bluuebunny/crossref_metadata_2025 huggingface dataset:
THE USE OF EXCHANGE TRANSFUSION FOR THE TREATMENT OF SEVERE ERYTHROBLASTOSIS DUE TO A-B SENSITIZATION, WITH OBSERVATIONS ON THE PATHOGENESIS OF THE DISEASE
Authors: WIENER A. S. , WEXLER I. B. , HURST J. G.
Published: October 2019

Two unusual cases of severe erythroblastosis due to A and B sensitization have been presented. When injections of A and B group substances failed to arrest the disease, exchange transfusions were carried out, using 900 to 1,000 cc. of fresh group O blood. In each case the response was prompt and dramatic, although the convalescence in one was prolonged by an intercurrent diarrhea. Both infants have made complete recoveries and have developed normally both physically and mentally.

Observations have been presented regarding the pathogenesis of erythroblastosis and icterus precox due to A-B sensitization. The following conclusions seem to be warranted on the basis of the evidence presented:

1. The greatest majority of cases of jaundice and anemia of the newborn that cannot be explained on the basis of Rh incompatibility are caused by incompatibility of the major blood groups.

2. High maternal alpha and beta antibody titers per se are not necessarily correlated with disease in the infant.

3. Univalent alpha and beta antibodies present in the maternal serum traverse the placenta and are the cause of the disease in the infant. Bivalent antibodies are held back by the intact placenta and play no or hardly any role in the causation of the disease. Univalent alpha and beta antibodies are demonstrable in the sera of a large proportion of "normal" individuals.

4. A-B sensitization in pregnancy occurs mainly when the infant belongs to the secretor type.

5. A theory is suggested that the quality of the alpha and beta antibodies, namely, whether they are homospecific or heterospecific, may affect the severity of the manifestations in the infant.

Technics of titrating alpha and beta and Rh antibodies are described and discussed. A table has been prepared which converts antibody titers into concentrations of immune globulin in the serum, and demonstrates the impossibility of certain extravagantly high titers claimed in the literature.
MULTIPLE MYELOMA AS A FORM OF LEUKEMIA
Authors: RUBINSTEIN MICHAEL A.
Published: October 2019

The conventional points in the differential diagnosis between myeloma and leukemia have been discussed. Evidence has been brought to show that these points of distinction cannot be regarded as being of fundamental nature. Instances are abstracted where cases of multiple myeloma show the various characteristics of leukemia and vice versa.

1. Leukemic features in myeloma have been shown in:

a. diffuse infiltration in multiple myeloma without circumscribed tumor formation and without any gross bone destruction;

b. extraskeletal visceral myelomatous spread involving the kidney, spleen, lymph nodes, etc.;

c. invasion of peripheral blood in myeloma—occasional myeloma cells (corresponding to the aleukemic forms of leukemia) may frequently be found in concentrated smears, even though they may be missed on routine examination; however, massive invasion of peripheral blood is rare;

d. increased uric acid content of the blood and elevated basal metabolism, characteristic of leukemia, frequently seen also in myeloma;

e. occurrence of myeloma in youth;

f. symptomatology of multiple myeloma at times not referable to the osseous system.

2. Myeloma features in leukemia have been shown in:

a. skeletal involvement in leukemia;

b. very rare medullary forms of leukemia (without visceral involvement);

c. occurrence of Bence-Jones proteinuria or

d. hyperproteinemia with hyperglobulinemia in rare cases of leukemia;

e. instances when the symptomatology of leukemia was referable to the osseous system.

3. Coexistence of multiple myeloma and leukemia is reviewed from the literature, and a case is reported of extensive mixed lymphocytic and plasma cell infiltration.

In conclusion, the difference between myeloma and leukemia, as far as the listed conventional distinguishing features are concerned, is merely one of incidence: what is rare in one disease, is common in the other, and vice versa. Multiple myeloma is in all probability a leukemia of plasma cells.
Erythrocyte Protoporphyrin
Authors: Langer E. E. , Haining R. G. , Labbe R. F. , Jacobs P. , Crosby E. F. , Finch C. A.
Published: October 2019

Blood protoporphyrin (PROTO) concentration in man and animals has been studied as a possible means of assessing the relationship between iron supply and marrow requirements. There appear to be two fractions of PROTO: one at a level of about 30 µg/ 100 ml unrelated to either iron supply or cell age, and a second fraction that appears when iron supply is limited and that has an elution T½ of 2-4 wk. Animal studies have demonstrated that increased erythropoiesis and reticulocytosis per se do not change PROTO, providing that there is an adequate (increased) plasma iron level. In phlebotomized man, within 1 or 2 wk following a decrease in plasma iron saturation to less than 15%, the PROTO levels become significantly elevated. In more chronic disease states associated with near normal rates of erythropoiesis, a transferrin saturation less than 15% is usually associated with increased PROTO. In patients with hemolytic anemia, the PROTO level rises even though plasma iron and per cent saturation values are higher. Evidence is presented suggesting that both the extent of marrow proliferation and erythropoietin stimulation may affect the PROTO response. The red cell PROTO concentration is an important parameter for assessing iron-deficient erythropoiesis, either relative or absolute. The usefulness of this parameter is compared with red cell indices, plasma iron, and transferrin saturation data.
The Metabolic Significance of Reduced Serum B12 in Folate Deficiency
Authors: Van Der Weyden Martin B. , Rother Mary , Firkin Barry G.
Published: October 2019

The depressed serum B12 levels accompanying folate deficiency generally increase following folic acid therapy, and this phenomenon is cited as evidence that true B12 deficiency did not preexist in such instances. In this study, the metabolic significance of reduced serum B12 levels complicating folate deficiency was determined in bone marrow cultures by evaluation of abnormal incorporation of deoxyuridine into DNA-thymine, a defect characteristic of megaloblastic maturation due to folate or B12 deficiency. In in vitro marrow cultures of seven patients with folate deficiency and normal serum B12 levels, added B12 resulted in no change in the depressed incorporation of deoxyuridine into DNA-thymine, with complete correction of the defect by added folate. However, in marrow cultures of five patients with folate deficiency and depressed serum B12 levels, added B12 produced a partial correction of the defective deoxyuridine incorporation, with complete correction by added folate. In vivo pharmacologic doses of B12 in a patient with folate deficiency, but normal serum B12 levels, resulted in no alteration in the degree of morphologic megaloblastic maturation or the abnormal deoxyuridine incorporation into DNA-thymine. In contrast, in a patient with both B12 and folate deficiency, B12 therapy resulted in partial correction of the abnormal deoxyuridine incorporation into DNA-thymine. with simultaneous reduction in the degree of morphologic megaloblastic maturation. However, abnormal deoxyuridine incorporation into thymine-DNA, consequent to folate deficiency, persisted. Similar findings were obtained in a patient with folate deficiency and associated reduced serum B12. It is suggested that the depressed serum B12 in patients with folate deficiency represents a true deficiency for hemopoietic tissue and contributes to the megaloblastic maturation by its effect on folate metabolism.
Augmentation of Leukemic Lymphocyte Reactivity to Phytohemagglutinin by Salivary Receptor
Authors: Brody Jerome I.
Published: October 2019

This study demonstrates that the deficiency of phytohemagglutinin (PHA) receptors recently shown to be present on the leukemic lymphocyte may be ameliorated by incubating these cells with a biologically analogous material obtained from human saliva. This manuever, performed under controlled, standardized conditions, doubled the capacity of leukemic lymphocytes to incorporate 14C-thymidine during stimulation with phytohemagglutinin in cell culture. The present experiments serve as a prototype for possible in vivo modification of the leukemic lymphocyte surface to make this cell amenable to immunogenic stimuli and potentially more susceptible to chemotherapeutic agents.
Anatomy of Red Cell Damage by Plasmodium falciparum in Man
Authors: Balcerzak Stanley P. , Arnold John D. , Martin Daniel C.
Published: October 2019

The manner in which the malarial parasite, Plasmodium falciparum, invades and destroys human red cells is uncertain. Surface and internal anatomy of erythrocytes from subjects with parasitemia was examined in an effort to understand this process better. P. falciparum causes marked distortion of the surface of red cells. In parasitized cells, the bulk of the organism lies under a smooth erythrocyte exterior, but part of it is often associated with a highly irregular red cell surface defect. Many cells without parasites have cavitary surface defects. Their appearance suggests that they previously may have contained parasites. These morphologic observations offer possible explanations for premature destruction of parasitized as well as nonparasitized red cells.
Size Dependence of Ghosts From Stored Erythrocytes on Calcium and Adenosine Triphosphate
Authors: Palek Jiri , Curby William A. , Lionetti Fabian J.
Published: October 2019

Heterogeneity within ghosts prepared from stored erythrocytes was studied by multichannel particle analysis of size distributions of reconstituted ghosts. On restoration of isotonicity of hemolysates from fresh erythrocytes, ghosts were smaller than the corresponding red cells. After subsequent incubation for 15 min, they swelled to a final stable volume. The hemolysis of stored erythrocytes and restoration of isotonicity yielded ghosts similar to those from fresh cells, but, after subsequent incubation, a second population of small ghosts appeared. This population resulted from markedly diminished ghost swelling, that is attributed to decreased sodium permeability and increased membrane rigidity, causing resistance to changes in volume. Erythrocyte ATP depletion during storage of ACD blood was associated with an increase in the percentage of small ghosts. Similar ghosts were produced from fresh cells when CaCl2 (1 x 10-6M) was introduced into ghosts during hemolysis. The erythrocyte calcium content increased during prolonged storage from 11.3 ± 6.3 µg atoms/liter of cells (stored for 1-2 wk) to 22.0 ± 7.0 µg atoms/liter of cells, after 7-9 wk of storage. The introduction of nucleotides (2 x 10-3M) into ghosts during hemolysis of stored cells prevented the appearance of small ghosts. The inhibitory effect was greater than predicted from stability constants of calcium nucleotide complexes, indicating the specific interaction of nucleotides with the membrane. The percentage of small ghosts from red cells stored for various times agreed with the percentage of nonviable cells derived from the literature. It is concluded that the decrease in ATP and the accumulation of calcium in stored erythrocytes induce conformational changes of membrane fibrous (contractile) proteins that results in decreases in membrane elasticity and permeability, which is in turn reflected by formation of small ghosts.
Increased Proportion of Complement-Receptor Lymphocytes in the Peripheral Blood of Patients With Chronic Lymphocytic Leukemia
Authors: Pincus Seth , Bianco Celso , Nussenzweig Victor
Published: October 2019

In the present study we present evidence that the proportion of complement-receptor lymphocytes (CRL) is greatly increased in the circulation in most cases of chronic lymphocytic leukemia (CLL). Lymphocytes (> 99% pure, 70% recovery) were obtained from the peripheral blood of normal individuals by separation of the mononuclear cells from the leukocyte-enriched plasma by differential flotation in Hypaque-Ficoll and incubation of the mononuclear cells with iron-containing particles followed by removal of the phagocytes with a magnet. Complement - receptor lymphocytes were detected by incubating lymphocytes with sheep erythrocytes coated with antibody and mouse complement (EAC) and counting the EAC—CRL rosettes under the microscope. 7.1 ± 3.8% of normal peripheral blood lymphocytes, 31.0 ± 6.9% of lymph node, and 59.6 ± 13.2% of tonsil lymphocytes bind EAC. The binding was C3-dependent since it could be inhibited specifically by papain fragments of rabbit antibodies to mouse C3. Among lymphocytes from the peripheral blood of patients with CLL, 50.7 ± 25.0% bear the complement receptor. These results suggest that CLL preferentially affects B cells.
The Effect of Postirradiation Bleeding or Endotoxin on Proliferation and Differentiation of Hematopoietic Stem Cells
Authors: Boggs Sallie S. , Chervenick Paul A. , Boggs Dane R.
Published: October 2019

Bleeding after irradiation failed to affect the time of onset or rate of regeneration of the hematopoietic stem cell compartment as measured by a split-dose irradiation method. Bleeding after a single 600 rad exposure hastened the time of onset of erythropoiesis as measured by spleen colonies and 59Fe uptake, but the early rise was abortive and the second increase began at the same time as the first increase seen in irradiated controls. The largest abortive increase was seen when bleeding occurred within 4 hr of irradiation. Lesser effects were seen when bleeding occurred 12 or 24 hr after and no effect 48 hr after irradiation. A generation time of 6.4 hr for a colony-forming cell that forms a colony in 4 days was calculated from the estimated number of cells in one such colony. Injection of cytosine arabinoside at the time of bleeding reduced colony numbers and 59Fe uptake equally in bled and control mice. Injection of 25 µg Salmonella typhosa endotoxin just after irradiation produced a similar early abortive rise in microscopic granulocytic colonies. These results are compatible with a model for pluripotential stem cell compartment in which: (1) differentiation and self-replication occur concomitantly unless the compartment is reduced below approximately 1O% of normal size; then self-replication occurs without appreciable differentiation; (2) for a short time (∼ 24 hr) after depletion below the threshold, differentiation can occur in response to strong stimuli.
Distinctions Between Idiopathic Ineffective Erythropoiesis and di Guglielmo’s Disease: Clinical and Biochemical Differences
Authors: Eastman Philip M. , Schwartz Richard , Schrier Stanley L.
Published: October 2019

While idiopathic ineffective erythropoiesis (IIE) and di Guglielmo’s disease (DD) are both characterized by intramedullary hemolysis, they can be distinguished clinically and biochemically. Twelve patients with IIE had normal platelet counts and morphologically normal myelopoiesis. Three patients with DD presented with pancytopenia and marrow myeloid immaturity. Conversion to acute myeloid leukemia occurred in the three DD patients but did not occur in the 12 IIE patients, who had a mean duration of anemia of 10.7 yr. Hemoglobin synthesis was well preserved in two DD patients, while six IIE patients had significant defects of both heme and globin synthesis. Defective heme synthesis in IIE could not be attributed to a defect of the heme synthetic enzyme δ-aminolevulinic acid (ALA) synthetase. The nature of the heme and globin synthesis defects in IIE remains unclear but may reflect a more fundamental abnormality of cell maturation or cell division in this disorder.
Survey of Staff Positions in Academic Hematology in 1971
Authors: Ranney Helen M. , Kinyon Louis , Sultz Harry A.
Published: October 2019

A minimal estimate of the number of positions in academic hematology in the United States was 1159 of which 10% were unfilled in the fall of 1971. Exclusive of positions in federal institutions (Veterans Administration and military hospitals), 72% of the salary support for filled positions was derived from "hard money", and similar nogrant sources were available for the support of 74% of the salaries for unfilled positions. Private institutions had slightly less "hard money" salary support than did public institutions. A probable maximum of one-third of the positions now supported by grants would be supported by "hard money" were grant support to terminate.

The numbers of positions in academic hematology tripled in the 11 yr from 1960 to 1971. Because of the staffing needs for new medical schools, and the expansion of classes in existing medical schools as well as the need for physician-scientists in the developing programs in oncology and sickle cell disease, the growth of hematology will probably continue, albeit at a slower rate.

Academic hematologists’ research interests were divided among several areas. The primary interests of the largest numbers of researchers were oncology, red blood cells, hemostasis and coagulation, and immunohematology. Attention was directed to the rather small numbers of academic hematologists with research interests in blood banking, clinical laboratories, and nutrition. It is not clear whether efficient development of larger programs in oncology and sickle cell disease will require more academic hematologists with experience in these areas than are now available.

These data do not provide information about the overall national needs for hematologists in service laboratories in nonacademic institutions or in the delivery of health care. Nor do they provide the basis for any recommendations about the size or composition of divisions of hematology in medical schools. They do provide the first overall appraisal of the size, funding, and research areas in academic hematology in this country.
Red Cell 2,3-Diphosphoglycerate and Intracellular Arterial pH in Acidosis and Alkalosis
Authors: Desforges Jane F. , Slawsky Philip
Published: October 2019

With the use of 14C-DMO (14C-5, 5-dimethyl-2,3-oxazolidinedione), a weak organic acid, we measured the intraerythrocytic hydrogen ion concentration in 16 acidotic and alkalotic patients. Whole blood pH, red cell 2,3-diphosphoglycerate, hemoglobin, oxyhemoglobin, plasma pCO2, and plasma bicarbonate were measured simultaneously on heparinized arterial blood. The results show: (1) hydrogen ion concentration in the red cell varies directly with that of whole blood, (2) red cell concentration of 2,3-diphosphoglycerate varies inversely with the whole blood hydrogen ion concentration, and (3) red cell 2,3-diphosphoglycerate concentration also varies inversely with the intracellular hydrogen ion concentration. There were no significant relationships between the arterial total hemoglobin or oxyhemoglobin and intracellular or whole blood pH, nor was there any relationship between plasma pCO2 or plasma bicarbonate and intracellular or whole blood pH. We concluded that in a number of clinical conditions in which the hydrogen ion concentration is altered, the cellular pH parallels that of the whole blood and that the 2,3-diphosphoglycerate concentration varies with the hydrogen ion concentration.
Hemoglobin and Erythrocyte Catabolism in Rat Liver: The Separate Roles of Parenchymal and Sinusoidal Cells
Authors: Bissell D. Montgomery , Hammaker Lydia , Schmid Rudi
Published: October 2019

The liver participates in the removal from the circulation of both damaged red blood cells (RBC) and plasma hemoglobin. The specific hepatic cell types involved in these processes have been identified by fractionation of rat liver into pure isolates of parenchymal and sinusoidal cells. After injection of 59Fe-labeled hemoglobin, 85%-95% of the radioactivity in the liver was associated with the parenchymal cells, regardless of whether the hemoglobin was bound to haptoglobin or was free in plasma. By contrast, 59Fe-labeled spherocytic RBC were sequestered entirely by the sinusoidal cell population. Stimulation of microsomal heme oxygenase by administered hemoglobin or RBC indicated that these cell fractions not only sequester but also degrade the ingested hemoglobin-heme. Infusion of doubly labeled 59Fe, 125-I-hemoglobin indicated that the hepatic parenchymal cells remove the intact hemoglobin molecule without exchange or transfer of the heme moiety to other carrier proteins. By contrast, heme bound to albumin was detached from the albumin before its uptake by the parenchymal cells. These findings suggest that, contrary to previous belief, hepatic parenchymal cells play a key role in the metabolism of plasma hemoglobin.
Hemoglobin Biosynthesis in Murine Virus-induced Leukemic Cells In Vitro: Structure and Amounts of Globin Chains Produced
Authors: Boyer Samuel H. , Wuu Kuang Dong , Noyes Andrea N. , Young Rondall , Scher William , Friend Charlotte , Preisler Harvey D. , Bank Arthur
Published: October 2019

Tryptic peptides characteristic of mouse hemoglobin α- and diffuse-type β-chains were isolated from dimethylsulfoxide-treated mouse leukemia virus-infected cell cultures. Quantitative estimates of in vitro hemoglobin synthesis by such cultures were obtained by two different methods: by analysis of radioactive amino acid incorporation, and by single-cell radial immunodiffusion assay. The amounts produced, approximately 4 pg/cell/17 hr, reflect a synthetic capacity that is probably sufficient for 32P labeling of hemoglobin messenger RNAs (mRNA) in quantities commensurate with structural characterization of mRNAs by radioautographic methods.
Leukofibrinolysis
Authors: Lewis Jessica H. , Szeto Isabel L. F. , Bayer William L. , Curiel Dario C.
Published: October 2019

Glycogen-stimulated dog peritoneal leukocytes phagocytize particulate fibrin in a manner similar to that described for phagocytosis of bacteria. After phagocytosis the fibrin is solubilized, and degradation products, called here MISFI (molecules immunologically similar to fibrinogen), are released into the surrounding media. Whole, viable leukocytes are necessary; disrupted cells have little or no activity. This process of leukocytic ingestion and digestion of fibrin is called leukofibrinolysis. It is inhibited by many of the same substances that inhibit fibrinolysis. Serum, a potent fibrinolytic inhibitor, does not inhibit leukofibrinolysis.
Negative Direct Coombs’ Tests in Narcotic Addicts Receiving Maintenance Doses of Methadone
Authors: Sherwood Geoffrey K. , McGinniss Mary H. , Katon Richard N. , DuPont Robert L. , Webster J. Blair
Published: October 2019

Direct Coombs’ tests (antiglobulin tests) were performed on blood from 103 opiate users prior to methadone maintenance therapy and 67 long-term methadone maintenance patients. No positive tests were observed in either group. Drug urinalyses revealed that all of the methadone maintenance patients were, in fact, taking methadone, as well as other drugs. This result conflicts with a report in which 85% of the methadone maintenance patients had positive direct Coombs’ tests.
Cyclic Fluctuation in Blood Granulocyte DNA Labeling: Comparison of Tritiated Thymidine and Radiophosphorus
Authors: Walker Richard I. , Cole Enser W. , Glasser Robert M. , Herion John C. , Palmer Jeffress G.
Published: October 2019

DNA labeling studies with 3HT and 32P have been done in horses. Frequent sampling has defined cyclic fluctuations in blood granulocyte DNA label content with a cycle time of around 27 hr. Simultaneous labeling studies in the same animals have produced blood granulocyte DNA labeling curves that are nearly identical indicating significant reutilization of 3HT.
Studies on the Hemoglobins of Pinnipeds
Authors: Lincoln David R. , Edmunds Diana T. , Gribble T. John , Schwartz Herbert C.
Published: October 2019

The hemoglobins of seven species of pinnipeds-elephant, ribbon, fur, harbor, and grey seals, walrus, and California sea lion-had two major and one minor hemoglobin fractions on electrophoresis at pH 8.6. One of the major fractions in all seven species had the same electrophoretic mobility. The second fractions of the gray, harbor, and ribbon seals were similar, but different from the second fractions of the walrus, fur seal, and sea lion. The second fraction of the elephant seal was different from all the others. The proportion of the two major fractions was about 3:1 in the elephant, grey, ribbon, and harbor seals, and about 1:1 in the fur seal, walrus, and sea lion. These results correlated well with the pinniped phylogenetic chart derived by classical morphology. All hemoglobin fractions were found to be alkali sensitive and heat stable. Gel filtration studies with Sephadex G-75 and G-100 indicated that the elephant seal hemoglobins had a mol wt of about 65,000. The amino acid compositions of the chains isolated from the hemoglobin fractions suggested that in the elephant seal one major fraction had two alpha and two beta chains, and the other major fraction had four like chains. The presence of a hemoglobin which is composed of a tetramer of like chains could be functionally advantageous to deep diving mammals.
Chemotherapy of Mouse Myeloma: Quantitative Cell Cultures Predictive of Response In Vivo
Authors: Ogawa M. , Bergsagel D. E. , McCulloch E. A.
Published: October 2019

The effects of chemotherapeutic agents on mouse myeloma and bone marrow precursor cells were studied using cell culture and spleen colony assay techniques, and the results were assessed for their values in predicting therapeutic effectiveness. For cyclophosphamide, nitrogen mustard, and 1,3 bis (2 chloroethyl)-1-nitrosourea (BCNU), selective toxic effects on mouse myeloma (Adj. PC-5) cells were seen while no such differential effect was observed for 5-fluorouracil. The differential effects of these agents could not be explained by the cell cycle effects but appeared to be dependent on the intrinsic properties of the two cell classes. Marked differences were noted in the sensitivity of three mouse myelomas to melphalan. The ratio of the melphalan dose required to reduce marrow CFU to 37% (D37) to the dose required to reduce myeloma CFU equally was 75 for Adj. PC-5, 18 for MOPC 46B, and 7 for MOPC 460D. These results predict that melphalan would be more effective than 5-fluorouracil for Adj. PC-5 and that melphalan would be relatively ineffective for MOPC 460D. These predictions were confirmed by survival tests.
The Hemolytic Anemia of Magnesium Deficiency in Adult Rats
Authors: Piomelli Sergio , Jansen Valerie , Dancis Joseph
Published: October 2019

The administration of a Mg-deficient diet to adult rats for 4-5 wk causes anemia. The RBC are slightly smaller and flatter, and have a reduced hemoglobin component and a decreased osmotic fragility. 51Cr survival time is shortened when the affected cells are infused into normal adult rats. In vitro synthesis of heme and globin, as measured with 14C-glycine was the same as in control rats with "reticulocytosis-rich" anemia produced by bleeding or immunologically. The activity of a series of enzymes associated with energy production also failed to yield findings specific for Mg deficiency. It is suggested that the anemia of Mg deficiency is hemolytic and results from the combination of a reversible extrinsic defect and of an irreversible structural defect in the RBC.
Histone Biosynthesis in Pernicious Anemia Proerythroblasts and Megaloblasts
Authors: Kass Lawrence
Published: October 2019

Histone biosynthesis was investigated in proerythroblasts and megaloblasts obtained from patients with untreated pernicious anemia. Radioautography, using tritium-labeled L-arginine, L-lysine, and L-trytophane, acrylamide gel electrophoresis of histone fractions, acrylamide gel radioautography, uptake of radioisotopes into lysine-rich and arginine-rich histone fractions, and amino acid analysis of histone fractions, was performed. In untreated pernicious anemia proerythroblasts and megaloblasts, there was a small uptake of arginine and lysine as seen radioautographically, and incorporation into isolated histone fractions was scant. Amino acid analyses showed these histones to be lysine rich. After these erythroid precursors were exposed to cyanocobalamin in vivo or to coenzyme B12 in vitro, there was a marked (up to 100-fold) incorporation of only tritium-labeled L-arginine into erythroid nuclei, as seen radioautographically, and into isolated histone fractions as well. Amino acid analyses demonstrated that the histones had become more arginine rich. These studies indicate that vitamin B12 facilitates the biosynthesis of arginine-rich histones in vitamin B12-deficient erythroid precursors.
IgG Cryoglobulinemia Associated With Amyloidosis
Authors: Maldonado Jorge E. , McNutt D. R. , Kyle Robert A. , Baggenstoss Archie H. , Fudenberg H. H.
Published: October 2019

A patient with symptomatic primary cryoglobulinemia was followed for 9 yr and was found at autopsy to have generalized amyloidosis. There was a monoclonal serum protein spike of IgG kappa type that was cryoglobulin. The cryoglobulin was further characterized as IgG2 kappa Gm (n-). This case constitutes, to our knowledge, the first example of amyloidosis associated with monoclonal IgG cryoglobulinemia, with characterization of the monoclonal serum cryoglobulin, and also the first reported case of successful symptomatic treatment of cryoglobulinemia by plasmapheresis.
Membrane-mediated Synthesis of Tissue Factor (Thromboplastin) in Cultured Fibroblasts
Authors: Zacharski Leo R. , McIntyre O. Ross
Published: October 2019

A potent procoagulant synthesized by cultured human skin fibroblasts has been identified as tissue factor (factor III, thromboplastin), since it binds factor VII and is blocked by a specific antitissue factor antibody. Fibroblast tissue factor is, at least in part, a labile superficial, membrane-associated substance the synthesis of which is mediated by cell adhesion but is inhibited by actinomycin-D and puromycin. Tissue factor production is related to the shape change that occurs as the cells spread on the floor of the culture vessel, but tissue factor is not synonymous with the configuration on the cell surface responsible for cell adhesion. These observations suggest that cell membranes may play a significant role in hemostasis and thrombosis by virtue of their tissue factor content.
Properties of the Platelet Retention (von Willebrand) Factor and Its Similarity to the Antihemophilic Factor (AHF)
Authors: Weiss Harvey J. , Rogers John , Brand Harvey
Published: October 2019

The abnormal retention of platelets in glass-bead filters in von Willebrand’s disease was corrected by a fraction of normal cryoprecipitate that eluted, along with antihemophilic factor (AHF), in the void volume after chromatography on Bio-Gel 5 M. This platelet retention factor had an apparent molecular weight in excess of 5 x 106, was also present in hemophilic cryoprecipitate, but was not detectable in the void volume fractions of cryoprecipitate prepared from the plasma of a patient with von Willebrand’s disease. The adsorptive and thermal stability properties of the retention (von Willebrand) factor were similar to those of AHF. Platelet retention is the result of a complex interaction between red cells, platelets, and the von Willebrand factor, and it is suggested that the activity of the latter factor may be associated with the same high molecular weight protein that possesses coagulant (AHF) activity in normal subjects but that lacks this activity in hemophiliacs. The deficiency of this protein in von Willebrand’s disease may account for the hemostatic defect in this disorder.
Pyridoxine-responsive Anemia: Influence of Tryptophan on Pyridoxine Responsiveness
Authors: Horrigan Daniel L.
Published: October 2019

This study presents evidence that the indolic amino acid, tryptophan, critically influences pyridoxine responsiveness in a patient with pyridoxine-responsive anemia. Continuing observations for 18 yr on this now 54-yr-old white man have shown responsiveness to oral crude liver extract and to pyridoxine. In addition, remissions of 8-mo duration followed oral administration of fractions of liver extract in doses of 2 mg daily. These nonprotein fractions contained acidic substances characterized as indoles. From 1959 to 1970, oral pyridoxine, in daily doses of 12.5 mg for 5 days, predictably produced prompt reticulocytosis, fall in serum iron content, and rise in hematocrit to nearly normal levels. Such responses to pyridoxine consistently lasted less than 2 mo. More recently, relative refractoriness to this dose of pyridoxine has developed. However, responsiveness has been restored by oral administration of I-tryptophan, 750 mg daily, an amount alone insufficient to maintain the hematocrit at optimal levels. These observations indicate relationships of tryptophan and pyridoxine in erythropoiesis that have not been recognized previously. Addition of I-tryptophan to the therapy of certain pyridoxine-responsive and other sideroblastic anemias might be considered.
Effect of Phenylhydrazine-induced Hemolytic Anemia on Nuclear RNA Polymerase Activity of the Mouse Spleen
Authors: Spivak Jerry L. , Toretti Dennis , Dickerman Herbert W.
Published: October 2019

The DNA-dependent RNA polymerase of nuclei from lymphoid-rich and erythroid-rich mouse spleens was compared in regard to requirements and conditions of the reactions. The inhibition by either actinomycin D or pancreatic DNase indicated that a DNA template was required for the observed reactions. Following the induction of a hemolytic anemia by the administration of phenylhydrazine, there was a tenfold increase in the nuclear polymerase activity per milligram nuclear DNA of the developing erythropoietic spleen when the assays were done at low ionic strength and more than a threefold increase at high ionic strength. The peak rise in polymerase activity precedes the maximal development of the erythropoietic spleen by 3 days.
Comparison of Two Methods of Preventing Central Nervous System Leukemia
Authors: Aur Rhomes J. A. , Hustu H. Omar , Verzosa Manuel S. , Wood Adynel , Simone Joseph V.
Published: October 2019

This controlled study of children with ALL was designed to determine in a prospective manner the relative efficacy and toxicity of two forms of "prophylactic" CNS therapy for preventing CNS relapse and of periodic vincristine-prednisone "pulses" during multiple agent chemotherapy. Following cranial irradiation (2400 rads) plus intrathecal methotrexate, 3 of 45 patients developed CNS leukemia. Following craniospinal irradiation (2400 rads), 2 of 49 developed CNS leukemia. Craniospinal irradiation was associated with more leukopenia and interruptions of chemotherapy. "Pulses" were not associated with improvement of remission duration. Our current choice of CNS therapy is cranial irradiation plus intrathecal methotrexate because it takes less time and may avoid demonstrated short-term side effects and possible long-term effects of spinal irradiation.
Treatment of Established Graft-Versus-Host Disease in Dogs by Antithymocyte Serum or Prednisone
Authors: Storb R. , Kolb H. J. , Graham T. C. , Kolb H. , Weiden P. L. , Thomas E. D.
Published: October 2019

Marrow grafts after 1200 R of whole-body irradiation were carried out between pairs of unrelated dogs of different breeds that were incompatible for dog histocompatibility antigens. Three groups of recipients were studied. Recipients in all groups were treated with the immunosuppressive agent methotrexate (MTX), 0.4 mg/kg, on days 1, 3, 6, and 11, and then once weekly until day 102 after grafting. Dogs in group 1 were given MTX only. Thirty of 35 recipients died between 11 and 51 days and five survived more than 102 days. Median survival time was 20 days. Dogs in group 2 were treated with rabbit antidog antithymocyte serum (ATS) when graft-versus-host (GVH) disease became established. Eight of ten recipients died between 19 and 76 days and two survived more than 102 days. Median survival time was 45 days. Dogs in group 3 were treated with daily injections of prednisone when GVH disease became apparent. Seven of nine recipients died between 11 and 34 days and two survived more than 102 days. Median survival time was 24 days.

It was concluded that established GVH disease in dogs with histoincompatible marrow grafts can be favorably influenced by ATS with significant (p < 0.01) prolongation of survival. However, there was no evidence that treatment with ATS increased the fraction of long-term survivors in this histoincompatible setting. Prednisone was ineffective and did not prolong survival (p > 0.1).
The Elevation of Adenosine-Triphosphate Levels in Human Erythrocytes
Authors: Warrendorf Elizabeth M. , Rubinstein David
Published: October 2019

It has previously been possible to double the level of ATP in human erythrocytes by incubation of the cells at 37° for 10 hr with glucose and adenine. The present study describes a further increase in the ATP level and some of the possible mechanisms involved. Addition of 5 mM pyruvate to a medium containing 32 mM inorganic phosphate, glucose, and adenine elevated the level of ATP threefold during a 10-hr incubation. Pyruvate could be replaced by inosine but the presence of both limited the elevation of ATP to twice that of fresh cells. This limitation may be overcome by the use of 96 mM phosphate in the incubation medium, in which case the intracellular level of ATP is tripled within 2 hr. The conditions which limit the accumulation of ATP are associated with low intracellular phosphate concentrations and the accumulation of organic phosphates, especially, in the presence of inosine, 2,3-diphosphoglycerate. Utilizing 14C-glucose labeled in carbons 1, 2, or 6, it has been shown that when ATP is being rapidly elevated, the pentose moiety of the adenine nucleotides is mainly supplied (about 80%) by oxidation of carbon 1 of glucose, catalyzed by the dehydrogenases of the hexosemonophosphate shunt. In the presence of pyruvate this activity is doubled. Pyruvate reoxidizes NADPH formed by this pathway, since lactic dehydrogenase has some specificity towards the NADPH. The involvement of the dehydrogenases of the hexosemonophosphate shunt is illustrated by the use of erythrocytes deficient in glucose-6-phosphate dehydrogenase. Incubation of these cells for 5 hr with glucose and adenine results in only a slight increase in ATP formation, and pyruvate has no additional effect. Addition of inosine, however, leads to the same increment in ATP levels seen in normal cells. The ATP and 2,3-diphosphoglycerate levels in 6-wk preserved blood can also be increased to three times that of fresh cells by incubation with glucose, adenine, pyruvate, and inosine in a medium high in inorganic phosphate.
Defective Capacity of Bone Marrow From Nude Mice to Restore Lethally Irradiated Recipients
Authors: Zipori Dov , Trainin Nathan
Published: October 2019

The proliferative capacity of bone marrow cells from thymus-deprived nude mice was investigated in lethally irradiated recipients. Although the colony-forming capacity of these cells was found to be similar to that of normal littermates, a reduction in the number of nucleated cells was observed in the bone marrow of nude mice. Moreover when the radioprotective effect of such cells was studied, it was found that 5 x 105 or 2 x 106 bone marrow cells from nude mice were less effective in restoring hemopoiesis and establishing permanent chimerism than similar amounts of bone marrow cells of normal controls. In addition, irradiated animals surviving after injection of bone marrow cells from nude mice were found to have lower immune responses to SRBC than normal chimeras. The possibility that mortality of irradiated recipients injected with bone marrow of nude mice is due to the presence of a latent infective agent or of some inhibitory factor of hematopoiesis in the bone marrow of such nude mice is shown to be improbable. Alternatively it is suggested that nude mice suffer from an intrinsic defect in the proliferative capacity of their bone marrow colony-forming cells (CFUs).
Chloroma and Other Myeloblastic Tumors
Authors: Muss Hyman B. , Moloney William C.
Published: October 2019

Fifteen cases (3.1%) of localized myeloblastic tumors occurring among 478 patients with acute granulocytic leukemia (AGL) and chronic granulocytic leukemia (CGL) are described. The majority of tumors were discovered at autopsy. Numerous cases of chloroma associated with AGL have been reported; however, in this series, the incidence of myeloblastic tumors in CGL was twice as high. The importance of employing histochemical methods for myeloperoxidase activity to identify myeloblastic tumors is pointed out. Experience in this group of cases confirm the frequent involvement of the ovary and the common localization of myeloblastic tumors to perineural and epidural structures. With CNS involvement by myeloblastic tumors, pain and compression symptoms may be effectively relieved by laminectomy and local x-ray therapy. After the appearance of a myelogenous tumor in CGL, the course of the disease is rapidly progressive.
Genetic Implications of the Interaction of Two Types of Beta-Thalassemia Genes in a Patient With Thalassemia Major
Authors: Russo Giuseppe , Mollica Florindo , Pavone Lorenzo , Musumeci Salvatore , Baglioni Corrado
Published: October 2019

A patient with thalassemia major is described in which two types of thalassemia genes are present, one that reduces β-chain synthesis and the other that suppresses it completely. The identification of these two types of β-thalassemia genes is based on the presence or absence of HbA in other members of the same family who are also HbC carriers. The genetic implications of the interaction of these two thalassemia genes are discussed in view of recent theories on the nature of the molecular defect characteristic of each type of thalassemia.
Hemoglobin Köln in a Black: Preand PostSplenectomy Red Cell Survival (DF32P and 51Cr) and the Pathogenesis of Hemoglobin Instability
Authors: Pedersen Paul R. , McCurdy Paul R. , Wrightstone R. N. , Wilson J. B. , Smith L. L. , Huisman T. H. J.
Published: October 2019

A 17-yr-old black male with hemolysis and pigmenturia but no anemia was found to have hemoglobin Köln (α2β298 val→met [FG5]). Splenectomy was done because of complicating thrombocytopenia. Thrombokinetic studies with 51Cr tagged platelets suggested hypersplenism, and after surgery the platelet count returned to normal. The red cell t ½ 51Cr was more than doubled, but the red cell life span (DF32P) was more modestly improved (30.6 → 47.2 days). The "elution" of 51Cr from the red cells presplenectomy was 5.6%/day, whereas after surgery it was normal (1.9%/day), accounting for the disparity between the survival methods. Study of the isolated cyanferri derivative of hemoglobin Köln by ultracentrifugation at various salt concentrations and various pH’s indicated an increased tendency to dimer formation under conditions where normal hemoglobin is a tetramer. This results from the site and type of amino acid substitution and accounts in part for its instability.
The Ausria Test: Critical Evaluation of Sensitivity and Specificity
Authors: Alter Harvey J. , Holland Paul V. , Purcell Robert H. , Gerin John L.
Published: October 2019

Ausria was shown to be considerably more sensitive than CEP by comparing titers of HBAg+ sera and by testing selected proficiency panels, sera from hepatitis patients, and sera from experimentally infected rhesus monkeys; CEP+, Ausria-sera were never encountered. However, in testing NIH donors and personnel, 19 of 20 Ausria+, CEP-sera were shown by neutralization studies to be nonspecific for HBAg, i.e., false positives. Nonspecificity was confirmed by an alternate radioimmunoassay procedure and, in one serum, by density-gradiant ultracentrifugation. Testing of 35 additional Ausria+, CEP-sera from New Jersey donors showed 13 specific and 22 (63%) nonspecific reactions. It is mandatory that serum from every Ausria+, CEP-donor undergo specificity testing. In addition to the 14 specific Ausria+, CEP-sera, two sera, subsequently shown to be CEP+, were undetected on the initial CEP test (one was transfused and resulted in hepatitis). These sera were strongly positive by Ausria; sera subject to reader error in CEP are unequivocally positive by Ausria. Ausria tests on CEP-donors suspected of transmitting HBAg failed to implicate a donor in each of eight cases. Some HBAg+ hepatitis will continue to occur despite universal application of Ausria or other tests of equal sensitivity.
Induction of Sustained Hemopoiesis in Fatty Marrow
Authors: Tavassoli Mehdi , Maniatis Alice , Crosby William H.
Published: October 2019

Evacuation of the fatty marrow cavity results in a sequence of regeneration which is associated with a phase of hemopoiesis. Hemopoietic activity is, however, transient, being replaced by adipose tissue, so that 6 mo after evacuation the marrow is once again fatty. This phase of transient hemopoiesis can be sustained by phenylhydrazine-induced hemolytic stress. Hemolysis per se does not induce significant hemopoietic activity in nonevacuated totally fatty marrow.
Paroxysmal Nocturnal Hemoglobinuria with Elevated Fetal Hemoglobin
Authors: Rassiga-Pidot Anne L. , Cornwell Gibbons G. , McIntyre O. Ross
Published: October 2019

A persistent elevation of the fetal hemoglobin (Hgb F) level (5%-15%) was observed in a 22-yr-old white male with paroxysmal nocturnal hemoglobinuria (PNH). Acid treatment of the peripheral smear (Betke-Kleihauer technique) demonstrated a heterogeneous distribution of Hgb F in the red cells. As expected, the lowest acetylcholinesterase activity and the most hemolysis after acid stress were found in the low-density, reticulocyte-rich cell fraction. In contrast, the highest Hgb F levels were found in the high-density, reticulocyte-poor fraction. Further evidence for the segregation of these two abnormalties was obtained from the observation that less Hgb F was present in the hemolysate obtained after acid lysis than was present in the mixed blood sample or the remaining nonhemolyzed red cells.
Effect of Cyanate on Erythrocyte Deformability
Authors: Durocher John R. , Glader Bertil E. , Gaines Lelia T. , Conrad Marcel E.
Published: October 2019

Cyanate is undergoing study as a drug to prevent occlusive sickle cell crises. Carbamylation of hemoglobin S increases its oxygen affinity, thereby decreasing its tendency to aggregate at low oxygen tensions. The cell membrane has also been shown to be carbamylated. We studied the effect of carbamylation on deformability of sickle, normal, and stored normal erythrocytes. Deformability was measured as filtration time of erythrocyte suspensions through 3-µ polycarbonate filters. Oxygenated carbamylated sickle erythrocytes had a marked shortening of filtration time that could not be explained by changes in morphology. In addition, normal erythrocytes became more filterable with carbamylation. Decreased filterability after storage at 4°C for 48 hr was returned to normal following carbamylation and incubation with glucose. No correlation was made with changes in either morphology, cell size, or ATP levels. Therefore, it was postulated that carbamylation affected filterability by binding either the cell membrane or cell contents or both.
The Intravascular Survival of Neutrophils Labeled In Vivo
Authors: Vincent Paul C. , Chanana Arjun D. , Cronkite Eugene P. , Joel Darrel D.
Published: October 2019

The survival of blood neutrophils labeled in vivo was studied in the calf. Disappearance of labeled neutrophils from the blood of calves was followed after a period of cross circulation with their chimeric, immunologically tolerant twins, which had been given tritiated thymidine 6½ days previously. Under these conditions, neutrophils were shown to leave the blood in a random exponential fashion, with half-disappearance times of between 6.4 and 7.5 hr. Hydrocortisone given to one calf 48 hr after cross circulation caused a neutrophilic leukocytosis, during which substantial numbers of labeled neutrophils reappeared in the blood.