bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and Biological Aspects of the HL-A System of Human Histocompatibility
Authors: DAUSSET J. , COLOMBANI J. , LEGRAND L. , FEINGOLD N. , RAPAPORT F. T. 
Published: October 2019

Abstract
The HL-A system of leukocyte group antigens is a system of great complexity and polymorphism, governed by an autosomal region which includes a number of subunits or subloci. It constitutes the principal system of histo-compatibility in man.
Extensive population and family studies have resulted in the identification of two HL-A subloci. The first sublocus determines antigens HL-A 1, 2, 3, 9, Da 15 and Da 17 as alternative alleles. Antigens HL-A 5, 7, 8, Da 4, Da 6, HN, and probably Da 9 and Da 18 are determined in similar fashion at a second sublocus. The products of 20 per cent of the genes of the first sublocus, and of 29 per cent of the genes of the second sublocus are still unknown.
Study of 113 families has documented 226 human HL-A genotypes and 452 haplotypes. The observed gene and haplotype frequencies were in close agreement with the anticipated values calculated on the basis of Mendelian laws. This result supports the concept that the HL-A system is in equilibrium.
Although the HL-A system plays a major role as a determinant of human allograft responses, its primordial function may be of relevance to other fundamental biological problems, with particular reference to host defenses against microorganisms, viruses and neoplastic cells.
Cyclic Leukocyte Oscillations in Chronic Myelogenous Leukemia During Hydroxyurea Therapy
Authors: KENNEDY B. J. 
Published: October 2019

Abstract
Cyclic fluctuations of the leukocyte and platelet counts were observed in five patients with chronic myelogenous leukemia during treatment with hydroxyurea. The cyclic periods ranged from 30 to 50 days, were similar in each individual, but the peak-to-trough values of single cycles varied in magnitude. A second biorhythm was a cyclic undulation of the leukocyte count with heights of the peaks at nine-to-20-month intervals. Rhythmic variations of the platelet counts were also observed; the period and phase of the cycle being the same as that of the leukocyte cycle. No cyclic oscillations were noted in the hemoglobin or reticulocyte counts. The recognition of the phenomenon may aid in the use of hydroxyurea or other chemotherapeutic agents in the control of myelogenous leukemia. Chronopharmacology may more accurately develop the use of antitumor agents by its investigation of drug effects on biologic characteristics as a function of biologic timing.
Relationship of Erythropoietin Effectiveness to the Generative Cycle of Erythroid Precursor Cell
Authors: MORSE BERNARD S. , RENCRICCA NICHOLAS J. , STOHLMAN FREDERICK 
Published: October 2019

Abstract
Hydroxyurea, a cytotoxic agent that kills cells in DNA synthesis, was used to study the relationship between erythropoietin and the generative cycle of the immediate erythroid precursor cell. When OHU and EP were administered simultaneously to hypertransfused mice, the resultant erythroid response was diminished relative to EP treated controls. OHU given at intervals after EP resulted in a progressively greater diminution of erythroid response.
From these studies, then, we would suggest that in the suppressed animal the committed stem cell compartment is in cycle but with a prolonged G1. After EP there is a shortening of the generation time and an increase in the rate of turnover of the committed stem cells. The data also indicate that cells in cycle are differentiated into the pronormoblast compartment. It further may be suggested that erythropoietin is effective throughout the bulk of the generative cycle although it seems unlikely that differentiation is accomplished during the mitotic phase. Whether erythropoietin must be present in both G1 and S as suggested by Kretchmar cannot be answered by the present studies. The data also indicate that cells of the pluripotential compartment are normally in G0 or perhaps a prolonged G1. Damage to the committed compartment appears to be in part repaired by the influx of cells from the pluripotential compartment.
Stimulation of Thrombocytopoiesis in Irradiated Mice
Authors: EBBE SHIRLEY , STOHLMAN FREDERICK 
Published: October 2019

Abstract
Platelet depletion in mice, by injection of heterologous anti-platelet serum (APS), resulted in apparent stimulation of megakaryocytopoiesis as evidenced by a subsequent over-compensation of the level of circulating platelets. Injection of APS immediately before or after exposure to sublethal radiation or a day after exposure appeared to modify the response to radiation. Radiation-induced thrombocytopenia was neither as severe nor as prolonged in animals so treated as in irradiated controls. More chronic thrombocytopenia at the time of irradiation, however, appeared to increase the radiosensitivity of the megakaryocytic system.
Immunologic Studies of Antihemophilic Factor (AHF, Factor VIII) II. Properties of Cross-reacting Material
Authors: HOYER LEON W. , BRECKENRIDGE ROBERT T. 
Published: October 2019

Abstract
Patients with a genetic variant of hemophilia A have in their plasmas material which has antigenic characteristics similar to those of antihemophilic factor (AHF). The physical properties of the biologically inactive cross-reacting material (CRM) are like those of AHF from normal plasma. The CRM is concentrated in Cohn fraction I and in cryoprecipitates and is not adsorbed from plasma by calcium phosphate or barium sulfate. It is inactivated by heating to 56° for 30 minutes. The CRM is less sensitive to thrombin inactivation than AHF and is recovered in serum. The similar properties of AHF and CRM support the hypothesis that patients with this genetic variant of hemophilia A synthesize a material similar to AHF but lacking procoagulant activity.
Hemorrhagic Thrombocythemia; Control of Postsplenectomy Thrombocytosis with Melphalan
Authors: BENSINGER THOMAS A. , LOGUE GERALD L. , RUNDLES R. WAYNE 
Published: October 2019

Abstract
Hemorrhagic thrombocythemia is a relatively well-defined myeloproliferative disease in which the major abnormality is the excessive production of megakaryocytes and platelets. In its natural evolution acute and chronic bleeding from the gastrointestinal tract, thromboembolic phenomena, gastric and esophageal varices, and infarction atrophy of the spleen are the important clinical features. Disastrous complications may follow splenectomy. Removal of the spleen by surgery, or infarction and atrophy allows masses of platelets to circulate which produce thrombi or emboli in small vessels and ultimately hemorrhage. Effective treatment requires the suppression of megakaryocyte growth and thrombopoiesis. In four patients who developed severe postsplenectomy hemorrhagic thrombocythemia, melphalan (L-phenylalanine mustard) therapy effectively controlled the abnormal thrombocytosis and clinical evidence of disease.
Transmural Cellular Passage in Vascular Sinuses of Rat Bone Marrow
Authors: WEISS LEON 
Published: October 2019

Abstract
The structure of vascular sinuses in rat bone marrow is modified as cells cross their wall. Endotoxin, by causing withdrawal of granulocytes from the circulation, induces a compensatory discharge of fresh granulocytes through the wall of sinuses. As a result the sinus wall becomes infiltrated by clusters of late-stage hematopoietic cells which appear in transmural passage. Two correlates of such infiltration are elevation of adventitial cells from the wall and the creation of adventitial spurs extending into perisinusal hematopoietic spaces. In untreated rats adventitial cells cover, on the average, about 65 per cent of the sinus wall. After 0.04 µg. endotoxin the cover is reduced, fitting a slope regressing at the rate of 0.22 per cent/min. (t = 3.1038, p = < 0.003), the last determinations made at 120 minutes. Values for the percentage of adventitial cover calculated from observations after endotoxin are 52.5 per cent in 90 minutes and 32 per cent in 120 minutes. Even after endotoxin, a number of sinuses retain full cover while a number of control sinuses, likely reflecting normal cell passages, have little adventitial cover. Endothelial cells form a continuous layer. Apertures occur in the wall normally and increase in number after endotoxin. These apertures may contain cells, apparently in passage, or may be free of cells. Lysosomal disruption occurs in mural cells, particularly in segments of wall associated with cellular passage and with gelatinous change.
Pulmonary Bed Sequestration of Neutrophils During Hemodialysis
Authors: TOREN MICHAEL , GOFFINET JOHN A. , KAPLOW LEONARD S. 
Published: October 2019

Abstract
A severe, transient granulocytopenia occurs shortly after the beginning of hemodialysis in the dog, as has been previously shown in man. Simultaneous blood sampling across the pulmonary vascular bed indicates that the process of granulocyte removal begins almost instantaneously and that the pulmonary vascular bed is a major site of granulocyte sequestration.
Patterns of Granulocyte Kinetics in Acute Myelogenous and Myelomonocytic Leukemia
Authors: GALBRAITH PETER R. , CHIKKAPPA GUNDABHAKTHA , ABU-ZAHRA HAKAM T. 
Published: October 2019

Abstract
Granulocyte kinetic studies, using radioactive diisopropylfluorophosphate (DF32P), were performed in 15 patients with acute myelogenous leukemia (AML) and 10 patients with the myelomonocytic variety (AMML). Attention was focused upon the more differentiated cells present in the blood of the leukemic patients. The patterns of disappearance of in vitro labeled leukocytes from the blood, and the patterns of emergence of in vivo labeled leukocytes from the bone marrow were variable. Nonuniformity in the results suggests that the terms AML and AMML cover a spectrum of disorders, and that broad generalizations concerning their kinetics cannot be made. The implications of these findings are discussed, and new evidence suggesting that the mature neutrophils in the blood of leukemic patients may arise from abnormal or leukemic precursors is presented.
Endogenous Production of 14CO: A Method for Calculation of RBC Life-span In Vivo
Authors: LANDAW STEPHEN A. , WINCHELL H. SAUL 
Published: October 2019

Abstract
A kinetic model is presented for estimation of the degradation rate of labeled heme by measurement of appearance of 14CO in the breath following injection of glycine-2-14C. This method does not require sampling of blood or other body fluids, is absolutely independent of circulating blood volume and relatively independent of erythropoietic rate, and estimates the relative contribution to 14CO production from destruction of circulating RBC hemoglobin heme and that arising from other heme sources. For circulating RBC, rate of random hemolysis, mean potential lifespan and spread of lifespans about this mean can be calculated. Mean overall RBC lifespan and the fraction of RBC dying of senescence can be derived from these calculations. In normal male buffalo rats, the average value for random hemolysis was 0.67 per cent per day, corrected mean potential lifespan 66.2 days and standard deviation about this mean of 7.6 days. For normal female LAF1 mice, the corresponding average values were 0.60, 51.8 and 9.1, respectively. Results in two other inbred mouse strains were similar save for a shorter mean potential lifespan of 47.1 days in SEC/1Re mice and a longer mean potential lifespan of 57.3 days in WC-B6 mice. Following splenectomy in the rat, an isolated significant increase in mean potential lifespan was seen. An isolated decrease in mean potential lifespan was seen in three rats recovering from phenylhydrazine-induced anemia. An example of markedly increased random hemolysis, together with shortened mean potential life-span, was seen in a gastrectomized rat with a severe hypochromic anemia. The present method is shown to simultaneously determine the major parameters defining RBC survival, and as such, should be quite useful in the study of red blood cell disorders in animals and man.
A Difference Between Spleen-derived and Bone Marrow-derived Colony-forming Units in Ability to Protect Lethally Irradiated Mice
Authors: KRETCHMAR A. L. , CONOVER W. R. 
Published: October 2019

Abstract
Suspensions of cells in the bone marrow and in the spleen of normal mice were prepared. Two groups of lethally irradiated mice were given cells from bone marrow and two groups of lethally irradiated mice were given cells from the spleen of the same donor mouse. One of the groups injected with bone marrow and one injected with spleen cells were killed at 9 days for determination of CFU. The remaining animals were followed for 100 days to determine the mortality statistics. The mortality among mice not given cells was 100 per cent; among mice injected with cells, the mortality was reduced. The data permit a comparison of the reduction in mortality (protection) following injection of bone marrow CFU with protection following injection of spleen CFU. Protection with CFU of bone marrow was different from protection with CFU of spleen. It seems possible that both hemopoietic pluripotent "stem cells" and "early differentiated progenitors" can form spleen colonies and that the ratio of these CFU may be different for bone marrow and spleen.
Colony Formation by Normal and Leukemic Human Marrow Cells in Culture: Effect of Conditioned Medium From Human Leukocytes
Authors: ISCOVE N. N. , SENN J. S. , TILL J. E. , MCCULLOCH E. A. 
Published: October 2019

Abstract
"Conditioned medium" obtained from cultures of human peripheral leukocytes promoted the growth of human marrow cells in cell culture. This material also permitted the growth of small colonies from the marrow of patients with acute myelogenous leukemia in relapse; in its absence, only occasional colonies were observed.
Surface Morphology of Human Leukocytes
Authors: MICHAELIS THOMAS W. , LARRIMER NYE R. , METZ EARL N. , BALCERZAK STANLEY P. 
Published: October 2019

Abstract
Surface morphology of individual leukocytes was correlated with their light microscopic appearance by a simple, direct technique. Circulating leukocytes of all types were roughened spheres with diameters similar to red cells, and leukocyte types could not be distinguished consistently by surface morphology. After surface contact, leukocytes increased in diameter and exhibited a variety of projections. Cells spread on surfaces could be identified by external morphology. Several stages in the phagocytosis of latex particles were demonstrated. The study of surface contours by scanning electron microscopy represents a new approach to morphology.
Serum Vitamin B12-Binding Capacity and Muramidase Changes With Cyclic Neutropenia Induced by Cytosine Arabinoside
Authors: CARMEL RALPH , COLTMAN CHARLES A. 
Published: October 2019

Abstract
A patient with acute leukemia in sustained complete remission was studied for 8 months. Periodic maintenance chemotherapy with cytosine arabinoside regularly induced granulocytopenia, with granulocytosis upon marrow recovery. Changes in serum unbound B12-binding capacity (UBBC) occurred simultaneously with peripheral granulocyte fluctuations. Both α- and β-globulin UBBC were affected. Serum muramidase rose and fell out of phase with the granulocyte and UBBC fluctuations, preceding them by several days. These data support the concept that serum UBBC and serum muramidase reflect different aspects of granulocyte activity.
Functional Studies of Young Versus Old Platelets in a Patient With Chronic Thrombocytopenia
Authors: JOHNSON CHRISTINE A. , ABILDGAARD CHARLES F. , SCHULMAN IRVING 
Published: October 2019

Abstract
Results of a comparative study of the functional capacity of young versus old platelets are presented. A girl with thrombopoietin deficiency, who predictably produced platelets in response to plasma transfusion, was used as platelet donor. Her platelets obtained 4 days after infusion were used as young test cells. Platelets obtained at 18 or 21 days after infusion were used as old cells. Young platelets were found to be associated with normal bleeding times, normal clot retraction, normal or increased platelet adhesiveness, normal aggregation to ADP and collagen, and normal platelet factor 3 availability. Old platelets were found to be associated with long bleeding times, decreased platelet adhesiveness in vivo and in vitro, and deficient platelet factor 3 availability. The clot retraction and aggregation to ADP and collagen of old platelets, however, was normal. No differences between young and old platelets were observed by electron microscopy.
Evidence for a Circulating Stem Cell: Newly Formed Erythroblasts Found in Autologous Leukocyte-filled Diffusion Chambers Inserted into Bled Rabbits
Authors: GRIGORIU G. , ANTONESCU MONICA , IERCAN E. 
Published: October 2019

Abstract
Leukocytes from severely bled rabbits were sedimented and introduced in diffusion chambers that were implanted intraperitoneally into donor animals during the same day. Erythroblasts were found in the Millipore chambers on the fourth day culture. They were present in large numbers from the seventh to eighth day when they comprised 47.5 per cent of the nucleated cells present. Concomitantly, the young classes of reticulocytes, never found in controls, were detected in the diffusion chambers of bled animals, after more than 4 days of culture. It was assumed that: (1) Some circulating leukocytes may develop into erythroblasts under the influence of endogenous erythropoietin. (2) Under the experimental conditions employed, bleeding promoted only erythropoiesis within the implanted diffusion chambers containing leukocytes. There was no evidence of granulopoiesis and thrombopoiesis.
Accelerated Regeneration of Transplanted Hematopoietic Stem Cells in Irradiated Mice Pretreated With Cyclophosphamide
Authors: GREGORY S. A. , FRIED W. , KNOSPE W. H. , TROBAUGH F. E. 
Published: October 2019

Abstract
Results of experiments are reported which indicate that colony-forming units (CFU) regenerate more rapidly when transplanted into the marrow of lethally irradiated hosts pretreated with cyclophosphamide (CY) than when transplanted into those pretreated with saline. This effect is probably unrelated to the immunosuppressive properties of CY because it occurs in isogeneic strains as well as in randomly bred CF1 mice. It also does not result from an increase in the radioresistance of cells which survive after injection of CY. The data presented here are compatible with the concept that CY somehow improves the environment for hematopoietic stem cell (HSC) proliferation and thereby causes an increased rate of regeneration of transplanted HSC in the marrow cavity of the host. The possibility that this is caused by release of HSC from an inhibitory effect of cell-cell interactions on proliferation or by the release of a humoral stimulus to HSC regeneration is discussed.
Studies of Marrow Transplantation, Chemotherapy and Cross-circulation in Canine Lymphosarcoma
Authors: EPSTEIN ROBERT B. , GRAHAM THEODORE C. , STORB RAINER , THOMAS E. DONNALL 
Published: October 2019

Abstract
During a 4-year period 75 dogs with malignant neoplasms were referred by veterinarians to a medical research unit interested in the study of canine lymphoma and leukemia. Sixty dogs had lymphoblastic lymphosarcoma, six had leukemia, and nine had nonhemopoietic malignancies. Twenty-nine allogeneic marrow grafts were attempted following 1200 R of whole-body irradiation. Seven dogs with lymphosarcoma and one dog with anaplastic carcinoma survived beyond the first postirradiation week and demonstrated evidence of allogeneic marrow engraftment. All animals died, two following graft rejection, two with intercurrent sepsis and three of secondary disease. The two longest survivors, dying of secondary disease on days 46 and 60, were free of clinical or histologic evidence of tumor. Four dogs with lymphosarcoma were treated for 18 to 30 days with L-asparaginase. Rapid tumor regression was noted in all. Eleven dogs were treated with weekly intravenous cyclophosphamide. Moderate to marked node regression occurred in nine cases. Lymphocytes from normal dogs presensitized with tumor tissue were given by cross circulation to tumor-bearing hosts. Tumor regression occurred in two of five dogs. It was concluded that canine lymphosarcoma is a disease with uniform histologic and clinical features suitable for evaluation of therapeutic procedures in the treatment of a spontaneous malignancy in a randomly bred species.
Origin of Repopulating Cells in a Mechanically Depleted Medullary Cavity as Determined by Studies With Marrow Transplants
Authors: FONG PHILIP L. , MALONEY MARY A. , PATT HARVEY M. 
Published: October 2019

Abstract
The restoration of marrow in a mechanically depleted segment of rabbit femur has been reported to be a local phenomenon initiated by cells normally resident in bone. That marrow regeneration in an evacuated femur is independent of circulating stem cells has been confirmed in mice bearing a heterologous marrow transplant. Mice were given 800 R of whole-body X-radiation with experimental femur shielded. Rat marrow cells, histochemically distinguishable from those of the mouse by alkaline phosphatase staining, were then transplanted to the irradiated animals. The shielded femur diaphysis was evacuated by dextran perfusion, and 2 weeks later the animal was sacrificed. Imprints were made of the spleen and of the marrow in the contralateral limb, the epiphyseal ends of the depopulated femur, and the depopulated section of the femur. Alkaline phosphatase staining showed that all of the areas involved except the evacuated femur section had an abundance of alkaline-positive rat cells. The depopulated femur diaphysis showed a typical regenerating marrow tissue at 14 days and the cell constituents were of mouse cell origin.
Vinblastine: Colchicine-like Effects on Human Blood Leukocytes During Phagocytosis
Authors: MALAWISTA STEPHEN E. 
Published: October 2019

Abstract
Vinblastine and colchicine interfere with the normal organization of microtubules both in the mitotic spindle of dividing cells—causing metaphase arrest—and in the cytoplasm of nondividing cells such as polymorphonuclear leukocytes, with effects less well understood. In addition to this ultrastructural alteration, colchicine has other morphologic, enzymic, and metabolic effects on phagocytizing leukocytes, that may contribute to its anti-inflammatory properties in vivo. In the present work, effects of vinblastine were compared to those of colchicine. The effects of vinblastine 2.5 x 10-5 M were in all respects similar to those of colchicine and, on a molar basis, at least as strong. There was inhibition of the increased oxygen consumption and glucose-1-14C oxidation that normally accompany phagocytosis. There was also inhibition of lysosomal degranulation and the formation of digestive vacuoles, indicated both in morphologic studies and in measurements of granule-associated acid phosphatase activity after phagocytosis. In this system there was no demonstrable effect either on the ingestion process itself or on the intracellular killing of Staphylococcus aureus. If, however, leukocytes in buffer were incubated with preopsonized staphylococci, they ingested bacteria more rapidly than in the serum system. Under those circumstances, if the concentration of drug was doubled (to 5 x 10-5 M), there was still no difference in ingestion of bacteria between drug-treated and control leukocytes, but both vinblastine and colchicine inhibited intracellular killing of staphylococci. However, this inhibition, though statistically significant, was trivial compared to the percentages of the inocula ingested and killed by both treated and control leukocytes. These findings support the hypothesis that common structural and functional effects of vinblastine and colchicine may ultimately be traced to common ultrastructural effects on microtubules. Moreover, microtubules may facilitate the fusion of lysosomes with vacuoles containing ingested material.