bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum erythropoietin concentration in chronic renal failure: relationship to degree of anemia and excretory renal function
Authors: Radtke HW , Claussner A , Erbes PM , Scheuermann EH , Schoeppe W , Koch KM
Published: October 2019

By use of the fetal mouse liver cell assay, serum erythropoietin (SEp) concentration was measured in 135 patients at various stages of chronic renal failure and in 59 healthy subjects. In patients with creatinine clearances (CCr) ranging from 2 to 40 ml/min/1.73 sq m, endocrine renal function was found to deteriorate in parallel to excretory renal function. The known negative correlation between SEp and hematocrit (Hct) was not apparent, probably because of the loss of renal mass accompanying progress of anemia and renal insufficiency. In contrast, in patients with minimal variation of residual excretory renal function, as in individual patients investigated repeatedly within a short period of time, changes of Hct were always accompanied by opposite changes of corresponding SEp concentrations. Thus, patients with chronic renal failure have a sustained regulatory feedback mechanism between Hct and SEp, which probably works at a lower level.
Induction of erythropoietic colonies in a human chronic myelogenous leukemia cell line
Authors: Hoffman R , Murnane MJ , Benz EJ Jr , Prohaska R , Floyd V , Dainiak N , Forget BG , Furthmayr H
Published: October 2019

The ability of cells derived from the K562 cell line to generate erythropoietic colonies was studied. The K562 cell line was derived from a patient with chronic myelogenous leukemia 8 yr ago by Lozzio and Lozzio. Rare benzidine-positive colonies formed when these cells were cloned in plasma clots (3 +/- 1/10(4) cells), and their number was not substantially increased by the addition of erythropoietin (9.5 +/- 1/10(4) cells). Sodium butyrate was capable of markedly enhancing the number of benzidine-positive colonies (19.5 +/- 1/10(4) cells) formed, while the combination of sodium butyrate plus erythropoietin exerted a synergistic effect on erythropoietic colony formation (57 +/- 4/10(4) cells). The K562 cell line is a long-term culture system that contains human erythropoietic stem cells. This cell line should be useful in future studies on the cellular and molecular events associated with human erythroid cell differentiation.
Analytical Review: Conversion Factors and Accelerators in the Formation of Thrombin
Authors: STEFANINI MARIO
Published: October 2019

Prothrombin and fibrinogen represent the fundamental materials in the formation of the solid clot. During the process of blood coagulation, prothrombin is converted to thrombin, and this enzyme, in turn, clots fibrinogen.

The formation of thrombin is the essential step in the clotting of blood. Besides prothrombin, at least five other agents participate in the reaction. They may be divided into: a) conversion factors, agents actively participating and indispensable for the formation of thrombin, at least for physiologic needs; and b) accelerators, which increase the speed of the conversion of prothrombin to thrombin and the yield of this enzyme once the process has been initiated. The first group includes thromboplastin, calcium and a plasma prothrombin conversion factor (PPCF); the second, a serum accelerator and a platelet accelerator. Platelets may also supply a factor which accelerates the formation of fibrin from fibrinogen.

Thrombin, once formed, is able to accelerate its own production (autocatalysis), thus determining an "explosive" formation of fibrin. This mechanism is of great importance in assuring efficient hemostasis. Adsorption of the thrombin on the fibrin clot and neutralization of the enzyme by the natural plasma antithrombin when it is slowly released during the retraction of the clot are two known mechanisms by which the organism protects itself from any undue extension of the intravascular thrombus.
Hermatologic Changes with ACTH and Cortisone Therapy of Rheumatoid Arthritis
Authors: FINCH STUART C. , CROCKETT CHARLES L. , Ross JOSEPH F. , BAYLES THEODORE B.
Published: October 2019

1. Detailed hematologic observations, bone marrow aspirations and blood volume determinations were made on 20 patients with rheumatoid arthritis and allied disorders before, during and after the administration of either ACTH or cortisone.

2. Significant reticulocytosis occurred in every patient during therapy, but its magnitude was poorly correlated with either the initial degree of anemia or subsequent increase in circulating red cell mass.

3. There was an increase in hematocrit and total circulating red cell mass of all anemic patients who responded clinically to either ACTH or cortisone. There was little or no improvement of anemia when the clinical response was poor.

4. Polycythemia did not occur in any patient during prolonged therapy or with repeated courses of either ACTH or cortisone.

5. Hemodilution and hemoconcentration were much more profound during and after ACTH administration than they were with cortisone.

6. Bone marrow studies revealed moderate depression of the erythroid series before treatment. At the end of therapy erythroid elements were normal.

7. Significant polymorphonuclear leukocytosis occurred its all patients during therapy while lymphopenia was inconstant and unsustained. Circulating eosinophils were depressed more with ACTH than with cortisone treatment.

8. Before treatment eosinophils and their precursors were present in the bone marrow its normal or increased numbers. During therapy the number of these cells was unchanged in the marrow, even when there was profound peripheral eosinopenia

9. The role of ACTH and cortisone in the physiologic mechanism of hematopoiesis is discussed.

10. The improvement in the anemia associated with inflammatory disease in response to ACTH or cortisone therapy probably is a reflection of the control of the underlying disease rather than a primary "stimulation" of the bone marrow.
The Rhesus Antibody Anti-E in Pregnancy and Blood Transfusion
Authors: MALONE R. H. , DUNSFORD I.
Published: October 2019

1. Twelve cases of immunization by pregnancy or blood transfusion in which the Rhesus antibody anti-E was found, to the exclusion of anti-D or any other Rh antibody are reported.

2. Two hundred and fifty Rh antibodies were discovered in this laboratory during 1949 in 37,972 antenatal cases not previously tested, i.e., 1 in 152. Seven of these were pure anti-E, i.e., 2.8 per cent. This frequency is considerably higher than any previously reported.

3. All of the anti-E sera tested possessed to some degree, and 5 of them to a marked degree, the property of distinguishing cells with a double from those with a single dose of the antigen E.

4. The presence, in cells of various genotypes, of tine antigen D in association with the antigen E reduced their agglutinability with the same anti-E serum in such a manner as to suggest that the agglutinability of these cells depends upon the relative quantities of the E and D anitigens present.

5. By means of parallel titrations with a genotyping anti-E serum, against cells of known and unknown genotypes, it was possible to distinguish E/E from E/e cells in the presence or absence of associated D and, as a corollary, to distinguish D/D from D/d cells in the presence of associated E/E or E/e.

6. These results fit the hypothesis that the specific Rhesus antigens C, D and E are produced from a limited amount of "basic raw material" by the activity of the three genes: that the genes act independently and in competition and that the amount of each antigen produced is proportional to the dosage and "competitive value" of the corresponding gene.
Observations on Erythrocyte and Plasma Cholinesterase Activity in Dyscrasias of the Blood
Authors: SCUDAMORE HAROLD H. , VORHAUS LOUIS J. , KARK ROBERT M.
Published: October 2019

1. Erythrocyte and plasma cholinesterase activities of the blood were determined by Michel’s potentiometric method in 20 healthy individuals and in 20 patients ill with various blood dyscrasias.

2. The mean erythrocyte cholinesterase activity in the blood of healthy individuals was 0.71 ± 0.11 Δ pH/hr. and the mean plasma cholinesterase activity was 0.98 ± 0.17 Δ pH/hr.

3. Low erythrocyte cholinesterase activity was found in the blood of patients ill with pernicious anemia or ill with hypoplastic anemia.

4. High erythrocyte cholinesterase activity was found in the blood of patients suffering with anemia secondary to hemorrhage and of patients ill with pernicious anemia or macrocytic anemia of nontropical sprue in early remission.

5. The plasma cholinesterase activity of blood from patients ill with blood dyscrasias usually reflected the general clinical status of the patients and, in general, was related to the albumin concentration in the serum.

6. The low erythrocyte cholinesterase activity increased following multiple blood transfusions and during a reticulocyte response in a case of hypoplastic anemia, whereas the plasma cholinesterase activity remained unchanged.

7. The erythrocyte cholinesterase activity in patients ill with pernicious anemia or macrocytic anemia of nontropical sprue increased rapidly during therapy beginning with the reticulocyte response and continuing during the period of increased erythropoietic activity. The plasma cholinesterase activity increased slowly parallel to improvement in hematologic and clinical status.

8. The possible relationships between alterations in erythrocyte cholinesterase activity in blood dyscrasias and reticulocytosis and erythropoiesis are discussed.
Urethane-Caused Blood and Bone Marrow Changes in Agranulocytosis and Panmyelopathy of the Cat
Authors: MOESCHLIN S. , BODMER A.
Published: October 2019

The investigations reported in the present paper deal with the behavior of the peripheral blood and the bone marrow in urethane-produced agranulocytosis and panmyelopathy in the cat. The principal conclusions follow:

1. A severe panmyelopathy can be produced regularly in cats by the administration of relatively small doses of urethane: viz., 0.05 to 0.1 Gm. per Kg. per day. The panmyelopathy is still reversible if the urethane is stopped early enough and if the animal is maintained with antibacterial therapy.

2. The time required for recovery of the bone marrow after cessation of urethane administration depends on the total dosage of the drug. After small doses recovery occurs rapidly; after large doses much more slowly. Individual sensitivity of the experimental animal also plays a role, however.

3. The effect of smaller doses of urethane (0.05 Gm./Kg./day) on the bone marrow is to produce inhibition of maturation of granulocytopoiesis, and, to a lesser degree, of thrombocytopoiesis. To a still lesser extent, there is also inhibition of maturation of the red cell series.

4. The effect of larger doses of urethane (0.1 Gm./Kg./day) on the bone marrow, the effect on maturation is overshadowed by a generalized depletion of all marrow cells. Part of this effect is due to a decrease in the number of mitoses, with reduction of the mitotic index; as well as qualitative alterations in the mitotic patterns. It is probable that the effect on mitoses results in the formation of cells which are incapable of life as well as in an overall decrease in the formation of cells.

5. In the cat, the neutrophilic granulocytes are most sensitive to the action of urethane. The lymphocytes are next most sensitive; then the megakaryocytes, finally the erythroblasts. The eosinophils were remarkably insensitive.

6. The normal plasmacellular reticulum cells are relatively insensitive to urethane. This is in contrast to the neoplastic myeloma cells in human beings which have been reported to be sensitive to urethane.

7. The administration of folic acid or of vitamin B6 to the experimental animals had no effect on the course of urethane agranulocytosis.

8. The normal granulocytopoiesis of the cat is about as sensitive towards urethane as the pathologic granulocytopoiesis of chronic myeloid leukoses of human beings. This is in contrast to the findings in other animals, and to normal granulocytopoiesis of man. The variation in behavior possibly indicates variations in enzyme systems in the various types of granulocytopoiesis, with only certain enzymes being affected by urethane.

9. Further experiments are in progress to determine if the effect of urethane on the bone marrow can be counteracted by means of other growth substances. It is hoped that better insight may thus be gained into the mechanism of action of urethane.
The Inheritance of the Sickling Phenomenon, with Particular Reference to Sickle Cell Disease
Authors: NEEL JAMES V.
Published: October 2019

1. The manner of inheritance of the sickling phenomenon has been investigated in 75 kindreds, with hematologic observations on 465 persons.

2. Data are presented to support the contention that with a possible rare exception, the differential diagnosis between the sickle cell trait and sickle cell anemia is readily made.

3. The hematologic findings pertinent to a decision as to the mode of heredity of the sickle cell trait and sickle cell disease are as follows:

a. Out of a total of 94 parents of children with sickle cell disease, 93 have shown the sickle cell trait.

b. The incidence of sickle cell disease in segregating sibships would appear to lie between 0.18 and 0.26.

c. In sibships segregating for sickle cell disease, the ratio of sickle cell trait to normal is approximately 2:1, but in sibships resulting from the marriage of a normal person with an individual with the sickle cell trait, the ratio of sickle cell trait to normal is significantly less than 1:1.

d. Of the 4 children in this series who have a parent with sickle cell disease, all have the sickle cell trait.

4. The most reasonable hypothesis which will render the above data intelligible is that the sickling phenomenon is due to a gene which in single dose (heterozygous condition) produces only the sickle cell trait, and in double dose (homozygous condition), sickle cell disease. The chief and only discrepancy between theory and fact at the present time appears to lie in a deficiency of individuals with the sickle cell trait in certain types of matings.

5. No clear cut differences between normal and sickle cell trait were observed with respect to erythrocyte number, hemoglobin level, hematocrit, the cell constants, the leukocyte number or the differential count.

6. Certain minor hematologic abnormalities encountered in the kindreds under study and not obviously related to the sickling phenomenon are described.
Methods: Demonstration of the "L. E." Cell without Use of Anticoagulants
Authors: EPPES WILLIFORD , LUDOVIC ETHEL
Published: October 2019

"L. E." cells and rosettes were demonstrated in the blood of patients with systemic lupus erythematosus without the use of anticoagulants. Concentration technics using defibrinated blood and unmodified blood in silicone coated tubes were employed.
The Effect of Massive Doses of Cortisone on the Peripheral Blood and Bone Marrow of the Mouse
Authors: QUITTNER HOWARD , WALD NIEL , SUSSMAN LEON N. , ANTOPOL WILLIAM
Published: October 2019

1. The subcutaneous administration of a single massive dose of cortisone to mature male albino mice produces: (1) A prompt and prolonged fall in the level of circulating lymphocytes and eosinophils which persists as long as nine days after the administration of the hormone. (2) A granulocytopenia which resolves at two days and is accompanied by a period of bone marrow blocking followed by resumption of delivery and myeloid hyperplasia.

2. No inhibitory effect of cortisone on cell proliferation is seen in the bone marrow.

3. There is no change in hemoglobin concentration following cortisone treatment.

4. Adult male albino mice are satisfactory animals for serial observations of the effect of cortisone on the circulating blood elements and the bone marrow.
Relation of Methemoglobin to Hemolysis
Authors: CLARK BYRON B. , MORRISSEY ROBERT W. , BLAIR DOROTHY
Published: October 2019

Experiments are described which attempt to define the relation of methemoglobin to hemolysis. A comparison was made in vitro of the resistance of erythrocytes containing chiefly oxyhemoglobin or methemoglobin to hemolysis by saponin, hypotonic saline, bile salts and lysolecithin. These data are interpreted to indicate that intracorpuscular methemoglobin does not alter the resistance of erythrocytes to hemolysis by these lysins, although there are certain peculiarities in the results with bile salts and lysolecithin.

In the case of bile salts and lysolecithin, oxyhemoglobin or methemoglobin may have an equal or different inhibitory effect on hemolysis depending upon the conditions of pH and temperature.

Chronic methemoglobinemia in dogs maintained by the administration of sodium nitrite does not produce an anemia.

These data suggest that the formation of methemoglobin is an independent effect and not a part of the hemolytic action of certain chemical agents.
Analytical Review: Certain Hemolytic Mechanisms in Hemolytic Anemia
Authors: PONDER ERIC
Published: October 2019

The factors which normally limit the life of the red cell are described as being a continuous metabolic process involving the enzymatic oxidation of Hb and a terminal event, which may be hemolysis, fragmentation or phagocytosis.

A number of lytic substances, such as soaps, lipids and lysolecithin-like substances can be extracted from plasma and from tissues. These substances are associated with inhibitors and accelerators to form complexes. The activity of these naturally occurring hemolytic complexes tends to be small, although it can increase to such an extent that appreciable red cell destruction results. Instances are given in which hemolysis in vivo results from the concentration of one of these lysins increasing (as when fat is fed), from an accelerator of one of the lysins being introduced (usually as a drug), and from the concentration of inhibitory material being reduced (as by a low cholesterol diet).

Most hemolytic episodes are due to the establishment of a new hemolytic mechanism, which may appear after the introduction of a drug, of an agglutinin such as silicic acid or ricin, of an immune agglutinin which is not itself a hemolysin or of an agglutinin which is a lysin in the presence of complement. The various mechanisms which may result in hemolysis are discussed. The case in which the agglutinin becomes a lysin in the presence of complement presents no difficulty; in other cases the mechanism of hemolysis is not so clear, nor is it clear whether red cell destruction depends primarily on hemolysis or primarily on phagocytosis.

Special processes are involved in the destruction of red cells which have intrinsic defects of structure. The abnormally thick red cells of congenital hemolytic icterus are selectively sequestered in the spleen, where there are a number of hemolytic mechanisms which can destroy them the more readily because of their abnormal shape. The sickle cell, with its poor osmotic properties, its reduced mechanical fragility, and its tendency to lose part of its structure as filaments at each disk-sickle transformation, is destroyed by processes which are probably hemolytic but less easy to specify. The flat red cells of Mediterranean disease are abnormally prone to fragmentation. In all these diseases the abnormal shape of the red cell seems to be accompanied by peculiarities in its contained hemoglobin, an observation which requires further study before its significance is clear.
An Improved Technic of Bone Marrow Aspiration
Authors: PROPP SIMON
Published: October 2019

1. The original Arinkin technic of sternal puncture has been modified to include iliac, spinous process and tibial marrow aspiration.

2. There has been a need for improvement and standardization of the method of handling aspirated bone marrow.

3. An improved technic of marrow aspiration is described which combines direct Arinkin type smears with marrow particle and concentrate preparations. Fixed sections may also be obtained. An important innovation is the use of a dilute solution of sodium heparin in the aspirating syringe to prevent clotting so that all marrow obtained may be utilized.

4. The "pure" marrow fragment or particle smear is the most valuable for diagnostic purposes. Smears prepared from concentrated marrow cells and directly from the mixed aspirate are also studied routinely but are chiefly of value when marrow particle smears either can not be obtained or are unsatisfactory. Section of marrow particles is rarely indicated. Surgical trephine biopsy of the sternum is still performed when repeated aspirations fail to procure adequate marrow.

5. A gradual transition from the Arinkin method to the use of marrow fragments and concentrate smears is advisable because of the differences in cellular content and appearance of the preparations. A knowledge of the normal is essential.

6. The use of this combined technic of marrow aspiration has resulted in improved knowledge of normal and abnormal marrow obtained by the puncture method. It is of great value in the study of cells of the lymphocytic, plasmocytic and megakaryocytic series, and in routine search for the "L. E." cell. A higher degree of accuracy has been attained in diagnosis than was possible by the Arinkin technic. The procedure is especially valuable in the diagnosis of lymphosarcoma, plasma cell myeloma, thrombocytopenic purpura, leukopenic and pancytopenic states, hypoplastic and aplastic anemias and aleukemic leukemias.
The Dilution of Blood Plasma by Calcium-Combining Anticoagulants
Authors: ADAMS ALDEN ROSS , MOSHER WILLIAM A.
Published: October 2019

When used in equimolar concentrations, five different calcium-combining anticoagulants produced uniform dilution of a given blood sample.

The potassium anticoagulants seem to exert a hemolytic effect on the erythrocytes.

The plasma dilution caused by a given concentration of the calcium-combining anticoagulants ranged from 8 to 20 per cent in the bloods examined. This shows the importance of using serum or unoxalated plasma for comparing the plasma protein concentrations of individual blood samples.
Thrombotic Thrombocytopenic Purpura
Authors: MEACHAM GORDON C. , ORBISON J. LOWELL , HEINLE ROBERT W. , STEELE HOWARD J. , SCHAEFER J. ALPERT
Published: October 2019

1. Two patients with a syndrome of hemolytic anemia, thrombocytopenic purpura and arteriolar occlusions are described.

2. In one patient, a long remission followed splenectomy, and improvement for ten days followed the administration of ACTH. No claim is made that either form of therapy induced the remission, but trial of these procedures in other cases is indicated.

3. Evidence is presented that the primary vascular lesion is a degenerative process in the arteriolar and capillary walls rather than thrombus formation in the lumen of the vessel. The occurrence of aneurysms in arterioles and precapillanes was a striking observation.

4. The histologic changes suggest a relationship to the so-called collagen group of diseases.

5. It is suggested that the term, thrombotic thrombocytopenic purpura, be retained until further study of the conditions permits application of a more suitable name.
The Clot Accelerating Effect of Dilution on Blood and Plasma. Relation to the Mechanism of Coagulation of Normal and Hemophilic Blood
Authors: TOCANTINS L. M. , CARROLL R. T. , HOLBURN R. H.
Published: October 2019

Dilution with physiologic saline solution and other fluids accelerates the coagulation of properly collected normal and hemophilic blood and plasma in silicone coated vessels, with or without the aid of activating agents such as platelets, thromboplastin, cephalin, glass particles or plasma euglobulin fractions. When normal plasma is diluted under a concentration of about 20 per cent, its rate of clotting is prolonged, principally because of diminution in prothrombin.

Regardless of the activating agent used, the rate of coagulation of hemophilic plasma can be made equal to that of normal plasma by appropriate dilution. These findings speak against the existence in hemophilic blood or plasma of a deficiency in any procoagulant factor, and support the concept of the presence in excess of a stabilizing inhibitor which slows the conversion of prothrombin to thrombin by one or both of the following mechanisms: (1) reducing or inactivating the effect of released coagulants (antithromboplastin activity) (2) conjugation with a procoagulant thereby maintaining it in an inactive form (anti Ac-globulin activity).
Lymphokine-induced phagocytosis in angiocentric immunoproliferative lesions (AIL) and malignant lymphoma arising in AIL
Authors: Simrell CR , Margolick JB , Crabtree GR , Cossman J , Fauci AS , Jaffe ES
Published: October 2019

A factor that augmented the phagocytosis of IgG-coated ox red blood cells by the human monocyte/macrophage line U937 was identified in cell culture supernatants from two of two patients with angiocentric peripheral T cell lymphomas, three of three patients with angiocentric immunoproliferative lesions that were not frankly malignant, and one of two patients with T lymphoblastic malignancies. The factor was not present in supernatants derived from 14 nonangiocentric peripheral T cell lymphomas of other histologic types nor in ten cases of B cell lymphoma and two cases of Hodgkin's disease. A similar factor was present in the supernatants of concanavalin A (Con A)-stimulated normal peripheral blood mononuclear cells and in the supernatants of IL-2- dependent T cell lines derived from normal peripheral blood. The factor had an apparent mol wt of greater than 50,000 daltons, was heat labile (100 degrees C for two minutes), and stable at pH 2.0. Its stimulation of phagocytosis was independent of any increase in number of Fc receptors. Thus, this factor is probably not gamma-interferon. This factor may play a pathogenetic role in the hemophagocytic syndromes associated with certain T cell malignancies and immunodeficient states.
The proliferation in suspension of the progenitors of the blast cells in acute myeloblastic leukemia
Authors: Nara N , McCulloch EA
Published: October 2019

A minority of blast cells in acute myeloblastic leukemia (AML) form colonies in culture in methylcellulose when stimulated by media conditioned by normal leukocytes in the presence of phytohemagglutinin (PHA-LCM). Blast colonies can be replated successfully, either as pooled cells or suspensions from single colonies. However, the plating efficiency declines with repeated passages, and more than four subcultures have not been achieved. In this study, blast populations were cultured in suspension, with fetal calf serum, alpha-minimal essential medium and PHA-LCM. In cells from 17 of 18 patients, exponential growth of clonogenic blast cells was maintained for six to seven days without reculturing. Colonies obtained from progenitors taken from liquid culture and replated in methylcellulose were replated to obtain the secondary plating efficiency (PE2). In 14 cases, this value was maintained or increased. In three instances, PE2 fell following culture in methylcellulose. When cells in suspension were recultured, exponential growth continued. In nine instances, exponential growth was maintained for from seven to 70 days. During this time, PE2 was maintained. Results from experiments using velocity sedimentation separation and analysis of single colonies were consistent with the view that the increase in clonogenic cells in suspension was a manifestation of their self-renewal capacity. The observations also support a model of blast progenitor growth that contains the postulate that these are capable not only of self-renewal but also of determination-like events leading to loss of proliferative capacity.
Autologous bone marrow transplantation in acute leukemia: a phase I study of in vitro treatment of marrow with 4- hydroperoxycyclophosphamide to purge tumor cells
Authors: Kaizer H , Stuart RK , Brookmeyer R , Beschorner WE , Braine HG , Burns WH , Fuller DJ , Korbling M , Mangan KF , Saral R
Published: October 2019

This phase I study was conducted to determine the maximal safe concentration of 4-hydroperoxycyclophosphamide (4HC) that could be used for in vitro treatment of bone marrow from patients with acute leukemia undergoing autologous bone marrow transplantation. Concentrations of 40 to 120 micrograms/mL of 4HC were used in 30 patients with relapsed or high-risk acute leukemia and in six patients with nonleukemic malignancies. All patients received marrow-lethal cytoreductive therapy followed by infusion of the 4HC-treated marrow. Complete inhibition of granulocyte and macrophage colony-forming cells was obtained at 80 micrograms/mL. Nevertheless, only one transplant-related death and otherwise full hematologic recovery was observed at concentrations of 4HC up to 100 micrograms/mL. At 120 micrograms/mL, there were three transplant-related deaths, including two of the three patients who required the infusion of reserve marrow. Among the acute leukemia patients, three remain in complete remission at 1,337, 1,017, and 967 days after transplant. Among the nonleukemic patients, two remain in complete remission at 1,081 and 1,017 days after transplant. At the maximum safe concentration of 4HC (100 micrograms/mL), satisfactory hematologic recovery can be obtained, despite elimination of detectable hematopoietic progenitors.
Multiple Spontaneous Remissions in a Child with Acute Leukemia
Authors: BASSEN FRANK A. , KOHN JEROME L.
Published: October 2019

1. A case of acute leukemia with four observed spontaneous remissions is presented.

2. Spontaneous remissions in acute leukemia are infrequent and multiple remissions rare.

3. Spontaneous remissions in acute leukemia follow a pattern in that they occur after the development of a leukopenic agranulocytic phase and hypoplasia or aplasia of the marrow.

4. Remissions in acute leukemia when therapeutically induced probably follow a similar pattern.

5. The significance of agranulocytosis in acute leukemia has been discussed. When it occurs, before the diagnosis of leukemia is definitely made, and recovery ensues, one should be alerted for the possible later development of a characteristic picture of leukemia.

6. The possibility that idiopathic aplastic anemia is no more than a phase of acute leukemia has been discussed.
Studies on Copper Metabolisn
Authors: LAHEY M. E. , GUBLER C. J. , CHASE M. S. , CARTWRIGHT G. E. , WINTROBE M. M.
Published: October 2019

1. A total of 70 swine were fed a diet consisting only of evaporated cow’s milk. Copper and iron were added to the diet of 10 of the pigs. Iron only was added to the diet of 46 of the pigs. Copper only was added to the diet of 10 of the pigs. Four pigs received neither iron or copper.

2. The animals deficient in copper developed skeletal abnormalities, microcytic hypochromic anemia, leukopenia, neutropenia, normoblastic hyperplasia of the bone marrow, hypoferremia, an increase in the iron-binding capacity of the plasma, hypocupremia and reduced erythrocyte copper as well as tissue copper. No abnormality in porphyrin metabolism was observed and tissue as well as erythrocyte catalase activity was not significantly reduced. Following the administration of copper, the blood of the animals was rapidly and completely restored to normal.

3. The animals deficient in iron developed a severe microcytic, hypochromic anemia, normoblastic hyperplasia of the bone marrow, hypoferremia and an increase in the total iron-binding capacity of the plasma. No abnormality in copper or porphyrin metabolism was observed in these animals except for a slight elevation in the plasma copper level and a marked increase in liver copper.

4. The animals deficient in both copper and iron developed all of the manifestations noted in the copper-deficient pigs. These changes occurred more rapidly and to a greater degree than in the swine with a deficiency of either element alone.

5. The morphologic and biochemical similarities between anemia due to copper deficiency and anemia due to iron deficiency suggest that in copper-deficient swine there is an abnormality in the metabolism of iron and that, furthermore, the anemia may be the consequence of this abnormality.
Studies on Copper Metabolism
Authors: GUBLER C. J. , LAHEY M. E. , CHASE M. S. , CARTWRIGHT G. E. , WINTROBE M. M.
Published: October 2019

Studies are described which deal with the metabolism of irons in swine made anemic by feeding a milk diet low in copper. Evidence is presented that in such animals there is (1) impaired ability to absorb irons from the gastro-instestinal tract; (2) incomplete mobilizations of irons from the tissues; and (3) inability to utilize parenterally administered irons for hemoglobin synsthesis evens when it is presented to the bone marrow in normal quantities.
Methods: A Microhematocrit Method and Its Use with Citrated Blood
Authors: SABINE JEAN CAPTAIN , NICKOLAI DOROTHY J.
Published: October 2019

1. A method is described whereby accurate hematocrit values can be made from 0.1 ml. blood using equipment which can be made easily and cheaply.

2. Under controlled conditions, a correction factor can be used to convert hematocrit determinations on citrated blood to standard Wintrobe values. Under our experimental conditions the factor is 1.10.
An Automatic Micro Slide Projector and Procedures for Staining and Cleaning Large Numbers of Slides
Authors: NEWTON GEORGE W. , SHARP D. G. , ECKERT E. A. , BEARD DOROTHY , BEARD J. W.
Published: October 2019

There is described an automatic micro slide projector with which blood smears can be examined at a magnification of 430 x at a rate more than 3 times greater than that possible with a microscope. A procedure is described by means of which 320 blood smears can be stained in 6 minutes. There is described, also, a convenient method for cleaning and handling large numbers of slides.
Chronic Hemolytic Anemia Associated with Thalassemia and Sickling Traits
Authors: STURGEON PHILLIP , ITANO HARVEY A. , VALENTINE WILLIAM N.
Published: October 2019

The family history, case history and genealogy of a 6 year old girl suffering from a chronic hemolytic anemia is presented. The disease, resulting from her inheritance of both the gene for sickle trait and that for thalassemia trait, is compared to a similar case in a 38 year old male reported by Powell, et al.

To date the child has had no clinical evidence of an hemolytic anemia, except for an enlarged spleen. Hematologically, however, all findings indicate the presence of a brisk hemolytic process.

Electrophoretic analysis of the patienst’s hemoglobin reveals a unique pattern intermediate between the usual sickle cell trait and sickle anemia patterns.
Changes in Cellular Composition of the Lymph Caused by Ionizing Radiations
Authors: ROSS M. H. , FURTH J. , BIGELOW R. R.
Published: October 2019

Erythrocytes appear in large numbers in the lymph of rats and dogs after massive exposure to x rays. The peak of endothelial fragility, as indicated by the erythrocyte counts in the lymph, is reached on the ninth to fourteenth day in rats and the eleventh to seventeenth day in dogs. In both species the erythrocyte count in the lymph frequently exceeds one million.

Diversion of erythrocytes into the lymph compartment causes a relative anemia; excessive destruction of erythrocytes, presumably related to extravasation and not to a direct irradiation injury, is responsible in part for the absolute anemia. It is suggested that similar changes may contribute to the anemia of leukemia and other blood diseases associated with capillary fragility.

The drop in lymphocyte counts in both lymph and blood is precipitous within 5 to 10 hours after irradiation. During the fourth to eighth hours after irradiation, injured and dead lymphocytes are present in the lymph in large numbers. During the recovery phase, the per cent of large lymphocytes in the lymph greatly increases, there are many abnormal large lymphoid cells and mitotic figures, and tissue mast cells appear in blood smears.

It is concluded that diversion of erythrocytes into the lymph caused by massive irradiation, if severe, becomes a self-aggravating process and leads to death.
Dual Sensitization to the rh'' (E) and hr' (c) Factors Detected Antenatally. A Case Report
Authors: DUNNE CHARLES J. , INNELLA FILOMENA P.
Published: October 2019

A case of dual sensitization to the rh'' (E) and hr' (c) factors which was detected antenatally has been presented.

The rh'' (E) antibodies probably were caused by a previous blood transfusion which may also have been responsible for the initial stimulation to the hr' (c) antibodies. The subsequent hr' (c) antibodies can be attributed to the hr' (c) factor present in the patient’s three children.

In this study the enzyme-treated red blood cell and the antiglobulin tests were more sensitive than the plasma-albumin test in the detection of the antibodies.
Report of 193 Marrow Biopsy Specimens Cultured for Histoplasma Capsulatum
Authors: SCHWARTZ STEVEN O. , BARSKY SIDNEY , WOOLSEY CARRIE , GANT HELEN L.
Published: October 2019

One hundred ninety-three cultures of marrows were studied for the presence of fungi.

Many of the cases studied had one or more of the classical conditions of histoplasmosis, such as anemia, leukopenia, splenomegaly, hepatomegaly, irregular elevations in temperature, pulmonary disease, and generalized lymphadenopathy.

Histoplasma capsulatum was found in only one case.

Considering the high incidence of histoplasmin reactors in this locality, it appears that routine cultures of the marrow for Histoplasma capsulatum have little value in histoplasmosis case findings.
The Release of Leukocytes and Platelets from the Pulmonary Circulation by Epinephrine
Authors: BIERMAN H. R. , KELLY K. H. , CORDES F. L. , BYRON R. L. , POLHEMUS J. A. , RAPPOPORT S.
Published: October 2019

1. The leukocyte and platelet contents of arterial and venous blood of 12 patients were determined simultaneously during and following the intravenous administration of 0.1 to 0.3 mg. of epinephrine, l-epinephrine or norepinephrine.

2. Within 30 to 60 seconds after the start of the epinephrine administration, an initial arterial leukocytosis and thrombocytosis occurred in 10 and 8 instances respectively and continued for at least 5 minutes before it declined. A leukocytosis also occurred in the venous blood but followed the arterial rise by 30 to 120 seconds.

3. It is concluded that the initial phase of the leukocytosis and thrombocytosis following intravenous epinephrine infusion is primarily from the pulmonary circulation.

4. The data indicate that the pulmonary circulation in man is a sizable reservoir of leukocytes and platelets which may be readily discharged into the circulation under proper stimulation.
The Agglutination Mechanism of Trypsin Modified Red Cells
Authors: DAUSSET J.
Published: October 2019

1. It is suggested that the incomplete antibody is essentially bivalent; one valence is nonreactive, and the other can become reactive under certain conditions.

2. The nonreactive valence of the incomplete antibody is believed to fix the antigen following trypsinization, or to fix nontrypsinized antigen with the aid of the colloid plasma factor.

3. The data obtained from our patients with acquired hemolytic anemia, further support the hypothesis presented; in addition, the data suggest the possibility of a special type of antibody, which acts essentially as a "doubly incomplete antibody," that is to say, that it possesses two nonreactive valences identical to the nonreactive valence of the incomplete antibody.
Thrombospondin inhibits adhesion of platelets to glass and protein- covered substrata
Authors: Lahav J
Published: October 2019

Glass and protein-covered surfaces when treated with the platelet- secreted glycoprotein thrombospondin lose their capacity to bind unstimulated platelets. In comparison to the number that bind to fibronectin-covered glass surfaces, less than 3% bind to thrombospondin- covered glass surfaces. When the fibronectin-covered surface is incubated with thrombospondin, it loses 87% of its binding capacity for platelets. The inhibitory effect of thrombospondin on platelet binding increases with increasing amounts of the adsorbed protein and reaches maximal values at 65% saturation of the adsorption of thrombospondin to the surface. Platelet spreading on the surface is also completely inhibited by thrombospondin. These data suggest that thrombospondin is nonthrombogenic and can modulate platelet adhesion to the subendothelium.
Prominent expansion of circulating lymphocytes bearing gamma T-cell receptors, with preferential expression of variable gamma genes after allogeneic bone marrow transplantation
Authors: Vilmer E , Triebel F , David V , Rabian C , Schumpp M , Leca G , Degos L , Hercend T , Sigaux F , Bensussan A
Published: October 2019

The presence of two distinct T-cell receptors (TCR) alpha/beta dimers or gamma/delta dimers, was systematically analyzed in peripheral blood lymphocytes form 26 recipients of allogeneic bone marrow transplants for leukemia. When using monoclonal antibody WT31, which recognizes a common epitope on the alpha/beta heterodimer, the expansion of peripheral CD3+, WT31- cells to 40% of the PBLSs was detected in two patients. In patient 2, the presence of circulating TCR gamma-bearing cells was directly demonstrated with monoclonal antibody Ti gamma A directed against the V gamma 9 J gamma p gene products. From CD3, WT31- clones derived from patients 1 and 2, sequential immunoprecipitations were performed with anti-CD3 and anti-C gamma to determine the CD3- associated structure. Molecular weights of gamma subunits were different in both patients, thus indicating structural heterogeneity. The ability of TCR gamma clones to proliferate when stimulated with anti-CD3 beads was observed for clones from patient 2, whereas this response required exogenous interleukin-2 for clones from patient 1. We have already shown that the TCR gamma cells from patient 1 might have played a role in the immunodeficient state. Similar conclusions cannot be drawn from patient 2. Southern blot analysis of total PBL gamma cell lines and clones indicated that this major circulating subset of TCR gamma cells retained a TCR beta gene in germline configuration and preferentially expressed a single V gamma gene, V gamma 5 for patient 1 and V gamma 9 for patient 2.
Conformational states of vitronectin: preferential expression of an antigenic epitope when vitronectin is covalently and noncovalently complexed with thrombin-antithrombin III or treated with urea
Authors: Tomasini BR , Mosher DF
Published: October 2019

A difference in recognition of the adhesive glycoprotein vitronectin (also called S-protein, serum spreading factor, and epibolin) by monoclonal antibody 8E6 (Hayman EG, et al, Proc Natl Acad Sci USA 80:4003, 1983) was investigated using a competitive enzyme- immunosorbent assay and immunoaffinity chromatography. Recognition of vitronectin in serum was approximately 50-fold greater than recognition of vitronectin in plasma. Recognition of vitronectin incubated with heparin, thrombin-antithrombin III complex, or heparin and thrombin- antithrombin III complex together was 2.5-, 7-, or 32-fold greater, respectively, than recognition of vitronectin alone. Thrombin or antithrombin III by itself did not induce the antigenic change. Factor Xa-antithrombin III was less effective than thrombin-antithrombin III in induction of the change. Dextran sulfate and fucoidan were more potent than heparin in induction of the antigenic change, whereas dermatan sulfate, hyaluronic acid, heparan sulfate, chondroitin sulfate, or keratan sulfate were less effective. Immunoblotting analysis of serum and of vitronectin incubated with thrombin and antithrombin III demonstrated the presence of complexes composed of vitronectin and thrombin-antithrombin III that could only be dissociated with reducing agent. N-ethylmaleimide completely blocked the formation of the presumably disulfide-bonded complexes and partially blocked the antigenic change. Both non-disulfide-bonded and disulfide-bonded vitronectin bound to antibody-Sepharose from a mixture of vitronectin and thrombin-antithrombin III. Treatment of vitronectin with 8 mol/L urea resulted in enhanced recognition by the monoclonal antibody. Thus, the 8E6 antibody reacts with an epitope that is preferentially expressed by noncovalently and covalently linked vitronectin/thrombin-antithrombin III complexes and by urea-treated vitronectin. The change in vitronectin induced by thrombin-antithrombin III, therefore, is a physiological correlate of urea treatment and of adsorption of vitronectin onto tissue culture plastic (as is done in cell adhesion assays). The change may be important for expression of vitronectin activity.
Therapeutic potential of recombinant granulocyte-macrophage colony- stimulating factor and interleukin-3 in murine B-cell leukemia
Authors: Fabian I , Kletter Y , Slavin S
Published: October 2019

The antileukemic activity of murine recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and a combination of rGM-CSF and recombinant interleukin-3 (rIL-3) was examined by using a murine model of spontaneous B-cell leukemia (BCL1) in BALB/c mice. All untreated mice inoculated with 2 x 10(2) BCL1 cells developed leukemia within 4 weeks, with extreme lymphocytosis and a massive increase in both spleen weight and cell number while the number of myeloid progenitors (CFU-C) per spleen was decreased. In contrast, rGM-CSF-or rGM-CSF- and rIL-3- treated recipients did not show any evidence of leukemia or splenomegaly at 4 weeks and showed a significant increase in CFU-C per spleen. Hematologic parameters in the peripheral blood of untreated mice showed anemia and thrombocytopenia. Significant elevations in these parameters were recorded in mice treated with either protocol of CSF. Treatment of recipient mice with either rGM-CSF or rGM-CSF and rIL- 3 prolonged their median survival from 6 weeks in untreated controls (range, 5 to 9 weeks) up to the time they were killed at 105 days. Adoptive transfer of spleen cells obtained from mice treated with rGM- CSF, mice treated with a combination of rGM-CSF and rIL-3, and untreated controls, into normal secondary recipients indicated improved survival in recipients inoculated with rGM-CSF. These data indicate that CSFs may inhibit in vivo expansion of leukemic cells of lymphoid origin.
Direct stimulation of cells expressing receptors for macrophage colony- stimulating factor (CSF-1) by a plasma membrane-bound precursor of human CSF-1
Authors: Stein J , Borzillo GV , Rettenmier CW
Published: October 2019

Secreted forms of macrophage colony-stimulating factor (M-CSF or CSF-1) are generated by proteolytic cleavage of membrane-bound glycoprotein precursors. Alternatively spliced transcripts of the human CSF-1 gene encode at least two different transmembrane precursors that are differentially processed in mammalian expression systems. The larger precursor rapidly undergoes proteolysis to yield the secreted growth factor and does not give rise to forms of CSF-1 detected on the cell surface. By contrast, the smaller human CSF-1 precursor is stably expressed on the plasma membrane where it is inefficiently cleaved to release a soluble molecule. To determine whether the smaller precursor is biologically active on the cell surface, mouse NIH-3T3 fibroblasts expressing the different forms of human CSF-1 were killed by chemical fixation and tested for their ability to support the proliferation of cells that require this growth factor. Only fixed cells expressing human CSF-1 precursors on their surface stimulated the growth in vitro of a murine macrophage cell line or normal mouse bone marrow-derived mononuclear phagocytes. The ability of these nonviable fibroblasts to induce the proliferation of CSF-1-dependent cells was not mediated by release of soluble growth factor, required direct contact with the target cells, and was blocked by neutralizing antiserum to CSF-1. These results demonstrate that the cell surface form of the human CSF-1 precursor is biologically active and indicate that plasma membrane- bound growth factors can functionally interact with receptor-bearing targets by direct cell-cell contact.