bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Sodium Cyanate on Globin Synthesis
Authors: Habib Michael , Watson Veronica , Schwartz Elias
Published: October 2019

The incubation of peripheral blood with sodium cyanate produced dose-related suppression of hemoglobin synthesis. Addition of 5 mM sodium cyanate reduced globin synthesis in the peripheral blood of a patient with sickle cell disease by 34%, while 25 mM cyanate reduced synthesis by 92%. The relative synthesis of α- and β-chains remained constant despite the reduction of total synthesis. The effects were also found in peripheral blood and bone marrow of patients without hemoglobinopathies. The results suggest that further studies of the effect of cyanate on protein synthesis are necessary before widespread use of the drug in sickle cell disease.
Immunochemical Characterization of a Human Antibody to Factor XIII
Authors: Graham James E. , Yount William J. , Roberts Harold R.
Published: October 2019

Antibodies to factor XIII have not been previously characterized in detail. An acquired inhibitor to factor XIII, which developed in a patient following thrombectomy for a femoral artery occlusion, has been characterized as to immunoglobulin composition. A highly sensitive monodansylcadaverine assay for factor XIII was employed. The inhibitor was completely neutralized by antisera specific for the γG class, γG1 subclass, and λ light-chain type. Antisera to γG2, γG3, γG4, γA, γM, γD, γE, and k light-chains had no detectable effect. Preparative zone electrophoresis revealed the inhibitor to be in the cathodal portion of the gamma peak, with moderately restricted electrophoretic mobility. The factor XIII inhibitor is thus characterized as a γGl, λ immunoglobulin and resembles other human antibodies to clotting factors that are restricted in immunoglobulin composition.
Glucosephosphate Isomerase Deficiency: Evidence for In Vivo Instability of an Enzyme Variant With Hemolysis
Authors: Arnold Heidwolf , Blume Karl-Georg , Engelhardt Rupert , Löhr Georg Wilhelm
Published: October 2019

Pathogenesis of hemolysis in glucose-phosphate isomerase (GPI) deficiency was studied. Red cell populations of different ages were obtained by density centrifugation. In comparison to cell populations with comparable amount of reticulocytes, GPI activity decreased faster in the deficient red cells. A method to simulate aging blood cells in vitro was devised. On the first day the rate of glycolysis was normal in the deficient cells, but by the eighth day of the incubation period, the metabolic capacity decreased markedly, and hemolysis was observed. Using mannose as a source of energy, the rate of glycolysis was still normal by the eighth day, which reflects the cause and effect relationship between impairment of energy metabolism and GPI deficiency. It may be concluded that hemolytic anemia in this case of GPI deficiency is caused by the synthesis of a qualitatively changed subunit of the GPI molecule, which is associated with faster inactivation of the enzyme in vivo.
Effects of Cell Concentration and Various Anticoagulants on Neutrophil Migration
Authors: Patten Ethel , Gallin John I. , Clark Robert A. , Kimball Harry R.
Published: October 2019

The effects of cell concentration and anticoagulants on neutrophil passive migration and chemotaxis were examined. A relationship between passive migration and cell numbers was documented using blood neutrophils from neutropenic and normal individuals, as well as with purified granulocytes suspended in autologous serum. At granulocyte levels below 1500/cu mm, passive migration is impaired. The apparent defect in neutropenic patients can be normalized by adjusting cell counts to normal levels. Inhibition of passive migration by standard concentrations of heparin and chelator anticoagulants necessitates the use of small and carefully controlled amounts of these agents. Cell concentration and anticoagulants likewise influence chemotaxis. EDTA, oxalate, and citrate prevent the formation of chemotactic factor(s), whereas heparin appears to inhibit chemotaxis by a different mechanism possibly related to a direct cell effect. A knowledge of these variables is essential for proper evaluation of leukocyte migration studies.
Marked Immunosuppression With Minimal Myelosuppression by Bleomycin In Vitro
Authors: Tisman Glenn , Herbert Victor , Go Le Teng , Brenner Lois
Published: October 2019

Bleomycin, in concentrations similar to those present after drug administration, was a potent inhibitor in vitro of both human phytohemagglutinin (PHA)-stimulated and pokeweed mitogen (PMW)-stimulated lymphocyte transformation, but lower concentrations were much more inhibitory to the former. Bleomycin showed minimal or no in vitro myelosuppression. The similarity of these in vitro results to in vivo results by others suggests the in vitro system used here may be useful to screen new drugs for potential in vivo suppression of either the myeloid or the lymphoid tissue. The data suggest that by adjusting the dose of bleomycin inhibition of lymphocytes stimulated by PHA with only minimal inhibition of lymphocytes stimulated by PWM may be possible. Variable response of lymphoid neoplasia to bleomycin may in part reflect whether the cell type is T or B in origin, in view of work by others suggesting that PHA is more stimulatory to T cells and PWM is stimulatory to both B and T cells.
Influence of Cytochalasin B on the Shape Change Induced in Platelets by Cold
Authors: White James G. , Krumwiede Marlys
Published: October 2019

The present investigation has employed transmission and scanning electron microscopy to examine the influence of cytochalasin B (CB) on the shape change and pseudopod formation that develop when discoid blood platelets are exposed to low temperature. CB in two concentrations protected platelets from the physical alterations induced by cold. The greater of the two amounts of drug was more effective, suggesting a dose dependence. Microtubules were absent from untreated control platelets chilled for brief periods of time but remained in approximately 20% of CB-treated cells exposed to low temperature for an hour. The findings support the concept that CB preserves discoid shape by stabilizing structural elements of the cytoskeletal support system in blood platelets.
Nucleotide Profiles of the Formed Elements of Human Blood Determined by High-Pressure Liquid Chromatography
Authors: Scholar E. M. , Brown Phyllis R. , Parks R. E. , Calabresi P.
Published: October 2019

The nucleotide patterns of the acid soluble extracts of the formed elements of human peripheral blood were determined by high-pressure liquid chromatography. The patterns are remarkably reproducible for each of the respective elements, and the concentration of each major nucleotide present was determined. Erythrocytes are characterized by relatively simple nucleotide patterns with high adenine and very low guanine concentrations. The chromatograms of granulocytes and lymphocytes are difficult to distinguish from one another and demonstrate substantially greater UTP and guanine nucleotide levels than are observed in erythrocytes. The nucleotide patterns of platelets revealed a significantly lower ATP/ADP ratio than did either leukocytes or erythrocytes. The unique potential of this new technique for monitoring changes in nucleotide pools in normal and disease states is discussed.
Expression and Linkage of Genes for X-linked Hemophilias A and B in the Dog
Authors: Brinkhous K. M. , Davis P. D. , Graham John B. , Dodds W. Jean
Published: October 2019

In the article "Expression and Linkage of Genes for X-linked Hemophilias A and B in the Dog" by Brinkhous et al. (Blood, Vol. 41, No. 4, April 1973, pp. 577-585) the following items should read as given below:

Page 579, paragraph 3, Results

Once doubly heterozygous adult females were available, they were bred to determine the recombination frequency among the progeny. The sires were of the three phenotypes: normal, hemophilia A, and hemophilia B. The results from 15 litters, with 78 tested progeny, are shown in Table 2. The male:female ratio was 33:45 (x2 = 2.45; p > 0.10). From these matings, four male genotypes are possible, and all were observed. The crossover ratio was 15:18 in males, suggesting a deficiency of doubly hemophilic males (aXbY) from the XY · aXXb and aXY · aXXb matings.

Page 579, paragraph 5, Results

The ratio of crossovers to noncrossovers for all progeny, both male and females, of the double heterozygotes is 41:37. This is so close to the maximum 50% frequency of 39:39 that the linkage distance is too great to be measured.

Page 580, Table 2, line 4, Genotype of Noncrossover Females, should read aXXb.

Page 584, first paragraph at top of page, the last sentence is:

These data thus suggest that X-inactivation was indeed random, without respect to the paternal or maternal source of the X-chromosome.
A Comprehensive Modeling Procedure for the Human Granulopoietic System: Over-all View and Summary of Data
Authors: Blumenson Leslie E.
Published: October 2019

Understanding of the granulopoietic system in both normal and diseased states might be assisted by the use of a quantitative modeling procedure that relates the underlying cellular events of granulopoiesis studied in the laboratory to the marrow and peripheral blood picture as it might be seen in the clinic. In this way, the modeling procedure could become both an adjunct to ongoing laboratory research, as well as a means for rationally deciding on modes of treatment for pathologic conditions. The depth and rapid pace of modern granulopoietic research require that the modeling procedure be, on the one hand, detailed enough to permit the inclusion of the pertinent events at the cellular level as they are known today, while on the other hand, remain flexible enough to permit both the modification of any part and the possibility of seeing the predicted consequences of this modification for both the normal and diseased states. A detailed procedure was developed for an hour-by-hour description of the interrelationship of the kinetics of the various marrow cell types with the events in the peripheral blood and tissue spaces. The model was extended to include the toxic effects of a drug (5-fluorouracil) administered according to the protocol of an actual trial with cancer patients, and the temporal pattern of the predicted effects of the drug on the peripheral blood count was compared with that found in the clinic.
Lymphoblastic Leukemia with Marked Eosinophilia: A Report of Two Cases
Authors: Spitzer Gary , Garson O. Margaret
Published: October 2019

Two cases of acute lymphoblastic leukemia with eosinophilia are described. The degree of eosinophilia was such that at presentation, a provisional diagnosis of eosinophilic leukemia was made. Cytogenetic evidence is presented, indicating that the eosinophilia is reactive to the leukemic process rather than part of it. A mechanism for the production of the eosinophilia is discussed, and it is suggested, on the basis of our findings, that acute eosinophilic leukemia may be of rarer occurrence than is already accepted.
The Influence of Thymus Cells in Hemopoiesis: Stimulation of Hemopoietic Stem Cells in a Syngeneic, In Vivo, Situation
Authors: Lord B. I. , Schofield R.
Published: October 2019

Using the spleen colony-forming technique to assay hemopoietic stem cells, (CFUs) experiments have been carried out to investigate the role of thymus cells in hemopoiesis. The experiments were carried out by injecting live or killed thymus cells into lethally-irradiated mice together with hemopoietic tissue containing CFUs. The effect of thymus cells on endogenous colony formation in sublethally-irradiated mice was also investigated. Colony formation by normal bone marrow or spleen is unaffected by the addition of thymus cells, but cell populations damaged by radiation all demonstrate increased colony numbers when live thymus cells are injected within 48 hr of initiating colony formation. Endogenous colony formation resulting from an x-ray dose of 475 red is increased 2.9 times: exogenous colony formation from bone marrow or spleen populations whose CFUs content has been reduced to approximately 20% of normal with 180-rad γ-rays is increased 2.1 times. Studies investigating this enhancement demonstrate that at least some of the colonyforming cells require the cooperation of live thymus cells. Under the conditions of these experiments, at least 106 thymus cells must be injected to produce maximum enhancement.
Immunologic Response of Patients With Acute Leukemia to Platelet Transfusions
Authors: Tejada Francisco , Bias Wilma B. , Santos George W. , Zieve Philip D.
Published: October 2019

Nine leukemic patients in aplasia received platelet concentrates from random donors over a period of 5 to 32 wk (an average of 31 transfusions per patient). All nine developed lymphocytotoxic activity (presumably HL-A antibodies) in their serum against cells from a panel of 40 selected donors within 20-50 days after transfusions were begun. Lymphocytotoxic activity markedly diminished in the sera of seven surviving patients over a period of 8-24 wk despite continued occasional platelet transfusions. When lymphocytotoxic activity was present in the serum of these patients, survival of transfused platelets was significantly reduced. Sera in which lymphocytotoxic activity was detected released endogenous serotonin (26 ± 5% SEM) from washed human platelets (but not from dog or rabbit platelets) when incubated at 37°C for 30 min. In contrast, sera from these patients, obtained when lymphocytotoxic activity was not detected, released minimal amounts of serotonin (6 ± 2%) and sera from nine healthy subjects released none (0 ± 1%). The ability of serum to release serotonin was abolished, and lymphocytotoxic activity was markedly diminished, after preincubation with allogeneic platelets.
Tissue Immunoglobulins in Nodular Lymphomas as Compared With Reactive Follicular Hyperplasias
Authors: Braylan Raul C. , Rappaport Henry
Published: October 2019

Frozen tissue sections of lymph nodes and spleens from twelve patients with nodular (follicular) lymphomas were studied with fluorescein-labeled antisera against human immunoglobulins. Immunoglobulins detected by this method in the neoplastic nodules were minimal or absent. Furthermore, in no instance could the characteristic network pattern of immunoglobulin distribution which is readily demonstrable in active germinal centers be observed within these nodules. It is suggested that the preservation of the follicular network of immunoglobulins as observed by fluorescent antihuman IgG, IgM, or polyvalent antisera indicates functionally intact germinal centers. The detection, by this rather simple method, of large amounts of immunoglobulin distributed in such a distinctive pattern may thus be very useful for the differentiation between severe benign follicular hyperplasia and malignant lymphoma with nodular pattern, which may be difficult to distinguish by routine histological methods.
The Importance of Bone Marrow Biopsy in the Staging of Patients With Lymphosarcoma
Authors: Vinciguerra Vincent , Silver Richard T.
Published: October 2019

Owing to printers’ errors, the following errata appeared in the June 1973 issue of Blood (Vol. 41, No. 6).

"The Importance of Bone Marrow Biopsy in the Staging of Patients With Lymphosarcoma" by Vincent Vinciguerra and Richard T. Silver (pp. 913-920).

On page 913, in the Abstract, left-hand column, fifth line from the bottom, should read "9 of 12 (75%) stage II patients, and 27 of…"

On page 913, the legends for Figs. 2 and 3 are reversed.
Two Cases of Familial Erythrocytosis With Increased Erythropoietin Activity in Plasma and Urine
Authors: Yonemitsu H. , Yamaguchi K. , Shigeta H. , Okuda K. , Takaku F.
Published: October 2019

Two brothers with familial erythrocytosis born to parents of a consanguinous marriage are described. Two other siblings were unaffected. There was a marked increase in erythropoietin concentration in both the plasma and urine, suggesting that a congenital defect led to erythropoietindependent polycythemia. Other causes of polycythemia were excluded.
Effect of Storage on Sulfhydryl and Disulfide Groups of Human Platelets
Authors: Ando Yasuhiko , Steiner Manfred , Baldini Mario G.
Published: October 2019

Free sulfhydryl and disulfide groups of an acid-soluble and acid-precipitable fraction and of isolated plasma membranes were quantified in fresh and stored human platelets. Fresh platelets contained 26.6 x 10-8 moles of total thiols including free sulfhydryl and disulfide groups per 109 cells. One-third of these thiols were present as disulfides. Acid-soluble thiols accounted for one-tenth of the total platelet thiols. Storage of platelets produced a reduction in the level of acid-soluble sulfhydryl and disulfide groups which was rapid during the first 24 hr and was precipitous in platelets stored at 22°C. Free sulfhydryl groups of the acid-precipitable fraction and of isolated platelet membranes showed a relatively rapid decrease during the first 24 hr of storage and declined thereafter very slowly. The disulfide levels of these cell fractions showed a reciprocal increase which complemented the fall in the number of free sulfhydryl groups. The storage temperature did not significantly influence these changes in protein thiols and disulfides. The coincidence of loss of platelet functions and of severe decrease in the level of free sulfhydryl groups during platelet storage at room temperature may suggest a cause-effect relationship between the two.
Toxic Effects of High-Dose Cyanate Administration in Rodents
Authors: Alter Blanche P. , Kan Yuet Wai , Nathan David G.
Published: October 2019

Cyanate inhibits hemoglobin synthesis in vitro. In vivo studies were performed to determine the effect of the drug on erythropoiesis. Adult female rats received daily intraperitoneal injections of 400 µmoles of cyanate, leading to over 3 CNO/Hb by 3 wk. Controls received sodium chloride. DPG was measured in a small number of animals and declined from 5.5 to 4.1 mmoles/liter (p < 0.02). At 4 wk, Hb, Hct, and red cell counts in cardiac blood of the treated group were all higher (p < 0.05); MCHC was normal. Mean plasma iron was 175 in treated versus 129 µg/100 ml in controls. Plasma iron turnover in mg/day increased from 0.143 to 0.260 (p < 0.01), as did erythron iron turnover, from 0.096 to 0.195 mg/day (p < 0.05). Thus the erythroid marrow of cyanate-treated animals could respond to carbamylation-induced increase in oxygen affinity, though the adequacy of the response with respect to the increase in oxygen affinity is difficult to assess. Furthermore, severe clinical toxicity was observed. Treated animals lost a mean of 62 g, compared with a gain of 25 g in controls. Twenty-five per cent died by 4 wk. The neuromuscular system appeared to be more sensitive to high-dose in vivo cyanate administration than the erythropoietic system.
Protein - Quinone Interaction: In Vitro Induction of Indirect Antiglobulin Reactions With Methyldopa
Authors: Gottlieb Arlan J. , Wurzel Harold A.
Published: October 2019

Methyldopa-treated gamma globulin can be demonstrated serologically on either the red cell surface or on latex beads by the indirect antiglobulin reaction. The development of a positive antiglobulin reaction was related to methyldopa concentration and the length and temperature of incubation of methyldopa with protein and could be partially inhibited by the addition of albumin to the incubation mixtures. After more prolonged incubation, antiglobulin positivity also developed with plasma-treated with methyldopa. 14C-methyldopa was covalently bound to gamma globulin. Aggregation of gamma globulin following treatment with methyldopa could be demonstrated by both sedimentation velocity and molecular weight determinations employing low-speed equilibrium centrifugation. Protein aggregation was a function of time, temperature, and methyldopa concentration. Detectability by the antiglobulin reaction, the darkening noted in solutions to which methyldopa or hydroquinone had been added, as well as the aggregation of protein was inhibited by a reducing agent which prevented formation of a quinone from the hydroquinone. Some of the immunologically atypical features of the sensitization of red cells by methyldopa or its structural analogues are explicable by the adherence, in vivo, of chemically modified, nonantibody gamma globulin which renders the red cell directly antiglobulin positive.
Macroglobulinemia in a Child With Acute Leukemia
Authors: Čejka Jan , Bollinger Robert O. , Schuit Henrica R.E. , Lusher Jeanne M. , Chang Chung-Ho , Zuelzer Wolf W.
Published: October 2019

A 12-yr-old boy with acute leukemia was found to have paraproteinemia and Bence-Jones proteinuria. The paraprotein was characterized as immunoglobulin M, type κ and the Bence Jones protein as free κ-chains. Increased amounts of β2-microglobulin were found in the patient’s serum and urine. Electron microscopic and immunofluorescence studies provided evidence of the presence of lymphoid leukemia cells apparently responsible for the production of the paraprotein.
Granulocyte Function in the Chediak-Higashi Syndrome of Mice
Authors: Gallin John I. , Bujak Joseph S. , Patten Ethel , Wolff Sheldon M.
Published: October 2019

Granulocyte function was evaluated using peritoneal exudate granulocytes from a strain of beige mice with the Chediak-Higashi syndrome (CHS). Defective granulocyte chemotaxis of CHS cells (43% normal) was documented. There was no abnormality in the ability of CHS serum to function as a chemotactic stimulus. Phagocytosis of 14C-labeled Staphylococcus aureus by CHS granulocytes was normal. However, there was reduced bactericidal activity of S. aureus and group D streptococcus by CHS cells through 90 min of incubation. The bactericidal defect was most pronounced at early time periods and was related to impaired intracellular killing. These defects of CHS mice granulocytes were analogous to those reported in man and it is concluded that the CHS mouse is a most convenient and representative model of the CHS of man.
Familial Thrombosis Due to Antithrombin III Deficiency
Authors: Marciniak Ewa , Farley Claude H. , DeSimone Philip A.
Published: October 2019

A large kindred from eastern Kentucky, with extensive history of recurrent venous thrombosis and pulmonary embolism, was studied. Low antithrombin III titers, ranging from 26% to 49% of normal values, were found in plasma of nine members in three consecutive generations; another five members, four of whom were not available for study, are suspected of having the biochemical defect. There was a good correlation between clinical symptoms and antithrombin III deficiency, although three of the younger members with the defect still remained free of thrombosis. In serum of the affected subjects antithrombin III was almost completely utilized, which indicates that stoichiometric binding to coagulation enzymes dominates under biological conditions. Antithrombin and antifactor Xa activities residing in the macroglobulin region of plasma and serum remained unchanged. The responsiveness to heparin in vitro and in vivo confirmed the evidence that antithrombin III is the sole blood component through which heparin exerts its anticoagulant effect. In five affected members therapy with oral anticoagulants increased very significantly the level of antithrombin III in plasma and contributed to a remarkable increase of residual antithrombin III in serum. This objective improvement after warfarin therapy may create significant difficulties in the laboratory diagnosis of antithrombin III deficiency.
Intranuclear Hemoglobin in Erythroblasts of β-Thalassemia
Authors: Yataganas Xenophon , Gahrton Gösta , Thorell Bo
Published: October 2019

The amount and distribution of intranuclear hemoglobin in erythroblasts of normal subjects and patients with homozygous β-thalassemia were studied by microspectrophotometric methods. The mean intranuclear hemoglobin content of the mature erythroblasts represented 33%-40% of the total hemoglobin content both in normal and thalassemic cells. Distinct absorption peaks in transmission scanning lines recorded over thalassemic erythroblasts suggested the presence of intranuclear hemoglobin precipitation in some cells. Similar characteristic absorption peaks of denatured ferric hemoglobin were recorded over large inclusions of the cytoplasm and small intranuclear precipitates. Intranuclear inclusion bodies may be responsible for the disturbance of erythroblast proliferation in thalassemia, thus explaining in part the ineffective erythropoiesis occurring in this disease.
Hemoglobin Rush [β101 (G3) Glutamine]: A New Unstable Hemoglobin Causing Mild Hemolytic Anemia
Authors: Adams J. G. , Winter W. P. , Tausk K. , Heller P.
Published: October 2019

A mild hemolytic anemia in a 43-yr-old black woman was attributed to the presence of an abnormal hemoglobin (Hb Rush) which migrated cathodically to Hb A at pH 8.0. Its structural abnormality was found to be in the β-chain, β101 (G3) glu → gln. Another electrophoretic band at pH 8.0 proved to be a hybrid tetramer (αA2βAβRush). Hb Rush is heat unstable. A likely explanation of the instability is the presence of an uncovered positive charge in the central cavity where normally glutamic acid in position 101 neutralizes arginine in position 104 contributing to the net neutrality in this region. This neutrality is disturbed by the substitution of glutamic acid by glutamine in Hb Rush.
Fetal Rat Utilization of 55Fe Absorbed by Fetal Intestine From Swallowed Amniotic Fluid
Authors: Orlic Donald , Lev Robert , Rosenthal William S.
Published: October 2019

Radioiron(55Fe) injected directly into the amniotic cavity of 21-day rat fetuses is swallowed and rapidly absorbed by the intestine. The radioisotope is then transported from the intestine and is utilized in the liver and spleen, fetal erythropoietic and iron-storing organs. The level of incorporation in intestine, spleen, and liver, as measured by scintillation counting, is relatively low during the first hour, but increases 3 and 6 hr postinjection. Radioautograms at 6 hr demonstrate extensive labeling in the cytoplasm of absorptive cells in the intestinal mucosa. In liver the 55Fe is observed in parenchymal and reticuloendothelial cells and in developing red cells. Erythroid cells are the principal 55Fe-labeled cells in the spleen. Recirculation of some 55Fe occurred between 55Fe-injected fetuses, maternal organs, and control fetuses. Fetal swallowing of 55Fe within amniotic fluid followed by intestinal absorption of the radioisotope demonstrates the existence of a pathway by which nutrients can be delivered to the fetus. This finding is of potential benefit to the human fetus since a number of compounds, including certain drugs, may possibly be administered via this route.
The Determination of Erythrocyte Folate Concentration Using a Two-Phase Ligand-binding Radioassay
Authors: Rothenberg Sheldon P. , da Costa Maria , Lawson John , Rosenberg Zoltan
Published: October 2019

The concentration of folate in erythrocytes was determined using a two-phase ligand-binding radioassay procedure described previously for measuring serum folate. The mean (± SD) folate concentration in erythrocytes of 20 normal subjects was 210 ± 57 ng/ml. In 12 patients clinically folate deficient who had normal serum B12 concentration, the mean (± SD) erythrocyte folate was 71 ± 39 ng/ml. Incubation of the lysed erythrocytes for 2 hr prior to boiling increased the radioassayable folate. The radioassayable folate decreased rapidly if the whole blood was stored at 4°C without ascorbate. Extracts of blood prepared with ascorbate could be stored at -20°C for several days. The radioassayable concentration of erythrocyte folate was similar to the values obtained using Lactobacillus casei when the concentration was 200 ng/ ml or less. With values higher by L. casei, the radioassayable folate was significantly lower even though the normal and folate-deficient groups were distinctly separated. This radioassay provides a rapid and reliable method of measuring erythrocyte folate, a parameter which reflects folate stores more reliably than serum folate concentration.
Plasma Cell Dyscrasia Associated With the Production of Incomplete (? Deleted) IgGλ Molecules, Gamma Heavy Chains, and Free Lambda Chains Containing Carbohydrate: Description of the First Case
Authors: Isobe Takashi , Osserman Elliott F.
Published: October 2019

The clinical, hematologic, and immunoglobulin features of a new form of plasma cell dyscrasia (deleted H and L chain disease) are described. The clinical manifestations are periodic fever and weakness, lymphadenopathy, and hepatosplenomegaly. The hematologic abnormalities are anemia, leukopenia, lymphocytosis, thrombocytopenia, and increased plasma cells in lymph nodes and bone marrow. The protein abnormalities have been identified as (1) monoclonal IgG1λ A serum globulin (5-6 g/100 ml) with deletions in both H and L chains and an estimated mol wt of 110,000; (2) free γ Fc fragment in serum and urine; (3) urinary excretion (10-20 g/day) of deleted λ-chains (Uλ) with an estimated mol wt of 15,000. Uλ and the λL chains of the IgG are apparently identical. Uλ was shown to contain approximately 26 moles of carbohydrate, with an average of 2.2 moles of sialic acid per 15,000 mol wt. Uλ displayed marked electrophoretic heterogeneity which was related to a variable number of sialic acid residues. The N terminus of Uλ is blocked (PCA). The deletions of both the λ- and the H chains were localized to their respective V regions and are of similar magnitudes (approximately 10,000 daltons). Possible genetic mechanisms to explain apparently comparable H- and L-chain deletions in a single IgG molecule are considered.
Neutrophil and Monocyte Kinetics in a Case of Cyclic Neutropenia
Authors: Meuret G. , Fliedner T. M.
Published: October 2019

The kinetics of neutrophilic granulocytes and monocytes were examined simultaneously in a patient suffering from cyclic neutropenia. During the remission phase of the disease the observed kinetic data for both cell types did not deviate significantly from the normal range. At a stage just before the minimal blood granulocyte count was reached, the total blood granulocyte pool was diminished and the granulocyte half disappearance time shortened to 2.3 hr. Moreover, the intravascular granulocyte distribution changed in favor of the marginal granulocyte pool. During the neutropenic phase, the intravascular monocyte pools were Increased and monocyte half-disappearance time was prolonged to 14 hr; the monocyte turnover rate was 2.4-fold higher than during remission.
Ferritin in Serum: Diagnosis of Iron Deficiency and Iron Overload in Infants and Children
Authors: Siimes Martti A. , Addiego Joseph E. , Dallman Peter R.
Published: October 2019

Ferritin in serum was quantitated by radioimmunoassay to determine the usefulness of this assay in reflecting iron stores during normal development and in the diagnosis of iron deficiency and iron overload in infants and children. In the adult, serum ferritin has been reported to correspond to the magnitude of iron stores throughout a wide range. In 573 normal infants and children, we found the concentration of serum ferritin to parallel known changes in iron stores during development. The median serum ferritin concentration was 101 ng/ml at birth, rose to 356 ng/ml at 1 mo of age, and then fell rapidly to a median value near 30 ng/ml (95% confidence limits: 7-142 ng/ml) between 6 mo and 15 yr of age. In the adult, median concentrations diverged according to sex, 39 ng/ml in the female and 140 ng/ml in the male. In 13 children with iron-deficiency anemia, the serum ferritin concentration was 9 ng/ml or less. Overlap with the normal population was small, and no conditions were found to give "false" low values. In children with β-thalassemia major and sickle cell anemia, median values were elevated to 850 and 160 ng/ml, respectively. Possibly misleading, elevated values were obtained in some patients with acute infection and in acute lymphoblastic leukemia. The serum ferritin assay promises to be a useful tool in the evaluation of iron status, particularly in children.
Degradation of Bovine Factor VIII by Plasmin and Trypsin
Authors: Kirby Edward P. , Martin Neil , Marder Victor J.
Published: October 2019

The degradation of bovine Factor VIII by plasmin, trypsin, and thrombin was monitored with polyacrylamide gel electrophoresis in a urea—acetic acid system. The sequences of plasmic and tryptic proteolysis were very similar, proceeding via several intermediate, enzyme-sensitive products to smaller derivatives which were relatively resistant to further degradation. The intermediate degradation products were similar for both enzymes, although prolonged digestion with trypsin produced final products which were smaller than those observed with plasmin. Stages of digestion which reflect the degree of completeness of proteolysis were defined on the basis of the presence or absence of these distinct components in the electrophoretic profiles. Thrombin treatment of Factor VIII caused a loss of coagulant activity but did not yield products small enough to be characterized in this electrophoretic system. During the course of plasmic and tryptic digestion, there was a rapid loss of all coagulant activity without the generation of anticoagulant activity. Agarose chromatography of a 24-hr plasmic digest revealed three major protein peaks, which corresponded to individual electrophoretic bands on polyacrylamide gel electrophoresis in a nondenaturing system at pH 8.8. Upon polyacrylamide gel electrophoresis in the urea—acetic acid system, the components of the first two of these peaks dissociated into two and three separate fragments, respectively. Immunoelectrophoresis demonstrated two major distinct antigenic determinants in these first two elution peaks.
A Syndrome of Platelet-release Abnormality and Mild Hemophilia
Authors: Chesney Carolyn , Colman Robert W. , Pechet Liberto
Published: October 2019

Two families were studied because of a hemorrhagic tendency. The presumptive diagnosis of von Willebrand’s disease was suggested by low factor VIII levels (7.5%-33%), prolonged template Ivy bleeding time (9.5-17 min), low platelet adhesiveness (0%-8%), normal platelet factor 3, and normal clot retraction. Further studies, however, showed abnormal platelet aggregation with ADP, epinephrine, and collagen, and deficient release of platelet antiheparin activity and 14C serotonin. Patients’ platelets, rendered free of plasma by gel filtration, continued to show abnormal aggregation when resuspended in normal plasma. Plasma from the patients contained greater than 200% factor VIII by immunologic assay. The patients’ coagulant factor VIII level returned to base line within 24 hr after plasma or cryoprecipitate transfusions. Unlike von Willebrand’s disease, management of these patients required both platelets and cryoprecipitate to prevent bleeding.
Ultrastructure of Sickled Deer Erythrocytes. II. The Matchstick Cell
Authors: Taylor W. J. , Simpson C. F.
Published: October 2019

The matchstick cell is a unique form of sickled deer erythrocytes which is related to a specific β2-chain type in the white-tailed deer. Like the typical crescent form of sickled cell, it is an in vitro phenomenon which is induced by high pH and POO2 and reverses to the usual discoid form with deoxygenation and lowering of the pH. Transmission electron microscopy revealed a precise intracellular structure with polymerization of the hemoglobin into long filaments which were aligned in one axis of the cell, so that they appeared as long rods at relatively low magnification. A second feature, which contrasts to typical sickle forms of deer or man, is an absence of any type of microtubular structure. This suggests a different mode of intermolecular bonding related to primary structural variations of the β-chains which are associated with the matchstick cells and with typical sickle cells. Elucidation of the various structural differences between these β-chains may give additional clues to the mechanism of hemoglobin aggregation in the human sickle cell.
Agar Culture Studies in 127 Cases of Untreated Acute Leukemia: The Prognostic Value of Reclassification of Leukemia According to In Vitro Growth Characteristics
Authors: Moore M. A. S. , Spitzer G. , Williams N. , Metcalf D. , Buckley J.
Published: October 2019

Agar culture of marrow and blood from 127 cases of acute leukemia (including 108 cases of myeloid leukemia and variants) has revealed a spectrum of abnormalities. The observations of deranged proliferation and maturation of granulocyte—macrophage progenitor cells (in vitro CFC), together with abnormalities in CFC buoyant density, was of considerable diagnostic value. The morphologic, hematologic, and cytogenetic heterogeneity of acute myeloid leukemia did not correlate with heterogeneity of in vitro growth parameters, and grouping of patients by conventional hematologic parameters was of no value in predicting response to therapy. Indeed, the age of the patient was the only significant conventional parameter which influenced remission rate. By in vitro criteria, increase in the number of CFC of abnormally light buoyant density and high in vitro "plating efficiency" of the leukemic blast cells adversely affected remission probability. Reclassification of acute myeloid leukemia by in vitro growth pattern was of greatest prognostic value, and four main growth patterns were recognized: (1) colony forming, (2) large cluster forming (maximum cluster size, 40 cells), (3) small cluster forming (maximum cluster size, 20 cells), and (4) nongrowing. Highly significant differences in remission rate were observed in the different growth types. All cases of AML could be divided on the basis of growth pattern into a good prognosis group of 66 patients with a remission rate of 52% and a poor prognosis group of 42 cases with a 10% remission. The influence of age was evident in both groups, and of 30 patients less than 40 yr of age, remission in the favorable prognosis group was 91% and in the poor prognosis group only 14%. The ability to detect, at first diagnosis, a substantial number of patients whose disease is resistant to present therapeutic protocols could lead to application of alternative forms of therapy that may improve prognosis in this category.
Macrophage-Eosinophil Interactions in the Inflammatory Response to Trichinella spiralis
Authors: Walls Ronald S. , Hersey Peter , Quie Paul G.
Published: October 2019

Little is understood of the reasons why eosinophils accumulate in vivo, although a tissue reaction to administered antigen has been shown to be a prerequisite for the response. The present experiments aim to understand the significance of the tissue reaction to parasitic larvae in the chain of events leading to eosinophilia. Trichinella spiralis larvae were injected intraperitoneally in rats, and the peritoneal exudate was examined at intervals. Eosinophils were closely associated with macrophages rather than with other cell types or with parasites. A striking collection of eosinophils around individual macrophages was noted 48 hr after injection, and in particular following a second challenge. Use of indirect immunofluorescence techniques showed that these coincided with presence of immunoglobulin on macrophage surfaces. Incubation of peritoneal cells in medium containing 0.25% trypsin reduced macrophage surface immunofluorescence and numbers of rosettes. Rosettes could be constituted in vitro by incubation of normal peritoneal cells in medium containing antigen and antibody. These findings suggest that in the tissue reaction to parasitic larvae a close association exists between eosinophils and macrophages.
An Animal Model of Chronic Aplastic Marrow Failure. I. Late Marrow Failure After Busulfan
Authors: Morley Alec , Blake Judith
Published: October 2019

An animal model of chronic aplastic marrow failure was produced by administering busulfan to mice in high dosage for a prolonged period. Mice which survived 60 or more days following cessation of the drug appeared well: in 59% the blood was normal, and in 35% the marrow cellularity was within the normal range; those mice with evident abnormality in the blood and marrow showed only minimal cytopenia in the peripheral blood and moderate decreases in marrow cellularity. Nevertheless, by 240 days 80% of the mice had become ill and died. Sacrifice prior to death showed that aplasia of the marrow and cytopenia (most often pancytopenia) were present in the majority of mice. These syndromes of persistent mild marrow hypoplasia and late severe marrow failure which followed busulfan may be suitable experimental models for studying the late effects of myelotoxic agents and the syndrome of chronic aplastic marrow failure in man.
Cationic Proteins of Human Granulocytes. II. Separation of the Cationic Proteins of the Granules of Leukemic Myeloid Cells
Authors: Olsson I. , Venge P.
Published: October 2019

The highly cationic proteins of human granulocytes, whose electrophoretic mobilities toward the cathode are faster than that for lysozyme, were isolated from the cytoplasmic granules of leukocytes, obtained from patients with chronic myeloid leukemia. The granule extract was subjected to chromatography on Sephadex G-75 and E-aminocaproic acid-Sepharose ion adsorbant followed by preparative electrophoresis on agarose. Seven cationic protein components were identified, and five of these were obtained in a pure form. One group of cationic proteins, including components 1-4, exhibited molecular weights in the range 25,500-28,500, almost identical amino acid composition, and complete immunologic identity. Another group of proteins, including components 5-7, exhibited molecular weights in the range 21,000-29,000 and also showed complete immunologic identity; amino acid analysis performed on component 5 indicated a different amino acid composition from that of components 1-4. Cationic proteins with similar electrophoretic mobilities and immunochemical identities were also detected in granule extracts of granulocytes from healthy individuals. The proteins isolated from human granulocytes have a higher molecular weight and a lower content of basic amino acids than the cationic proteins with antibacterial and permeability-increasing properties previously demonstrated in rabbit polymorphonuclear granulocytes.
Impaired Erythropoietin Response in Anemic Premature Infants
Authors: Buchanan George R. , Schwartz Allen D.
Published: October 2019

Serum erythrepoietin (ESF) levels were measured by the polycythemic mouse bioassay in a group of normal premature infants with physiologic anemia. No ESF was detected in these infants, while a group of older anemic children with similar hematocrit values had elevated levels. An impaired ESF response in these infants may be an important factor in the pathogenesis of the anemia of prematurity. Tissue oxygen requirements in the premature infant are probably met in some way despite diminished ESF production and low hematocrit levels.
Teaching Blood Morphology: Audiovisual Method Compared to Microscope Slides With Written Text and Instructor
Authors: Stanley John , Reich Paul
Published: October 2019

Two methods of teaching first-year medical students peripheral blood morphology were compared. A group of 27 students learned using a self-teaching audiovisual method of 35-mm color slides accompanied by an audio tape explanation. A group of 20 students were taught using the classic method of microscope slides explained by a written text, with an instructor to point out morphology. Both methods presented the same information to the students. Both groups were evaluated by a quiz consisting of actual blood smears. Although the mean learning time per student for the color slide group was significantly shorter than that for the microscope group, there was no significant difference between the mean quiz scores of the two groups, and both were significantly greater than the mean score of a control group which had no learning session.
Type I Dyserythropoietic Anemia in an Elderly Patient
Authors: Maldonado Jorge E. , Taswell Howard F.
Published: October 2019

A 58-yr-old woman is described in whom light and electron microscopic studies of bone marrow revealed the typical features of type I dyserythropoietic anemia. This form of anemia may be first diagnosed late in life, and caution should be exerted to avoid its confusion with preleukemia or erythroleukemia.
Hemoglobin Andrew-Minneapolis αA2β144 Lys → Asn2: A New High-Oxygen-Affinity Mutant Human Hemoglobin
Authors: Zak Solomon J. , Brimhall Bernadine , Jones Richard T. , Kaplan Manuel E.
Published: October 2019

The functional properties and primary structure of a new β-chain mutant of human hemoglobin are described. The mutant was transmitted as an autosomal dominant characteristic. Affected members of the kindred exhibited marked erythrocytosis due to the high oxygen affinity of the resultant hemoglobin. The abnormality is associated with a substitution of an asparaginyl residue for lysine in the 144 position of the β-chain, αA2β144Lys→Asn2, presumably due to an AAA/G to AAA/U transversion. The mutant hemoglobin displayed a profound increase in oxygen affinity, with a P50 of the fresh whole blood of 14 mm Hg. The isolated mutant hemoglobin exhibited near normal heme—heme interaction, a half-normal Bohr effect, and normal reactivity with 2,3-diphosphoglycerate.
The Dependence of Shape of Human Erythrocyte Ghosts on Calcium, Magnesium, and Adenosine Triphosphate
Authors: Palek Jiri , Stewart Gwendolyn , Lionetti Fabian J.
Published: October 2019

ATP depletion of erythrocytes is associated with discocyte-echinocyte transformation and accumulation of calcium. This study was undertaken to evaluate whether this shape transformation results from interaction of Ca2+, Mg2+, and ATP with structural proteins of the membrane. ATP, Mg2+, or Ca2+ were incorporated into ghosts during hypotonic hemolysis followed by restoration of isotonicity with NaCl and incubation. Reconstituted ghosts were examined by electron microscope after osmium tetroxide fixation followed by platinum and carbon shadowing and in-phase contrast microscope. Four ghost configurations were observed: (1) flat, discoidal electron-penetrable ghosts were produced when ghosts were prepared without any additives, or with ATP alone, Mg2+ alone, or EDTA; (2) biconcave and cup-shaped less electron-penetrable ghosts predominated when equimolar concentrations of Mg2+ and ATP (0.5-2 mM) were introduced into ghosts during hemolysis; (3) spherical, spiculated, or markedly deformed electron-dense ghosts of smaller volume were the prevalent shape forms when Ca2+ alone was introduced during hemolysis; (4) small, smooth, electron-dense spheroids were present when both Ca2+ and Mg ATP (2 mM) were added during hemolysis. The above shapes were independent of ouabain, monovalent cations (NaCl, KCl, or choline chloride), transmembrane osmotic gradient, and ghost volume. The shape effects of Ca2+ and Mg ATP were prevented by preincubation of red cells with SH-blocking agent N-ethylmaleimide (4 mM) and by repeated ghost washing, which was associated with removal of water-soluble fibrous proteins from membranes. It is concluded that the interaction of Ca2+, Mg2+, and ATP with membrane structural proteins exerts a significant role in the control of shape of human erythrocytes.
Erythropoietic Colonies in Cultures of Human Marrow
Authors: Tepperman A. D. , Curtis J. E. , McCulloch E. A.
Published: October 2019

The cell culture method originally devised by Stephenson and Axelrad for erythropoietin-dependent erythropoietic colony formation (CFU-E) by mouse cells has been adapted to human marrow. Erythropoietic colonies from human marrow contain between eight and 150 cells and reach maximum growth after 7-9 days of incubation. Progenitors of larger colonies differ from the total pool of human CFU-E in that they have a slower mean sedimentation velocity and a greater erythropoietin requirement. The assay is quantitative and was used to determine the radiation sensitivity of human erythropoietic progenitors. The parameters of the survival curve are: Do = 113 ± 7.8, n = 1.5 ± 0.15.