bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure of Combined Factor VIII and Cyclophosphamide to Suppress Antibody to Factor VIII in Hemophilia
Authors: Hruby Marilyn A. , Schulman Irving
Published: October 2019

Two patients with hemophilia A and antifactor VIII antibodies were treated with infusions of factor VIII concentrates and intravenous cyclophosphamide in an attempt to suppress the antibody response. Factor VIII levels of 23% and 95% were achieved immediately postinfusion, and prompt control of bleeding ensued. Sequential antibody titers demonstrated no change in antibody response in either patient when compared to previous studies following factor VIII infusion alone. These results are in contrast to the previously reported suppression of factor VIII antibody in a nonhemophilic patient using an identical regimen.
Factors That Influence the Appearance of Central Nervous System Leukemia
Authors: Pavlovsky Santiago , Eppinger-Helft Mariana , Muriel Federico Sackmann
Published: October 2019

At present, central nervous system (CNS) leukemia is one of the principal causes for termination of complete remission in acute lymphocytic leukemia (ALL). The factors which influence the increase of CNS infiltration have been studied comparing different parameters (age, initial peripheral WBC count, type of leukemia, and presence or absence of initial organomegaly) to determine the leukemia population with highest risk of developing this syndrome. A total of 127 cases of acute lymphoid leukemia (ALL) (98 children and 29 adults) and 101 acute myelocytic leukemia (AML) (41 children and 60 adults), on the same treatment protocol from 1967 to 1970, were included in this study. The median survival and the rate of incidence of symptomatic CNS leukemia was 18 mo and 32% in ALL and 4 mo and 7% in AML. The incidence of CNS leukemia per month of survival was similar in both groups: 4 mo, 3% in AML and 4% in ALL, at 8 mo, 13% in both ALL and AML. The incidence of CNS leukemia was higher in children with ALL than in adults: 41% in children and 19% in adults at 20-mo survival. Organomegaly (spleen, liver and/or lymph nodes) as an early manifestation increased the risk of CNS involvement. The CNS infiltration was significantly greater in patients with high initial peripheral WBC count. The incidence of meningeal leukemia did not differ in ALL and AML. In conclusion, CNS leukemia infiltration was more frequent in children with initial organomegaly and high WBC count at the time of diagnosis.
A Simple Method for Freezing Human Platelets Using 6% Dimethylsulfoxide and Storage at -80°C
Authors: Valeri C. R. , Feingold H. , Marchionni L. D.
Published: October 2019

Human platelets were preserved by freezing them with 6% DMSO in a mechanical refrigerator maintained at -80° C. The selection of 6% DMSO was arbitrary. After postthaw washing, the 51Cr recovery in vivo was about 45%, the in vitro recovery was about 75%, and the lifespan was about 8.5 days. The mean residual DMSO of 165 mg produced no adverse side effects. The number of platelets in the circulation 2 hr after the infusion of washed freeze-preserved platelets was about half that found with fresh platelets. The prolonged bleeding time induced by aspirin administration to healthy volunteers was corrected within 24 hr of transfusion of a single unit of previously frozen washed platelets; in nine of 12 studies a 50% reduction in the bleeding time occurred within 2 hr of infusion. We do not know though whether washed freeze-preserved platelets will be as effective in correcting the bleeding diathesis in thrombocytopenic patients.
Oxygen Transport by the Red Cell: Effects of Chronic Hemodialysis
Authors: Miller Marilyn E. , Zaroulis Charles G. , Valeri C. Robert , Stohlman Frederick
Published: October 2019

Ten patients undergoing chronic hemodialysis for end-stage renal disease were studied in order to determine the acute effects of hemodialysis on the metabolic function of the erythrocyte in anemic uremic patients. Prior to hemodialysis there was a mean red cell mass deficit of 148 g Hb/sq m. The affinity of hemoglobin for oxygen was decreased, and this was associated with an increase in intraerythrocytic levels of 2,3-DPG and ATP. The plasma phosphorus levels were also increased in the predialysis period. Following 5-6 hr of hemodialysis the affinity of hemoglobin for oxygen and the intraerythrocytic levels of 2,3-DPG were unchanged from the predialysis values despite a significant reduction in plasma phosphorus levels and a significant increase in both whole blood and intraerythrocytic pH.

From these data we conclude that the maintenance of the red cell’s decreased oxygen affinity resulted from the increase in intraerythrocytic pH which maintained the intraerythrocytic levels of 2,3-DPG despite a reduction in plasma phosphorus. The reduction in plasma phosphorus was primarily reflected in a decrease in red cell ATP.
Factor XIII Deficiency: A Genetic Study of Two Affected Kindreds in Finland
Authors: McDonagh Jan , McDonagh R. P. , Myllylä G. , Ikkala E.
Published: October 2019

Factor XIII deficiency is a congenital defect of the blood coagulation system. Activated factor XIII is the fibrin cross-linking enzyme that catalyzes the formation of N6-γ-glutamyllysyl bonds in fibrin. Congenital deficiency of factor XIII has been described in approximately 65 separate families. It is apparent that this is a hereditary trait, but the mode of inheritance is unclear. In this study two unrelated Finnish families with factor XIII deficiency were investigated in order to determine the pattern of inheritance. One family had only affected male members, and in the other both males and females were affected. Plasma factor XIII levels were measured by the fluorescent amine incorporation assay, which has been found to be sensitive to the detection of heterozygotes. In both families it was found that the parents of the affected children were indeed heterozygous for factor XIII, and as far as could be determined in the pedigrees each heterozygote had at least one heterozygous parent. This study indicates that in these two families the mechanism of inheritance of factor XIII deficiency is autosomal recessive. Comparison of these families with others reported in the literature suggests that an autosomal recessive pattern is the general mode of inheritance in factor XIII deficiency.
Effect of Chloramphenicol and Thiamphenicol on the In Vitro Colony-forming Cell
Authors: Ratzan R. Judith , Moore Malcolm A. S. , Yunis Adel A.
Published: October 2019

The effect of chloramphenicol and a chloramphenicol analog, thiamphenicol, on the growth of bone marrow colony-forming cells in agar was investigated. At concentrations within therapeutic range, both drugs cause a marked reduction in the number of colonies and in the size of aggregates, indicating suppressed cellular proliferation. The inhibition appears to be reversible within a 24-hr period of cell-drug contact. In addition to their effect on CFC proliferation, CAP and TAP appear to influence the type of CFC differentiation resulting in predominance of macrophage colonies.
Differences in Inducing Activity for Human Bone Marrow Colonies in Normal Serum and Serum From Patients With Leukemia
Authors: Mintz Un , Sachs Leo
Published: October 2019

In the article: "Difference in inducing activity for human bone marrow colonies in normal serum and serum from patients with leukemia," by Mintz and Sachs (Blood: 42, No. 3, September 1973, p. 331-339), on page 331, first paragraph of the text, line 7, it should be 15-18 instead of 15-19. The last reference number in this paragraph should be 19 instead of 23. Also, on page 337, line 4 of the first paragraph of the Discussion, the reference number should be 19 instead of 23.
A Monoclonal IgM With Antibodylike Specificity for Phospholipids in a Patient With Lymphoma
Authors: Cooper M. R. , Cohen H. J. , Huntley C. C. , Waite B. M. , Spees L. , Spurr C. L.
Published: October 2019

Both murine and human myeloma proteins have been shown to have antibodylike activity for serum lipoproteins. We studied a 58-yr-old woman (M.L.) with a lymphoma and a VDRL titer of 1:4096 and a nonreactive FTA-ABS. Serum electrophoresis revealed an M-component which was shown to be IgM-kappa by immunoelectrophoresis and 2-mercaptoethanol treatment of the serum reduced the VDRL titer to 1:64. Immunoelectrophoresis (IEP) of the purified IgM against sonicates of the specific components of the VDRL antigen (cardiolipin, lecithin, cholesterol) produced a precipitin line with both cardiolipin and lecithin. All IgM in the serum could be removed by absorption with cardiolipin, and elution experiments demonstrated the specificity of this reaction. A quantitative precipitin test demonstrated that at the point of equivalence, 0.009 mg of antigen (cardiolipin) reacted with 0.4 mg of IgM (antibody). Additional studies showed that purified IgM (M.L.) gave a positive reaction with nine of 15 phospholipids tested. Similar studies on sera from 50 normal individuals, ten patient’s sera without M-components giving false positive VDRL reactions, and serum from one patient with a congenital absence of IgA and IgG and increased IgM showed no evidence of such a precipitin reaction with any phospholipid tested. Thus, it appeared that the IgM-kappa monoclonal protein behaved like an antibody directed against specific phospholipid antigenic components. The role of lipid antigens in the initiation of such neoplastic and immunologic abberrations should be further investigated and monoclonal proteins screened more extensively against such antigens.
Hemoglobin Duarte: (α2β262(E6)Ala→Pro): A New Unstable Hemoglobin With Increased Oxygen Affinity
Authors: Beutler E. , Lang A. , Lehmann H.
Published: October 2019

A patient with a normal blood hemoglobin level, but with evidence of brisk hemolysis, was found to have an unstable hemoglobin with a left-shifted oxygen dissociation curve. Two sisters of the patient had a history of hemolytic anemia. Both died of thromboembolic complications following splenectomy. Our patient was found to be heterozygous for a new β-chain mutation and β-thalassemia. All of the hemoglobin in his red cells was of the abnormal type, designated hemoglobin Duarte, and was shown to contain proline at the β62 (E6) position instead of alanine.
Sickle Hemoglobin: A Specific Radioimmunoassay
Authors: Rowley Peter T. , Doherty Richard A. , Rosecrans Cheryl , Cernichiari Elsa
Published: October 2019

For the quantitation of hemoglobin S, a radioimmunoassay has been developed which is specific and highly sensitive. Hemoglobin S was purified by column chromatography and injected with complete Freund’s adjuvant into goats. Each goat serum was tested for reactivity against hemoglobins A and S by immunodiffusion and by quantitative precipitation. Hemoglobin A reactivity was removed by absorption with hemoglobin A. One serum so treated was specific for hemoglobin S; it reacted negligibly with hemoglobins A or F. Hemoglobin S was labeled with 125I by the chloramine T method. In the radioimmunoassay, complete precipitation of the antigen—antibody complex was insured by the addition of rabbit antigoat gamma globulin. This assay offers reliable and specific quantitation of as little as 1 ng of hemoglobin S. Assuming that 10% of the hemoglobin in fetal blood at 16 wk gestation is of adult type, this assay is capable of detecting the amount of hemoglobin S in 10-7 ml of homozygous hemoglobin S blood. The prenatal diagnosis of sickle cell anemia by radioimmunoassay will require, in addition, a method for demonstrating the absence of hemoglobin A and a safe method for obtaining fetal erythrocytes without significant contamination by maternal erythrocytes.
A New Case of Mu Heavy Chain Disease: Clinical and Immunochemical Studies
Authors: Dammacco Franco , Bonomo Lorenzo , Franklin Edward C.
Published: October 2019

A new case of mu heavy chain disease is described. The patient, a 48-yr-old Italian housewife, suffered from chronic lymphocytic leukemia of 3 yr duration with anemia and hepatosplenomegaly, but no peripheral lymph node enlargement. Serum protein studies disclosed a small M component with gamma-1 mobility ascribable to free kappa chains, hypogammaglobulinemia, and mu chain fragments with abnormally anodic mobility. Appreciable amounts of kappa chains were also detected in the urine. The mu chain disease protein had a molecular weight of approximately 54,000 and a heterogeneous NH2 terminus, alanine being the main identifiable residue. The NH2 terminal of the kappa chain was glutamic acid. No J chain was detected by polyacrylamide electrophoresis of the partially reduced and alkylated mu chain disease protein.
Restrained Adenyl Cyclase in Human Neutrophils: Stimulation of Cyclic Adenosine 3':5'-Monophosphate Formation and Adenyl Cyclase Activity by Phagocytosis and Prostaglandins
Authors: Stolc Viktor
Published: October 2019

We observed that prostuglandins (PG) E1, E2, A1, A2, B1, and F2 alpha increase cAMP concentration in resting neutrophils. In phagocytosing cells, an additional enhancement was seen with PG E1 and PG A2. Such a stimulatory effect of Pg E1 was noted any time during phagocytosis of latex microparticles (3-18 min). Adrenergic inhibitors, phentolamine and propranolol, did not interfere with the stimulatory action of PG E1 on cAMP level in resting and phagocytosing leukocytes. Both aforementioned inhibitors enhanced cAMP level in resting and phagocytosing neutrophils at 1 mM concentration, and an additional increase was seen in PG E1stimulated leukocytes. Although phosphodiesterase activity was unchanged by phagocytosis and PG E1 action, adenylate cyclase (AC) activity was significantly higher in neutrophil homogenates after phagocytosis of latex particles. In contrary, contact of human lymphocytes with latex particles revealed a decrease in AC activity. These data indicate that AC-cAMP system is partly in a restrained state in resting neutrophils and can be relieved by phagocytosis.
Cytochemical and Radioautographic Identification of Cells Induced to Synthesize Hemoglobin
Authors: Rosse Cornelius , Trotter John A.
Published: October 2019

In order to facilitate the identification of bone marrow cells in which hemoglobin synthesis is initiated, erythropoiesis was first suppressed in guinea pigs through the induction of posthypoxic polycythemia, and then it was restimulated by bleeding and reexposure to hypoxia. Hemoglobin synthesis was detected with 55Fe incorporation on radioautographs, and its presence was demonstrated in the light microscope with the benzidine reaction and absorption of monochromatic light at λ 4046 Å. In the electron microscope, hemoglobin was detected in the cytoplasm by a general increase in electron density after treating the tissue with diaminobenzidine (DAB) and OsO4. Densitometric measurements were carried out on electronmicroscopic negatives, using reticular cell cytoplasm as a base line. In normal marrow, proerythroblasts were the earliest cells in which hemoglobin could be detected, but during the early phase of erythropoietic stimulation, hemoglobin was demonstrated in transitional cells with all the methods employed. Without the specific demonstration of hemoglobin, these cells could not be recognized morphologically as erythroblasts nor could they be distinguished from the precursors of bone marrow small lymphocytes. Transitional cells were numerous in the marrow at the time of stimulation, and 40 hr later a small number of them were labeled with 55Fe and synthesized hemoglobin in detectable amounts. Proerythroblasts were absent at the time of the stimulus, and when they reappeared the majority were benzidine or DAB positive and had incorporated 55Fe. The findings suggest that progenitor cells of erythroblasts are among the basophilic members of the transitional cell population, and erythropoietic stimulation induces hemoglobin synthesis in them. The relationship of these cells to the progenitors of other hemopoietic cells, as well as to the pluripotent stem cell, is discussed.
Ultrastructure of Sickled Deer Erythrocytes. I. The Typical Crescent and Holly Leaf Forms
Authors: Simpson C. F. , Taylor W. J.
Published: October 2019

The typical crescent and holly leaf forms of sickled erythrocytes from white-tailed deer were examined by transmission electron microscopy. These cellular aberrations were induced in those animals which are homozygous for the β3-chain and are reversibly related to elevations of pH and POO2. The internal structure of the typically sickled cell was organized into polymerized aggregates. At very high magnification, cross-sections of the cells revealed microtubules, with a diameter of 160-190 Å, which were compared to those which have been described in human sickle cells. The tubules beneath the plasmalemma or extending into protruding spicules were more or less parallel and oriented in a single direction, whereas the aggregates in the remainder of the cell cytoplasm were randomly dispersed. In view of the association of the sickling of deer erythrocytes with a specific hemoglobin β-chain and the marked similarity of the internal architecture of these cells to human sickle cells, the deer erythrocytes provide a model for hemoglobin polymerization which may lead to insights that are applicable to the human condition.
Response to Prednisolone of Cultured Immunoglobulin-producing Human Lymphoid Cells
Authors: Strong James E. , Drewinko Benjamin
Published: October 2019

The survival of asynchronously growing lymphoid cells (T1 cells) in vitro decreased to 50% viability after 1 hr treatment with concentrations of prednisolone above 10 µg/ml. Treatment with prednisolone for 24 hr produced a decrease in cell survival to a plateau of 30% viability for concentrations above 10 µg/ml. After 48 hr treatment, 10 µ/ml prednisolone reduced viability to 12%. Synchronously growing T1 cells were least sensitive to prednisolone treatment (50 µg/ml) during S phase (DNA synthesis period) and most sensitive during G1 (pre-DNA-synthesis period). This cell cycle specificity is postulated to be an explanation for the presence of prednisolone-resistant cells in asynchronously growing populations. Immunofluorescence studies on the effect of prednisolone (100 µg/ml) on immunoglobulin production indicated there was no correlation between the length of drug treatment and reduction in the percentage of immunoglobulin-producing cells. These results suggest that the mechanism of prednisolone-induced immunosuppression in lymphoid cells is primarily lymphopenia.
In Vitro Production of Erythropoietin by Kidneys Perfused With a Serum-free Solution
Authors: Erslev Allan J.
Published: October 2019

Normal rabbits exposed to 0.4 atmospheric pressure for 3 hr will generate about 40-60 U of erythropoietin during a subsequent 3-hr period. If the kidneys were removed from 3-hr hypoxic animals, washed carefully, and perfused for 3 hr by recirculation with a serum-tissue culture mixture, each kidney generated about 14 U of erythropoietin in vitro. Perfusion of normal kidneys did not result in the production of erythropoietin, and only small amounts were generated if the perfusate contained Puromycin. Three-hour hypoxic kidneys perfused for 3 hr with a serum-free tissue culture medium were found to generate about 8 U of erythropoietin per kidney and similar kidneys perfused with saline about 1 U. These results indicate that erythropoietin is synthesized by kidney tissue and not produced by enzymatic activation of a plasma substrate.
Cycling Characteristics of Human Lymphocytes In Vitro
Authors: Schiffer Lewis M. , Markoe Arnold M. , Winkelstein Alan , Nelson Janet S. R. , Mikulla John M.
Published: October 2019

The cycling characteristics of human peripheral blood lymphocytes in phytohemagglutinin-stimulated cultures were examined by means of a new technique employing radioautographic methods which assay the fraction of cells whose nuclei contain DNA polymerase utilizing exogenous and/or endogenous DNA primer-template capability. The fraction of cells labeled by these techniques increases 5-11 hr prior to the onset of DNA synthesis. Estimates of cell cycle time, G1 time, and fraction of cycling cells are made for the first 4 days in culture. Evidence is presented to support the hypothesis that daughter cells of the first divisions may be retired from cycle by virtue of loss of primer-template availability, rather than by loss of DNA polymerase.
Human Cyclic Neutropenia: Urinary Colony-stimulating Factor and Erythropoietin Levels
Authors: Guerry DuPont , Adamson John W. , Dale David C. , Wolff Sheldon M.
Published: October 2019

Daily levels of urinary colony-stimulating factor (CSF) were measured in two patients with cyclic neutropenia. The CSF levels increased during the neutropenic period concomitant with the maximum peripheral monocytosis. Simultaneous erythropoietin (ESF) levels were measured in one of these patients. ESF also increased in the neutropenic period antecedent to the periodic reticulocytosis. These studies are compatible with a negative feedback system regulating both granulocytopoiesis and erythropoiesis. Whether the cyclic fluctuations of these substances are causally related to the cyclic marrow proliferation is uncertain.
A New Variant of Glucose-6-Phosphate Dehydrogenase Deficiency Hereditary Hemolytic Anemia, G6PD Cornell: Erythrocyte, Leukocyte, and Platelet Studies
Authors: Miller Denis R. , Wollman Michael R.
Published: October 2019

A variant of glucose-6-phosphate-dehydrogenase deficiency associated with chronic hereditary hemolytic anemia was discovered in a 9-yr-old white male. The erythrocytes contained 5% of normal enzyme activity, the Km NADP was two to three times normal, the pH optimum was decreased, and the heat stability was markedly decreased. The Km G6PD, electrophoretic mobility (B), and utilization of substrate analogues 2-deoxy-G6P and deamino-NADP were normal. The activity of G6PD in the leukocytes and platelets was 15% and 28% of normal values, respectively, but bactericidal activity and platelet function were unaffected by the deficiency of G6PD.
Primary Amyloidosis and Acute Leukemia Associated With Melphalan Therapy
Authors: Kyle Robert A. , Pierre Robert V. , Bayrd Edwin D.
Published: October 2019

Amyloid fibrils consist in part of immunoglobulin light chains. Because light chains are synthesized by plasma cells, it seems reasonable to treat patients with amyloidosis with alkylating agents. Two patients who had primary amyloidosis and were treated with melphalan subsequently developed a rapidly fatal acute leukemia. Since melphalan may play a significant role in the development of acute leukemia, we suggest that alkylating agents not be used in the treatment of patients with amyloidosis without full consideration of risks involved, particularly until it has been proved that these drugs are beneficial.
Lack of Recovery of Murine Hematopoietic Stromal Cells After Irradiation-induced Damage
Authors: Chamberlin W. , Barone J. , Kedo A. , Fried W.
Published: October 2019

The rates of recovery of colony-forming units (CFU) and of hematopoietic stroma following x-irradiation were compared. Hematopoietic stromal function of femurs and spleens was assessed by assaying the number of CFU in those sites 6 wk after implanting them subcutaneously into isogeneic hosts. Whereas the number of CFU returned to preirradiation levels in 6 wk, the hematopoietic stroma did not recover significantly in 9 wk. The reasons for regeneration of CFU in a defective stroma were next investigated. Two contributing factors were identified: (1) Stromal damage following 950 rads is such as to retard the rate of regeneration of CFU without significantly limiting the eventual number of CFU in the site, and (2) Radiated mice contain factor(s), possibly humoral, which accelerate the rate of regeneration of CFU.
Inhibition of Endotoxic Lipopolysaccharide-mediated Platelet Aggregation by Cobra Venom Anticomplementary Factor
Authors: Fong Jack S. C. , White James G. , Good Robert A.
Published: October 2019

Aggregometry studies on endotoxic lipopolysaccharide (LPS)-mediated rabbit platelet aggregation were performed. Different preparations of LPS showed characteristic aggregometry profiles, and LPS with potent anticomplementary activities generally had a more vigorous platelet aggregation function than did LPS preparations with lesser anticomplementary functions. Cobra venom anticomplementary factor (CVF) inhibited LPS-platelet interaction, and the inhibition was both time and dose dependent. Dose-response curves of CVF inhibition on LPS or zymosan-mediated platelet aggregation were essentially identical. In vitro and in vivo studies showed that CVF inhibition persisted even when hemolytic complement activities reached more than 70% of those originally present. At the critical time of days 5 or 6 following CVF administration, the lack of platelet responses towards LPS could be restored by addition of fresh plasma from normal or C6-deficient rabbits, but not with plasma that had been treated with antigen— antibody complexes, zymosan, or heating at 56° for 30 min. The experimental data indicate that serum protein(s) other than the terminal complement components are involved in LPS-platelet interaction. It seems most likely that the factor(s) perturbed reside in the mechanisms involved in activation of the alternate pathway. Furthermore, it appears quite possible that LPS-platelet interactions can be inhibited by manipulating the humoral factor(s) involved rather than by altering the platelets themselves.
Thrombocytosis in Chronic Granulocytic Leukemia: Incidence and Clinical Significance
Authors: Mason Joe E. , DeVita Vincent T. , Canellos George P.
Published: October 2019

The clinical significance of an elevated platelet count in the course of chronic granulocytic leukemia was studied in a group of 111 previously untreated patients, whose entire course was evaluated by one clinic. Seventy-one patients (64%) developed a platelet count >450,000/cu mm either at diagnosis (56 patients) or in the subsequent course (15 patients). Twenty-nine of the 71 patients had counts in excess of 1 x 106/cu mm. Four patients had serious thrombohemorrhagic complications. None were fatal, and all occurred in the group with counts over a 1 x 106/cu mm. The occurrence of thrombocytosis as a new observation in the face of previous normal counts (15 patients) was associated with frank blastic crisis (six cases) or heralded its onset with a median duration of 8 mo (nine cases). Thrombocytosis per se was associated with a shorter survival (median 36 mo) as opposed to 45 mo in the group (40 cases) whose count was never elevated.
Some Factors Influencing Granulocytic Colony Formation In Vitro by Human White Blood Cells
Authors: Heit Wolfgang , Kern Peter , Kubanek Bernhard , Heimpel Hermann
Published: October 2019

The experiments presented in this paper were designed to characterize the colony-stimulating activity (CSA) from white blood cell feeder layers on colony formation by peripheral blood CFCs in soft agar double-layer cultures. The data confirm earlier observations that mononuclear cells are essential for CSA production but document the importance of neutrophilic granulocytes to enhance colony formation. Possible differences between colony enhancement by granulocytes and red cell hemolysate are discussed.
Globin Synthesis in Iron-deficiency Anemia
Authors: Ben-Bassat Isaac , Mozel Miriam , Ramot Bracha
Published: October 2019

The α to β globin chain ratio has been determined in the peripheral red cells of 11 patients with iron deficiency anemia. The mean ratio was found to be 0.74 ± 0.07, which is significantly lower than the ratio of 0.97 ± 0.07 obtained in normals. When the stroma-free hemolysates were purified prior to globin preparation the α to β ratio did not change. On the other hand, globin extracted from whole iron-deficient cells, including the stroma, had a higher α to β ratio, 0.88 ± 0.04, but still significantly lower than normal. These results suggest that in iron deficiency there is a decrease in α-chain synthesis relative to β-chain and that there are membrane-bound globin chains, but no excessive increase in the free α-chain pool. Similar findings have been reported previously in other states of heme deficiency like sideroblastic anemia and lead poisoning.
Sickle Hemoglobin in Combination With Hb JBangkok (αA2β56 gly→asp2)
Authors: Gunay Unsal , Pauli Carol , Shamsuddin Mir , Mason R. George , Heinze William J. , Honig George R.
Published: October 2019

Several members of a black family from Southern Illinois were found to be heterozygous for HB JBangkok (αA2β56 gly→asp2), a hemoglobin abnormality previously described only in individuals of Thai, Chinese, or Indonesian ancestry. In two children (ages 3 and 8) Hb JBangkok was present in combination with sickle hemoglobin. Neither of these children demonstrated evidence of hemolytic disease, enlargement of the liver or spleen, or symptomatic sickle crises. The Hb J comprised 54%-59% of the total in all family members having this variant, in common with previous reports of this hemoglobin. Hb A2 and alkali-resistant hemoglobin were present in normal concentrations in all of the family members studied. Deoxygenated mixtures of Hbs S and JBangkok exhibited minimum gelation concentrations similar to those of equivalent mixtures of Hbs S and A.
The Relationship Between Platelets and Bacteria
Authors: Kahn Richard A. , Flinton Linda J.
Published: October 2019

In an attempt to clarify conflicting reports as to whether blood platelets are bactericidal, platelets were artificially contaminated with seven different bacteria: Bacillus subtilis, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, Staphylococcus epidermidis, Streptococcus faecaiis, and Sarcina lutea. Employing many variations in the circumstances of the exposure, platelets were bactericidal for only Bacillus and possibly Sarcina. When platelet concentrates were contaminated with bacteria and left at room temperature for 48 hr, all organisms but one (Sarcina) grew out of control. However, this organism was also killed in cell-free plasma. The presence of platelets in plasma was found to enhance the growth of some organisms. These experiments indicate that platelets not only have a very limited bactericidal capability, but can protect certain bacteria from death due to other blood components.
The Fate of Soluble Fibrin Monomer in Relation to Intravascular Fibrin Formation and Degradation in Rabbits
Authors: Gurewich Victor , Wetmore Robert , Nowak Andrzej , Lipinski Boguslaw
Published: October 2019

125I-labeled fibrinogen or fibrin monomer (FM) were infused into rabbits, and the radioactivity in the blood, certain organs, and urine was followed. In the FM rabbits, a progressive, relatively rapid loss of blood radioactivity occurred which was accompanied by radioactive deposits in the organs and the excretion of radioactivity in the urine. Extraction of radioactive material from homogenized organ tissues of FM-infused rabbits showed that most of it had the characteristics of stabilized fibrin. Administration of EACA did not change any of the measurements in the fibrinogen animals but increased the rate and extent of fibrin deposition in the FM animals. In animals made leukopenic with HN2, fibrin deposition was inhibited. The findings indicate that a major pathway of FM clearance from the blood involves fibrin formation and deposition with subsequent degradation and excretion. The reticuloendothelial system appeared to play a major role in FM clearance, since most of the fibrin deposits were found in the liver, and the highest concentration was in the spleen. A nonenzymatic mechanism of fibrin formation from soluble FM involving leukocytes is postulated.
Kinetics of Human Monocytopoiesis
Authors: Meuret Gerhard , Bammert Joachim , Hoffmann Günter
Published: October 2019

Information on the structure of human monocytopoiesis was derived from the chronologies of labeled monocytes entering the blood following injection of 3H-thymidine (3H-TDR) and 3H-diisopropylfluorophosphate (3H-DFP). It was found that monocytes are released into the blood directly from a proliferating precursor pool. The marrow cell egress was almost completely restricted to G1-phase monocytes. The egress rate increased with maturation time of promonocytes. The majority of the cells was released at maturation times between 50 and 60 hr. Under normal conditions promonocytes underwent a mean of two catenated cell cycles. The cell cycle time averaged 29 hr and DNA-synthesis time 10 hr. Direct investigations of the promonocytes demonstrated that the medullary promonocyte pool averages 6 x 108 cells/kg body weight in healthy adults. This pool produces a mean of 7 x 106 cells/kg-hr. Proliferation capacity of promonocytes is only partially utilized in normal monocytopoiesis. Induction of acute inflammatory reactions gave rise to an immediate enhancement of promonocyte proliferation activity, thus affording short-term adaptation of monocyte production to monocyte demand. Increase in monocyte production was associated with a shift of marrow release in favor of immature cells.
Acute leukemia with Burkitt's tumor cells: A study of six cases with special reference to lymphocyte surface markers
Authors: Flandrin G , Brouet JC , Daniel MT , Preud'homme JL
Published: October 2019

In six patients with acute leukemia (about 2% of the patients referred for acute lymphoblastic leukemia) the blast cells invading bone marrow and blood showed all the cytologic, cytochemical, and electron microscopy features of Burkitt's tumor cells. The presence of monoclonal surface immunoglobulins (their synthesis being proved by in vitro culture experiments), the binding of IgG aggregates, and the absence of rosette formation with sheep red cells documented the monoclonal B-cell origin of these blast cells which is in sharp contrast to the findings in common acute lymphoblastic leukemia. The course of the disease was usually rapidly fatal without chemotherapy- induced remission.
Canine cyclic neutropenia: Erythropoietin and platelet cycles after bone marrow transplantation
Authors: Jones JB , Lange RD , Yang TJ , Vodopick H , Jones ES
Published: October 2019

The marrow of a dog affected with cyclic neutropenia (CN) was transplanted into an unaffected supralethally irradiated litermate.Prompt engraftment occurred,and cyclic rises and falls in numbers of platelets, reticulocytes, and granulocytes were noted in the recipient soon after engraftment. Prior to transplantation and under hypoxic conditions,the donor had serum erythropoietin (ESF) peak levels at 11- 12-day intervals. Following transplatation and under hypoxic conditions,cyclic peaks of ESF occurred in the transplanted dog.
The relation of thrombokinetics to bone marrow megakaryocytes in idiopathic thrombocytopenic purpura (ITP)
Authors: Branehog I , Kutti J , Ridell B , Swolin B , Weinfeld A
Published: October 2019

In 23 patients with untreated idiopathic thrombocytopenic purpura (TP), the relation of thrombokinetics to quantitative determinations of megakaryocytes in bone marrow sections was studied. The megakaryocytes were classified into maturation stages, and platelet sizes were determined. Megarkaryocyte number and volume per microliter of bone marrow were significantly higher in ITP as compared to controls. The megakaryocyte number and volume were inversely related to the peripheral platelet count. Platelet production rate was significantly increased in ITP and related to the megakaryocyte number and volume. The megakaryocytes were shifted towards more immature forms in ITP, suggesting an increased turnover rate of the expanded recognizable metakaryocyte compartment. Platelet size was significantly increased in ITP, and the mean platelet diameter was 1.6 times normal. There was a significant relationship between platelet size and platelet production rate, as well as an inverse relationship between platelet size and platelet mean life-span (MLS). There was also a significant correlation between platelet size and the proportion of young megakaryocytes.
Acute myelogenous leukemia of the Wistar/Furth rat: establishment of a continuous tissue culture line producing lysozyme in vitro and in vivo
Authors: Greenberger JS , Rosenthal DS , Aaronson SA , Moloney WC
Published: October 2019

A transplantable myelogenous leukemia of an inbred Wistar/Furth rat has been established in tissue culture and cloned. The resulting transplantable leukemia line demonstrates in vitro doubling time of 20 hr, colony-forming efficiency of 5% in liquid and methylcellulos- containing medium, and a saturation density of 3.0 x 106 cells/sq cm in liquid medium. Following intraperitoneal inoculation, newborn rats developed solid tumors, ascities, and leukemia with ld50 of5 x 103 cells and mean latency of 60 days. The tumor cell morphology was consistent with that of acute myelogenous leukemia. Histochemical staining for myeloid enzymes revealed no evidence of myeloperoxidase, esterase, or leukocyte alkaline phosphatase; however, fluorescent antibody staining for lysozyme was markedly positive. Serum, urine, and ascitic fluid from rats with transplanted leukemia also contained elevated levels of lysozyme. There was no detectable type-CRNA virus production by this cell line after as long as 100 days in vitro. This inbred rat myelogenous leukemia should provide a useful model for studies of chemotherapy and immunoltherapy of human acute myelogenous leukemia.
Ultrastructural changes of endothelium associated with thrombocytopenia
Authors: Kitchens CS , Weiss L
Published: October 2019

In a study of the relationship between thrombocytopenia and increased vascular fragility, changes in the endothelium of capillaries and postcapillary venules of the tongue were examined by electron microscopy. Adult male albino rabbits (4 kg) were maintained thrombocytopenic (platelets less than 20,000/cu mm) up to 24 hr by one to three injections of guinea pig antirabbit platelet serum. Within 6 hr the normal projections and folds of the lumenal surface of the endothelial surface were largely effaced. In addition, the endothelium became thinner. In places, pores and membranous diaphragms were observed. Endothelial junctions appeared normal. Identical findings were observed if rabbits were made thrombocytopenic by administration of intraperitoneal busulfan. Intravenously administered Thorotrast was observed in endothelial cells and in the extravascular spaces within 3 min after injection into thrombocytopenic animals, while it was seen only intravascularly in control rabbits. With the spontaneous restoration of circulating platelets, the endothelium reverted to normal.
Terminal deoxynucleotidyl transferase activities in human blood leukocytes and lymphoblast cell lines: high levels in lymphoblast cell lines and in blast cells of some patients with chronic myelogenous leukemia in acute phase
Authors: Sarin PS , Anderson PN , Gallo RC
Published: October 2019

Terminal deoxynucleotidyl transferase, an enzyme which catalyzes the polymerization of deoxyribonucleoside triphosphates, elongating oligo- or polydeoxynucleotide chains, but without direction from a nucleic acid template, is thought to be specific for thymus gland and thymus- derived cells. We have confirmed the observations that high levels are characteristic of thymus gland with both human and calf tissue and that elevated levels may be found in some cases of acute lymphocytic leukemia. High levels were also found in human lymphoblast cell lines with T-cell characteristics, and insignificant activity was observed in leukocytes of patients with chronic myelogenous leukemia not in acute blast phase of the disease, chronic lymphocytic leukemia, human B- cells, and normal human blood lymphocytes even after stimulation with phytohemagglutinin. However, high levels (approximately 200 nmoles/hr/10(9) cells) equivalent to those in thymus tissue and lymphoblast cell lines with T-cell characteristics were found in the peripheral blood blast cells of four patients with chronic myelogenous leukemia in an acute blast phase of their disease. One hypothesis that may explain the present results is that in chronic myelogenous leukemia in acute blast phase of the disease the proliferative blast response may not always be myeloblasts but in some cases it may be lymphoblasts.
Differences in free fatty acid and glucose metabolism of human blood neutrophils and lymphocytes
Authors: Burns CP , Welshman IR , Spector AA
Published: October 2019

Comparison of isolated human neutrophils and lymphocytes in short-term tissue culture revealed marked differences in their rates of lipid biosynthesis. Ficoll-Hypaque gradients were used to separate lymphocytes and neutrophils from the blood of normal subjects. Neutrophils incorporated more palmitate into cell lipids (151.0 +/- 16.6 nmole/hr/10(8) cells) than lymphocytes (41.6 +/- 4.1). By contrast, the lymphocytes oxidized more palmitate (8.3 +/- 0.5 nmole/hr/10(8) cells) as compared to neutrophils (1.1 +/- 0.1). The greater fatty acid uptake by the neutrophils was due to a sixfold greater rate of incoporation of palmitate into their triglyceride fraction. Triglyceride synthesis by neutrophils increased as the molar ratio of free fatty acid to albumin was raised, whereas incorporation into phospholipids remained relatively constant; there was preferential labeling of neutrophil triglycerides throughout the physiologic range. Studies using linoleate and oleate gave similar results. The distribution of radioactivity into various phospholipids determined by thin-layer chromatography was similar for the two cell types. When labeled glucose was used as a substrate to measure incorporation primarily into the glycerol backbone of the cell lipids, neutrophils incorporated more radioactivity into total lipids and triglycerides than lymphocytes. These results indicate that neutrophils take up much more fatty acid than lymphocytes primarily because they synthesize much larger quantities of triglycerides, a storage form. Since cellular triglycerides may act as a source of fatty acid for lecithin synthesis during phagocytosis, the greater rate of fatty acid incorporation in the neutrophil may reflect a metabolic pattern that permits efficient phagocytosis.
Evaluation of extracorporeal alkylation of red cells as a potential treatment for sickle cell anemia
Authors: Charache S , Dreyer R , Zimmerman I , Hsu CK
Published: October 2019

Nitrogen mustard and nor-nitrogen mustard inhibit sickling, but the concentrations required would be associated with unacceptable toxicity if these agents were administered to patients. Red cells could be treated extracorporeally and infused back into donors, if the alkylating agent could be removed or inactivated, if the treatment per se did not significantly shorten red cell survival, and if viable alkylated lymphocytes could be eliminated from the treated blood. To estimate whether these conditions could be met in a clinical trial, red cells from four dogs were alkylated at 6-wk intervals. No toxic reactions were observed, although not all nor-nitrogen mustard was removed by the washing procedure. Red cell survival was shortened to about half that of control cells, using concentrations of alkylating agent which reduce sickling by 50%. Lymphocytes from treated blood could still exclude trypan blue, but could not be shown to circulate after reinfusion into donor dogs. If alkylating agents are used to treat patients' cells, inhibition of sickling may outweigh the shortening of red cell life span induced by the treatment; blood should probably be irradiated before infusion to avoid administration of alkylated and potentially mutated, but viable, lymphocytes.
Separation of megakaryocytes from mouse bone marrow by density gradient centrifugation
Authors: Nakeff A , Floeh DP
Published: October 2019

The density profile of mouse bone marrow megakaryocytes, as determined by discontinuous albumin density gradient centrifugation, was characterized by a single density population (1.088 to 1.119 g/ml) with a peak density of 1.10 g/ml and a maximum enrichment of 15.5. This single population comprised both mature and immature megakaryocytes. The density profile of small, acetylcholinesterase-positive cells, a class of potential megakaryocyte precursors, was almost identical to that of morphologically recognizable megakaryocytes.
A method for the recognition and separation of human blood monocytes on density gradients
Authors: Loos H , Blok-Schut B , van Doorn R , Hoksbergen R , Brutel de la Riviere A , Meerhof L
Published: October 2019

The density distribution of human mononuclear blood leukocytes was studied in order to define the optimal conditions for the separation of monocytes and lymphocytes by isopycnic centrifugation. Under standardized conditions, two populations of cells with partially overlapping, normally distributed densities were consistently found. The cells with the lowest density were recognized as monocytes, using phagocytosis and size distribution analysis as criteria. Since the density of monocytes continuously increased during the centrifugation, optimal separation of monocytes and lymphocytes could only be achieved by limiting the time of centrifugation to 10 min at 2200 g and 4 degrees C. The separation on discontinuous density gradients decreased when the load exceeded 8 X 10(6) mononuclear cells per sq cm. Analysis of the composition of the two cell populations obtained after separation on a three-layer discontinuous gradient revealed that the contamination of the monocytes with lymphocytes was due to the partial overlapping density distributions of both cell types. A small and a large scale method for isolation of monocytes from blood on discontinuous density gradients are presented. Under the described conditions, a preparation of functionally intact monocytes can be obtained which is comparable, both in yield and purity, to those obtained by methods based on surface adherence without the drawbacks of the latter methods.
DANGEROUS UNIVERSAL DONORS
Authors: ERVIN DONALD M. , YOUNG LAWRENCE E.
Published: October 2019

1. A severe hemolytic reaction was observed in an "A-intermediate" recipient following transfusion of group O blood containing A antibodies in high titer. Hemoglobinemia persisted for at least thirty hours, during which time the patient became markedly anemic. Azotemia, hyperbilirubinemia, spherocytosis and increased osmotic and mechanical fragilities of the patient’s erythrocytes were observed for nine days.

2. The recipient was rendered temporarily incompatible with prospective A1 donors as a result of incomplete absorption of the anti-A agglutinins in the transfused group O blood.

3. The A antibodies in the serum of the dangerous universal donor were shown to have the following peculiarities : (a) When normal AB serum was used as a diluent for the group O serum and as a medium for cell suspensions, the titer against A1 cells was higher than that obtained with saline as a diluent and suspension medium. (b) After "neutralization" with soluble A and B factors, the group O serum agglutinated neither A nor B cells in "saline systems," but in "serum systems" the treated O serum still agglutinated A1 cells in very high titer and A-intermediate cells in low titer. (c) A1 cells, but not A-intermediate or A2 cells, gave positive reactions with anti-human-globulin rabbit serum (indirect Coombs test) after exposure to the neutralized O serum. (d) The group O serum hemolyzed, and fixed complement with, all types of A cells but not B cells.

These peculiarities suggested that the group O donor had developed A antibodies of immune type and predominantly of A1 specificity, but the stimulus for production of these antibodies could not be ascertained.

4. It is emphasized that the type of antibody (i.e., natural or immune), as well as the titer, must be taken into account in any attempt to assess the dangers inherent in the use of universal donors, and that "conditioning" of group O blood by addition of soluble A and B factors in conventional quantities may not effectively neutralize immune A1 and B antibodies if such be present. It is pointed out, however, that further observations are needed to show whether or not neutralization of "saline" agglutinins and hemolysins by A and B factors may render dangerous bloods relatively safe despite the persistence of incomplete antibodies.

5. Possible mechanisms of prolonged erythrocyte destruction in this case are discussed.