microangiopathic Hemolytic Anemia in Rats with Malignant Hypertension
Authors: VENKATACHALAM M. A. , JONES DAVID B. , NELSON DOUGLAS A.
Published: October 2019

Unilaterally nephrectomized rats given desoxycorticosterone and salt load developed malignant hypertension with widespread vascular lesions and, coincidentally, a hemolytic anemia. The anemia was characterized by red cell fragmentation, increased erythrocyte osmotic fragility, and evidence of both intravascular and extravascular hemolysis. Thrombocytopenia was not observed. Male rats were more severely affected than female animals. The degree of anemia correlated well with the severity of the vascular lesions, but not with the level of blood urea nitrogen.

Based upon electron microscopic observations of the relationship of red cells to damaged endothelial cells and thrombi, possible mechanisms for the red cell fragmentation are discussed.
The Remission and Relapse Status of Acute Leukemia as Studied by the In Vitro Uptake of Tritiated Thymidine by Peripheral Blood Leukocytes
Authors: ZIMMERMAN THEODORE S. , GODWIN HERMAN A. , ZELEN MARVIN , PERRY SEYMOUR
Published: October 2019

H3TdR uptake by peripheral blood leukocytes has been measured in patients with acute leukemia and in hematologically normal controls. Patients with acute leukemia in remission and relapse generally had elevated uptakes and formed populations distinct from the normal population and from each other, although overlap of values between each population was present. The measurement of H3TdR uptake may prove useful as an additional parameter for studying acute leukemia.
Megakaryocyte Size in Thrombocytopenic and Normal Rats
Authors: EBBE SHIRLEY , STOHLMAN FREDERICK , OVERCASH JOAN , DONOVAN JANET , HOWARD DONALD
Published: October 2019

Thrombocytopenia was produced in rats by exchange transfusion with platelet-poor homologous blood or heterologous antiserum. The subsequent rapid rise in platelet counts to thrombocytotic levels suggested accelerated platelet production. During this recovery period macromegakaryocytes were present in the bone marrow. The findings suggested that thrombocytopenia affected megakaryocytopoiesis at the precursor cell level with resultant macrocytosis.
The Effect of Surgery on the Concentration of Circulating Megakaryocytes and Platelets
Authors: BRESLOW ALEXANDER , KAUFMAN RICHARD M. , LAWSKY ALAN R.
Published: October 2019

The mean concentration of megakaryocytes in antecubital vein blood of 43 normal men and women was 3.4/ml. (range 0-13). No circulating megakaryocytes were found in 6 patients with thrombocytopenia due to marrow failure. Following surgery the average maximal megakaryocyte level increased to 50/ml. (range 15-190) from a preoperative mean of 8/ml. The maximal level was reached on about the third postoperative day with the platelet concentration reaching maximal levels 3 to 6 days later.
Antisera for Tissue-Typing: The Production of Cytotoxic and Agglutinating Antibodies Following Intradermal Leukocyte Injections in Man
Authors: SHANBROM EDWARD , FEINGOLD ELAINE , SHEPHERD LESTER , WALFORD ROY
Published: October 2019

Both cytotoxic and agglutinating antibodies developed predictably in response to repeated intradermal injections of small amounts of leukocytes. In 3 of 5 such immunizations, the resulting antisera were monospecific and the donor-recipient matches revealed few antigenic differences. Restimulation caused a prompt appearance of antibody in high titer. Attempts to characterize a single serum sample in terms of its leukoagglutinating and cytotoxic activity may not be valid unless the serum used is known to contain comparable levels of antibody activity.

Further advances in leukocyte typing for organ transplantation should be facilitated by the availability of monospecific typing sera. Sera of this nature can be produced by immunization of recipients with closely matched donors.
Characteristics of the Terminal Phase of Chronic Granulocytic Leukemia
Authors: KARANAS ARTHUR , SILVER RICHARD T.
Published: October 2019

Data obtained retrospectively from a group of patients with chronic granulocytic leukemia provided the basis for characterizing the onset of the terminal phase of chronic granulocytic leukemia. Such characterization permits an opportunity to introduce in sufficient time new therapeutic agents for the treatment of a phase of a disease which heretofore has been refractory to conventional therapy. The suggested criteria marking the onset of the terminal phase may require revision as more information is systematically collected in the future.
A Histochemical Study of the Reticuloendothelial System of Human Marrow—Its Possible Transport Role
Authors: TRUBOWITZ S. , MASEK B.
Published: October 2019

Intense alkaline adenosine tri-, di- and monophosphatase activity is present in the capillary endothelial cells and reticular cells of the bone marrow as well as about the individual marrow cells. The phosphatase activity of the granulocytic cells is weak by comparison and offers no difficulty in differentiation. Iron is confined to a similar topographic distribution. The described observations are discussed in terms of transport. It is suggested that the reticuloendothelial system of the marrow is essentially a transport system for the differentiating hematopoietic cells.
Tryptophan Metabolism in Humans with Various Types of Anemias
Authors: HANKES L. V. , BROWN R. R. , SCHIFFER L. , SCHMAELER M.
Published: October 2019

Metabolic studies were performed in a number of patients to determine the effect of anemia on tryptophan metabolism. Patients were given a tracer dose of DL-tryptophan-2-C14 or the tracer dose plus a loading dose (2 Gm.) of L-tryptophan. In those patients given the loading dose, the C14O2 production over a 24 hour period was lower than that usually obtained in normals receiving the same dose. The loading dose did not have any significant effect on the total urinary radioactivity level. In some cases the post tryptophan loading urinary level of kynurenine, quinolinic acid, N1-methylnicotinamide and N1-methyl-2-pyridone-5-carboxamide were elevated. Vitamin B6 administration returned the kynurenine and N1-methylnicotinamide levels to normal but not the quinolinic acid or pyridone. The results obtained here indicate that in anemias the activity of the hematin dependent enzyme, tryptophan pyrrolase, was depressed as well as the enzymes converting the amino acid into CO2. The data suggest that not only are the kynurenine catabolism enzymes vitamin B6 dependent but that vitamin B6 is very important to the conversion of the tryptophan metabolite 3-hydroxy-anthranilic acid into α-amino-β-carboxymuconic-ε-semialdehyde and the conversion of the semialdehyde into acetate and CO2. In addition vitamin B6 may be involved in the further metabolism of quinolinic acid into the pyridone.
A Clockface Chromatin Pattern in the Intermediate Megaloblast of Vitamin B12 or Folate Deficiency
Authors: KASS LAWRENCE
Published: October 2019

In the fully-developed megaloblast of vitamin B12 or folate deficiency, unique alterations occur in the chromatin adherent to the nuclear membrane. This chromatin is often tenuously connected to or separated from other chromatin, and gives the nucleus a clockface appearance. A clockface chromatin pattern appears only rarely in "megaloblastoid" erythroblasts from cases of refractory megaloblastic anemia. Normal erythroblasts and developing erythroblasts from a variety of anemias do not exhibit this chromatin pattern. Although the pathogenesis of the "clockface sign" is unknown, alterations in megaloblast histone might cause both the clockface chromatin pattern and subsequent chromosomal abnormalities. When the "clockface sign" appears in an intermediate megaloblast, it may provide a morphological clue to a deficiency of vitamin B12 or folate.
Failure of Vitamin E Therapy in the Treatment of Anemia of Protein-Calorie Malnutrition
Authors: BAKER S. J. , PEREIRA S. M. , BEGUM ALMAS
Published: October 2019

A study is reported of the hematologic changes occurring in 16 children with protein-calorie malnutrition treated with vitamin E. Eight children showed no response. Two showed a very delayed rise in reticulocyte count and six had a peak reticulocyte response 5 to 8 days after starting therapy. None of the patients showing reticulocyte responses had a sustained rise in hemoglobin or packed cell volume. In none of the cases did the marrow become normoblastic following therapy and in five the marrow abnormalities became more marked.

The results of this study do not confirm the suggestion that vitamin E has a significant role in human hemopoeisis.
Mechanisms of Hemolysis in Iron Deficiency Anemia. Further Studies
Authors: DIEZ-EWALD MARIA , LAYRISSE MIGUEL , Ojeda Adelina
Published: October 2019

Red blood cell survival time as measured with 32DFP and 51Cr was studied in subjects with iron deficiency anemia associated and nonassociated with hook-worm infection. 51Cr T ½ was definitely shorter in all cases in which 32DFP showed marked excess hemolysis, but a normal 51Cr T ½ was found in some cases in which 32DFP survival was slightly reduced.

There was a high correlation between survival measured with 32DFP and the rate of abnormal red cells in the peripheral blood. Less correlation was found between the proportion of hypochromic microcytic red cells and 32DFP, and even less correlation, although significant, was observed when 51Cr T ½ was compared with the red cell parameters.

Results of the red cell survival studies with erythrocytes from subjects with iron deficiency anemia injected into the donor subject, normal recipients, and splenectomized subjects, as well as body 51Cr surface countings, indicated that excess hemolysis in this type of anemia is due to an intrinsic defect of the red blood cells and that the spleen is the principal sites of destruction of these cells.
Hemopoietic Progenitor Cells in Marrow and Spleen of Mice with Hereditary Iron Deficiency Anemia
Authors: BENNETT M. , PINKERTON P. H. , CUDKOWICZ G. , BANNERMAN R. M.
Published: October 2019

Sex-linked hypochromic anemia is the result of iron deficiency, apparently caused by malabsorption of iron. Progenitor cells in marrow and spleen of male anemic (genotype, sla/-) and normal (+/-) littermate mice were studied by quantitative transplantation into irradiated, but otherwise normal, recipient mice. The progeny of grafted cells were assessed by isotope uptake technics. Progenitor cells of sla/- mice were capable of extensive production of erythroid cells, which synthesized DNA and hemoglobin, and of leukocytic elements, which synthesized DNA but not hemoglobin. Proliferation of the latter cell types was assayed in recipient mice rendered polycythemic with red cell infusions to suppress erythropoiesis. The mature red cells produced by transplanted sla/- marrow and spleen were normal with respect to volume, size, and hemoglobin content. The grossly enlarged spleens of sla/- mice contained 20 times the normal number of erythropoietic progenitor units (EPU); parenteral iron therapy cured the anemia and caused the spleen to revert to normal. The ratio of EPU to leukopoietic progenitor units (LPU) was abnormally high in marrow and spleen of sla/- mice; in addition, the EPU:LPU ratio was higher in spleen than in marrow of normal and anemic mice. The high EPU:LPU ratio of sla/- bone marrow persisted after transplantation to a lesser, but significant, extent for at least 52 days. We conclude that: 1) the sla mutant gene does not affect hemopoietic cells directly, but that iron deficiency alters the ratio of EPU to LPU by committing more primitive pluripotent stem cells to erythropoiesis, and 2) EPU and LPU are separate progenitor cells with restricted potential for differentiation. Persistence of the altered EPU:LPU ratio in sla/- marrow chimeras may be explained by extensive and independent self-replication of EPU and/or LPU, especially after grafting relatively small numbers (1.6 million) of marrow cells into irradiated mice.
Brief Report: A Cytogenetic Study of Acute Erythroleukemia in Children
Authors: DYMENT PAUL G. , MELNYK JOHN , BRUBAKER CHARLES A.
Published: October 2019

Three children with acute erythroleukemia were studied for chromosomal changes. Two of them had persistently normal karyotypes despite relapse. The third patient was missing a C chromosome, and had 45/46 mosaicism in the bone marrow and a dichotomy between blood (mode of 46) and bone marrow (mode of 45). All of these abnormalities were only evident when he was in relapse. Following partial remission induced with cytosine arabinoside, all subsequent analyses were normal. This is the third case reported of a child with erythroleukemia with aneuploidy in the C group of the chromosomes.
Hypothesis: Studies on Human Platelets III. A Contractile Protein Model for Platelet Aggregation
Authors: BOOYSE F. M. , RAFELSON MAX E.
Published: October 2019

A new hypothesis is proposed for platelet aggregation. The model involves the formation of intermolecular platelet actomyosin bridges between platelet actin and platelet myosin moieties localized on or near the surface of adjacent platelets. These intermolecular platelet actomyosin bridges can then contract in the presence of ATP, drawing the platelets into a tight mass or thrombus.
Intravascular Hemagglutination Studied with the Living Extracorporeal Eye
Authors: SEAMAN ARTHUR J. , LUTCHER C. LAWRENCE , MOFFAT CHARLOTTE
Published: October 2019

Direct and filmed observations of events during intravascular hemagglutination have been made using our Living Extracorporeal Eye preparation.

Agglutinated erythrocyte masses in the arterioles are separated by plasma gaps but tied to one another in short chains by fibrin threads and have a surface deposition of fibrin. This fibrin forms under circumstances that make autocatalytic coagulation unlikely. This seems to indicate that if thrombin evolution occurs, it must be localized to the areas of exposed erythrocyte stroma and adjacent endothelial cell surfaces altered by deoxygenation.

These masses plug some of the microcirculatory channels and venous many-tailed casts build from multicentric sites at the exits of venules with stilled flow. The light and electron microscopic structure of such casts shows a core of aggregated erythrocytes with surface fibrin and platelet deposition.

The above events are not prevented by prothrombinopenic, leukopenic or thrombocytopenic reacting bloods but are abolished by resuspending from each of the reacting bloods, the autologous erythrocytes, leukocytes, and platelets in the supernate of its centrifuged heat-defibrinated plasma.

Hydrocortisone, benadryl and 6 per cent clinical dextran do not alter the reaction.

When calcium ion binding agents are also present, heparin abolishes the fibrin formation and sharply reduces the magnitude of erythrocyte aggregates so that vigorous perfusion of the microcirculation continues. Heparin alone is ineffective in suppressing interspecies hemagglutination and erythothrombus formation when non-anticoagulated bovine blood is intermixed with heparinized diluted human blood.

The obstructing arteriolar masses and the many-tailed venous cast induced by hemagglutination, are promptly and completely disaggregated by plasma plus streptokinase or by urokinase or by 5M urea solution perfusion.

Osmotically lysed erythrocytes lead to similar erythrothrombosis only when stasis is induced by interrupting arterial perfusion for a minute or more.
Cytogenetic Abnormalities in a Plasmacytoma
Authors: MANCINELLI SERGIO , DURANT JOHN R. , HAMMACK WILLIAM J.
Published: October 2019

Cytogenetic studies from a plasmacytoma, bone marrow, and peripheral blood of a patient with myelomatosis have been described. Studies on the plasmacytoma revealed a marker chromosome in 72 per cent of the cells. Ninety-eight per cent of these contained an abnormal acrocentric marker similar to that reported by Tassoni et al.2 and approximately 50 per cent of the marker-positive cells contained an MG-like chromosome. The origin of the acrocentric marker appeared to involve a translocation from an unknown chromosome to a normal D group member, and that of the MG-like marker to involve pericentric inversion of a normal A group member.

The high percentage of cells from the tumor which contained the marker chromosomes makes it likely that these markers, described in low percentage in marrow or peripheral blood by others, actually were obtained from myeloma cells.
Leukapheresis* by Continuous Flow Centrifugation (CFC) in Patients with Chronic Myelocytic Leukemia (CML)
Authors: BUCKNER DEAN , GRAW ROBERT G. , EISEL ROBERT J. , HENDERSON EDWARD S. , PERRY SEYMOUR
Published: October 2019

A closed continuous flow centrifuge (NCI-IBM Blood Cell Separator) was utilized to collect large quantities of leukocytes from donors with chronic myelocytic leukemia. Ninety-eight separate centrifugations of one to six hours duration were performed in 12 patients. Quantities of blood between 2.4-20.3 liters were processed during each centrifugation representing 0.4-3.2 donor blood volumes. An additional five centrifugations were attempted unsuccessfully. Buffy coat cells were collected while plasma and red blood cells were returned to the donor without change in flow or gravitational field. White blood cell yields of up to 75 per cent were obtained while platelet yields were electively varied from 0.1 per cent in donors with thrombocytopenia to 61.0 per cent in donors with thrombocytosis.

Red blood cell hemolysis and excessive platelet losses with thrombocytopenia were not observed. One patient developed chills and fever of unknown etiology on two separate occasions, once during and once following CFC

Leukocytes collected by this method and transfused into granulocytopenic recipients resulted in granulocyte increments of 2.0 x 103 per mm3 per 1011 granulocytes per m2 of body surface area. The persistence of cells with the Ph1 chromosome in the bone marrow of recipients demonstrated that viable proliferating cells survived the procedure.
Gaucher Cells in Chronic Myelocytic Leukemia: An Acquired Abnormality
Authors: KATTLOVE HERMAN E. , WILLIAMS JEANNINE C. , GAYNOR EVELYN , SPIVACK MORTON , BRADLEY ROY M. , BRADY ROSCOE O.
Published: October 2019

A patient with CML is presented in whom Gaucher’s cells were seen in the bone marrow and other tissues. Biochemical and electron microscopic studies established the similarity of these cells to those found in Gaucher’s disease. Evidence is presented which indicates that the granulocyte is normally the major source of sphingolipid and that the Gaucher’s cells seen in CML arise from excessive granulocyte turnover.
An Adaptation of Methacrylate Embedding for Routine Histopathologic Use
Authors: ZAMBERNARD JOSEPH , BLOCK MATTHEW , VATTER ALBERT , TRENNER LEW
Published: October 2019

A plastic tissue embedding technic which is rapid and simple enough for routine clinical and research usage has been described. Tissues were routinely processed at 2 µ and 4 µ in a hospital laboratory within 16 hours. The quality of the sections was superior to those obtained with paraffin so that cell types are clearly recognizable. Advantages of this process over paraffin embedding include ease of storage and superior preservation of cytological detail.
Thymic Lymphopoiesis and Cell Loss in Newborn Mice
Authors: MICHALKE W. D. , HESS M. W. , RIEDWYL H. , STONER R. D. , COTTIER H.
Published: October 2019

Thymic lymphopoiesis in 2 day old Swiss albino mice (Hale-Stoner strain) was studied autoradiographically based on the variation of mitotic labeling indices and intensities after a single intraabdominal injection of 3H-thymidine. Best estimates for the duration of various phases of the generative cell cycle are as follows: G2 for the majority of cells: 86-94 minutes, shortest possible duration for a small fraction of cells: 35-48 minutes; mitosis: 27-44 minutes; DNA synthesis: 7 hours; generation time: 9¼ hours. G1 could not be determined directly by the methods used but probably is short. The present data do not indicate different generation times for proliferating thymic lymphoid cells of unequal size although the very largest elements must be excluded from this statement because of rare occurrence. The results obtained in this study together with data on changes of thymic weight and proliferative activity in the neonatal period indicate that during the third day after birth, a fraction corresponding to one third of all lymphoid cells present in the organ at the end of this period is lost. In view of the extremely low pyknotic index in the thymus at this age, the present data provide support in favor of an extensive emigration of lymphoid cells being the major cause of this cell loss.
Humoral Factors Influencing Erythropoiesis in the Fish (Blue Gourami—Trichogaster trichopterus)
Authors: ZANJANI ESMAIL D. , YU MAN-LIM , PERLMUTTER ALFRED , GORDON ALBERT S.
Published: October 2019

Evidence is presented for the existence of a circulating erythropoiesis stimulating factor in the bled fish (blue gourami).

Erythropoiesis is inhibited by starvation and increased following a single bleeding in the gourami.

Administration of serum from the bled gourami to the starved gourami evokes a highly significant increase in erythropoiesis. Serum from normal non-bled fish fails to produce this effect.

Large doses of sheep plasma ESF and human urinary ESF (16 units/100 Gm. body weight) stimulate erythropoiesis in the starved gourami. Smaller amounts, highly active in the polycythemic mouse, are without effect in the gourami.

No in vitro stimulatory effect on radioiron uptake by peripheral red blood cells of the gourami was exerted by anemic gourami serum or mammalian ESF.

The starved gourami may find use as a test animal for erythropoietic factors from other lower vertebrates.
Erythrocyte Acetylcholinesterase Deficiency in Paroxysmal Nocturnal Hemoglobinuria (PNH)—A Comparison of the Complement-Sensitive and Insensitive Populations
Authors: KUNSTLING T. R. , ROSSE WENDELL F.
Published: October 2019

1. The complement-sensitive and -insensitive cells of patients with paroxysmal nocturnal hemoglobinuria have been separated by differential lysis using a cold agglutinin antibody and limiting concentrations of complement. The erythrocyte acetylcholinesterase (AChE) activity of each population of cells was determined.

2. The membranes of the complement-sensitive cells characteristic of PNH completely lack AChE activity.

3. The membranes of the complement-insensitive cells usually contain less AChE than normal and the degree of decrease roughly parallels the degree of increased sensitivity to complement.

4. Lysis of normal cells by complement does not alter the AChE activity of their membranes.

5. The inhibition of AChE activity by neostigmine methylsulfate (Prostigmin®) does not increase the sensitivity of normal red cells to lysis by C’.
Brief Report: Protein Synthesis in Aging Blood Platelets
Authors: STEINER MANFRED , BALDINI MARIO
Published: October 2019

Platelet cohorts were produced in rats following immunologically induced thrombocytopenia. Young platelets had a significantly greater rate and magnitude of amino acid incorporation into protein than aged ones. This indicates a similar maturation process in platelets as in reticulocytes.
The Relationship of Bartonella Bacilliformis to the Red Blood Cell as Revealed by Electron Microscopy
Authors: CUADRA MANUEL , TAKANO JUAN
Published: October 2019

Ultrathin sections of erythrocytosis parasitized by B. bacilliformis have been examined by electron microscopy. The study concerns three Oroya Fever patients whose blood smears showed B. bacilliformis predominantly in its coccoid form as parastizing over 70 per cent of the red cells.

B. bacilliformis is termed as a bacterium in its structure and appears to lie not only on the host red cells but predominantly within them. Therefore, this organism might have the capacity to penetrate into the red cell. This finding does not change the basic concept regarding the mechanism of the anemia of Oroya Fever.
"Myeloma Protein" in a Patient with Monocytic Leukemia
Authors: POULIK M. DAVE , BERMAN LAWRENCE , PRASAD ANANDA S.
Published: October 2019

A 74 year old man with monocytic leukemia was found to have serum and urinary protein findings typical of myelomatosis. Lysozyme excretion in the urine was in the range characteristic of monocytic leukemia. There were no x-ray findings indicative of myeloma. Aspirated bone marrow specimens contained one to three per cent plasma cells, and less than 0.1 per cent atypical plasma cells. The leukemia responded temporarily but without remission to treatment with 6MP and steroid, with no effect on the myeloma protein profile or excretion of the urinary proteins.

The leukemia was present without overt morphologic or x-ray findings of myeloma, and the case differs from a similar example of the association of myeloma protein with monocytic leukemia in which the leukemia occurred as a terminal event in a previously well-documented myelomatosis.

The serum contained a fast-moving "myeloma gamma globulin" which was classified as γ-1, Kappa; Gm. (a + b - f -) Inv. (a). This protein was heterogeneous by starch gel electrophoresis. The urine contained large amounts of lysozyme, Fab, Fc and F'c fragments of the "myeloma gamma globulin," light chains of type Kappa, as well as whole gamma globulin. Small amounts of other serum proteins were also found.

The possibility of two neoplastic proliferations involving both the monocytes and plasma cells has been considered. Possible role of monocytoid stem cells with giant nucleoli in the synthesis of "myeloma protein" has been discussed.
Defective Bactericidal Activity of Monocytes in Fatal Granulomatous Disease
Authors: RODEY GLENN E. , PARK B. H. , WINDHORST DOROTHY B. , GOOD ROBERT A.
Published: October 2019

The bactericidal activity of monocyte-rich cell suspensions obtained from the peripheral blood of patients with fatal granulomatous disease (FGD), their mothers and normal controls was studied. Defective killing of Staphylococcus aureus, Strain 502A, by monocyte-rich cell suspensions from children with FGD was found when compared with monocyte-rich suspensions from normal controls. This defect, less severe, was also observed in the mothers of affected patients. In this selected population of mothers, the monocyte defect varied in parallel with the previously described neutrophil defect.
The Mononucleosis Cell III. Electron Microscopy
Authors: SCHUMACHER H. R. , McFEELY A. E. , MAUGEL T. K.
Published: October 2019

The peripheral mononucleosis lymphocytes from eleven patients with infectious mononucleosis were studied by means of electron microscopy. They were compared to normal lymphocytes in linear and area measurements, and in cellular characteristics by random selection of electron micrographs. The mononucleosis lymphocyte showed significantly greater cell and cytoplasmic area, greater cell length, more nucleoli, polyribosomes and compound vacuoles, than the normal lymphocyte. These ultrastructural findings are discussed in the light of our present biochemical knowledge of the mononucleosis cell. A tentative hypothesis concerning the pathogenesis of the mononucleosis cell is presented.
Cytogenetic Findings in Erythroleukemia
Authors: Heath Clark W. , Bennett John M. , Whang-Peng Jacqueline , Berry Elizabeth W. , Wiernick Peter H.
Published: October 2019

Cytogenetic Findings in Erythroleukemia by Heath et al. Page 453—Peter H. Wiernik’s name was misspelled.
Hemoglobin L Ferrara in a Jewish Family Associated with a Hemolytic State in the Propositus
Authors: NAGEL RONALD L. , RANNEY HELEN M. , BRADLEY THOMAS B. , JACOBS ALAN , UDEM LINDA
Published: October 2019

A Jewish family in which Hb L Ferrara (α247 Asp → Gly β2) occurred is reported. Studies of some of the properties of this hemoglobin demonstrated that its oxygen equilibria, number of readily reactive-SH groups, and spectro-photometric tyrosine titration were indistinguishable from Hb A. Nevertheless, Hb LF was more unstable than Hb A at 55 C. The propositus had accelerated blood destruction although six other heterozygotes for Hb LF did not. A second defect in red cell enzymes or red cell lipids of the propositus was not demonstrable with the technics used but the possibility that the simultaneous occurrence of Hb LF and an otherwise "silent" red cell defect may lead to a hemolytic state remains an attractive explanation. The data provided by this family study did not permit a definite conclusion about the relationship of clinically evident hemolysis in the propositus to the presence of the abnormal hemoglobin.
Serologic Specificity of Human Anti-IgA and its Significance in Transfusion
Authors: VYAS G. N. , HOLMDAHL L. , PERKINS H. A. , FUDENBERG H. H.
Published: October 2019

Anti-IgA antibodies detected by a passive hemagglutination assay are either specific for the IgA class or they are of limited specificity. Persons lacking IgA can produce class-specific anti-IgA as a result of parenteral exposure to incompatible IgA globulin in blood and its components. In contrast, persons with normal levels of IgA may produce anti-IgA of limited specificity. Either type of anti-IgA antibodies was present in 86 per cent of anaphylactoid and urticarial transfusion reactions. A majority of these antibodies are of the IgG class.
The Separation of Normal Human Leukocytes by Density and Classification by Size
Authors: ZUCKER ROBERT M. , CASSEN BENEDICT
Published: October 2019

Leukocytes of hematologically normal human blood have been studied by separating them in bovine serum albumin gradients. The blood cells of the density fractions have been characterized by electronic volume sizing and microscope differential counts. The electronic volumes of different leukocyte populations have been determined from density gradient experiments. Lymphocytes of various sizes can be separated by differences in density. The small lymphocyte population is the most dense while the large population is the least dense. The density of blood cell populations in BSA in order of increasing density were: monocytes, lymphocytes, granulocytes and erythrocytes.
Citrate Stabilization of Chromatographically Purified Factor VIII
Authors: HYNES HENRY E. , OWEN CHARLES A. , BOWIE E. J. WALTER , THOMPSON JOHN H.
Published: October 2019

When oxalated or resin-decalcified human plasma was adsorbed with barium sulfate, equilibrated with 0.0175M phosphate buffer (pH 6.3), and chromatographed through diethylaminoethyl (DEAE) cellulose, most of the plasma’s fibrinogen emerged from the column and factor XII was detected. No factor VIII was found. A second buffer phase, in which 0.04M phosphate buffer (pH 5.9) was used, removed more protein but not fibrinogen or factor VIII. A third phase, 0.10M phosphate buffer (pH 5.6), produced additional fibrinogen and, unlike the first fibrinogen fraction, factor XIII; but again, no factor VIII. A fourth and final phase, 0.40 to 0.50M phosphate buffer (pH 5.3), removed factors VIII and V, and the eluate contained no fibrinogen.

Although separation of fibrinogen into two components required the four-buffer system, maximal yields of factor VIII were achieved by compressing the first three buffer phases into one. Specific activities of about 50-fold, from large volumes of plasma, and 200-fold, from small volumes, were obtained.

Refined factor VIII was unstable unless citrate was added to a concentration of 0.4 per cent.
Brief Report: Prolonged Intravenous Iron-Dextran Therapy in a Patient with Multiple Hereditary Telangiectasia
Authors: CHERNELCH MILAN , WINCHELL HARRY SAUL , POLLYCOVE MYRON , SARGENT THORNTON , KUSUBOV NATALIA
Published: October 2019

Quantitative measurements of blood and iron whole body radioiron loss, total body iron, and iron and erythrocyte kinetics are presented in a patient with hereditary hemorrhagic telangiectasia treated with massive quantities of an iron-dextran complex given intravenously. This iron therapy enabled the patient to maintain a hemoglobin concentration of 6 Gm./100 ml. despite the loss of 600-900 ml. of blood per day. Though considerable hemosiderosis was present at the time of death, no apparent tissue injury was present. The excess iron present constituted a very small fraction of the total iron administered, was only slowly mobilizable for hemoglobin synthesis and, consequently, did not obviate the need for continued administration of fresh dextran iron.
Brief Report: Lipid Peroxidation in Aging Platelets
Authors: OKUMA MINORU , STEINER MANFRED , BALDINI MARIO
Published: October 2019

Blood platelets showed an age dependent accumulation of lipid peroxides. Lipid peroxidation stimulated by heavy metal also increased with platelet age and rose at a much faster rate than the spontaneous peroxide formation. This suggests the loss of a cellular defense mechanism against lipid peroxidation in aging blood platelets.
On the Development of Slowly-turning-over Cell Types in Neonatal Rat Bone Marrow (Studies Utilizing the Complete Tritiated Thymidine Labeling Method Complemented by C-14 Thymidine Administration)
Authors: HAAS R. J. , BOHNE F. , FLIEDNER T. M.
Published: October 2019

1. The continuous H3-thymidine (H3-TdR) intravenous infusion of rats from day 9 of pregnancy until term results in the labeling of every single cell nucleus in the body of the offspring. Completely labeled newborn rats were sacrificed at serial intervals after birth. This provided the opportunity to follow the labeling pattern of all bone marrow cells during the development of this organ. Cytokinetically three types of cell renewal systems could be found: one type showed a rapid turnover losing all H3-TdR within 6 days, e.g., erythropoietic and myelopoietic cells. Another lost most of its labeling throughout the same time except a small but significant fraction (bone marrow lymphocytes). The third retained a high fraction of labeled cells with a high labeling intensity for weeks and months (reticular cells and endothelial cells).

2. A continuation of H3-TdR administration of 100 per cent labeled newborn rats throughout the first three weeks of neonatal life resulted cytokinetically in the same three different cell types. However, a larger fraction of reticular and endothelial cells as well as bone marrow lymphocytes remained labeled weeks and months after the last injection as compared with the first group of 100 per cent labeled animals.

3. An administration of C14-TdR to 100 per cent labeled newborn animals throughout the first 6 days after birth Showed that 30 to 40 per cent of the "resting" bone marrow cells have turned into a resting state before or at least at the time of birth. Forty per cent of these cells still had some proliferative capacity during the first 6 days of life. Twenty per cent showed in the first days after birth a rapid turnover whereas later on they acquired their final cytokinetic state. The possible influence of radiation toxicity on the time of establishment of resting cells is discussed. This approach appears of use to study the functional properties of resting bone marrow cell types in regenerative processes and the cellular origin in the bone marrow.
Identification of the Philadelphia (Ph-1) Chromosome
Authors: PRIETO FELIX , EGOZCUE JOSE , FORTEZA GERONIMO , MARCO FELIX
Published: October 2019

The presence of a marker G, which later converted into the Ph-1 chromosome, in a female patient with chronic myelogenous leukemia, permitted identification of the G chromosome from which the Ph-1 originated as a member of the early replicating, G-22 pair.
Diagnosis of Erythrocyte Glucose-6-Phosphate Dehydrogenase Deficiency in the Negro Male Despite Hemolytic Crisis
Authors: HERZ FRITZ , KAPLAN EUGENE , SCHEYE ELSIE S.
Published: October 2019

A simple procedure for the diagnosis of erythrocyte glucose-6-phosphate dehydrogenase deficiency in Negro males experiencing hemolytic crisis is described. By measuring enzyme activity in the persisting older erythrocytes, the deficiency can be recognized without having to wait until the hemolytic episode and its reticulocyte response have subsided.
Absorption of Hemoglobin Iron: The Role of Xanthine Oxidase in the Intestinal Heme-Splitting Reaction
Authors: DAWSON R. BEN , RAFAL SHEILA , WEINTRAUB LEWIS R.
Published: October 2019

Heme from ingested hemoglobin—59Fe is taken into the epithelial cell of the small intestinal mucosa of the dog and the 59Fe subsequently appears in the plasma bound to transferrin. A substance was demonstrated in homogenates of the mucosa which releases iron from a hemoglobin substrate in vitro. Thus: (1) The addition of catalase to the mucosal homogenate reduces the "heme-splitting" reaction. In contrast, sodium azide, a catalase inhibitor, potentiates the reaction. This suggests that a peroxide generating system participates in the "heme-splitting" reaction. (2) Xanthine oxidase, an enzyme present in the intestinal epithelial cell, produces H2O2 by oxidation of its substrate. The addition of allopurinol, a xanthine oxidase inhibitor, to the intestinal mucosal homogenate diminishes the "heme-splitting" reaction. (3) Fractionation of the 50,000 Gm. supernatant of the mucosal homogenate on a G-200 Sephadex column shows the "heme-splitting" activity to have the same elution volume as xanthine oxidase, indicating a similar molecular weight. (4) The addition of a mucosal homogenate to a xanthine substrate results in the production of uric acid. These data suggest that xanthine oxidase in the intestinal epithelial cell is important in the release of iron from absorbed heme. The enzyme mediates the "heme-splitting" reaction by the generation of peroxides which, in turn, oxidize the alpha-methene bridge of the heme ring releasing iron and forming biliverdin.
Brief Report: Aspirin Ingestion Compared with Bleeding Disorders—Search for a Useful Platelet Antiaggregant
Authors: WEISS HARVEY J.
Published: October 2019

The effects on human platelets produced by ingesting aspirin have been compared with the types of platelet abnormalities observed in patients with bleeding disorders. The inhibitory effect of aspirin on platelet function appears to be relatively weak and suggests a continued search for antiaggregant agents which may prove to be useful in preventing thrombosis.
Inheritable Differences in the Electrophoretic Pattern of Hemoglobin Revealed in a Local Random-Bred Colony of Albino Rats
Authors: MARTINOVIC JOVO V. , MARINKOVIC DOBRIVOJE V. , KANAZIR DUSAN T. , MARTINOVITCH PETER N.
Published: October 2019

In a local colony of random-bred Albino rats, three different patterns of hemoglobin, arbitrarily denoted as patterns I, II and III, were detected by means of starch-gel electrophoresis in a discontinuous buffer system. Mating experiments showed that rats bearing pattern I and pattern III hemoglobin bred true. Crosses of pattern I with pattern III animals yielded only pattern II animals, and when the latter were mated inter se, the resultant F2 generation showed approximately a ratio of 1:2:1 for patterns I, II and III, respectively. When F1 animals from pattern I with pattern III crosses were mated back to animals of either parental type, the resultant ratio was found to be one pattern II: one pattern I or pattern III.
Brief Report: Absence of Special Fetal Hemoglobin in Beagle Dogs
Authors: LECRONE CAROL N.
Published: October 2019

A distinctive fetal hemoglobin compound easily distinguishable in late prenatal and early postnatal life is present in most mammals. This study, however, has shown no differences between the fetal, immature and adult beagle dog hemoglobin.
Plasma and Erythrocyte Folate in Iron Deficiency and Folate Deficiency
Authors: OMER A. , FINLAYSON N. D. C. , SHEARMAN D. J. C. , SAMSON R. R. , GIRDWOOD R. H.
Published: October 2019

Erythrocyte and plasma folate levels were studied before treatment in 20 patients with iron deficiency anemia and in 23 patients with megaloblastic anemia due to folate deficiency. Fourteen of the cases of iron deficiency anemia were also studied after treatment with oral iron alone. Fifty-seven normal persons were used as controls.

The mean erythrocyte folate (ng./ml. packed cells) was significantly increased in iron deficiency anemia and significantly depressed in folate deficiency anemia. After treatment with oral iron alone, the mean erythrocyte folate level fell to normal in the iron deficiency anemia group. The mean corpuscular folate (ng. x 108-8) was also significantly raised in iron deficiency: in eight of 10 cases this fell after treatment, but the overall fall was not significant. The plasma folate rose in iron deficiency anemia after oral iron treatment.
Paroxysmal Nocturnal Hemoglobinuria: Evidence for Monoclonal Origin of Abnormal Red Cells
Authors: ONI S. B. , OSUNKOYA B. O. , LUZZATTO L.
Published: October 2019

Paroxysmal nocturnal hemoglobinuria (PNH) was diagnosed in a 26-year-old Nigerian woman who subsequently died of amebic colitis. The patient’s red cells exhibited mosaicism with respect to glucose 6-phosphate dehydrogenase, in that some of them had the A, and some of them had the B variant of this enzyme (as expected in female subjects heterozygous at this sex-linked locus). The red cells bearing the PNH abnormality only had the B variant, suggesting that they all belonged to a single abnormal clone.
Platelet Cold Agglutinins
Authors: WATKINS STANLEY P. , SHULMAN N. RAPHAEL
Published: October 2019

A "cold" platelet agglutinin is described which is present in plasma and serum, is greater than 100,000 in molecular weight, appears to be a protein of the immunoglobulin type, is adsorbed by platelets in the absence of bivalent cations, and reacts only at temperatures below 34°C. It agglutinates homologous and autologous platelets but appears to have no effect on in vivo platelet function. It is seen in patients with systemic disease and can cause spuriously low platelet counts.
A Note on the Relationship Between Bone Marrow Lymphocytosis and Remission Duration in Acute Leukemia
Authors: BRESLOW NORMAN , ZANDSTRA RICHARD
Published: October 2019

In a sample of 148 children with acute leukemia a positive correlation was found between the duration of remission and the highest percentage bone marrow lymphocyte count observed during remission; a negative correlation was found between remission duration and the average lymphocyte count. The first finding is probably a statistical artifact, while the second supports the view that bone marrow lymphocytosis occurring repeatedly during remission may be a poor prognostic sign.
Leukocyte Antigen-Antibody Reaction and Lysis of Paroxysmal Nocturnal Hemoglobinuria Erythrocytes
Authors: SIRCHIA GIROLAMO , FERRONE SOLDANO , MERCURIALI FRANCESCO
Published: October 2019

The interaction between leukocyte antigens and specific antibodies can cause lysis of the red cells of paroxysmal nocturnal hemoglobinuria (PNH) in vitro. It is suggested that the activation of complement ensuing from the antigen-antibody interaction is responsible for PNH cell lysis. The clinical implications of this finding are briefly outlined.
Brief Report: Philadelphia Chromosome in Acute Lymphocytic Leukemia
Authors: PROPP SIMON , LIZZI FRANK A.
Published: October 2019

It is recognized that the Ph1 chromosome anomaly is characteristic of chronic granulocytic leukemia. It has been shown however, to occur rarely in other myeloproliferative diseases. We have reported a 53-year-old roentgenologist with acute lymphocytic leukemia who showed a high percentage of Ph1 chromosomes in his marrow cells. The possible role of radiation exposure in the production of the abnormal chromosome in this patient is discussed. The data presented is evidence against the specificity of the Ph1 chromosome for myeloproliferative disorders.