bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: Establishment of Long-term Lines from Small Aliquots of Normal Lymphocytes
Authors: BRODER SUSAN W. , GLADE P. R. , HIRSCHHORN K.
Published: October 2019

A highly purified, non-hemagglutinating PHA used in minimal blastogenic doses was non-toxic to established human lymphoid cell lines. PHA given at the beginning of primary culture or repeatedly throughout the initial six weeks of culture did not interfere with the establishment of peripheral lymphocytes in long-term suspension culture. Permanent cell lines have been obtained following weekly administration of PHA in blastogenic and subthreshold doses. Nonhemagglutinating PHA appeared to be non-toxic to these peripheral lymphocyte cultures and may increase their potential for long-term proliferation.
Cold Reacting Antibody in NZB/Bl Mice
Authors: COSTEA NICOLAS , YAKULIS VINCENT , HELLER PAUL
Published: October 2019

NZB/Bl mice produce throughout life cold reacting antibodies (CRA) with specificity to the I-erythrocyte antigen. These antibodies do not react with autologous erythrocytes since intact mouse erythrocytes do not carry reactive I-antigen. This antigen on the other hand is widely distributed in NZB/Bl mouse tissues. Newborn CF1 mice injected with cell-free filtrates of NZB/Bl mouse spleen produce CRA. The untreated offspring of these animals also synthesize this type of antibody suggesting that this immune response is induced by a self-replicating, ultrafilterable immunogen. CRA in NZB/Bl mice may, therefore, be another example of the induction of an auto-immune response by an infectious agent.
Allogeneic Marrow Engraftment Following Whole Body Irradiation in a Patient with Leukemia
Authors: BUCKNER C. DEAN , EPSTEIN ROBERT B. , RUDOLPH ROBERT H. , CLIFT REGINALD A. , STORB RAINER , THOMAS E. DONNALL
Published: October 2019

A 46-year-old man with blastic crisis of chronic myelogenous leukemia was given 950 rads whole-body irradiation followed immediately by 17.6 x 109 marrow cells. The marrow donor was the patient's sister who matched the patient in 11 of 12 HL-A groups and whose leukocytes reacted to the patient's leukemic cells in mixed leukocyte culture. The patient's white blood cell count began to go up on the 13th day and marrow engraftment was confirmed by repeated cytogenetic analyses. Secondary disease with skin rash and diarrhea was evident by the end of the second week but appeared to be controlled by methotrexate. The patient then developed fever, recurrent diarrhea and pneumonitis and died 56 days after irradiation. Autopsy showed inclusion bodies typical of cytomegalovirus. There was no histological evidence of acute secondary disease nor of leukemia.
Megakaryocytopoiesis in Rats With Special Reference to Polyploidy
Authors: ODELL T. T. , JACKSON C. W. , FRIDAY T. J.
Published: October 2019

The morphologic stage of maturation, ploidy level, and cell size of individual megakaryocytes from the marrow of normal rats were determined; the initial labeling index of this population of megakaryocytes 30 minutes after injection of 3HTdr was also determined. The results suggested some inferences about the flow of cells through the various ploidy and differentiation compartments during the maturation of megakaryocytes. Most 8N Type-I megakaryocytes endoreduplicate and become 16N Type-I cells, while a few mature to 8N Type-II megakaryocytes. Most 16N I cells mature to 16N II although a few endoreduplicate to become 32N I cells; the 32N I cells mature only to 32N II. The Type-I morphologic stage contains two subcompartments that we have not distinguished morphologically, an endoreduplicating subcompartment and a post-DNA-synthesis subcompartment. The time parameter of the latter ranges from about nine to 19 hours. The time parameter of the former depends on the number of endoreduplications undergone by an individual megakaryocyte. The size of megakaryocytes increases both with increases in ploidy level and with cell differentiation.
Clotting of Bovine Fibrinogen by Liver Transamidase
Authors: FARRELL JUDITH , LAKI K.
Published: October 2019

It was found that pure liver transamidase (transglutaminase) clotted bovine fibrinogen without prior release of cofibrin (fibrinopeptide) by cross-bonding fibrinogen molecules.
Complexing of Transcobalamin 2 and Apparent Combination With Heparin
Authors: COOPER BERNARD A.
Published: October 2019

57Co cyanocobalamin mixed with serum filters through sephadex G-150 in two fractions, corresponding to apparent molecular weights of about 120,000 and 36,000, respectively. Much of the native B12 also filters in these fractions, but some is excluded from the gel, and a large fraction filters in the position of free B12. When heparin is mixed with serum or plasma, most of the B12 filters with the 120,000 fraction. When EDTA is mixed with serum or plasma not containing heparin, less 57CoB12 filters in the 120,000 fraction, and more filters in the 36,000 fraction. The 120,000 and 36,000 fractions cannot therefore be assumed to correspond precisely with transcobalamin 1 and 2, respectively.

It is suggested that heparin binds transcobalamin 2 and that EDTA dissociates either TC2 complexes or some of the TC1.
G-6-PD Tripler: A Unique Variant Associated with Chronic Hemolytic Disease
Authors: ENGSTROM PAUL F. , BEUTLER ERNEST
Published: October 2019

A 52-year-old Caucasian was hospitalized for recurring jaundice. Laboratory tests established a compensated hemolytic anemia due to partial erythrocyte G-6-PD deficiency. Biochemical characterization of the affected enzyme uncovered a unique variant: G-6-PD Tripler. Its significant properties include marked thermal instability, an electrophoretic mobility slower than the normal B variant in all systems studied, and slightly increased affinity for the substrate G-6-P.
Acrylamide Gel Electrophoresis Studies of Human Erythrocyte Membrane
Authors: LIMBER GERALD K. , DAVIS ROY F. , BAKERMAN SEYMOUR
Published: October 2019

A sensitive system has been presented for the isolation of erythrocyte membrane and the separation of its solubilized components by acrylamide gel electrophoresis. Comparisons were made between the membrane from both normal patients and patients with hereditary spherocytosis. While variation in a specific band on electrophoresis could be correlated with the disease state, no such variation existed among the normal membrane samples. The possible reasons for these observations are discussed.
Brief Report: Aspirin Ingestion Compared with Bleeding Disorders—Search for a Useful Platelet Antiaggregant
Authors: WEISS HARVEY J.
Published: October 2019

In Aspirin Ingestion Compared with Bleeding Disorders—Search for a Useful Platelet Antiaggregant, by Harvey J. Weiss (Blood 35: No. 3, March, 333-340, 1970), Table 1, third column, fifth line, + + + 0 should read 0.
Cold-reacting Antibodies: Differences in the Reaction of Anti-I Antibodies with Adult and Cord Red Blood Cells
Authors: ROSSE WENDELL F. , SHERWOOD JUDITH BRIMBERG
Published: October 2019

The reactions of anti-I cold-agglutinin antibodies with the red cells from normal adults (adult-I) and adult-i donors and from newborn infants have been investigated by the use of the C'1a Fixation and Transfer Test of Borsos and Rapp. Agglutination and high concentration of serum reduce the amounts of the C'1a fixation by these antibodies. Inhibition by serum is due to an inhibitor of C'1a. A single molecule of antibody is required for the fixation of one molecule of C'1a to either adult or cord cells. There was great variability in the amount of anti-I antibody and C'1a fixed by different adult cells and by different cord cells. Although the two ranges overlapped considerably, the amount of antibody fixed by cord cells was somewhat less than that fixed by adult cells. The difference between cord cells or "low-reactivity" adult-I cells and "high-reactivity" adult-I cells is not due to the presence of different or extra antigens on the latter since cord and "low-reactivity" adult I cells are able to absorb all antibody from the antiserum which reacts with "high-reactivity" adult-I cells. The difference between adult-I and cord cells (or adult-i cells) was reduced by pretreatment of the cells with papain and was increased by increasing the temperature at which the reactions were performed. These studies suggest that the difference between adult red cells and cord (or adult i) red cells with regard to the fixation of cold agglutinin antibody is due in large part to a difference in the "affinity" of the antibody and the antigen on the cell surface rather than to a major difference in the number of antigen sites.
A Study on Time- and Radiation-dependent Changes in the Frequency of Lymphocytes with Chromosome Aberrations in the Circulation, Following Multiple Exposures of the Pelvis to γ-Irradiation
Authors: TAMURA HIROAKI , SAKURAI MASAHARU , SUGAHARA TSUTOMU
Published: October 2019

Unstable chromosome aberrations of peripheral lymphocytes were observed during the course of radiotherapy in patients with cervical cancer. They did not increase monotonously with repeated exposures, but a plateau was observed around the second week of treatment. Similar tendencies were observed in both 72-hour and 50-hour culture experiments, although the number of abberrations was lower in the former. The distribution of numbers of dicentrics per cell fitted well the Poisson pattern throughout the period of observation. Peripheral lymphocyte counts reached a low plateau before the fifth exposure, and dropped again in the third week. It was speculated that the "member exchange" and/or mobilization of lymphocytes caused the nonlinear increase in chromosome aberrations.
Studies on the Use of "Prophylactic" Intrathecal Amethopterin in Childhood Leukemia
Authors: MELHORN DAVID K. , GROSS SAMUEL , FISHER BARRY J. , NEWMAN ARTHUR J.
Published: October 2019

Central nervous system infiltration was studied in a group of 47 children with acute leukemia. CNS involvement was found to occur more frequently and appear more rapidly in patients who presented with elevated peripheral WBC counts. CNS infiltration not suspected clinically was identified by spinal fluid examination in a significant minority of children at the time of the initial diagnosis of leukemia, indicating that lumbar puncture should be a routine part of the initial evaluation of patients with acute leukemia. Intrathecal amethopterin administered "prophylactically" at the time of initial diagnosis of leukemia did not prevent or decrease the frequency of occurrence of CNS infiltration. However, it did delay the onset of CNS involvement in patients with elevated WBC counts. Intrathecal amethopterin administered before the onset of CNS infiltration appears to be useful in delaying morbidity resulting from CNS involvement in children who present with elevated peripheral WBC counts.
Energy Metabolism in Human Platelets:Interrelationship Between Glycolysis and Oxidative Metabolism
Authors: DOERY J. C.G. , HIRSH J. , COOPER I.
Published: October 2019

Glycolysis and oxidative metabolism were assessed in washed human platelets incubated in a Ca++ and Mg++ free Krebs-Ringer bicarbonate buffer, pH 7.4 at 37° C for 1 hour. Glycolytic rate was 45-65 per cent lower under aerobic than anaerobic conditions. Glycolysis was decreased further when albumin was present in the incubation medium and under these conditions glucose uptake, glycogen utilization and lactate production were 21.4, 15.8 and 78 µmoles/hr. per 1011 platelets, respectively. The oxidation of 6-14C glucose was 0.39 µmoles/hr. per 1011 platelets and of U-14C palmitate 0.19 µmoles/hr. per 1011 platelets, and the rate of oxidation of either substrate was increased in the absence of the other. The uncoupling agent, dinitrophenol, stimulated oxidation of glucose to a much larger extent than fatty acid. It is concluded that both glycolysis and oxidative phosphorylation are important to platelet energy metabolism, that either pathway may compensate for decreased activity of the other and that, under conditions of metabolic stress, glucose is preferred to fatty acids as a substrate for oxidative metabolism.
Variant of Factor IX Deficiency in Female with 45, X Turner’s Syndrome
Authors: BITHELL THOMAS C. , PIZARRO ALEJANDRO , MACDIARMID WILLIAM D.
Published: October 2019

The case of an 11-year-old girl with a severe bleeding diathesis, a factor IX level of 4 per cent, and 45, X Turner’s syndrome is described. Family studies revealed severe factor IX deficiency in 4 male relatives and mild deficiencies in 4 heterozygous female carriers. The Bm or B+ variant of this disorder was demonstrated in all affected members of the kindred.
The Effect of Transferrin-free Serum on the Utilization of Iron by Rabbit Reticulocytes
Authors: ELDOR A. , MANNY N. , IZAK G.
Published: October 2019

A transferrin-free serum, produced by removing the siderophilin with a specific antitransferrin antibody, was incapable of stimulating the entry of iron into reticulocytes, unless it was reconstituted with pure transferrin-iron complex. These observations militate against the existence of serum factor(s), other than transferrin, capable of stimulating the incorporation of iron into reticulocytes. Comparing the effects of whole serum, pure transferrin, transferrin-free serum, and the latter reconstituted with pure transferrin, it was found that normal, pooled human serum augmented the utilization of intracellular iron for heme production, which transferrin alone did not achieve.
Relative Labeling of Leukocytes, Erythrocytes and Platelets in Human Blood by 51Chromium
Authors: EYRE HARMON J. , ROSEN PETER J. , PERRY SEYMOUR
Published: October 2019

Relative labeling of peripheral blood cells by 51-chromium was determined by means of a sucrose gradient density separation technic and confirmed by radioautography. Large lymphocytes and monocytes were found to be more heavily labeled than small lymphocytes and granulocytes. Erythrocytes and platelets were relatively lightly labeled. These differences in labeling are important in evaluating data obtained when 51-chromium is utilized as a cell label for the study of leukocyte kinetics.
Hematological Observations on the Anemia Associated with Blood Type Rhnull
Authors: STURGEON PHILLIP
Published: October 2019

The purpose of this report is to direct attention of hematologists to a mild chronic hemolytic anemia, of unexplained etiology, characterized by the remarkable absence of all Rh-Hr factors. There are also defects in the Ss, U blood group determinants. The anemia has most of the routine hematological characteristics of mild stomatocytosis and/or hereditary spherocytosis. Like hereditary spherocytosis, it shows no abnormalities of intraerythrocytic enzymes nor of membrane lipids. Unlike hereditary spherocytosis, however, its inheritance is recessive. The proposed basis for this hemolytic anemia is homozygosity for a gene whose normal allele produces components of the erythrocyte membrane which function in the maintenance of intracellular osmotic equilibrium and which serves as substrate for the action of both the products of the Rh-Hr genes and of the genes of the MNSs, U and, possibly, of the Fy systems.
Autoradiography of Diffusible Compounds in Human Nonnucleated Erythrocytes: Studies with Tritiated Glucose and Adenine
Authors: GREENWALT TIBOR J. , PAIGE JOSEPH C. , ETOH NOBUKOH , STEANE EDWIN A.
Published: October 2019

In Autoradiography of Diffusible Compounds in Human Nonnucleated Erythrocytes: Studies with Tritiated Glucose and Adenine by Greenwalt et al. (Blood 35: No. 5, May, 624-636), Table 1, last line, P < 0.1 should read P > 0.1; page 631, second paragraph, seventh line, 98, 20 and 11 per cent should read 88, 23 and 11 per cent.
Leukocyte Transfusions: Function of Transfused Granulocytes from Donors with Chronic Myelocytic Leukemia
Authors: EYRE HARMON J. , GOLDSTEIN IRA M. , PERRY SEYMOUR , GRAW ROBERT G.
Published: October 2019

The in vivo function of chronic myelocytic leukemia (CML) leukocytes transfused into infected patients with severe neutropenia was evaluated and the results in four representative patients are reported. The intravascular survival, extravascular migration, and phagocytic capacity of these cells appeared normal in two patients without preformed leukoagglutinins. In two other patients who had only small transient increments in circulating granulocytes and severe transfusion reactions, preformed leukoagglutinins were found. The poor granulocyte recoveries in these patients with antibody could probably be explained by splenic sequestration of the transfused cells. These studies provide evidence supporting the use of CML leukocyte transfusions in patients without preformed leukocyte antibodies.
The Morphological Identity of Maternal Cells in Newborn Mice
Authors: BARNES RONALD D. , HOLLIDAY JEAN
Published: October 2019

The placenta has been considered an anatomical barrier which prevents maternal rejection of the fetal allograft. This view is no longer tenable since, in one particular inbred strain of mouse, maternal blood cells have been identified by means of radioisotope labels in newborn mice. Both maternal red cells and lymphocytes labeled, respectively, with radiochromium and tritiated thymidine have been detected in newborn mice. This phenomenon appears independent of the trauma of normal delivery and, what is more, occurs before term.
Erythropoietin and the Regulation of Erythropoiesis in DiGuglielmo’s Syndrome
Authors: ADAMSON J. W. , FINCH C. A.
Published: October 2019

Observations relating to the regulation of red cell production in four patients with DiGuglielmo’s syndrome and one with malignant lymphoma are presented. Erythropoiesis in these patients was characterized by bizarre forms, marked erythroid hyperplasia and ineffective erythropoiesis. Erythropoietin excretion was elevated, in keeping with the degree of anemia. Hypertransfusion of these patients resulted in a marked decrease in erythropoietin excretion and a reduction in marrow erythroid hyperplasia although morphologic abnormalities of the individual cells in both granulocytic and erythroid cell lines remained. The alteration in marrow function in response to transfusions was reflected by the E:G ratio and in iron kinetic and reticulocyte measurements which demonstrated a decline in both total and effective erythropoiesis. It is concluded that proliferation of the erythroid marrow in these patients is under physiologic regulation and that the defects observed are expressed during cell maturation.
Long-term Effects of Local Irradiation of the Marrow on Erythron and Red Cell Function
Authors: NELP WIL B. , GOHIL MAHENDRA N. , LARSON STEVEN M. , BOWER RAE ELLEN
Published: October 2019

Changes in erythron and RE cell function were examined in the marrow of the rabbit after 250-5000 R of localized irradiation by comparing the amount of 59Fe and 99mTc sulfur colloid concentrated in the irradiated tibiofibula to that in the unirradiated control. At all levels of irradiation, there was immediate and severe loss of erythron function while RE cell activity remained nearly intact. Erythron function showed prompt partial recovery to a maximum level at approximately 8 days but with doses greater than 1000 R there was a secondary decline to 20 per cent of normal during the next 8 weeks. After 15 days, RE cell function had decreased to the same level as the erythron and subsequently fell in parallel with it. After 15 months, the marrow showed a secondary recovery of both RE cell and erythron function to 50 and 66 per cent of normal. The results of these experiments suggest that radiocolloid photoscans of the marrow showing decreased or absent RE cell activity will reflect a similar degree of erythropoietic damage if the studies are obtained weeks or months following radiation therapy.
Perturbation of Generation Cycle of Human Leukemic Blast Cells by Cytostatic Therapy In Vivo: Effect of Corticosteroids
Authors: ERNST PETER , KILLMANN SVEN-AAGE
Published: October 2019

The in vivo cell cycle effects of intensive short-term corticosteroid treatment on bone marrow lymphoblasts have been studied in five patients with acute lymphoblastic leukemia. In repeated bone marrow samples, the following parameters were determined: mitotic index, stathmokinetic index after vincristine, 3H-thymidine labeling index and single cell DNA content. It is concluded that prednisone has a general destructive effect both on actively proliferating and on quiescent leukemic lymphoblasts. Besides, prednisone has an additional effect on proliferating lymphoblasts which manifests itself by a decreased influx from G1 phase into DNA synthesis phase. From the present data it cannot be decided whether this is due to a depopulation of the G1 pool or results from an arrest of cells in G1. No evidence has been found for selective cell death during DNA synthesis. Some implications of this cytokinetic perturbation for therapeutic combination of corticosteroids with methotrexate and vincristine are discussed.
Variation in Survival Among Patients With Acute Lymphocytic Leukemia
Authors: ZIPPIN C. , CUTLER S. J. , REEVES W. J. , LUM D.
Published: October 2019

Survival of 873 acute lymphocytic leukemia patients has been reviewed in relation to a number of patient and disease characteristics at first hospital admission. Study of survival by individual years of age at diagnosis led to the selection of five age intervals: 1-3, 4-10, 11-19, 20-49, and 50 years and over. For each sex the survival after age 10 was considerably poorer than for the younger ages. The best survival for any age-sex group was that for girls 4-10, who had a median survival time of 14.0 months compared with an overall median survival time of 7.8 months for patients of both sexes over 1 year of age. We attempted to determine whether a favorable distribution of other factors related to survival might work to the advantage of girls in the 4-10 year age group. However, in studying factors such as symptoms and hematological characteristics it was the pattern, rather than the exception, to find within most levels of a characteristic under study, that girls 4-10 had the best survival. It would be interesting and potentially valuable to see whether the findings in this study are confirmed in other series. If a specific age-sex group tends to maintain a superior survival pattern, additional exploration of prognostic factors may uncover important leads concerning the biology of the disease.
The In Vitro Colony-forming Cell and the Response to Neutropenia
Authors: RICKARD KEVIN A. , MORLEY ALEC , HOWARD DONALD , STOHLMAN FREDERICK
Published: October 2019

The in vitro colony-forming cell has been studied in murine bone marrow during a phase of enhanced granulopoiesis secondary to irradiation-induced neutropenia. It is suggested that the in vitro colony-forming cell derives from a primitive proliferating granulocytic precursor cell. The primary bone marrow response to neutropenia appears to occur in this committed myeloid stem cell compartment, the size of which appears inversely related to the blood neutrophil level. Because of these findings, a humoral regulator of granulopoiesis with a primary site of action at the committed myeloid stem cell level has been postulated.
Identity and Proliferation of Small Lymphocyte Precursors in Cultures of Lymphocyte-rich Fractions of Guinea Pig Bone Marrow
Authors: YOSHIDA Y. , OSMOND D. G.
Published: October 2019

Radioautography with 3H-thymidine was used to examine the proliferative activity of bone marrow lymphoid cells and to identify the precursor cells of small lymphocytes in short-term cultures of lymphocyte-rich marrow fractions. High concentrations of small lymphocytes (nuclear diameters less than 8.0 µ in smears) together with large lymphoid ("transitional") cells (nuclear diameters greater than 8.0 µ) were separated from suspensions of guinea pig bone marrow by centrifugation in linear sucrose-serum density gradients. When such lymphocyte-rich marrow fractions were cultured in vitro the labeling and mitotic indices following either continuous or terminal exposure to 3H-thymidine indicated that the large lymphoid cells were confined mainly to the pre-DNA-synthetic (G1) and early DNA-synthetic (S) phases at first, but proceeded subsequently through S phase and mitosis. From these data tentative values were derived for the in vitro duration of G1 (12 hours) and S (13.7 hours). Further cultures were followed radioautographically after a 1-hour pulse of 3H-thymidine at 6-7 hours of culture. The absolute numbers of labeled large lymphoid cells declined during the subsequent 21 hours but, simultaneously, labeled small lymphocytes appeared and increased progressively in absolute numbers to 44.4 ± 8.1 per cent of the initial numbers of labeled large lymphoid cells. The mean grain count of labeled small lymphocytes was half that of the initially labeled large lymphoid cells. Very few labeled undifferentiated cells other than large lymphoid cells were observed. The results demonstrate that lymphocyte-rich marrow fractions are capable of sustaining the production of small lymphocytes in short-term cultures and that the immediate precursors of marrow small lymphocytes are contained within a population of large lymphoid cells.
Cytologic Studies of Tumors. L. Clonal Proliferation of Four Stemlines in Three Hematopoietic Tissues of a Patient With Reticulosarcoma
Authors: OBARA YOSHITAKA , SASAKI MOTOMICHI , MAKINO SAJIRO , MIKUNI CHIKARA
Published: October 2019

A case of reticulosarcoma was found to have four chromosomally different stem-lines in peripheral blood, lymph node and bone marrow. The four lines are recognized to be of monoclonal origin on the basis of the closely allied karyotypes characterized by trisomy for E16, E17 and E15, the loss of one A1, two F and two to four C elements in addition to M and R markers. The markers characterize three kinds of hematopoietic tissues: an M1, R1, R2 line occurs in lymph node, and an M1, M2, M3, R1 line in peripheral blood and M1, M4 and M1, M2, M3 lines in bone marrow. Cytogenetic variability of malignant cells was highest in peripheralblood. Information was provided to suggest that of the four stemlines, the lymph node line may be original, the peripheral blood line may be a derivative of the lymph node line and, finally, two marrow lines may have originated from the blood line or from one of the mutated cells slightly different from the marrow lines. The M markers were discussed in relation to malignant evolution of hematopoietic cells of this patient. The suggestion was made that the chromosomes of the patients with malignant hematopoietic disorders should be examined in different tissues.
Correlation Between Various Blood White Cell Pools and the Serum B12-binding Capacities
Authors: CHIKKAPPA G. , CORCINO J. , GREENBERG M. L. , HERBERT V.
Published: October 2019

Twenty-four patients with various hematologic and nonhematologic diseases were studied to correlate the various fractions of the serum B12-binding capacity with the blood granulocyte and leukocyte pools and granulocyte turnover rates. The total blood granulocyte pools correlated well with the serum unsaturated B12-binding capacity, especially with the alpha fraction. At least part of the serum B12-binding protein appears to be derived from the neutrophil and from the eosinophil but little or none from the myeloblast. The serum unsaturated B12-binding capacity appears to be a simple index of the total blood granulocyte pool.
Double Heterozygosity for Hemoglobin G (α68Lys2βA2) and Hemoglobin D (αA2β121Gln2)
Authors: ROTHMAN MELVIN C. , RANNEY HELEN M.
Published: October 2019

An electrophoretic pattern which revealed three major hemoglobin components was found in five members of an Afro-American family. The composition of the hemoglobin resulted from heterozygosity both at the α locus for hemoglobin GPhiladelphia, in which lysine replaces the normal asparagine at the 68th residue and at the β locus for hemoglobin DPunjab in which glutamine replaces normal glutamic acid at residue 121. The simultaneous presence of these α and β chain variants did not lead to any well defined clinical abnormalities. The pattern of inheritance of hemoglobin variants in this family provided further evidence for independent segregation of the loci responsible for α and β chain synthesis.
Central Nervous System Therapy and Combination Chemotherapy of Childhood Lymphocytic Leukemia
Authors: AUR RHOMES J. A. , SIMONE JOSEPH , HUSTU H. OMAR , WALTERS THOMAS , BORELLA LUIS , PRATT CHARLES , PINKEL DONALD
Published: October 2019

In earlier combination chemotherapy regimens for childhood acute lymphocytic leukemia, nervous system leukemia terminated complete remission in over half the patients in a median time of 11 months. In the present study, cranial radiation (2400 R, 60Co) and intrathecal methotrexate given early in remission were added to combination chemotherapy in an attempt to prevent or delay central nervous system relapse and termination of complete remission. Of 35 consecutive children with previously untreated acute lymphocytic leukemia, 20 of 30 who attained remission and received all initial phases of therapy have been in continuous complete remission for 23 to 30 months. Complete remission was terminated by nervous system relapse in three patients and by hematological relapse in five. Two patients died in complete remission of viral infections and others experienced reversible drug toxicity. We conclude that this combined therapy reduces the incidence of nervous system relapse in the first 2 years and prolongs complete remission.
The Transfer RNA Methylases of Human Lymphocytes. I. Induction by PHA in Normal Lymphocytes
Authors: RIDDICK DAVID H. , GALLO ROBERT C.
Published: October 2019

Assays were performed that measured both the rate and extent (or total capacity) of transfer RNA methylases in extracts of lymphocytes cultured in the presence and absence of phytohemagglutinin (PHA). The tRNA methylases of human peripheral blood lymphocytes undergoing blastogenesis in culture with PHA had a five- to sixfold increase in rate and a three- to sevenfold increase in extent of methylation of heterologous tRNA. These data suggest that PHA transformed lymphocytes not only contain elevated levels of tRNA methylases, but that the increase includes qualitatively different enzymes from those found in normal peripheral blood lymphocytes. Experiments in which lymphocytes were incubated for various times with PHA revealed that tRNA methylase induction occurred late in or after DNA synthesis and after morphologic transformation, but prior to mitosis. Rate and extent of tRNA methylation increased simultaneously. PHA induction of tRNA methylase activity was dependent on the synthesis of new RNA in lymphocytes cultured from 40 to 45 hours. The increase was not due to different levels of inhibitors or activators or preferential degradation of reaction components. The data suggest that quantitative and qualitative changes occur in the tRNA methylases of the normal human peripheral blood lymphocyte stimulated by PHA to undergo transition to an undifferentiated cell "in cycle." The possible significance of these findings to control of protein synthesis in PHA transformed lymphocytes is discussed.
Additional Kinetic Distinctions Between Normal Pyruvate Kinase and a Mutant Isozyme From Human Erythrocytes. Correction of the Kinetic Anomaly by Fructose-1,6-diphosphate
Authors: PAGLIA DONALD E. , VALENTINE WILLIAM N.
Published: October 2019

Several cases have been reported in which chronic hemolytic anemia was thought to be secondary to the same mutant isozyme of erythrocyte PK. In crude hemolysates from one of these cases, defective kinetic characteristics of the isozyme were found to be completely correctable in vitro by low concentrations of the PK activator, fructose-1,6-diphosphate. The patterns of response to the activator further distinguished this isozyme from normal PK and suggested that the isozymes in these cases, previously thought to be identical, more probably represent three subtly distinct mutant forms.
Influence of Repeated Acute Thrombocytopenias on the Reappearance of Circulating Blood Platelets
Authors: KRAYTMAN M.
Published: October 2019

Repeated experimental thrombocytopenia has been performed in three groups of dogs, at intervals of 2 days, 5-7 days, and 10 days. In the first two of these groups, the circulating thrombocytes reappear significantly more rapidly and the maximal platelet counts average respectively 138 per cent (p < 0.02) and 174 per cent (p < 0.001) of the peak observed after a single platelet depletion. If the thrombocytopenic stimulus is repeated at a 10-day interval, this modification in the rate of reappearance of platelets and in the platelet counts does not occur. It is concluded that platelet production induced by a single acute depletion does not represent the maximal medullary response and that thrombocytopoiesis can be further increased if the stimulus is repeated 2-7 days after a first one. Recovery curves after platelet depletion alone or followed by bleeding are similar, suggesting that thrombocytopoiesis is not influenced by a factor stimulating erythropoiesis.
Monocytic Vitamin B12-binding Protein
Authors: CARMEL RALPH , COLTMAN CHARLES A.
Published: October 2019

Granulocytes are rich in vitamin B12-binding protein resembling serum alpha-globulin binder. Lymphocytes and erythrocytes contain lesser amounts of the protein, but monocytes have not heretofore been studied. Characterization of our patient’s monocytic B12 binder by gel filtration, radioautography, immunologic studies, and mediation of reticulocyte uptake of vitamin B12 showed it was identical to granulocytic binder. Monocytic B12-binding was low, but, due to the monocytosis in the subject, monocytes accounted for more total binding than did her granulocytes. The serum had markedly elevated B12-binding capacity. However, the elevation was of beta-globulin primarily. The reason for this remains unclear. In vitro incubation of cellular extract with serum did not alter the characteristics of the cellular B12-binding protein.
Effects of Bacterial Endotoxin on the Fibrinolytic Activity of Normal Human Leukocytes
Authors: GOLDSTEIN IRA M. , WÜNSCHMANN BARBARA , ASTRUP TAGE , HENDERSON EDWARD S.
Published: October 2019

Two modifications of Todd’s histochemical fibrin slide technique were used to study the effect of bacterial endotoxin on the plasminogen activator activity of intact normal human leukocytes in vitro. Leukocyte suspensions were obtained from heparinized peripheral blood by dextran sedimentation. Plasminogen activator activity was measured as the percentage of individual cells producing zones of fibrinolysis in plasminogen-rich fibrin. Of the cells from normal individuals, 27 ± 2 per cent were fibrinolytically active. The addition of lipopolysaccharide B from Salmonella abortus equi resulted in a marked increase in the percentage of active cells without impairment of cell viability. The stimulation of plasminogen activator release appeared to be dose-related, since at higher endotoxin concentrations the number of active cells gradually approached the granulocyte level. Maximum effect on leukocytes was observed 2 hours after addition of endotoxin, followed by a steady decline in activity. Plasminogen activator activity in the suspending medium became detectable after 2 hours’ incubation. Simultaneous assays of beta-glucuronidase revealed increasing amounts of this lysosomal enzyme in the suspending medium during incubation. Addition of endotoxin enhanced the rate of this increase. The parallel appearance of plasminogen activator and beta-glucuronidase activities without concomitant cell destruction from unstimulated and endotoxin-treated leukocytes is consistent with the release of both compounds from lysosomes following noncytocidal stimulation.
Quantitative Studies on the Sensitivity to Complement Lysis of Red Cells Treated With Thiol-reactive Reagents
Authors: STEAD NANCY W. , ROSSE WENDELL F.
Published: October 2019

The effect of reduced glutathione on the complement sensitivity of normal and paroxysmal nocturnal hemoglobinuria (PNH) red cells was determined quantitatively. The susceptibility to complement lysis was increased in normal and complement-sensitive and complement-insensitive PNH cells; the percentage increase in susceptibility was inversely related to the initial complement-sensitivity. P-chloromercuribenzene sulfonate (PCMBS) likewise increased the sensitivity of normal cells to lysis by complement; the effect with both compounds appeared to be due to reaction with membrane thiol groups. GSH-treated normal cells were similar to PNH cells in that the susceptibility to immune lysis occurred without concomitant increase in fixation of antibody or first component of complement. GSH-treated normal cells differed from PNH cells in that the membrane acetylcholinesterase activity was normal and the cells were not stable during preparation and short-term storage.
Transplantation of HL-A Identical Allogeneic Bone Marrow to a Patient With Acute Lymphocytic Leukemia
Authors: GRAW ROBERT G. , BROWN JAMES A. , YANKEE RONALD A. , LEVENTHAL BRIGID G. , WHANG-PENG JACQUELINE , ROGENTINE G. NICHOLAS , HENDERSON EDWARD S.
Published: October 2019

In Transplantation of HL-A Identical Allogeneic Bone Marrow to a Patient With Acute Lymphocytic Leukemia, by Graw et al. (Blood 36: No. 6, December, 736-747, 1970), Table 2 on page 741 was printed incorrectly. The table below is correct.

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The Effect of Erythropoietin on Human Bone Marrow Cells In Vitro. I. Studies of Nine Cases of Bone Marrow Failure
Authors: MIZOGUCHI HIDEAKI , MIURA YASUSADA , TAKAKU FUMIMARO , SASSA SHIGERU , CHIBA SHYOZO , NAKAO KIKU
Published: October 2019

The in vitro response to erythropoietin of bone marrow from nine patients with bone marrow failure were studied. Two types of patients were observed, those in which the marrow was responsive to erythropoietin and those which were nonresponsive. Ferrokinetic data corresponded well with the response to erythropoietin in vitro. In the nonresponsive group, a recovery of sensitivity to erythropoietin was observed when the patients improved clinically. The nature of the bone marrow failure was discussed in relation to erythropoietin and stem cells.
Neutrophiia-inducing Activity in Plasma of Neutropenic Human Beings
Authors: MARSH JOHN C. , LEVITT MARTIN
Published: October 2019

Humoral factors have been implicated in the bone marrow release of neutrophils in experimental animals in response to neutropenia. No comparable studies have yet been reported in man, although a humoral mechanism has been described in the neutrophilic response to endotoxin. Three patients with reversible drug-induced neutropenia were studied for the presence of neutrophilia-inducing activity by obtaining plasma during neutropenia and after recovery. When the blood neutrophil concentration and marrow granulocyte reserves were normal, the paired plasmas were returned to the donors on different days, and the blood neutrophil concentrations sequentially measured. Reinfusion of the plasmas obtained from the two patients with marked neutropenia was associated with a 2.5-3.5-fold increase in the total neutrophil concentration and an 8.5-fold increase in the nonsegmented neutrophils, with the peak 30-60 min after infusion. In contrast, plasma obtained when the blood neutrophil concentration was normal did not have this effect. Plasma from the patient with only slight neutropenia was not associated with neutrophilia-inducing activity. Neutrophilia-inducing activity is present in increased concentration in the plasma of severely neutropenic human beings and we suggest that it plays a role in regulating the blood neutrophil concentration by causing release of neutrophils from the bone marrow.
Factor VII Antibody-neutralizing Material in Hereditary and Acquired Factor VII Deficiency
Authors: GOODNIGHT SCOTT H. , FEINSTEIN DONALD I. , ØSTERUD BJARNE , RAPAPORT SAMUEL I.
Published: October 2019

Evidence is provided for the existence of at least two types of hereditary factor VII deficiency. In one type there is synthesis of a protein which neutralizes a factor VII antibody but lacks coagulant activity. In the second type, no factor VII antibody neutralizing material is present. Evidence is also provided for the existence of two types of acquired factor VII deficiency. Apparently, low factor VII activity in liver disease results from decreased synthesis of factor VII protein. In contrast, warfarin administration or vitamin K deficiency leads to the synthesis of factor VII protein that lacks clotting activity.
The Origin of Some Bone Marrow Fibroblasts
Authors: HENTEL JEAN , HIRSCHHORN KURT
Published: October 2019

An attempt was made to determine the origin of bone marrow fibroblasts which almost always appear when bone marrow aspirates and explants are grown on solid surfaces in tissue culture. Bone marrow aspirates from an individual with chronic myelogenous leukemia demonstrating the Ph-1 chromosome and from an individual with acute leukemia demonstrating C-group trisomy in marrow cells served as sources of the fibroblasts. The fibroblasts that grew from these aspirates were analyzed for the presence of these chromosome markers found in the leukemic cells. The positive findings of the Ph-1 chromosome and C-group trisomy in a proportion of the fibroblasts indicates that at least some leukemic bone marrow fibroblasts are derived from hemopoietic cells. The origin of the bone marrow fibroblasts are derived from hemopoietic somes remains unknown. They could be derived from (1) hemopoietic cells cytogenetically unaffected by the leukemic process, (2) stromal elements of the bone marrow, or (3) both cytogenetically unaffected hemopoietic cells and stromal elements.
Skin Window Studies of the Acute Inflammatory Responses of Neutropenic Patients
Authors: DALE D. C. , WOLFF S. M.
Published: October 2019

The acute inflammatory responses of three cyclic neutropenic and 15 chronic neutropenic patients were studied with the Rebuck skin window technique. The neutrophil responses at 3 and 5 hr after initiation of the inflammation were roughly proportional to the blood neutrophil counts. Cyclic neutropenics in their neutropenic phase and severe chronic neutropenics both showed normal mononuclear cell responses. These observations indicate that neutrophil accumulation at an inflammatory site is not necessary to initiate the mononuclear cell response as previously postulated. It is further suggested that in these patients with decreased neutrophils but normal monocyte counts the monocytes play a vital role in preventing serious infections.
Colony-stimulating Factor and Inhibitor Levels in Acute Granulocytic Leukemia
Authors: METCALF DONALD , CHAN SOH HA , GUNZ FREDERICK W. , VINCENT PAUL , RAVICH ROBERT B. M.
Published: October 2019

Assays were performed on bone marrow colony-stimulating-factor (CSF) levels in the serum and urine of 33 patients with acute granulocytic and myelomonocytic leukemia. Of 251 serum samples, 30% showed elevated CSF levels as did 53% of 1422 urines tested. Levels of serum inhibitors of colony formation were abnormally low or undetectable in 57% of sera from leukemic patients. Patients in relapse were unable to respond to infections by developing high serum CSF levels and low serum-inhibitor levels were more common in patients with a short survival time and in some types of patient during relapses.
Leukemic Reticuloendotheliosis
Authors: TRUBOWITZ SIDNEY , MASEK BERTHA , FRASCA JULIO M.
Published: October 2019

The anatomical and functional features of the hairy cells of leukemic reticuloendothelisis were investigated by time lapse cinematography; phytohemagglutinin stimulation; adherence to siliconized surfaces; a variety of cytochemical methods; and phase, transmission, and scanning electron microscopy. The scanning electron microscopic image supports the morphologic evidence for a relationship between the hairy and the reticular cells.
In Vitro Chromosomal Radiosensitivity in Fanconi’s Anemia
Authors: HIGURASHI MAKOTO , CONEN PATRICK E.
Published: October 2019

Peripheral blood samples and skin fibroblast cultures from five children with Fanconi’s anemia and four normal children were irradiated with 10 and 100 rads. Nonirradiated duplicate cultures were used as controls. Blood cultures were harvested after 52 and 72 hr of incubation and fibroblast cultures were harvested 24 hr after irradiation. The frequency of chromosomal breakage caused by irradiation was calculated by subtracting figures for nonirradiated samples from those for irradiated samples. After irradiation, the number of breaks/cell/rad in samples from Fanconi’s anemia was approximately four-fold greater in lymphocytes and twofold greater in fibroblasts than in the controls. The number of dicentrics and rings per cell in cultured lymphocytes after 100 rads was significantly greater in the Fanconi’s anemia samples than controls. Therefore, in vitro, chromosomes of cells from children with Fanconi’s anemia were significantly more radiosensitive than those of controls (p < 0.01).
Variations in the Relationships Between Total 59Fe Uptake and the Uptakes Into Heme and Nonheme Fractions of Spleen and Bone Marrow in Irradiated Mice and Mouse Radiation Chimeras
Authors: GRESHAM P. A. , BARNETT M. , GOKSOY K. , SMITH S. VAUGHAN
Published: October 2019

A chemical method for the separation of heme and nonheme iron-containing fractions in mouse tissues has been used to study the uptake of 59Fe into both the heme and nonheme iron fractions in spleen and femoral bone marrow, in order to investigate the possible relationships between the total uptake into spleen tissue and the rate of uptake into the heme fractions. In control mice, only about one third of the 59Fe is directly associated with heme during the first day after administration, and this fraction decreases as radioactive red cells are released from the spleen into blood. Ten days after X-irradiation of mice, the proportion of 59Fe in the spleen heme fraction 6 hr after intraperitoneal administration decreased from about 30 to 10% of the total splenic activity as the radiation dose was increased from 500 to 750 rads. A similar alteration in the proportion of 59 Fe in the spleen haem fraction occurred in mouse radiation chimeras as the dose of injected syngeneic bonemarrow cells was reduced from 5 x 105 to zero. Similar results were found in femoral bone marrow. These results indicate that in this system the rate of uptake into whole tissue is not a measure of the uptake into heme; it is necessary, therefore, to use the method involving the measurement of iron uptake into heme, rather than the total tissue uptake, when estimating hemoglobin synthesis or erythropoiesis.
The Effect of Erythrocytes on Mouse Bone Marrow Colony Development In Vitro
Authors: BRADLEY T. R. , TELFER P. A. , FRY PHYLLIS
Published: October 2019

The development of colonies in nutrient agar in vitro from mouse hemopoietic cells, in the presence of a maximal dose of colony-stimulating activity (CSA), was greatly enhanced by the addition of washed red cells to the culture system. Human, sheep, guinea pig, rat, and mouse (syngeneic or allogeneic), but not rabbit, red cells exhibited enhancing ability, as did osmotically lysed erythrocyte preparations from rats. The use of red cells in the culture system, in addition to a maximum concentration of CSA, has resulted in revised estimates of the numbers of agar colony-forming units in hemopoietic tissues.