bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukokinetic Studies. VII. Morphology of the Bone Marrow and Blood of Dogs Given Vinblastine Sulfate
Authors: BOGGS DANE R. , ATHENS JOHN W. , HAAB OTTO P. , CANCILLA PASQUALE A. , RAAB SPENCER O. , CARTWRIGHT GEORGE E. , WINTROBE MAXWELL M.
Published: October 2019

The effect of a single injection of vinblastine sulfate was studied in 50 mongrel dogs. Nine of 34 dogs given 0.2 mg./Kg. of VLB died with gastrointestinal toxicity and the mortality rate increased as the dosage of VLB was increased. The morphologic pattern of leukocyte suppression and recovery in the bone marrow and blood was studied in detail in surviving animals.

The cells of the bone marrow were markedly affected by VLB. Within 4 hours there was an increase in the number of cells in metaphase and, by day 1, virtually all proliferating leukocytes and erythrocytes had disappeared. An orderly repopulation of the bone marrow followed.

The neutrophils, eosinophils, lymphocytes and monocytes of the blood were all markedly altered in concentration after VLB. Each type of cell first decreased to abnormally small numbers and then increased to abnormally large numbers in the blood. The curve of disappearance from and reappearance in the blood differed for each cell type.

The changes in blood neutrophil number and morphology were correlated with changes in the blood neutrophil precursor cells of the marrow. The following conclusions were reached concerning the neutrophils and the assumptions implicit to these conclusions were detailed.

1. In the dog, the marrow contains enough post-mitotic granulocytes to replace those lost from the blood for at least 3 to 4 days.

2. The release of mature neutrophils from the bone marrow is a function of the rate at which blood neutrophils are lost and proceeds normally even when the marrow granulocyte reserve is partially depleted.
Cytologic Features and Cellular Migration in the Cortex and Medulla of Thymus in the Young Adult Rat
Authors: SAINTE-MARIE G. , LEBLOND C. P.
Published: October 2019

The cells of the cortex and medulla of thymus and their mitoses were described in 10-week old (200 Gm.) male rats.

The four main cell types found in cortex (reticular cells, large, medium and small lymphocytes were related to each other by transitional cell types. The presence of numerous mitoses of the four cell types indicates rapid cell production. Since the thymus of 10-week old rats is not growing and, therefore, each cell population must be in a steady state, the mitotic production of new cells of a given type must be balanced by transformation into cells of another type or by emigration out of the cortex. Evidence is presented in support of the transformation of reticular cells into large lymphocytes; and of these into lesser and lesser sized lymphocytes. As for small lymphocytes, the evidence indicates that they migrate form cortex to medulla.

The medulla contains numerous small lymphocytes, some reticular cells, and rare large and medium lymphocytes. The lymphocytes of the medulla (presumed to have migrated from the cortex) often show nuclear processes which are attributed to ameboid motion.

The medulla of the rat thymus contains many blood vessels, most of which are enclosed within "perivascular channels." Diapedesis of lymphocytes, chiefly small ones, is frequently seen across the walls of both the perivascular channels and the blood vessels themselves. Furthermore, higher counts of lymphocytes in venous than in arterial blood of thymus indicate that these cells directly enter the blood circulation.

In conclusion, cells of the lymphocytic series are produced by mitosis in the cortex of the thymus. The evidence indicates that lymphocytes arising in this region migrate into the medulla. Thence, these cells pass into perivascular channels and into the enclosed blood vessels to reach the circulation.
Brief Report: Studies on Subcellular Platelet Particles
Authors: MARCUS AARON J. , ZUCKER-FRANKLIN DOROTHEA
Published: October 2019

The phospholipids of subcellular platelet particles are very similar to those of the intact platelet. However, they contain a higher proportion of long-chain, highly unsaturated fatty acids, which confers upon them physical characteristics suggesting a dynamic biological system.
Early and Late Cytologic Effects of Whole Body Irradiation on Human Marrow
Authors: FLIEDNER T. M. , ANDREWS GOULD A. , CRONKITE EUGENE P. , BOND VICTOR P.
Published: October 2019

1. Serial marrow studies were performed during the first few days in eight men accidentally exposed to a mixed neutron gamma irradiation. They showed the occurrence of a wave of cytologic abnormalities. These were identical with those seen in animal experiments 1-3 days after whole body irradiation. They were considered to be "mitotically connected" (M. C. Abn.) and included the occurrence of chromosomal bridges and chromosomal fragments in mitoses. In interphase cells, the main abnormalities were nuclear fragments ("karyomeres") in the cytoplasm of erythroblasts, myelocytic cells and lymphocytes; bi- and multinucleated cells; and giant cells. The peak of abnormalities in the erythropoietic forms was reachéd after 2 days; that in the myelopoietic cells 4 days after exposure. On the 4th day, there was a distinct dose-dependent difference in these abnormalities between the high dose group (236-365 rads) and the low dose group (22-68 rads).

2. Some cytologic abnormalities, as seen in increased regeneratory activity of the marrow, were found in marrow smears 3.5 years after the accident, although the peripheral blood counts and mitotic indices of the marrow were within normal range. Their significance is obscure.

3. A careful cytologic evaluation of serially aspirated marrow samples during the first hours and days after whole body exposure proves to be an additional important aid in the assessment of the exposed individual and may well prove to be useful in determining the degree of injury and thus the prognosis.
The Acridine Orange Viability Test Applied to Bone Marrow Cells I. Correlation with Trypan Blue and Eosin Dye Exclusion and Tissue Culture Transformation
Authors: HATHAWAY WILLIAM E. , NEWBY LOUIS A. , GITHENS JOHN H.
Published: October 2019

Suspensions of murine bone marrow cells were stained with acridine orange (A-O) and observed under fluorescent microscopy after treatment with various injurious agents in order to establish the staining characteristics of "live" and "dead" cells. The percentage of viable cells demonstrated by the "A-O viability test" were correlated with eosin and trypan blue dye exclusion and tissue culture transformation viability tests. In general, the A-O test demonstrated the viability of cells preserved by freezing as effectively as the other in vitro tests. In addition, the A-O test may be more sensitive in determining the viability of cells where metabolic processes have been injured by poisons or change in pH.
A Direct Assay for Dihydrofolate Reductase in Human Leukocytes
Authors: MISRA D. K.
Published: October 2019

A new direct spectrophotometric assay for dihydrofolate reductase has been developed. The reaction is observed at 282 mµ and is based on the disappearance of dihydrofolate. Based on this assay, the values for normal leukocytes are 0-5 mµmoles of dihydrofolate reduced to tetrahydrofolate, per mg. of protein per hour at 28 C. The respective values for chronic myelogenous leukemic granulocytes are 25-67, chronic lymphocytic leukemia 0-18, acute lymphocytic leukemia 7-19, and for leukocytes of leukemoid reaction 4 to 5.
Porphyria Cutanea Tarda Associated with Chronic Granulocytic Leukemia Treated with Busulfan (Myleran)
Authors: KYLE ROBERT A. , DAMESHEK WILLIAM
Published: October 2019

A patient with chronic granulocytic leukemia terminating in "blast crisis" and marked porphyria is presented. Quantitative porphyrin studies revealed: urinary uroporphyrin 8894 to 11,453 µg./24 hours, urinary coproporphyrin 107-486 µg./24 hours, fecal coproporphyrin 55-116 µg./Gm. dry weight and fecal protoporphyrin 22-38 µg./Gm. dry weight. A review of the clinical aspects of porphyria is briefly presented, together with some speculation as to the etiology of the porphyria in the present case. The possibility is present that the busulfan therapy either initiated the disorder or triggered its development from a previously occult state. If so, this would be another manifestation of busulfan toxicity, of which pigmentation is the most common.
Separation of Lymphocytes, Polymorphonuclear Leukocytes and Monocytes on Glass Columns, Including Tissue Culture Observations
Authors: RABINOWITZ YALE
Published: October 2019

A procedure was described for the separation of lymphocytes, polymorphonuclear (PMN) leukocytes and monocytes on Garvin’s glass bead columns. Dextran-sedimented leukocyte suspensions were added to columns and incubated at 37 C. Lymphocytes were eluted with fresh serum. The columns were then washed completely free of erythrocytes, platelets and lymphocytes while PMN leukocytes and monocytes continued to adhere. PMN leukocytes and monocytes were released from the glass with EDTA. Monocytes appeared in the effluents somewhat later than the PMN leukocytes, permitting a separation.

A fresh serum, heat labile, Ca+ +- and Mg+ +-requiring PMN leukocyte and monocyte adherence promoting factor was demonstrated and found to be essential to the procedure.

The viability of column-separated cells was shown by their non-staining with trypan blue, motility, phagocytic ability, oxygen consumption, and survival or development in tissue culture.

In tissue culture, macrophages developed only from monocytes, whereas Nowell’s blast-like, dividing, phytohemagglutinin cells were produced only in cultures containing lymphocytes.
The Morphologic Responses of the Lymphoid System to Homografts
Authors: ANDŔ-SCHWARTZ JANINE
Published: October 2019

An electron microscope study of the morphologic responses of the rabbit lymph node after skin homografting is described. The results demonstate: (a) the appearance of large, round, ribosome-rich cells—hemocytoblasts— during the first set reaction; (b) a striking proliferation of plasma cells during the second set reaction; (c) the absence of hemocytoblasts in the "6-MP tolerant" animals, and (d) large numbers of two types of unusual cells in the "6-MP resistant" animal. The presence of increased numbers of plasma cells in the second set homograft reaction is in agreement with the findings of circulating antibodies in transplantation immunity and indicates the fundamental unity of the dynamics of the cellular response in various immunological phenomena.
Acid Phosphatase Activity in Auer Bodies
Authors: GOLDBERG ARTHUR F.
Published: October 2019

Employing the Gomori lead salt method (pH 5.0), acid phosphatase activity was demonstrated in Auer bodies. The presence of this enzyme may be considered further evidence of the similarity between leukocyte granules, known to contain acid phosphatase, and this structure. No alkaline phosphatase activity was exhibited in these bodies. The significance of these findings is discussed.
A Variant of Hemoglobin A2 Found in a Negro Family
Authors: LEE RALPH C. , HUISMAN TITUS H. J.
Published: October 2019

The discovery of an abnormal minor hemoglobin in four heterozygous members of a Negro family is reported. The abnormality seems to be a variant of Hb-A2 and is probably identical with Hb-Flatbush.
Relative Folate Deficiency of Erythrocytes in Pernicious Anemia and its Correction with Cyanocobalamin
Authors: COOPER BERNARD A. , LOWENSTEIN LOUIS
Published: October 2019

1. A relationship has been observed between the serum and erythrocyte folate in normal subjects.

2. Patients with folate deficiency were more readily differentiated from normal subjects by determinations of serum folate activity than by determinations of erythrocyte folate activity.

3. In pernicious anemia in relapse, accumulation of serum folate and/or depletion of erythrocyte folate was observed in all patients, resulting in a disturbance of the normal relationship between the serum and erythrocyte folate activity. This altered relationship was corrected following the reticulocytosis induced by vitamin B12 therapy.

4. Patients receiving amethopterin therapy appear to incorporate the folate antagonist into maturing erythroid cells, since the erythroid cells so formed showed anti-bacterial activity for several weeks following the administration of the antagonist.

5. Preliminary fractionation of folate co-enzymes in erythroid cells of a patient with pernicious anemia before and after therapy revealed no significant difference in the distribution of the co-enzymes induced by therapy. A significant proportion of the folate activity of the erythroid cells was found in a fraction eluted from the DEAE column by sodium hydroxide.

6. The data presented are consistent with a direct effect of vitamin B12 on folate transport into the erythroblast.
Granulocytopoiesis. II. Emergence and Pattern of Labeling of Neutrophilic Granulocytes in Humans
Authors: FLIEDNER T. M. , CRONKITE E. P. , KILLMANN S. Å. , BOND V. P.
Published: October 2019

1. Following administration of H3-thymidine to 15 patients with a variety of hemopoietic conditions, the emergence and the pattern of labeling of neutrophilic granulocytes were studied in peripheral blood leukocytic concentrates. The hematologic diagnosis included five in which the hemopoiesis appeared to be in a steady state equilibrium at the time of study, three with various types of leukemia, one with lymphosarcoma, two with multiple myeloma, one with myelofibrosis, two with pernicious anemia (once before and once after therapy) and two with bacterial infections.

2. The emergence time of neutrophilic segmented granulocytes (time from H3-thymidine injection to the first appearance of labeled segmented forms in the peripheral blood) was found to vary in steady state equilibrium from 96 to 144 hours. It was shortened to 48 hours in two instances with bacterial infection. This was interpreted as indicating a faster than normal nuclear maturation with normal or delayed cytoplasmic maturation (dissociation in nuclear and cytoplasmic maturation).

3. The number of segments of neutrophilic granulocytes was found to be unrelated to cell age as had been hypothesized by Arneth many years ago. However, bandforms were found in the circulation about 24 hours earlier than segmented forms, suggesting that they are younger and that some are acceptable to the blood while others continue to mature to segmented forms. Pelgeroid cells with round or bilobed nuclei found in one case of subleukemic myelocytic leukemia were found to emerge simultaneously 132 hours after H3-thymidine injection. This suggests that both types are identical in their degree of maturation. Thus the cells with round nuclei are not band forms but result possibly from a delayed nuclear maturation.

4. In patients studied for at least 2 weeks, characteristic undulations of the labeling indices of the segmented granulocytes were found. If the sampling intervals were 24 hours, peaks were found 6 days apart, the second peak being about half of the labeling index of the first. If the sample interval was shorter, a finer structure was observed with undulations showing peak intervals of 2-3 days. Although the significance is obscure at present, the constancy of the findings suggest that there may be a constant input of cells with the index of labeling varying due to some synchrony of the precursor population(s). Alternative explanations are discussed.
Pathogenesis of Fibrinolysis in Defibrination Syndrome: Effect of Heparin Administration
Authors: MERSKEY CLARENCE , JOHNSON ALAN J. , PERT JAMES H. , WOHL HERBERT
Published: October 2019

1. Spontaneous local fibrinolysis occurred with, and was probably a consequence of thrombosis, with defibrination in vivo.

2. The efficacy of heparin in the prevention of defibrination was clearly demonstrated; warfarin therapy seemed to be ineffective.

3. The efficacy of heparin in the prevention of the associated fibrinolysis was clearly inferred.

4. Serum immunoelectrophoresis against anti-fibrinogen sera demonstrated abnormal precipitin bands, during defibrination and fibrinolysis, which disappeared during heparin administration.

5. The serum bands showed immunologic identity with in vitro plasmin digests of fibrinogen and the intensity and position of these precipitin bands appeared to depend on the amount of fibrinogen and the duration of the in vivo digestion period.

6. In this hypofibrinogenemic state, defibrination was indicated by markedly reduced levels of anti-hemophilic factor and Factor V and a fall in blood platelets. The presence of fibrinolysis was shown by the lowered levels of plasminogen, streptokinase and urokinase inhibitors, prolonged thrombin clotting times and fibrinolytic breakdown products in the serum even though little or no lysis occurred on fibrin plates and the euglobulin lysis times were within normal limits.

7. The administration of fibrinolytic inhibitors is strongly contraindicated under these circumstances.
Central Nervous System Involvement by Leukemia in Children. I. Relationship to Systemic Leukemia and Description of Clinical and Laboratory Manifestations
Authors: HYMAN CAROL B. , BOGLE JAMES M. , BRUBAKER CHARLES A. , WILLIAMS KENNETH , HAMMOND DENMAN
Published: October 2019

Observations on the course of 59 children who experienced 109 distinct episodes of CNS involvement by leukemia showed that:

1. This complication may be associated with all types of acute and subacute leukemia.

2. There is no single or combination of diagnostic criteria. Manifestations of increased CSF pressure, such as vomiting, headache, and papilledema are the most frequent clinical findings. However, it should be emphasized that CNS involvement may be associated with normal CSF findings.

3. CNS involvement may be present at the onset of leukemia or can occur at any time during the course.

4. Approximately 26 per cent of children with leukemia develop CNS involvement.

5. CNS involvement may occur when the disease is under apparently good therapeutic control as well as during relapse.

6. There is no relationship between the agents which had been previously used to treat the systemic disease and the later development of CNS involvement. However, the onset of CNS symptoms was less frequent when the systemic disease was under treatment with steroids.

7. The development of CNS involvement does not appear to shorten the survival time of patients with leukemia when treatment for CNS involvement is given.
Brief Report: Absorption Spectra of Inclusion Bodies in β-Thalassemia
Authors: FESSAS PHAEDON , LOUKOPOULOS DIMITRIS , THORELL BO
Published: October 2019

The spectroscopic properties of isolated or single erythroblastic and erythrocytic inclusions of homozygous β-thalassemia prove that these structures contain a hemoglobin-like component.
The Platelet-Fibrin Relationship in Human Blood Clots: An Ultrastructural Study Utilizing Ferritin-Conjugated Anti-Human Fibrinogen Antibody
Authors: White James G. , Krivit William , Vernier Robert L.
Published: October 2019

An ultrastructural study of clots formed in recalcified platelet-rich, human plasma has revealed an intimate platelet-fibrin association. A number of the dense platelet granules, the alpha granules, formed an osmophilic mass in the center of platelets undergoing viscous metamorphosis. Fibrin strands appeared to be connected to the altered alpha granulomere of these platelets.

The observed association between fibrin strands and platelets in the clot was supported by experiments with an electron dense stain for fibrinogen. Clots formed from platelet-rich plasma preincubated with fer-A.F. antibody contained altered platelets with an intracellular distribution of the ferritin conjugated antibody. Connections between intracellular fer-A.F. antibody and fibrin strands periodically banded by the ferritin stain were observed.

These observations indicate that the altered platelet granulomere attached to fibrin strands may play a role in clot retraction.
A Simple Rapid Method for Estimating Serum Plasmin Activity with Fibrin-Coated Latex Particles
Authors: Ferreira Humberto Costa
Published: October 2019

A new method is described for rapid determination of plasmin in serum. This method entails the production of clumps of latex particles held together by fine strands of artificially polymerized fibrin followed by the estimation of plasma turbidity as these particles are released from the aggregates by plasmin activity. The advantages and possible objections to this method are discussed.
Endocrine Relationships of Leukocyte Alkaline Phosphatase
Authors: ROSNER FRED , LEE STANLEY L.
Published: October 2019

Leukocyte alkaline phosphatase activity has been noted to be different in men and women. The mean leukocyte alkaline phosphatase activity for 74 normal men, aged 19 to 60 years, was 23 mg. of phosphorus per 1010 polvmorphonuclear leukocytes per hour. The corresponding mean value for 75 normal young women, age 19-48 years, was 35 (p < .001). No significant differences between boys and girls occurred until the time of puberty. After the menopause, the values for women approached the values for men. Women treated with androgens had lower leukocyte alkaline phosphatase activity than did control women. These results suggest that androgenic hormones inhibit this enzyme, and that other, as yet undefined endocrine influences, also affect its level of activity.

In vitro tests with various concentrations of androgens and estrogens failed to provide conclusive evidence of direct effect on leukocytes although some degree of direct inhibition by androgens was suggested. Studies using saponin to effect enzyme release from leukocyte granules did not demonstrate whether the differences between men and women are differences of enzyme release or of content of leukocyte alkaline phosphatase.
Brief Report: Commentary on Hemosiderin
Authors: RICHTER G. W. , BESSIS M. C.
Published: October 2019

In conclusion we should like to emphasize that the classical hemosiderin of the histologist is not a single or unique substance.8 The constitution of this material is quite variable. Removal of hemosiderin granules from cells for chemical analysis demands careful control based on morphologic criteria and is, in any case, not a substitute, but a concomitant of examination in situ in cells. One should bear in mind that in its natural state hemosiderin occurs in living tissues, not as a test tube isolate, or as a thin section.
Brief Report: Hereditary Methemoglobinemia in Greece
Authors: PAPASPYROU-ZONA ATHENA V. , GERALD PARK S. , SCOTT EDWARD M.
Published: October 2019

The cause of the methemoglobinemia described by Coudonis in four Greek families was found to be the absence of DPNH diaphorase in red cells.
The Amino Acid Composition of Hemoglobin. V. The Preparation of Purified Hemoglobin Fractions by Chromatography on Cellulose Exchangers and Their Identification by Starch Gel Electrophoresis Using Tris-Borate-EDTA Buffer
Authors: CHERNOFF AMOZ I. , PETTIT NELSON , NORTHROP JO
Published: October 2019

The chromatographic separation of hemoglobin on two cellulose exchangers, CMC and DEAE, is discussed. Problems related to the use of these technics are described. In addition, our experience with the use of Tris-Borate-EDTA buffer (Smithies) for hemoglobin electrophoresis in starch gel is presented.
Responsiveness of Hematopoietic Tissue to Erythropoietin in Relation to the Time of Administration and Duration of Action of the Hormone
Authors: SCHOOLEY JOHN C.
Published: October 2019

Following the injection of erythropoietin either in a single large dose or in multiple doses, a change in the responsiveness of the hematopoietic tissue occurs. The fact that different doses of erythropoietin stimulate erythropoiesis to the same extent when the action of the hormone is limited to 6 hours by the injection of antibody suggests that the stem cells are receptive to the action of erythropoietin only at some limited time in their individual life cycle. It is suggested that this period is sometime after metaphase and before the commencement of DNA synthesis in the interphase state of individual stem cells. It is further suggested that the increased responsiveness of the hematopoietic tissue to erythropoietin following injection is due to recruitment of stem cells into this receptive state. This recruitment may be due to both the division of stem cells and the movement of cells through cell cycle into the receptive state. The results are discussed in relation to two recent models of stem cell kinetics.
RNA Metabolism in Lymphocytes Stimulated by Phytohemagglutinin: Initial Responses to Phytohemagglutinin
Authors: COOPER HERBERT L. , RUBIN ARNOLD D.
Published: October 2019

The initial changes in lymphocyte RNA metabolism produced by treatment with phytohemogglutinin (PHA) are described. The earliest change was a decrease in total RNA (i-RNA), detectable after 30 minutes of exposure to PHA. This loss could not be localized to any of the major types of cellular RNA. After 1 hour, accelerated synthesis of RNA, shown by incorporation of u-H3, was detected, and a progressive increase in rate of synthesis continued for 24 hours.

The significance of the early loss of RNA as related to the onset of lymphocyte growth is discussed.
Quantitative Serologic and Isotopic Studies on the Rho Variant—Du
Authors: MASOUREDIS S. P. , STURGEON P.
Published: October 2019

1. Type Du cells take up less than 10 per cent of the I-131 anti-D bound to D positive cells, so that the quantity of cell bound I-131 did not differ significantly from that bound nonspecifically to D negative cells.

2. Papain modification of Du cells results in an almost threefold increase in the uptake of I-131 anti-D, whereas, D negative cells show no consistent increase after such treatment. Enzyme modification, therefore, serves to clearly delineate the two cell types.

3. The range of uptake of I-131 anti-D to enzyme treated Du cells is from approximately 7 to 17 per cent of that by R1R2 cells. Most of these results were obtained from studies on Mendelian Du types. Studies on several bloods from members of a family having Rh genotypes typical of the "gene interaction" Du configuration (C in transposition to D) revealed no significant reduction in I-131 anti-D uptake when compared with D positive cells.

4. Decreased antibody binding to Du cells was confirmed by the serologic methods used. Absorption of an anti-D serum and antiglobulin inhibition with sensitized Du cells indicated that the quantity of D antigen was less than that observed with the isotopic technic. Elution studies did not show as marked a reduction of D antigen on the Du cell as the other serologic technics indicated. Possible reasons for these differences have been discussed.

5. Although, from both the serologic and isotopic studies, the data indicate that the type Du red cell is quantitatively deficient in D antigen, they are inadequate to rule out other explanations for their reduced D antigen activity. Irrespective of the mechanism(s) responsible, the effective binding of anti-D by Du cells is reduced several fold; this would appear to be the primary cause of the weak second stage of red cell antigen-antibody reaction which characterizes type Du blood.
Alterations of Erythrocyte Lactate Dehydrogenase in Man
Authors: STARKWEATHER W. H. , COUSINEAU L. , SCHOCH H. K. , ZARAFONETIS C. J.
Published: October 2019

Erythrocyte preparations from normal men and women contain 5 isoenzymes of lactate dehydrogenase in constant proportions. LDH-5 is found exclusively in younger cells, and LDH-1 is the predominant fraction of aged erythrocytes. The apparent increase of LDH-1 in aged cells represents loss of activity of isoenzymes containing labile M subunits and not synthesis of H subunits.

When erythrocyte isoenzymes from patients with hematologic disease are assayed, increases in LDH-5 indicate active or hyperactive erythroid tissue, and absence of this fraction suggests nonfunctioning tissue. An increase in the relative percentage of LDH-1 suggests the presence of an older cell population. Thus the analysis of erythrocyte LDH isoenzymes appears to have clinical value in rapidly assessing erythropoietic activity.
Increased Hemolysis after Intramuscular Iron Administration in Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: MENGEL CHARLES E. , KANN HERBERT E. , O’MALLEY BERT W.
Published: October 2019

Four patients with PNH were described who developed accelerated activity of their disease after the intramuscular administration of iron-dextran for treatment of iron deficiency. This was considered to reflect a unique effect of iron on PNH erythrocytes. It was postulated that this effect resulted from cell damage caused by iron catalyzed peroxidation of erythrocyte lipids, a reaction to which PNH erythrocytes could be unusually susceptible by virtue of an increased content of unsaturated fatty acids or pro-oxidants or decreased content of antioxidants.
Failure of Thymectomy to Alter the Subsequent Course of Human Acute Leukemia in Drug-Induced Remission
Authors: JIJI ROUBEN M. , SACKS MILTON S. , LINBERG EUGENE J. , SPURLING CARROLL L.
Published: October 2019

Thymectomy was performed during the period of drug-induced remission of acute leukemia in 3 patients aged 16, 4, and 3 years. One case was characterized as acute erythromyeloid and 2 as acute lymphocytic leukemia. In each instance thymectomy apparently failed to influence the subsequent course of the disease. From these limited data, it does not appear that further experience with this procedure is warranted at the present time.
Chronic Granulocytic Leukemia Complicated by Ulcerative Colitis: Elevated Leukocyte Alkaline Phosphatase and Possible Modifier Gene Deletion
Authors: ROSEN ROBERT B. , TEPLITZ RAYMOND L.
Published: October 2019

A boy with Ph1-positive chronic granulocytic leukemia and coincidental active ulcerative colitis presented with high leukocyte alkaline phosphatase (LAP) scores. Recession of the inflammatory process was accompanied by a marked fall of enzyme activity to expected levels for chronic granulocytic leukemia.

The extreme variations of LAP under these and related circumstances appear inconsistent with a simple gene-dose hypothesis as applied to the partial deletion of chromosome 21.

A system of control based on studies of bacterial enzyme synthesis and involving sequential repression by a pair of regulatory genes on chromosome 21 is proposed. Loss of a regulator (modifier) rather than the structural gene for LAP is offered as being in closer accord with the known behavior of this enzyme in chronic granulocytic leukemia.
Correlation of S Hemoglobin with Glucose-6-Phosphate Dehydrogenase Deficiency and Its Significance
Authors: LEWIS ROGER A. , HATHORN MICHAEL
Published: October 2019

Hemoglobin electrophoresis and methemoglobin reduction tests have been carried out on 438 individuals with various hemoglobin patterns. The incidence of the enzyme defect rises stepwise from AA pattern through AS, Sth and SC to SS being greatest in the latter. From the data presented it is not possible to decide what factors have produced this selection.
Exaggerated Delayed Hypersensitivity to Mosquito Bites in Chronic Lymphocytic Leukemia
Authors: WEED ROBERT I.
Published: October 2019

This report has reviewed the clinical histories of 8 patients with chronic lymphocytic leukemia who manifested a marked delayed hypersensitivity type of local skin reaction to insect bites, and mosquito antigen and were capable of reacting normally to other delayed hypersensitivity antigens. We have suggested that this abnormality may represent another example of altered immunologic responsiveness in this disease, consistent with the notion that the lymphocyte is of prime importance for the development of delayed cutaneous hypersensitivity.
Qnantitation of Femoral Bone Marrow Cellularity of Rats with Acute Chloroleukemia
Authors: VARSA EVELYN E. , HANDLER EUGENE S. , GORDON ALBERT S.
Published: October 2019

Procedures of bone marrow quantitation have been applied to the study of the pathogenesis of a leukemia in rats. Mature Long-Evans rats developed an acute form of the Shay Chloroleukemia after intravenous administration of leukemic cells. Assessment of total nucleated cell numbers (normal and leukemic) per mg. of femoral bone marrow was made during the course of the pathogenesis (20 days). Reductions in the numbers of normal marrow elements were observed prior to significant increases in chloroleukemic cells. A progressive decrease in total marrow cellularity was noted in all subsequent stages. In animals surviving 17-20 days, the total number of hemic cells in the femoral marrow was found to be approximately 40 per cent of that seen in normal animals. The leukemia developed more rapidly in young than in adult animals. Using total and differential bone marrow cellularity as a criterion for the stage of pathogenesis, standardized leukemic rats can be prepared for experimentation.
Editorial: Therapy of Acute Leukemia, 1965
Authors: DAMESHEK WILLIAM , NECHELES THOMAS F. , FINKEL HARVEY E. , ALLEN DONALD M.
Published: October 2019

Dameshek, W., Necheles, T. F., Finkel, H. E., and Allen, D. M.: Therapy of acute leukemia, 1965. Blood 26(2):220, 1965.

In the August 1965 issue of Blood, a line of type was inadvertently omitted and a line repeated in the editorial, "Therapy of Acute Leukemia, 1965." The second paragraph of the editorial (p. 220) should read:

Following the introduction of the folic acid antagonists, corticosteroids and 6-mercaptopurine, there occurred an hiatus during which, although many agents were tested, little progress was made. Comparatively recently, the chemotherapy of acute leukemia has again advanced, this time in two directions. One has been the introduction of other effective antileukemic agents; the other parallels recent developments in the use of antibiotics, and might be termed "new ways with old drugs." An excellent review by Freireich and Frei of some of these advances has recently appeared.1
The Cellular Basis of the Genetically Determined Hemopoietic Defect in Anemic Mice of Genotype Sl/Sld
Authors: McCULLOCH E. A. , SIMINOVITCH L. , TILL J. E. , RUSSELL E. S. , BERNSTEIN S. E.
Published: October 2019

The proliferation and function of hemopoietic cells derived from genetically anemic Sl/Sld mice have been studied by the use of cell transplantation technics. It was found that marrow cells derived from anemic Sl/Sld or Sld/Sld mice, when implanted into heavily irradiated mice of genotype +sl/+sl, are capable of forming macroscopic spleen colonies, with approximately the same frequency as cells derived from normal +sl/+sl mice. Marrow cells derived from Sl/Sld animals were tested for their capacity to cure the anemia of W/Wr mice and were found to implant as rapidly and to have as long-lasting a beneficial effect as did marrow cells from +sl/+sl mice. The radiosensitivity of the colony-forming ability of marrow cells from Sl/Sld mice was found to be similar to that found previously for +sl/+sl marrow cells, although the anemic animals are known to be more sensitive to total-body irradiation than are their normal littermates. Marrow cells from +sl/+sl mice were found to proliferate more slowly in irradiated mice of genotype Sl/Sld than in irradiated +sl/+sl littermates, even when the anemic and the normal mice were joined in parabiosis. These observations indicate that the hemopoietic colony-forming cells in mice of genotype Sl/Sld are normal, but fail to function adequately because the tissues of mice of this genotype are unable to provide sufficient support for proliferation and differentiation of these progenitor cells.
Granulocytopoiesis in Human Bone Marrow Cultures Studied by Means of Kinematography
Authors: BOLL I. , KÜHN A.
Published: October 2019

1. In short-term human bone marrow cultures, the generation times of three myelocytes were measured by phase contrast kinematography to be 29-30.5 hours. Two of these myelocyte generations were in direct succession of each other.

2. The mean mitotic time of 93 myelocytic mitoses was found to be 88 ± 20 minutes normally and 142 ± 13 minutes in 13 leukemic blast cells. This difference was statistically significant.

3. The maturation of myelocytic cells after their last mitosis from the metamyelocyte into mature granulocytes was followed and found to vary between 7 and 37 hours. This time difference was the result of the fact that one of the cells underwent a further division, where the three sister cells did not divide but matured only. All five final cells acquired the characteristics of band forms at about the same time. In eight other cells, the metamyelocyte-bandform transition time was found to be 7 to 30 hours. In all cells studied, the morphologic characteristics changed repeatedly between those considered typical for myelocytes and metamyelocytes. Thus, metamyelocytes were found to undergo division under the conditions of this study.

4. No evidence was found for amitotic divisions. However, the development of tetraploid cells was observed to be the result of endomitosis, of postmitotic formation of binucleated cells, or of formation of giant metamyelocytes by nuclear fusion of a binucleated cell.
Effect of Heparin upon Various Forms of the Thrombohemorrhagic Phenomenon (THP)
Authors: SELYE HANS , TUCHWEBER BEATRIZ , GABBIANI GIULIO
Published: October 2019

In rats, a thrombohemorrhagic phenomenon (THP) can be elicited by the intravenous injection of various metal combinations, especially if these are given in conjunction with norepinephrine. The syndrome is characterized by multiple hemorrhages and microthromboses located mainly in the kidneys, duodenum, heart and lung. In addition, severe and sometimes necrotizing thrombohemorrhagic lesions are observed at the site of catecholamine injection. Intravenous administration of agar elicits essentially the same internal changes even without the concurrent administration of norepinephrine.

An anaphylactoid form of the THP is induced by agar plus dextran or egg white. Here, the usual internal lesions are associated with thrombohemorrhagic changes in the anaphylactoid shock organs, especially the paws, snout and the root of the tail.

All these forms of the THP are inhibited by pretreatment with heparin.
Intravascular Activation of the Clotting System with Phospholipids
Authors: RODRÍGUEZ-ERDMANN F.
Published: October 2019

The infusion of phospholipids containing platelet factor 3 activity or of Inosithin (soya bean phospholipid) in animals previously given thorotrast in the attempt to block the reticuloendothelial system, resulted in histologic changes and in severe alterations of the clotting mechanism. These morphologic and analytical alterations of the clotting system could not be distinguished from the findings observed in animals undergoing the classical generalized Shwartzman reaction produced with two injections of endotoxin.
Fine Structural Localization of Adenosine Triphosphatase in Human Platelets and Other Blood Cells
Authors: WHITE JAMES G. , KRIVIT WILLIAM
Published: October 2019

Adenosine triphosphatase activity has been localized in human blood cells by combined histochemical and electron microscopic technics. Deposits of lead phosphate, indicative of enzymic activity, were observed on the surface membranes of erythrocytes, lymphocytes and platelets. Intracellular ATPase activity was found in lymphocyte mitochondria and nucleoli. Blood platelets contained organelles in their hyaloplasm with dense accumulations of the enzyme reaction product. The distribution of lead phosphate in platelet organelles suggested that they were mitochondria, but some platelet granules may also contain ATPase activity.
An Epidemiological Study of Polycythemia Vera
Authors: MODAN BARUCH
Published: October 2019

An epidemiologic study based on all patients with polycythemia vera residing at the Baltimore Metropolitan Area is reported. A minimum annual incidence rate of 4 new cases per million was observed for the Metropolitan Area and 5 per million per year for Baltimore City. The incidence rate was lower in negroes than in whites, but if age adjustment was applied the ratio was more than 2:1. A marked increased frequency was noted among patients of Jewish origin. There was only a slight excess of males with a sex ratio 1.2:1. The age distribution confirmed the previous observations of only rare instances of the disease below the age of 30; the mean and median ages were about 60 years.
Two δ-Chain Abnormal Hemoglobins in One Individual
Authors: HUISMAN TITUS H. J. , LEE RALPH C.
Published: October 2019

Two abnormal minor hemoglobin components have been detected in the blood of a healthy Negro male. One component which was identified as the δ-chain abnormality Hb-A2' was inherited from the mother, whereas the second component, being identical with Hb-FlatbushGa, was inherited from the father. The complete absence of Hb-A2 in this individual definitely establishes the relationship of allelism between Hb-A2 and Hb-FlatbushGa. Hb-FlatbushGa, therefore, is the second hemoglobin abnormality for which indirect proof for allelism with Hb-A2 has been obtained; the discovery of three homozygous carriers of Hb-A2' (2 of these cases have been mentioned before,4 showing complete absence of Hb-A2) already established a similar relationship between Hb-A2 and Hb-A2'.
Hematologic and Biochemical Indices in the East African Baboon
Authors: FOY HENRY , KONDI ATHENA , MBAYA VERSTISTINE
Published: October 2019

Hematologic values for peripheral blood and marrow, serum proteins, B12 and folic acid levels are given for recently caught and captive baboons (P. anubis and P.sinocephalus) in Nairobi.

The hemaglobin levels were higher in captive than in wild animals. There was no change in the serum proteins unless the animals were on a riboflavindeficient diet.

Marrow activity as estimated by counting red cell precursors as a percentage of the total nucleated red cell population agreed with that of red cell uptake of Fe59 ferric chloride.

Hemosiderin was present in the marrow in all the animals.

Protein turnover studies using I131-labeled albumin with ion exchange resins indicated that the protein catabolic rate and turnover was high. This may have been due to the selective destruction of the human albumin in the baboon.
Platelet Tagging with Tritium Labeled Diisopropylfluorophosphate
Authors: ADELSON EDWARD , KAUFMAN RICHARD M. , BERDEGUEZ CIRO , LEAR ARNOLD A. , RHEINGOLD JACK J.
Published: October 2019

A method is described for tagging platelets either in vitro or in vivo with tritium labeled diisopropylfluorophosphate, burning the tagged platelets by a modification of the Schöniger combustion technic and counting the resultant tritiated water by liquid scintillation counting.

The curve of in vitro uptake of DFP-H3 by the platelet suggests that more than one protein in or on the platelet takes up the DFP. However, a saturation point is reached, as indicated by a plateau in the uptake curve.

The survival curve of in vivo tagged platelets in five normal dogs is exponential with a half-life of 2.4 days. This can be explained by random destruction of platelets or by elution of the tag.

The DFP-H3 tag has several advantages over the DFP32 tag. Either smaller doses of DFP or higher levels of radioactivity or both may be achieved with this technic.
Giant Hemangioma with Thrombocytopenia Radioisotopic Demonstration of Platelet Sequestration
Authors: BRIZEL HERBERT E. , RACCUGLIA GIOVANNI
Published: October 2019

A case of giant hemangioma with thrombocytopenia has been presented. Isotopic studies with Cr-51 tagged platelets indicated that the basic mechanism of thrombocytopenia in this patient involved platelet sequestration in the tumor. The platelet response in the peripheral blood following irradiation of the hemangioma gives additional evidence that the thrombocytopenia is related to pathological changes within the hemangioma.
Elaboration of a Model for the Formation of Lymphocytes in the Thymic Cortex of Young Adult Rats
Authors: SAINTE-MARIE G. , LEBLOND C. P.
Published: October 2019

In the hope of clarifying the sequence of cells in thymus, mitotic figures were classified into four types and counted in the cortex and medulla of thymus of young adult rats. The four types were designated as reticular cell mitoses (characterized by an unstained cytoplasm with a very large mitotic figure), and lymphocyte mitoses (characterized by a basophilic cytoplasm with a mitotic figure, which may be large, 5.6-8.0 µ, medium sized, 4.5-5.6 µ, or small, 3.5-4.5 µ). The relative mitotic counts of the four cell types in thymic cortex were 3, 46, 172 and 240 respectively.

Analysis of these counts, assuming equal mitotic duration and orderly sequence of the cells led to two sets of conclusions. (1) Large, light cells, the divisions of which are referred to as reticular cell mitoses, would produce large lymphocytes. These cells would proliferate to give rise to medium lymphocytes, which in turn would proliferate to give rise to small lymphocytes. (2) There would be 2-4, most probably 4, successive generations of large lymphocytes, followed by 2 successive generations of medium lymphocytes, which would in turn be followed by 1 generation of mitosable small lymphocytes, probably giving rise to another generation whose cells would not divide, at least in thymic cortex. A model of lymphocytopoiesis for the cortex of thymus is proposed on the basis of these conclusions.
Unstable Chromosome Changes in Tuberculin-Stimulated Leukocyte Cultures from Irradiated Patients. Evidence for Immunologically Committed, Long-Lived Lymphocytes in Human Blood
Authors: NOWELL PETER C.
Published: October 2019

Unstable chromosome aberrations (acentrics, dicentrics, rings) have been observed in tuberculin-stimulated leukocyte cultures from three patients up to six months after therapeutic irradiation. This is considered evidence that human blood contains immunologically committed, long-lived, nondividing small lymphocytes which retain the latent capacity to proliferate when re-exposed to the sensitizing antigen. "Immunologic memory" may reside in such cells, which, because they are not continually dividing, need not have undergone genetic alteration in becoming immunologically committed.
Brief Report: Bilirubin Formation in the Liver from Nonhemoglobin Sources
Authors: ROBINSON STEPHEN H. , OWEN CHARLES A. , FLOCK EUNICE V. , SCHMID RUDI
Published: October 2019

Rapid formation of C14-bilirubin from glycine-2-C14 or δ-aminolevulinic acid-4-C14 has been demonstrated in isolated, perfused rat liver. The kinetics of labeled bilirubin production in vitro were similar to those of the "early labeling" pigment fraction observed in intact rats. The magnitude of bile pigment formation from C14-ALA by isolated liver was comparable to that in intact animals. Derivation of the C14-bilirubin from hepatic degradation of labeled hemoglobin was excluded by perfusion of the liver with blood poor in reticulocytes, or with plasma. The findings identify the liver as an important source of the "early-labeling" pigment fraction.
The Splenic Platelet Pool
Authors: PENNY R. , ROZENBERG M. C. , FIRKIN B. G.
Published: October 2019

Surgically removed spleens from 14 subjects were perfused to determine their platelet content. Some patients had Cr51 labeled platelets prior to surgery, and radioactive platelet recoveries were also obtained. A sizable pool of splenic platelets has been demonstrated, which seems dependent on splenic size only. Increase in size of this pool in splenomegaly (and not suppression of thrombopoiesis) may be the sole reason for thrombocytopenia. A dynamic exchange between splenic and circulating platelets appears to be present. Awareness of the existence of a splenic platelet pool is important in considering variation in platelet survival and other platelet dynamic studies, especially in the presence of splenomegaly.