bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Coagulant Activity of Cultured Human Fibroblasts
Authors: GREEN DAVID , RYAN CATHY , MALANDRUCCOLO NANCY , NADLER HENRY L.
Published: October 2019

Skin fibroblasts were cultured from normal individuals, from patients with hemophilia, and from known and suspected carriers of hemophilia. All cell lysates studied had similar coagulant activity unaffected by incubation with a specific antibody to factor VIII and, therefore, presumably not factor VIII. Further investigation indicated that the coagulant had many properties indistinguishable from those associated with "tissue factor," including heat lability, sedimentation characteristics, and dependency on factor VII for expression of coagulant activity. The presence of tissue factor in skin fibroblasts is consistent with the wide distribution of this coagulant, and the ability to maintain this material in tissue culture provides an opportunity for further investigation of the role of tissue factor in normal and pathologic states.
The In Vitro Restoration of Red Cell 2,3-Diphosphoglycerate Levels in Banked Blood
Authors: OSKI FRANK A. , TRAVIS SUSAN F. , MILLER LEONARD D. , DELIVORIA-PAPADOPOULOS MARIA , CANNON ELIZABETH
Published: October 2019

The demonstration that red cell levels of 2,3-DPG play a central role in determining the affinity of hemoglobin for oxygen has resulted in a renewed interest in methods for maintaining or restoring the level of this organic phosphate in stored blood. The effects of addition of inorganic phosphate, inosine and pyruvate, individually or in various combinations, all in a final concentration of 10 mM were evaluated 1 and 4 hours after supplementation of ACD-stored blood, 21 to 28 days old. In 14 studies the initial 2,3-DPG level averaged 176 mµmoles/ ml. RBC. In normal fresh blood the 2,3-DPG was 4200 ± 400 mµmoles/ml. RBC. Inosine addition raised the 2,3-DPG to 1395, inosine and phosphate to 1528, inosine and pyruvate to 3363, while the combination of inosine, pyruvate and phosphate increased the level to 6637 mµmoles/ml. RBC. After 2-3 hours of incubation most of the 2,3-DPG restoration had occured. The maximum effects did not require prior pH correction of the blood. Although inosine in a final concentration of 10 mM was required for optimum effects, the phosphate and pyruvate concentrations could be reduced to 4 mM. In the presence of inosine and phosphate alone the red cell accumulated large quantities of triose phosphates, fructose diphosphate and glucose-6-phosphate. These levels were reduced by the addition of pyruvate. Pyruvate addition appears necessary to provide sufficient NAD for maximum 2,3-DPG synthesis. Associated with 2,3-DPG restoration of the stored blood there was a rise in the P50 (the oxygen tension at which hemoglobin is 50% saturated) from a mean of 16.7 to 31.6 mm. Hg.
The Transfer RNA Methylases of Human Lymphocytes. II. Delayed Induction by PHA in Lymphocytes From Patients With Chronic Lymphocytic Leukemia
Authors: RIDDICK DAVID H. , GALLO ROBERT C.
Published: October 2019

Treatment of lymphocytes from three patients with chronic lymphocytic leukemia (CLL) with phytohemagglutinin (PHA) resulted in a fivefold increase in transfer RNA (tRNA) methylase activity. Evidence was obtained which suggests that the increase included enzyme species not present prior to the induction. As with normal lymphocytes, the time of induction coincided with the formation of fully transformed PHA cells, which is markedly delayed compared with that occurring in normal lymphocytes stimulated with PHA. Although all three patients had an identical pattern of tRNA methylase induction, initial and induced absolute values were higher in the cells of one patient who had 10 per cent immature peripheral blood lymphocytes. The levels of transfer RNA methylase activity were similar in normal and CLL lymphocytes. These data suggest that PHA induces quantitative and qualitative changes in tRNA methylase enzymes of CLL lymphocytes similar to those previously reported in normal lymphocytes but that the sequence of events of PHA interaction with CLL lymphocytes leading to the subsequent enzyme induction is delayed.
Immunoglobulins Associated With Human Platelets
Authors: MCMILLAN ROBERT , SMITH RICHARD S. , LONGMIRE ROBERT L. , YELENOSKY ROBERT , REID ROBERT T. , CRADDOCK CHARLES G.
Published: October 2019

A technique for the accurate and reproducible quantitation of platelet associated immunoglobulins is described. The intact platelets of normal subjects were found to be associated with small quantities of Ig probably located at or near the platelet surface. Incubation of normal platelets in sera from some patients with immunologic purpura caused an increase in platelet immunoglobulin levels.
The Effect of Preirradiation of Recipient Mice on the Proliferation of Transplanted Hemopoietic Stem Cells
Authors: SHADDUCK RICHARD K. , RICKARD KEVIN A. , HOWARD DONALD E. , STOHLMAN FREDERICK
Published: October 2019

Syngeneic bone marrow was transplanted into recipients either immediately or 2 days after lethal doses of irradiation. In the preirradiated animals, the plating efficiency of 2 per cent was significantly less than the 13-15 per cent observed in animals receiving the bone marrow inoculum immediately after irradiation. It is suggested that the lower plating efficiency reflects a less favorable microenvironment with fewer ecologic niches. Once growth of colony-forming units (CFU) commenced, the growth rate in the preirradiated group was more rapid so that by the eighth day the splenic content of CFU was similar in both groups. Possible mechanisms for the latter are considered and it is suggested that the differentiation in growth rate may be ascribed to regulation of stem cell growth through a short range cell-cell interaction.
Primary Amyloidosis with Plasmacytic Dyscrasia and a Tetramer of Bence Jones Type Lambda Globulin in the Serum and Urine
Authors: PARR D. M. , PRUZANSKI W. , SCOTT J. G. , MILLS D. M.
Published: October 2019

An abnormal protein has been isolated from both the serum and urine of a patient with generalized amyloidosis and plasmacytic dyscrasia. Immunological and biochemical techniques were used to demonstrate that the proteins isolated from each source were identical and were a tetramer of a lambda-type Bence Jones globulin. This appears to be the first reported occurrence of a urinary Bence Jones tetramer. The sedimentation coefficient of the protein was 5.0S, and its molecular weight 79,000. Reduction and alkylation, electrophoresis, and ultracentrifugation showed it to consist of four monomers covalently bonded to form two dimers, which were in turn noncovalently bonded to form the tetramer.
The Life-span of Complement-sensitive and -insensitive Red Cells in Paroxysmal Nocturnal Hemoglobinuria
Authors: ROSSE WENDELL F.
Published: October 2019

The survival of the complement-sensitive and complement-insensitive red cells in four patients with paroxysmal nocturnal hemoglobinuria (PNH) have been determined using either a cohort or a random label. The complement-sensitive cells have a very short survival (T ½) of less than 6 days by either technique). The complement-insensitive cells have a longer survival, with a large component of random destruction. The complement-sensitive cells are not changed into complement-insensitive cells. The proportion of complement-sensitive cells produced per day is very much greater than the proportion of these cells in the circulating blood.
Normal Human Lymphocytes Treated in Vitro With the Sulfhydryl Compound AET: Relationship to the Lymphocytes of Paroxysmal Nocturnal Hemoglobinuria
Authors: SIRCHIA G. , FERRONE S.
Published: October 2019

Because in vitro treatment with the sulfhydryl compound AET is known to alter normal red cells in such a way that they become highly susceptible to the lytic action of complement, an investigation was carried out to evaluate whether the same substance could modify normal lymphocytes in a similar way. The lymphocytes from paroxysmal nocturnal hemoglobinuria were also studied as a comparison. AET lymphocytes appeared to be more sensitive than the same untreated cells to the lytic action of antibody and C, as indicated both by the percentage of stained cells and by the titers displayed by the antisera used in a dye exclusion cytotoxicity test. Two HL-A monospecific antisera that gave false negative results with untreated lymphocytes gave clear-cut positive results with the same cells treated with AET. AET-lymphocytes could be employed for the detection of leukocyte antigens and antibodies.
Factors Affecting the Conversion of Yellow to Red Marrow
Authors: MANIATIS ALICE , TAVASSOLI MEHDI , CROSBY WILLIAM H.
Published: October 2019

The tail vertebrae of the rat contain fatty marrow. The unamputated distal tail was implanted into the peritoneal cavity and disarticulated tail vertebrae were transplanted into the subcutaneous tissue of the abdomen in an effort to study the effect of environmental factors such as temperature and blood flow on the cellularity of the marrow. Transplantation alone increased only slightly the cellularity while the addition of phenylhydrazine treatment increased it greatly. These observations indicate that there is an inherent determinant of the cellularity of marrow in different sites, although this can be modified to a certain extent by environment and by physiologic stimulation.
Experimental Dysfibrinogenemia: In Vivo Studies With Arvin
Authors: RODRIGUEZ-ERDMANN FRANZ , CARPENTER C. B. , GALVANEK E. G.
Published: October 2019

Arvin (a fraction of the venom of the Malayan pit viper Ancistrodon rhodostoma) induces a transitory state of unclottability, during which the fibrinogen cannot be measured by thrombin-dependent methods. However, by immunoelectrophoresis, two main derivatives can be detected. One of these fractions polymerizes upon increasing the ionic strength of the milieu, depicting then a periodicity of 178 A.
Acid Mucopolysaccharides As Cofactor in Formation of Platelet-clumping Substance
Authors: MURASE HIROSHI , IJIRI HAGANO , SHIMAMOTO TATSUO , KOBAYASHI ITSURO , SHIMAMOTO TAKIO , YAMAZAKI HIROH
Published: October 2019

Incubation at 37°C for 30 min or the addition of CaCl2 (5 mM) generated platelet-clumping activity in citrated plasma and EDTA plasma previously acidified to pH 5.5 and in which heparin was added to give a concentration of 0.5 mg/ml. Similar treatment could not produce platelet-clumping activity in saline or denatured plasma that had been heated to 56°C. Heparin, chondroitin sulfate B, or heparan sulfate produced platelet-clumping activity in BaSO4-adsorbed serum over a given pH range. The effective pH range for each compound was; heparin 0.5 mg/ml, pH 5.16 ± 0.09 to 6.31 ± 0.14; chondroitin sulfate B 0.5 mg/ml, pH 5.62 ± 0.09 to 6.88 ± 0.06; 2 mg/ml, pH 5.17 ± 0.16 to 7.18 ± 0.16. The effect of heparan sulfate in generating platelet-clumping activity was estimated only qualitatively at pH 6.0 and proved to be positive. Chondroitin sulfate A, chondroitin sulfate C, and hyaluronic acid failed to yield platelet-clumping activity in BaSO4-adsorbed plasma. The minimal concentrations of heparin and chondroitin sulfate B necessary to induce platelet-clumping activity in the BaSO4-adsorbed serum were 0.5 mg/ml and 0.1 mg/ml, respectively.
Periodicity During Recovery of Immune Response After Cyclophosphamide Treatment
Authors: MANY AMIRA , SCHWARTZ ROBERT S.
Published: October 2019

The recovery of the immune response after a single dose of cyclophosphamide was studied in mice challenged with SRBC. Although the number of splenic antibody-forming cells was normal within 1 wk after the drug was given, it dropped below normal on two subsequent occasions (10 and 24 days after treatment). Disturbance of a feedback loop controlling the production of thymus-dependent lymphocytes was postulated.
The Ontogenesis of Hemoglobins in Macaca nemestrina
Authors: NUTE PETER E. , STAMATOYANNOPOULOS GEORGE
Published: October 2019

Macaca nemestrina have two fetal hemoglobins which differ in the structures of their γ chains. Thus animals of this species, like man, appear to possess duplicate γ-chain loci. In this study, the ontogenesis of hemoglobins in M. nemestrina was followed in animals ranging in age from the 60th day of gestation to adulthood. Fetuses in the 60th day of gestation had the two fetal hemoglobins and a small amount of presumed embryonic hemoglobin. Fetuses between 60 and 132 days’ gestation had only the two fetal hemoglobins. Adult hemoglobin appeared in the last month of gestation. The subsequent transition from γ- to β-chain formation was nearly completed by the end of the second postnatal month. The two fetal hemoglobins were present in 2:1 proportions throughout fetal development and the period spanning the shift from γ- to β-chain formation. The pattern of hemoglobin development in these macaques differs from that in man in the following ways: (1) The relative activities of the two γ-chain loci do not change. (2) α-Chain synthesis is adequate throughout gestation (no γ-chain tetramers were found). (3) The transition from γ- to β-chain synthesis is more abrupt.
In Vitro Induction of Myeloid Proliferation and Maturation in Infantile Genetic Agranulocytosis
Authors: BARAK YIGAL , PARAN MICHAEL , LEVIN STANLEY , SACHS LEO
Published: October 2019

A 3½-yr-old boy with infantile genetic agranulocytosis (IGA) has had recurrent infections since the age of 3 mo. Characteristically he shows permanent, almost complete neutropenia with relative monocytosis in the peripheral blood, together with a bone marrow rich in proliferative myeloid cells, but lacking in mature ones. Results of in vitro cloning of the patient’s bone marrow cells in soft agar indicate that human-spleen-conditioned medium can induce the formation of large granulocyte colonies with normal maturation. The cloning efficiency, colony size, and degree of maturation were no less than in cultures seeded with normal marrow cells. Neither the addition of patient’s serum to normal marrow culture, nor the addition of normal serum to patient’s marrow culture, caused any change in cloning efficiency or degree of maturation. These observations suggest that precursors of granulocytes in cases of IGA are potentially capable of normal proliferation and maturation provided that they are supplied with an inducer such as that derived from human spleen.
Congenital Abnormality of the Prothrombin Molecule (Factor II) in Four Siblings: Prothrombin Barcelona
Authors: JOSSO F. , DE SANCHEZ J. MONASTERIO , LAVERGNE J. M. , MENACHE D. , S0ULIER J. P.
Published: October 2019

A family is described in which four siblings suffer from an unusual hemorrhagic syndrome. In the patient’s plasma, the prothrombin level is only 5% of normal by standard clotting assay and 100% both by staphylocoagulase and immunochemical assays. Results of further investigations in these patients and their family are in favor of a genetic defect of the prothrombin molecule transmitted as a recessive autosomal trait. This abnormal prothrombin is slowly activated by prothrombinase and its electric charge differs from that of normal prothrombin.
X-ray and Alkylating Agents Alter Differentiation of Surviving Hematopoietic Stem Cells
Authors: HELLMAN SAMUEL , GRATE HELEN E.
Published: October 2019

Repopulation assays indicate that erythrocyte differentiation is preferentially impaired in the progeny of progenitor cells surviving radiation or alkylating agents. This was confirmed by study of the iron incorporation into spleen colonies produced by survivors of such treatments. These colonies were characterized by a reduced size and decreased radioactive iron incorporation. Thus, it appears that radiation and alkylating agents not only affect survival of stem cells, but also alter the differentation capacities of such surviving cells.
G6PD Deficiency and Chronic Hemolysis: Four New Mutants—Relationships Between Clinical Syndrome and Enzyme Kinetics
Authors: RATTAZZI MARIO C. , CORASH LAURENCE M. , VAN ZANEN GEORGE E. , JAFFÉ ERNST R. , PIOMELLI SERGIO
Published: October 2019

G6PD deficiency of the common type (GdA- and GdMediterranean) results in extremely mild chronic hemolysis. In contrast, 65 males (from 47 unrelated families) have been reported with a different syndrome of severe chronic hemolysis associated with a superficially similar deficiency in the activity of G6PD. Five new such patients (from four unrelated families) are reported. Biochemical characterization of the erythrocyte G6PD from these patients indicates that these four mutant enzymes are different from each other and from previously reported variants. These new mutants have tentatively been named G6PD New York, G6PD Englewood, G6PD Rotterdam and G6PD Den Haag. The congenital nonspherocytic hemolytic anemias associated with G6PD deficiency appear to be an extremely heterogeneous group from the point of view of biochemical kinetics. The relationships between the clinical syndrome and the various biochemical enzyme characteristics are discussed in the light of the information presently available.
Radioisotopic Assay for Measurement of Serum Folate Levels
Authors: WAXMAN SAMUEL , SCHREIBER CAROL , HERBERT VICTOR
Published: October 2019

A radioisotopic assay is reported that accurately measures an almost identical serum folate to that measured by Lactobacillus casei and can separate low, borderline, and normal folate levels. This assay utilizes a powdered milk available in any grocery. The assay takes less than 4 hr and can be run in unlimited quantity. This radioassay should simplify diagnosis of folate deficiency and be particularly useful in patients receiving antibiotics and folate antagonists, where the microbiological assay gives false low results.
Radioautographic Observations on Iron Absorption by the Normal Mouse Duodenum
Authors: BÉDARD YVAN C. , PINKERTON PETER H. , SIMON GÉRARD T.
Published: October 2019

The uptake of iron by the absorptive cells of the first part of the duodenum of the normal mouse, and the subsequent transfer of iron to the lamina propria, have been studied by radioautography at intervals in the first 24 hr after instillation of 55Fe into the stomach. Two phases of iron absorption are seen during this time. In the first 3 hr, iron is taken up very quickly by the brush border of the absorptive cells; the iron becomes localized mainly in areas rich in rough endoplasmic reticulum and free ribosomes; and there is rapid transfer of iron to the vessels of the lamina propria without evidence of any specific cell acting as a "carrier." The second or slow phase occurs between 3 and 24 hr. The uptake of iron by the absorptive cells and its transfer to the lamina propria appears minimal. During this period the radioactive iron is found mainly close to rough endoplasmic reticulum and free ribosomes and only a relatively small amount is seen over ferritin granules in lysosomes. Significant numbers of spots, representing radioactive iron, have not been observed at any stage over the mitochondria, nuclei, and Golgi zones.
Deoxycytidine Pathway in Separated Normal and Leukemic Leukocytes With Effects of Cell Culture
Authors: RABINOWITZ YALE , FARMER ROBERT , CZEBOTAR VIRGINIA
Published: October 2019

Enzymes of dC metabolism were studied in glass-column-separated normal and leukemic cells. Supernatants of sonicated cells were incubated with dC-3H or dCMP-3H and the end products separated with paper chromatography. Greatest recovery of dCTP, dUMP, and TTP occurred with myeloblasts and monoblasts. Mature granulocytes, and normal and leukemic lymphocytes gave the greatest breakdown to uracil. Myelocytes and lymphoblasts gave intermediate results. Leukemic lymphocytes from different patients varied greatly in their end products, but most did show evidence of TMP synthetase activity contrary to previous reports. Recovery of products of TMP synthetase and, to a lesser extent, dCMP deaminase and dC kinase activities was greatest in cells having or developing a potential for mitosis. CLL-L whose extracts showed appreciable production of dCTP, dUMP, and TdR compounds, however, did not regularly produce blast cells in response to PHA in culture. Cellular extracts of N-L, or CLL-L from cases which responded to PHA did show, on the other hand, a considerable increase in accumulation of these compounds from initial low values during culture.
Primary Acquired Red Cell Hypoplasia Associated With a Clonal Chromosomal Abnormality and Disturbed Erythroid Proliferation
Authors: FITZGERALD PETER H. , HAMER JACK W.
Published: October 2019

A 43-yr-old male patient with primary acquired red cell hypoplasia was studied over a course of 5 yr. Repeated bone marrow examinations showed marrow replacement by an abnormal cell clone characterized by deletion of most of the long arm of a B group chromosome (Bq-). Chromosomes of blood lymphocytes and skin fibroblasts were normal. 55Fe labeling of bone marrow metaphases demonstrated the abnormal chromosome in developing erythroid cells, and it was considered to be present in the common erythroid-myeloid precursor stem cell and its derivatives. Studies of bone marrow cell proliferation using 3H-thymidine autoradiography combined with DNA cytochemistry demonstrated a specific breakdown of erythroid differentiation at the stage of the early polychromatic normoblast. It is suggested that red cell hypoplasia was a function of the abnormal clone that replaced normal erythropoietic stem cells of the bone marrow, but proved to be defective in the metabolism required for red cell production. Such replacement of normal bone marrow tissue, presumably associated with the somatically acquired cytogenetic change, is regarded as a neoplastic though nonmalignant development. The patient died from complications of influenzal pneumonia without evidence of tumor or leukemia.
Paroxysmal Cold Hemoglobinuria: Report of a Case With an Exceptionally High Thermal Range Donath-Landsteiner Antibody
Authors: RIES CURT A. , GARRATTY GEORGE , PETZ LAWRENCE D. , FUDENBERG H. HUGH
Published: October 2019

A patient with idiopathic paroxysmal cold hemoglobinuria had severe hemolytic anemia despite minimal exposure to cold. The patient’s autoantibody demonstrated all the characteristic features of Donath-Landsteiner antibodies, except that strong hemolysis occurred with simple cooling (monophasic hemolysis), as well as with traditional cold-warm incubation (biphasic hemolysis). Monophasic hemolysis was caused by a Donath-Landsteiner antibody of exceptionally high thermal range, which caused red cell sensitization and hemolysis up to 32°C. The patient’s severe hemolytic anemia was probably a result of the high thermal range of the autoantibody, which would allow intravascular hemolysis with even minimal exposure to cold. Corticosteroids had a beneficial effect in controlling hemolysis; however, strict environmental control, with vigorous prophylaxis against even minimal cold, was the most important part of the therapeutic program.
Pure Red Cell Aplasia and Thymoma: Loss of Serum Inhibitor of Erythropoiesis Following Thymectomy
Authors: AL-MONDHIRY HAMID , ZANJANI ESMAIL D. , SPIVACK MORTON , ZALUSKY RALPH , GORDON ALBERT S.
Published: October 2019

A 32-yr-old black female with pure red cell aplasia and thymoma showed complete hematologic remission after thymectomy. Bioassay of preoperative serum and urine in exhypoxic polycythemic mice revealed the presence of significant levels of erythropoiesis-stimulating factor (ESF or erythropoietin). Antierythropoietin completely neutralized the erythropoietic effect of these samples. Utilizing both normal and exhypoxic polycythemic mice, the preoperative serum and urine were also found to contain a potent inhibitor of erythropoiesis. However, no such activity was demonstrated in saline extracts of the tumor tissue. The inhibitor was present in the serum IgG fraction. Serum to which excess ESF had been added, after prior neutralization of endogenous ESF with anti-ESF, failed to stimulate erythropoiesis in the polycythemic mouse.
Radioactive Vitamin B12 Absorption Studies: Comparison of the Whole-Body Retention, Urinary Excretion, and Eight-hour Plasma Levels of Radioactive Vitamin B12
Authors: COTTRALL M. F. , WELLS D. G. , TROTT N. G. , RICHARDSON N. E. G.
Published: October 2019

This paper reports the results of investigations designed to compare the whole-body retention, urinary excretion, and 8-hr plasma level of 58Co vitamin B12 in some 80 absorption tests on 50 subjects. Residual levels of radioactivity in the body were measured using a whole-body counter. A proportional relationship is demonstrated between the 9-day whole-body retention, the 8-hr plasma radioactivity and the 48-hr urinary excretion of vitamin B12. The constants of proportionality are determined, enabling the results of absorption tests carried out by different methods to be compared. The mean values and the range of the results obtained are tabulated for subjects in each of four clinical categories. It is shown that approximately one third of the activity absorbed from a 1-µg dose is excreted in the urine following a single intramuscular injection of 1 mg nonradioactive vitamin B12 at 3 hr. The administration of this flushing dose does not significantly alter the activity absorbed as represented by that retained together with that excreted in the urine. The plasma activity at 8 hr is increased by a factor of about 2 over that obtained without the flushing dose. Factors affecting the accuracy of the individual techniques have been studied and the poor reproducibility of successive tests is discussed.
Platelet Functional Abnormalities: A Report of Two Familial Defects in Interaction Between Collagen and Platelets and ADP Release
Authors: PAPAYANNIS A. G. , WATSON-WILLIAMS E. J. , ISRAËLS M. C. G.
Published: October 2019

Two families have been studied, members of which have a lifelong hemorrhagic diathesis. In both families, a platelet functional abnormality has been found, with the coagulation mechanism intact. Findings common to both families were a prolonged bleeding time, reduced platelet adhesiveness, absence of the second wave of aggregation with ADP and reduced ADP release from platelets. The clot retraction, platelet factor 3 availability and aggregation of platelets with ADP in a final concentration of 1.0 and 20.0 µM were normal. The differences between the families were the platelet morphology, the in vitro adherence of platelets to collagen fibrils, the collagen-induced aggregation, and the thrombin-induced aggregation. In one of them, the Windle family, the platelets were abnormally large in size and showed a delayed adherence to collagen fibrils. The aggregation with collagen was either absent or feeble, and with thrombin, showed an abnormal pattern. In the other, the Hughes family, the platelets were morphologically normal and adhered to collagen fibrils normally. The aggregation with collagen initiated normally but usually did not proceed to completion and the aggregation with thrombin was normal. It appears that in the Windle family the main abnormality concerns the reaction between platelet and collagen and the condition is associated with impaired ADP-release mechanism and abnormal thrombin-platelet reaction, and in the Hughes family the ADP-release mechanism of platelets is defective. On the basis of current information, including that from these families, a classification of the various platelet functional abnormalities and methods for characterizing them is proposed.
Congenital Dyserythropoietic Anemia Type II: Ultrastructural and Radioautographic Studies of Blood and Bone Marrow
Authors: Wong Kwan Yuen , Hug George , Lampkin Beatrice C.
Published: October 2019

A 12-yr-old white girl with congenital dyserythropoietic anemia (CDA) type II was studied. Excessive cytoplasmic membranes (appearing like "double membranes") were found in the majority of the normoblasts. There was marked decrease in the uptake of tritiated thymidine in the binucleated normoblasts as demonstrated by radioautography. The results suggest that the cells with more severe structural cytoplasmic abnormalities and/or decreased DNA synthesis are destroyed within the bone marrow, and the circulating red cells are derived from a less abnormal population of precursors.
Fine Structure of the Red Pulp of the Spleen in Hereditary Spherocytosis
Authors: MOLNAR ZELMA , RAPPAPORT HENRY
Published: October 2019

The spleens from two children and one adult with hereditary spherocytosis were studied in the electron microscope. Stagnation of the erythrocytes within the splenic cords is attributable to their lack of plasticity as evidenced by the absence of bilobed, tailed, or squeezed forms in transit through the walls of the sinuses. In contrast to the sections studied by conventional light microscopy, the splenic sinuses in hereditary spherocytosis were not "empty," but contained red blood cells, the majority of which had lost their hemoglobin content. Cordal macrophages were increased in all three cases and were abundant in the splenic cords of the adult patient, causing a further impediment to the rapid passage of erythrocytes. Macrophages, and, to a lesser degree, sinus endothelial cells contained the products of hemoglobin breakdown. The macrophages showed active erythrophagocytosis. Sinus endothelial cells rarely contained intact red blood cells, but showed pronounced pinocytotic activity, a probable mechanism of hemoglobin incorporation. Platelets within the endothelial cells of the sinuses were much more frequently seen in the three cases of hereditary spherocytosis than in control spleens. The presence of ferritin in platelets suggests that they too may play a role in clearing the end products of hemolysis from the spleen.
IgA Pyroglobulin, Hyperviscosity Syndrome and Coagulation Abnormality in a Patient With Multiple Myeloma
Authors: Sugai Susumu
Published: October 2019

A 48-yr-old woman with a bleeding diathesis and complaining of blurred vision, headache, paresthesias, and vomoting was diagnosed as having IgA, kappa type multiple myeloma. Markedly increaesed serum viscosity was noted. After plasmapheresis the signs and symptoms of high serum viscosity disappeared. Pyroglobulin was found in the M protein. The M protein had a prominent 15.5S peak and smaller 17.0 and 20S peaks, which decreased to a 6.7S peak after in vitro reduction with 0.1 M 2-mearcptoethanol, 2-mercaptoethylamine hydrochloride, or glutathione. The serum viscosity was decreased by treatment with these reducing agents. Pyroglobulin formation was presumably a noncovalent intermolecular reaction, as it was inhibited by 5.0 M guanidine hydrochloride, acidification and alkalinization, but not by reduction with sulfhydryl reagents. The M protein also had an antithrombin activity causing interference with the conversion of fibrinogen to fibrin and the phenomenon of gelification noted on blood clotting.
Hemopoiesis in Pituitary Dwarfs Treated With Human Growth Hormone and Testosterone
Authors: Jepson J. H. , McGarry E. E.
Published: October 2019

Prepubertal hypopituitary dwarfs are anemic and have reduced levels of erythropoietin-stimulating factor (ESF) in the urine. Treatment with human growth hormone (HGH) in doses sufficient to produce linear growth and weight gain induces bone marrow lymphocytosis, increased erythropoiesis indicated by an increase of the red cell mass (RCM) and improved iron kinetic studies. This was associated with increased concentrations of ESF in the urine, increased transferrin levels, and expansion of the plasma volume. The combination of testosterone and HGH increased further erythropoiesis but could not be specifically ascribed to testosterone, since the continued action of HGH could be responsible for the observed effects. The excretion of ESF was not increased further. Testosterone did, however, maintain ESF excretion on deletion of HGH from the regimen, suggesting at least one common mode of action for these hormones in the hypoanabolic subject. In contrast, testosterone failed to maintain the plasma volume increase induced by HGH and did not further effect the observed bone marrow lymphocytosis.
Serum Requirement for Apoferritin Induction in Rat Liver Slices
Authors: Smith Lester , Fineberg R. A.
Published: October 2019

In studies of ferritin induction, liver slices failed to respond favorably to iron added directly to the suspending medium unless serum was added. The addition of 5 µg Fe/ml to slices in whole serum accelerated the incorporation of radioleucine into ferritin 2.5-fold. The favorable effect of serum on iron-induced ferritin synthesis was correlated with its attenuation of the toxic effects of the iron on protein synthesis; the serum was also found to diminish the uptake of iron by the liver cells. Transferrin, purified from the serum by ion exchange, failed to mediate the iron induction of apoferritin while albumin, completely freed from transferrin as monitored with radioiron, was effective. Albumin, apparently by limiting the uptake of excess iron by the liver cells, modulates the nonspecific toxic effects of iron on protein synthesis and thereby permits the specific induction by iron of the biosynthesis of apoferritin.
Identification of the Bone Marrow Colony Mononuclear Phagocyte as a Macrophage
Authors: Cline Martin J. , Warner Noel L. , Metcalf Donald
Published: October 2019

Bone marrow colony-derived mononuclear phagocytes are macrophages on the basis of morphology, glass adherence, the phagocytosis of a range of particles including erythrocytes, yeast, and bacteria, and the possession of receptors for IgG of predominantly IgG2a specificity.
IgE Multiple Myeloma: A Report of the Third Case
Authors: Fishkin Ben G. , Orloff Natalie , Scaduto Louis E. , Borucki David T. , Spiegelberg Hans L.
Published: October 2019

The third known case of IgE multiple myeloma is described. The patient was a 65-yr-old woman who died 11 mo after a diagnosis of multiple myeloma was made by a surgical biopsy of the left iliac crest. Her serum contained approximately 2.7 g/100 ml of a paraprotein of mid-γ mobility. The isolated anomalous protein gave a reaction of identity with the IgE myeloma protein of the second reported case when reacted with a specific IgE antiserum. The light-chain type of the myeloma protein was κ in contrast to λ of the other two IgE myeloma proteins. Her clinical manifestations differed from the two previously reported cases in several respects. She had neither plasma cell leukemia nor overt Bence Jones proteinuria and developed rapidly progressive widespread osteosclerotic lesions that were associated with bone pain.
Possible Thrombosthenin Defect in Glanzmann’s Thrombasthenia
Authors: Booyse Francois , Kisieleski Donna , Seeler Ruth , Rafelson Max
Published: October 2019

Microquantitation of thrombosthenin by single radial immunodiffusion in conjunction with a specific immunohistochemical antibody staining technique has indicated an immunologic defect or absence of the surface-localized thrombosthenin (S-thrombosthenin) in platelets from Glanzmann’s thrombasthenic patients. In addition, ADP- and ATP-induced changes of the surface of normal platelets could not be demonstrated with Glanzmann’s thrombasthenic platelets.
Immunologic Studies of Antihemophilic Factor (AHF, Factor VIII). III. Comparative Binding Properties of Human and Rabbit Anti-AHF
Authors: Hoyer Leon W.
Published: October 2019

The binding properties of human and rabbit antibodies to antihemophilic factor (AHF, factor VIII) have been compared in experiments that sought the basis for their different specificities and secondary properties. Agarose gel filtration demonstrated the formation of stable complexes of AHF with rabbit anti-AHF but not with human anti-AHF. Measurement of bound radiolabeled rabbit anti-AHF provides a very sensitive assay for the AHF antigen that is present in normal and hemophilic plasmas but that is markedly reduced in plasmas from patients with von Willebrand’s disease.
Porphyrin Synthesis by Cultured Lymphocytes
Authors: Josephson Alan S. , Levere Richard D. , Lowenthal Ivan , Swerdlow Fred , Ginsberg Mark
Published: October 2019

Peripheral lymphocytes were cultured in the presence and absence of phytohemagglutinin (PHA). Porphyrin synthesis was visually estimated by fluorescence and quantitated by fluorometry. No visual fluorescence was noted in cells cultured with or without PHA. Addition of δ-aminolevulinic acid (ALA) to cultures of either transformed or nontransformed lymphocytes resulted in fluorescence, indicating porphyrin synthesis. Certain sex steroid metabolites stimulate porphyrin synthesis by induction of the rate-limiting enzyme ALA synthetase. Erythropoietin also increases the rate of heme synthesis. Phytohemagglutinin-transformed and nontransformed cells were cultured with the addition of either 11-keto pregnanolone or erythropoietin, and neither agent induced porphyrin synthesis. Only when ALA was added to the culture medium was the measured fluorescence statistically greater than in control cultures. These studies indicate that the enzymes of porphyrin synthesis distal to ALA synthetase, the rate-limiting enzyme, are present in all cultured lymphocytes. The rate-limiting enzyme is not induced by PHA transformation, even in the presence of a 5-β-H steroid metabolite or erythropoietin.
Ultrastructural Studies in Acute Promyelocytic Leukemia
Authors: Tan Henry K. , Wages Bettye , Gralnick Harvey R.
Published: October 2019

In this investigation, the cells of eight patients with acute promyelocytic leukemia were followed by light and electron microscopy. Promyelocytes from untreated patients were filled with large, splinter-shaped granules. The granules were lysosomes, with some showing the ultrastructural features of Auer bodies. In cases responsive to chemotherapy, promyelocytes contained only infrequently splinter-shaped lysosomes, while most lysosomes were of more uniform size and shape. The persistence of large numbers of splinter-shaped lysosomes within promyelocytes was associated with episodes of disseminated intravascular coagulation less responsive to heparin treatment. Promyelocytes from patients in remission were similar to promyeloctyes from nonleukemic bone marrow. The ultrastructural differences in lysosome morphology provide a better criterion for distinguishing malignant from normal promyelocytes than previously detectable by light microscopy alone.
Studies on Human Erythrocyte Nucleotide Metabolism. II. Nonspherocytic Hemolytic Anemia, High Red Cell ATP, and Ribosephosphate Pyrophosphokinase (RPK, E.C. 2.7.6.1) Deficiency
Authors: Valentine William N. , Anderson Helen M. , Paglia Donald E. , Jaffé Ernst R. , Konrad Patricia N. , Harris Susan R. , Kürschner Klaus K.
Published: October 2019

A 29-yr-old black woman was found to have a long-standing, nonspherocytic hemolytic disorder associated with a marked reduction in the activity of erythrocyte ribosephosphate pyrophosphokinase (RPK, PRPP synthetase, E.C. 2.7.6.1). Although the patient’s erythrocytes had about 50% of the average RPK activity of normal mature human erythrocytes, this level represented only about 20-30% of the activity in comparable reticulocyte-rich blood samples from patients with other types of hemolytic anemias. The concentrations of adenosine triphosphate adenosine diphosphate, adenosine monophosphate and, therefore, of total adenine nucleotides in her erythrocytes were markedly increased, even well above the levels in extracts of comparable reticulocyte-rich blood samples. ATPase activity was increased three- to fourfold, consistent with the reticulocytosis. Adenylate kinase and adenine phosphoribosyltransferase activities were normal. The activities of all enzymes of the Embden-Meyerhof and hexose monophosphate shunt pathways and enzymes related to glutathione metabolism were normal or increased, consistent with the reticulocytosis. The concentrations of glycolytic intermediates, other than adenine nucleotides, were normal. The conversion of glucose, adenosine, and inosine to lactate was normal or increased. Autohemolysis was of the Dacie Type II. The concentrations of erythrocyte-reduced glutathione were high normal or elevated. The stained blood film showed a striking degree of basophilic stippling of the erythrocytes. Studies of the erythrocytes of the patient’s only known relative, a son, have failed to reveal any hematologic or enzymatic abnormalities. A direct causal relationship between RPK deficiency, high ATP concentrations, and nonspherocytic hemolytic anemia could not be derived from data now available. The final decision as to whether the deficiency is primary and causative or is an epiphenomenon requires investigation of additional cases.
Hemoglobins in Human Fetuses: Evidence for Adult Hemoglobin Production After the 11th Gestational Week
Authors: Pataryas Haris A. , Stamatoyannopoulos George
Published: October 2019

Hemoglobin patterns were examined in human fetuses in order to determine the onset of synthesis of adult hemoglobin in fetal red cells. In fetuses younger than 11 gestational wk, hemoglobin A could not be detected with electrophoretic techniques. A small amount of adult hemoblobin was constantly present, however, in hemolysates from fetuses older than 11 gestational wk, and it had the structural properties of adult hemoglobin A. Heterozygous fetuses had hemoglobins C and A or S and A as early as the 11th and 13th gestational wk. The findings are compatible with onset of beta hemoglobin gene action as early as the 11th gestational wk and synthesis of approximately 5% of adult hemoglobin by the end of the first and throughout the second trimester of gestation.
Studies of the Hemopoietic Microenvironment. I. Changes in the Microvascular System and Stroma During Erythropoietic Regeneration and Suppression in the Spleens of CF1 Mice
Authors: McCuskey Robert S. , Meineke Howard A. , Townsend Samuel F.
Published: October 2019

Specific alterations in the microvascular and connective tissue compartments of the hemopoietic microenvironment have been examined during erythropoietic regeneration and suppression in the murine spleen and bone marrow using in vivo microscopic and histochemical methods. The results have confirmed the concept of specific hemopoietic microenvironments and have demonstrated specific alterations in the microenvironment during erythropoietic stimulation and repression. Elevated erythropoiesis in the splenic red pulp is accompanied by an elevation in blood flow through the microvascular system. Both the linear velocity of flow and the number of sinusoids with blood flow in them increased significantly. In contrast, erythropoietic repression was accompanied by a decreased linear velocity of blood flow, as well as a marked increase in the amount of blood being stored in the splenic sinusoids. This also was the picture when diffuse granulopoiesis was present in the red pulp, or when granuloid or undifferentiated colonies were present. The chemical composition of the stroma in the spleen and bone marrow also varied during states of hemopoietic activity and, in addition, there were differences in the composition of the stroma between these two organs. In both organs, foci of early proliferating cells were enveloped by a coating of sulfated acid mucopolysaccharide. This coat persisted on cells in later stages of granulopoiesis but not on cells in the later stages of erythropoiesis. The latter were enveloped with a coating of neutral mucopolysaccharide. A tentative hypothesis to explain the mechanisms involved in producing these changes is discussed.
Studies of the Hemopoietic Microenvironment. II. Effect of Erythropoietin on the Splenic Microvasculature of Polycythemic CF1 Mice
Authors: McCuskey Robert S. , Meineke Howard A. , Kaplan Stephen M.
Published: October 2019

The effect of erythropoietin on the splenic microvascular system of polycythemic CF1 mice was studied using in vivo microscopic methods. Administration of a single dose (3 U) of erythropoietin resulted in an increase in the linear velocity of blood flow through the splenic sinusoids and a reduction in the number of sinusoids storing blood. This response was first seen 4-6 hr after injection; it persisted for 48 hr and was reduced markedly by 72 hr. By 120 hr the spleens were indistinguishable from controls. The response was specific for erythrogenic tissue, since no response was seen in the adjacent nonerythropoietic pancreatic tissue. The results suggest that the splenic microvascular response to erythropoietin may be indirect and may be mediated by the release of a vasoactive metabolite from the erythrogenic tissues surrounding the sinusoids. Erythropoietin-sensitive stem cells are suggested to be the source of such a metabolite.
Embryonic Origin of the Mouse Macrophage
Authors: Cline M. J. , Moore M. A. S.
Published: October 2019

Progenitor cells capable of giving rise to functional macrophages in in vitro culture were first detectable in the fetal yolk sac of the mouse between day 7 and 8 of gestation. Macrophage progenitors were not detectable outside the yolk sac until day 11. Although the early yolk sac contained macrophage precursors, no cells with the morphologic or functional characteristics of mouse promonocytes or more mature macrophages were observed. Promonocytes and macrophages were first identified in the 10-day yolk sac and 11-day fetal liver. These cells were characterized by surface receptors for IgG immunoglobulin, peroxidase activity (promonocytes), glass adherence, and phagocytosis of a large yeast particle (macrophages). From these observations, we conclude that the early fetal yolk sac is the embryonic site of origin of the macrophage precursor and that this precursor is "proximal" to the promonocyte on the pathway of sequential macrophage maturation.
Lymphocytotoxins and Pernicious Anemia
Authors: Goldberg Leonard S. , Cunningham Jo Ellen , Terasaki Paul I.
Published: October 2019

Sera from 60 patients with pernicious anemia were studied for the presence of lymphocytotoxins (LCT), blocking and binding autoantibodies to intrinsic factor, and gastric parietal cell autoantibody. LCT were found in 21 sera. Cytotoxic activity was detected at 15°C but not at 24°C and did not appear to have HL-A specificity. Autocytotoxins were present in four of eight patients tested. Blocking antibody to intrinsic factor was found in 34 sera, binding antibody in 14 sera, and parietal cell antibody in 48 sera. Sera from 14 patients contained all three types of autoantibodies, and 12 sera were void of these autoantibodies. Of the 14 sera with three types of autoantibodies, LCT were detected in ten; none of the 12 sera without autoantibodies showed cytotoxic activity. These studies suggest that LCT may reflect the degree of autoimmune derangement in pernicious anemia; alternatively, LCT may represent naturally occurring immunosuppressants.