bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial Association of Thrombopathia and Antihemophilic Factor (AHF, Factor VIII) Deficiency
Authors: Crowell Edward B. , Eisner Eric V.
Published: October 2019

Five female members of a family manifesting a dominantly inherited bleeding disorder were investigated for coagulation and platelet abnormalities. A long bleeding time, mild thrombocytopenia, large platelets, low platelet factor-3 activity (PF-3), and low factor VIII levels were found in the proband. Long bleeding times, low PF-3, and low factor VIII levels were found in various combinations in the four other family members studied. PF-3 was abnormal by three techniques in the proband and could be corrected by adding ADP. Her platelets and those of one other member did not aggregate when exposed to collagen. The proband’s platelets did not release ADP on collagen exposure. The severity of bleeding was proportional to the number of laboratory abnormalities in the individual’s studied. The findings in this family overlap both hereditary thrombopathia and von Willebrand’s disease and were quite variable between family members. It appears that there exists a spectrum of dominant hereditary bleeding disorders with abnormalities in the platelets or factor VIII levels or both, with variable expressivity in family members.
Abnormal Iron Incorporation, Survival, Protoporphyrin Content and Fluorescence of One Red Cell Population in Preleukemic Sideroblastic Anemia
Authors: Riedler Georg F. , Straub P. Werner
Published: October 2019

The dimorphic blood picture in sideroblastic anemia suggests the coexistence of at least two types of erythrocyte, the populations with the smaller RBCs being responsible for the crucial abnormality, namely the impairment of iron incorporation into protoporphyrin. In a patient with sideroblastic anemia who subsequently developed acute myelocytic leukemia, we found a light and a heavy cell population to be morphologically different, the lighter cells showing a smaller MCV and lower MCH, a higher reticulocyte count, fluorocyte count and protoporphyrin content. Radioiron uptake and 51Cr survival were 3.5% and 8.2 days for the lighter fraction, 37% and 20 days for the heavier fraction. Thus, the impairment of iron incorporation, the high erythrocyte protoporphyrin content, and the reduced survival of red cells in this patient with sideroblastic anemia appeared to be largely confined to the red cell population with the smaller RBCs.
Cell-Cell Interaction in Vitro: Studied by Density Separation of Colony-forming, Stimulating, and Inhibiting Cells From Human Bone Marrow
Authors: Haskill J. S. , McKnight R. D. , Galbraith P. R.
Published: October 2019

Cell-cell interaction in vitro was studied by separating normal human bone marrow cells into fractions on the basis of their buoyant density in a linear gradient of bovine serum albumin and by assaying the colony forming ability of marrow fractions and combinations of marrow fractions in methylcellulose medium without an added extrinsic source of colony-stimulating factor. In this culture system unfractionated marrow cells seldom formed colonies, but colonies grew from the low-density fractions, suggesting that an inhibitor had been removed by cell fractionation. When cells from the low-density fraction were mixed with the cells from the middensity and highdensity fractions, stimulation and inhibition of colony size respectively were observed. These observations suggest that cell-cell interaction may play a role in regulation of granulopoiesis in vitro and suggests an approach to the investigation of granulopoiesis in disease.
The Effect of Cobra Venom Factor on Hemostasis in Guinea Pigs
Authors: Dodds W. Jean , Pickering Richard J.
Published: October 2019

Recent investigations have indicated an association between the coagulation and complement systems. Our present studies, designed to explore this association further, demonstrated that a purified anticomplementary fraction of cobra venom, cobra venom factor (CVF), produced significant changes in hemostasis when injected into guinea pigs. Some of the effects described may be secondary to the transient intravascular hemolysis produced by CVF. However, a more direct effect of purified CVF on platelet function is suggested by increased platelet factor 3 activity and inhibition of clot retraction and lysis. Furthermore, injection of purified CVF produced striking elevation of plasma fibrinogen without detectable fibrin or fibrinogen degradation products, altered plasminogen levels, and significantly reduced the activities of several extrinsic and intrinsic coagulation factors. These observations provide additional data to support the concept of a functional relationship between the mechanisms that initiate coagulation and activate complement.
Hageman Trait (Factor XII Deficiency): A Probable Second Genotype Inherited as an Autosomal Dominant Characteristic
Authors: Bennett Bruce , Ratnoff Oscar D. , Holt James B. , Roberts Harold R.
Published: October 2019

A family is described in which Hageman trait appeared to be inherited in an autosomal dominant manner in contrast to previously reported families in which the disorder behaves as an autosomal recessive characteristic. Immunologic studies suggested that the molecular defect was similar to that of the autosomal recessive form and consisted of deficiency of antigens related to Hageman factor.
Vitamin B12-binding Protein of Leukocytes as a Possible Major Source of the Third Vitamin B12-binding Protein of Serum
Authors: Carmel Ralph , Herbert Victor
Published: October 2019

Much evidence suggests that granulocytes are a major source of serum vitamin B12-binding protein (BBP). The latter has three components: α-1-globulin BBP (Transcobalamin I, TC I), β-globulin BBP (TC II), and a recently described third BBP. Granulocytic BBP has appeared to be identical to TC I except in electrophoretic mobility. In the present study, the dominant BBP of leukocyte extracts from subjects with and without myeloproliferative disease behaved like the third serum BBP. With a few exceptions, more than half the leukocytic binder eluted with the "β globulins" on rapid DEAE-cellulose chromatography. At pH 8.6, electrophoretic mobility of the leukocytic BBP was always α2 or β. At ph 4.5, normal and chronic myelogenous leukemia leukocytic BBP, unlike TC I and TC II, showed little electrophoretic migration. These findings suggest that leukocytic BBP is probably heterogenous and that its major component resembles the third serum BBP more than it does TC I. The third serum BBP, levels of which are elevated in some states of leukocytic proliferation, may derive directly from mature granulocytes. TC I may arise by addition of sialic acid to the third (granulocytic) BBP under certain circumstances or be released from other cells, such as less mature granulocytes. Much of the confusion in the literature regarding source and significance of serum BBP may relate to separating it into only two fractions (α globulin and "β globulin," or "TC I" and TC II) instead of into three fractions.
Studies of Antigens Associated With Hodgkin’s Disease
Authors: Order Stanley E. , Chism Stanley E. , Hellman Samuel
Published: October 2019

Following a previous preliminary report, this study was initiated to demonstate further evidence of tumor-associated antigens in Hodgkin’s disease and to determine if these antigens are found in other pathologic states. Tumor-associated antigens are now demonstrated by three techniques in 18 Hodgkin’s invoved spleens and are not found to be present in equal concentration in normal spleens. Using immunofluorescence techniques and absorbed tumor antisera, fluorescence is demonstrated in tumors but not in the normal region of the same tumor-bearing spleen or in normal spleens. Gel diffusion with absorbed tumor antisera revealed a common precipitin band in Hodgkin’s disease not present in normal spleens or spleens from other diseases. Studies with immunoelectrophoresis have demonstrated two antigens present in the tumors in the spleen. Eighteen out of 19 Hodgkin’s tumors from the spleen have such antigens identifiable by immunoelectrophoresis with concomitant negative normal splenic controls in each case. Five out of 18 spleens from other disease states shared one of the antigens. These data confirm the presence of common tumor-associated antigens in Hodgkin’s disease, and it is postulated that at least one antigen may be a host cell reactant substance.
The Platelet-stimulating Effects of 7-beta, 17-alpha-Dimethyltestosterone (Calusterone)
Authors: Horn Yoav , Halden Allan , Gordan G. S.
Published: October 2019

Calusterone, 200 mg daily by mouth, significantly raised platelet counts of 80 women with advanced breast cancer. It showed no erythropoietic activity. Simultaneous measurements in 27 patients receiving Δ1-testoloactone, 1000 mg a day, were not significantly different from those of 21 untreated patients. Calusterone is clinically well tolerated, is weakly androgenic, and, like other 17-alpha alkylated steroids, causes bromsulphalein retention but no hepatocellular damage or jaundice. Its thrombocytopoietic effect in women with advanced breast cancer warrants investigation in patients with thrombocytopenic purpura or aplastic anemia and in patients undergoing chemotherapy.
The Effect of Cold on Platelets. II. Platelet Function After Short-term Storage at Cold Temperatures
Authors: Kattlove Herman E. , Alexander Benjamin , White Frances
Published: October 2019

Citrated platelet-rich plasma (PRP) was kept at cold temperatures or room temperature. After 4 hr or more at these temperatures, the PRPs were warmed 1 hr at 37°C. This prevents the spontaneous aggregation seen in chilled PRP that is stirred immediately after warming. Platelet aggregation in response to connective tissue (CT), epinephrine, and adenosine diphosphate (ADP) was considerably greater in the PRPs originally kept at cold temperatures. In addition, chilling would restore the aggregation of platelets whose function had deteriorated due to prolonged storage at warm temperatures. Neither ADP-induced refractoriness, serotonin uptake, or CT-induced serotonin release was affected by cold. Retention in glass bead columns was greater in platelets that had been chilled than in platelets kept at room temperature or 37°C. Thus, the storage of platelets at cold temperatures leads to changes that improve platelet aggregation but may also increase platelet adhesion, which would account for the decreased in vivo survival of platelets preserved for transfusion at cold temperatures.
Growth of Leukemic Cells in Culture
Authors: Aye M. T. , Till J. E. , McCulloch E. A.
Published: October 2019

Peripheral blood cells from three patients with leukemia in relapse increased in numbers in short-term suspension cultures. This increase was dependent on the presence of either feeder populations containing a high percentage of blast cells or conditioned medium derived from such populations. Aneuploid cells present in direct marrow preparations were also prevalent in the cultures after 10 days. The apparent specificity of the increase for leukemic populations may provide a new approach to the study of leukemic blast cells.
Primary and Secondary Myelofibrosis: Its Relationship to "PNH-like Defect"
Authors: Kuo Chi-yen , Van Voolen G. Arthur , Morrison Alan N.
Published: October 2019

Twenty-two patients with primary myelofibrosis and myeloid metaplasia (MMM) and ten patients with MMM secondary to carcinoma were studied for the relationship of MMM to "PNH-like defect." Laboratory measurements included Ham’s test, sucrose hemolysis test, sugar-water test, leukocyte alkaline phosphatase, haptoglobin, and urinary hemosiderin. The defects of the red cell membrane, as evidenced by acid and sucrose lysis tests, were limited to those with primary MMM and occurred in 54% of the cases. Another 10% showed decreased haptoglobin level, positive sugar-water test, and/or hemosiderinuria suggestive of the syndrome.
Leukocyte Labeling With 51Chromium. IV. The Kinetics of Chronic Lymphocytic Leukemic Lymphocytes
Authors: Scott James L. , McMillan Robert , Marino Joseph V. , Davidson J. Gary
Published: October 2019

The kinetics of radiochromate-labeled autologous blood lymphocytes were studied in ten cases of chronic lymphocytic leukemia (CLL). The labeled cells equilibrated with an enlarged recirculating lymphocyte pool (RLP) distributed between the blood, the spleen, and the bone marrow. The size of the RLP, estimated from dilution of the labeled cells, was better correlated with the degree of splenomegaly and marrow infiltration than was the blood lymphocyte count. The marrow fraction of the RLP turned over more slowly than the splenic pool. The half-life of the labeled cells in the RLP varied in individual cases from one to 11 days. Lymphocyte life span was not related either to the blood lymphocyte count or to the size of the RLP. The mean half-life of 3.8 days was significantly shorter than the normal lymphocyte half-life of 18 days. We conclude that CLL is characterized by overproduction of a strain of abnormally short-lived lymphocytes.
Control of Erythropoiesis in Rats With Adjuvant-induced Chronic Inflammation
Authors: Lukens John N.
Published: October 2019

In order to characterize the defect in erythroid homeostasis in chronic inflammatory states, the relationship between erythropoietin production and erythropoietic response was examined in rats with adjuvant disease. Exposure of adjuvant-injected rats to graded levels of lowered barometric pressure induced increases in plasma erythropoietin which were significantly less than those measured in normal animals similarly stimulated. Erythropoietin inhibitors were not detected by in vitro or in vivo assay techniques: the biological activity of ovine erythropoietin was not modified by incubation with plasma from rats with adjuvant disease; the erythropoietic response of ex-hypoxic polycythemic mice to erythropoietin was not compromised by injections of test plasma; and the burst of erythropoiesis induced in ex-hypoxic polycythemic mice by a hypobaric stimulus was not modified by plasma given prior to or at various intervals after hypobaric exposure. Exogenous erythropoietin elicited nearly identical increases of radioiron incorporation in normal and adjuvant-injected rats whose endogenous erythropoietin was suppressed by hypertransfusion. It is concluded that the diminished erythropoietic response to anemia in adjuvant-induced chronic inflammation results from a relative failure in the production of biologically active erythropoietin.
An Unusual Pattern of Neutrophil Kinetics in Sickle Cell Anemia
Authors: Boggs Dane R. , Hyde Fred , Srodes Carl
Published: October 2019

Blood neutrophil kinetics were studied withwith DF32P in patients with sickle cell anemia. Neutrophil concentration in venous blood samples and the size of the circulating granulocyte pool (CGP) were high normal or abnormally high in all patients. The total blood granulocyte pool (TBGP) was not increased to the same degree as the CGP so that in part, the neutrophilia associated with sickle cell anemia represents a shift from marginated to circulating blood compartments. The half disappearance time (T½) of blood neutrophils tended to be short so that with an elevated or high normal TBGP the absolute granulocyte turnover rate (GTR) tended to be increased. The fractional GTR was regularly increased. In most types of neutrophilia the T½ tends to be increased rather than shortened and the fractional GTR may be normal, decreased, or increased. The increased fractional GTR observed in sickle cell anemia suggests that the absolute increase in neutrophil loss from the blood is not merely a function of increased pool size as was suggested previouslyy.
The Question of Cycling of the Blood Neutrophil Concentrations and Pitfalls in the Statistical Analysis of Sampled Data
Authors: Maughan W. Z. , Bishop C. R. , Pryor T. A. , Athens J. W.
Published: October 2019

To test the hypothesis that there is normally a 14-21 day cycle in blood neutrophil concentration, the blood of 13 normal male volunteers was sampled daily for 42 consecutive days. No evidence for cyclic variation in neutrophil concentration was found. The effect of deleting four samples per week and interpolating values linearly or parabolically was tested by power spectrum analysis, since this type of analysis was used in the studies in which cycling was found. The interpolation of missing values was found to introduce apparent cycling, and the results of the analysis of daily neutrophil counts was no different than that obtained with a series of random numbers.
Studies of the Neutropenia of Acute Malaria
Authors: Dale David C. , Wolff Sheldon M.
Published: October 2019

Neutrophil kinetics were studied in seven patients with acute malaria. Six patients with Plasmodium vivax had a mean neutrophil count of 1651 ± 282/ cu mm (range 360-2340); the neutrophil count in one patient with P. falciparum malaria was normal (4600/cu mm). In all of these patients, the numbers of circulating nonsegmented neutrophils were increased, neutrophil half-disappearance times were prolonged, and the total blood granulocyte pools were normal or increased. The marginal granulocyte pools were greatly enlarged but circulating pools were reduced, indicating that the apparent neutropenia was due to an altered intravascular granulocyte distribution. These patients had reduced numbers of mature marrow granulocytes and decreased marrow granulocyte reserves. These data provide a model for one mechanism of neutropenia in man: premature release of marrow granulocytes with a shift of the circulating cells into the marginal pool.
An Ultrastructural Study of the Red Pulp of the Spleen in Malaria
Authors: Schnitzer B. , Sodeman T. M. , Mead M. L. , Contacos P. G.
Published: October 2019

An ultrastructural study was undertaken of the spleen of a rhesus monkey infected with Plasmodium knowlesi to determine whether the spleen is able to pit malaria parasites from red cells. It was found that in the spleen parasitized cells are: (1) phagocytized in toto by cordal macrophages, (2) pitted of parasites, and (3) hemolyzed in the splenic microvasculature. Phagocytosis of the entire parasitized red cell appears to occur most frequently of the three mechanisms and probably accounts for most of the anemia. Pitting of parasitized red cells may account in part for the hemolysis in excess of the number of parasitized red cells seen in malaria. The red cells that have had their parasites removed would become spherocytic and hence, would be more susceptible to removal from the circulation during subsequent passages through the spleen.
B12 Dependence of Cell Uptake of Serum Folate: An Explanation for High Serum Folate and Cell Folate Depletion in B12 Deficiency
Authors: Tisman Glenn , Herbert Victor
Published: October 2019

Bone marrow cells from patients with vitamin B12 deficiency took up much less N5-methyltetrahydrofolate(MeTHF) than did normal bone marrow cells but showed no significant reduction in pterolyglutamate (PGA) uptake. Addition of B12 to the incubation medium enhanced the cell uptake of MeTHF only in B12-deficient patients. These data support the concept of a B12 requirement for cell uptake of MeTHF.
The Role of the Sinus Wall in the Passage of Erythrocytes Through the Spleen
Authors: Chen Li-Tsun , Weiss Leon
Published: October 2019

The passage of erythrocytes through the walls of splenic sinuses was studied in rats treated with phenylhydrazine. The sinus wall contained no preformed apertures. Instead, erythrocytes and other cells passing through the spleen entered interendothelial slits and squeezed through. The presence of phenylhydrazine-induced Heinz bodies within erythrocytes impeded their transmural passage. Normally, few erythrocytes were found in transit across the walls of sinuses. However, after phenylhydrazine, many of the interendothelial slits in sinuses were occupied by damaged erythrocytes. Virtually all of the interendothelial slits in sinuses appeared capable of passing erythrocytes. The slits seldom exceeded 0.2-0.5 µ in width, even with an erythrocyte in passage. Bands of intraendothelial microfilaments running alongside the interendothelial slits appeared to have a major role in causing the slits to remain narrow. Thus, the sinus wall, reinforced by microfilamentous bands, significantly controlled the circulation of erythrocytes through the spleen. Normal red cells were pliant enough to squeeze through, but cells containing large rigid inclusions were held in the slits or delayed in their passage. When many of the slits were occupied by cells slow in passage, the outflow track became blocked, and circulation through the spleen was impeded. Therefore, cells pooled in the cords, macrophages increased in number, and the sequences initiated that resulted in splenomegaly.
Expression and Linkage of Genes for X-linked Hemophilias A and B in the Dog
Authors: Brinkhous K. M. , Davis P. D. , Graham John B. , Dodds W. Jean
Published: October 2019

The linkage distance on the X chromosome between the genes for hemophilia A (classic hemophilia) and B (PTC deficiency, Christmas disease) was estimated directly by breeding two strains of dogs, each segregating for a different type of hemophilia. Gene expression was determined by bioassays of plasma factor VIII (antihemophilic factor) and factor IX (PTC, Christmas factor). Double heterozygotes in repulsion for both hemophilia A and B could be readily identified by intermediate plasma levels of both procoagulants. There was no evidence of a tendency toward preferential inactivation of the paternally derived X chromosome, and the procoagulant levels showed that random inactivation had occurred at both loci. When double heterozygotes were bred against normal males or males with hemophilia A and B, the progeny that resulted indicated that the genes recombined freely. Thus, the genes are at least 50 map units apart. The phenotypes of five new hemophilic genotypes are described as a result of the various crossbreedings, including males with double hemophilia AB. When both hemophilia genes are in the coupling phase, there is evidence of increased intrauterine or neonatal lethality in males. The data from this study, along with that on gene linkage of human hemophilia A and B, provide support for the thesis of homology of the X chromosome during speciation.
Fetal Thymic Transplant in Patients With Hodgkin’s Disease
Authors: Marcolongo Roberto , Di Paolo Nicola
Published: October 2019

Five patients with Hodgkin’s disease were treated by transplantation of fetal thymic tissue. Clinical and immunologic studies, carried out for over 5 mo thereafter, revealed a prompt improvement in previously defective cellular immune functions, including a significant rise of absolute lymphocytes in the peripheral blood and a normalization of tuberculin skin sensitivity and of the response of peripheral blood lymphocytes to phytohemagglutinin. It is suggested that fetal thymic transplant into patients with Hodgkin’s disease appears at present the best tool of improving their immunologic deficiency.
The Sickle-Unsickle Cycle: A Cause of Cell Fragmentation Leading to Permanently Deformed Cells
Authors: Padilla F. , Bromberg P. A. , Jensen W. N.
Published: October 2019

We are reporting in vitro observations of sickle-unsickle transformation of freely suspended single cells (HbSS) induced by oxygenation-deoxygenation. The events were recorded by cinematography (phase optics, 16 mm cinematography). In addition, cells were fixed after progressive increments of oxygenation for subsequent scanning-beam electron microscopy. These studies seem to warrant the following conclusions regarding HbSS erythrocytes: (1) There is variability in the propensity to sickling of cells seemingly subjected to the same environment. (2) Repetitive sickling of a single cell does not result in identical sickle deformities. (3) Disk to sickle to disk transformation may occur without apparent membrane loss or distortion or may be accompanied by the shedding of microspherules or by the loss of microspherules and permanent cell deformation. (4) Red cell "flicker" normally seen by phase-contrast cinemicrophotography disappears early in the sickling process and recurs during unsickling. (5) Sickling and unsickling as visually detected required 10-15 sec.
Ristocetin: A Means of Differentiating Von Willebrand’s Disease Into Two Groups
Authors: Howard Margaret A. , Sawers R. J. , Firkin B. G.
Published: October 2019

Earlier studies have shown that patients with von Willebrand’s disease are considered to have normal platelets, but they lack at least one plasma protein. Results are presented indicating that ristocetin, known to aggregate normal platelets, fails to cause platelet aggregation in the group of von Willebrand’s disease patients exhibiting no platelet adhesiveness. It is postulated that there may be two groups of patients within von Willebrand’s disease and, further, that ristocetin will provide a useful approach to study the plasma deficiency or abnormality in von Willebrand’s disease.
Normal Granulocyte Colony-forming Cells in the Bone Marrow of Yemenite Jews With Genetic Neutropenia
Authors: Mintz Uri , Sachs Leo
Published: October 2019

The frequency of normal granulocyte colony-forming cells in the bone marrow of Yemenite Jews with genetic, absolute neutropenia and no special tendency to infection has been studied with conditioned medium from human embryo fibroblasts. Cells from these neutropenic patients gave an average of about twice the number of granulocyte colonies as bone marrow cells from nonneutropenic patients. No morphologic abnormalities were observed in the granulocytes in bone marrow smears or in colonies formed in vitro. The results indicate that the neutropenia in these patients was not due to a deficiency of granulocyte colony-forming cells. It is suggested that the neutropenia is due to a defect in the release mechanism of mature granulocytes from the bone marrow to the peripheral blood.
The Role of Granulocytes in Endotoxin-induced Vascular Injury
Authors: Gaynor Evelyn
Published: October 2019

This study examines the role of neutrophils (PMN) in the pathogenesis of the endothelial lesion induced by a single sublethal dose of endotoxin. It is intended to clarify whether the margination of PMN on endothelium after endotoxin causes intimal injury or is a response to it. Neutropenic rabbits had mean PMN counts of 33/cu mm 72 hr after nitrogen mustard (HN2). They were heparinized and given either intravenous endotoxin or saline and were sacrificed 30-60 min later. Preterminal blood samples were positive for the presence of endothelium in 77% of endotoxin-treated neutropenic rabbits, in 87% of endotoxin-treated normal rabbits, and in only 12% of neutropenic rabbits given saline. Sections of aorta revealed marked abnormalities of endothelium in rabbits receiving endotoxin, whether neutropenic (90% had lesions) or normal (85% had lesions). Endothelial abnormalities included vacuolation and lysis, marked subendothelial edema, and desquamation. Similar lesions in control neutropenic rabbits were not found, and mild abnormalities were seen only rarely. These data indicate that neutropenia does not protect rabbits from endothelial injury due to endotoxin. They further suggest that HN2 may cause endothelial damage either directly or secondary to the effects of neutropenia.
Effect of Smoking on Tissue Oxygen Supply
Authors: Sagone Arthur L. , Lawrence Thomas , Balcerzak Stanley P.
Published: October 2019

The purpose of this study was to determine if chronic exposure to low levels of carbon monoxide (CO) in man results in tissue hypoxia. For this reason, nine smokers (more than one pack of cigarettes per day) were studied. The presence of hypoxia was assessed by measurement of red cell mass (RCM). The effect of CO on intraerythrocytic factors involved with oxygen delivery was determined by measurement of oxygen-hemoglobin affinity (P50) and of red cell 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP). Values were compared to those of 18 nonsmokers of similar age, sex, and race. Values for carboxyhemoglobin (COHb), RCM, hemoglobin, hematocrit, and red cell count were significantly higher in the smokers. DPG levels were unaltered, while P50 and ATP levels were significantly lower in smokers. These data suggest that chronic exposure to low levels of CO results in tissue hypoxia, probably as a result of decreased blood oxygen carrying capacity and increased blood-O2 affinity. Adaption is reflected in an increased RCM and not by intraerythrocytic changes. The response in RCM may be to levels seen in polycythemia vera, as evidenced by a value of 37.6 in one smoker whose RCM fell to normal after discontinuing cigarettes. This study indicates that smoking causes mild erythrocytosis comparable to that seen in spurious or stress polycythemia. It also suggests that chronic exposure to low levels of CO may further embarrass tissue oxygen supply in patients with anemia, heart disease, chronic lung disease, and cerebral vascular disease in whom oxygen delivery to tissues is already marginal.
Dyserythropoiesis, Refractory Anemia, and "Preleukemia:" Metabolic Features of the Erythrocytes
Authors: Valentine William N. , Konrad Patricia N. , Paglia Donald E.
Published: October 2019

Twenty-one enzymatic activities and red cell glutathione content are compared in cord blood, dyserythropoietic disorders, normal subjects, and subjects with hemolytic syndromes and reticulocytosis approximating that of the newborn. The dyserythropoietic states are heterogeneous and include several hereditary disorders, "preleukemia" and overt leukemia, refractory anemia with and without marrow ringed sideroblasts, and folate deficiency. Many activities exceeded those of cord erythrocytes and "high reticulocyte" controls by one or even several standard deviations. The low phosphoglycerate kinase and glutathione peroxidase and relatively low ribosophosphate pyrophosphokinase and adenine-phosphoribosyl transferase of cord erythrocytes were mimicked uncommonly. Pyruvate kinase was often relatively or absolutely low and sometimes dramatically so. Enzyme ratios were grossly aberrant. Capricious very high individual activities occurred in some instances. The heterogeneous nature of case material, including both hereditary and acquired syndromes, renders it difficult to interpret similarities often seen from case to case and sometimes to cord blood patterns on the basis of the reversion to fetal erythropoiesis as a common denominator. Rather, the cyto- and karyokinetic abnormalities characterizing dyserythropoiesis of diverse etiologies may result in exaggerations and distortions of a normal asynchronism in loss of functional genetic material governing enzyme synthesis as the nucleus degenerates and cytoplasmic organelles are lost.
The Importance of Bone Marrow Biopsy in the Staging of Patients With Lymphosarcoma
Authors: Vinciguerra Vincent , Silver Richard T.
Published: October 2019

The frequency of bone marrow involvement in patients with lymphosarcoma (LSA) and the particular value of the marrow biopsy, as compared with the aspiration smear technique, in the initial staging of this disease were investigated. Certain physical findings and laboratory studies were analyzed to determine whether the presence of marrow invasion could be predicted. Of 75 patients, 47 (63%) were found to have a positive marrow examination. The clinical stage of 40 of these 75 patients was changed to stage IV as a result of bone marrow biopsy; these included four of nine (44%) stage I patients, 9 of 12 (75%) stage 5 patients, and 27 of 41 (65%) stage III patients. Bone marrow biopsy more often yielded positive results (62%) than did aspiration smears (38%). Little correlation was found between extent of disease on initial physical examination and marrow involvement. A normal hematocrit, white blood cell count, and/or platelet count did not preclude the presence of marrow invasion. The technique of bone marrow biopsy is a simple and valuable procedure in the staging of lymphosarcoma. It uncovers unsuspected and widespread diseases in those patients whose illness appears restricted to even one or two node groups. The high frequency of marrow involvement in patients with LSA is evidence that many patients have widespread disease at the time of diagnosis; thus, marrow biopsy, when positive, is an invaluable test for their initial staging. We urge that it be performed routinely in all patients, irrespective of apparent clinical extent of disease.
Nitroblue Tetrazolium Reduction: False Positive and False Negative Results
Authors: Ashburn Philip , Cooper M. Robert , McCall Charles E. , DeChatelet Lawrence R.
Published: October 2019

Quantitative and histochemical nitroblue tetrazolium reduction (NBT) tests were performed on leukocytes of 13 patients with polycythemia vera, seven with chronic granulocytic leukemia, eight with neoplastic disease associated with fever, 16 with bacterial infection, and 13 healthy control individuals. No significant differences were detected in the quantitative test between any of the groups studied. The histochemical NBT test was significantly higher than control in the patients with polycythemia vera and neoplasia associated with fever, as well as in those with known bacterial infection. It is suggested that patients with neoplasia or polycythemia vera may show a false positive reaction in the histochemical NBT test. Conversely, the test was significantly lower than control in patients with chronic granulocytic leukemia. Such patients might show a false negative reaction in the test even if infection were present.
Hereditary Hemolytic Anemia Associated With Abnormal Membrane Lipid. II. Ion Permeability and Transport Abnormalities
Authors: Shohet Stephen B. , Nathan David G. , Livermore Barbara M. , Feig Stephen A. , Jaffé Ernst R.
Published: October 2019

A familial nonspherocytic hemolytic anemia with altered red cell membrane lipids has been described. The membrane lipid lesion is also accompanied by excessive cation permeability and ouabain-sensitive pumping, which is in turn associated with excessive glycolytic energy diverted to the pump. This permeability defect and its demands for glycolytic energy are thought to contribute significantly to the early demise of the red cell in this disorder.
Studies on the Uptake of Synthetic Conjugated Folates by Human Marrow Cells
Authors: Hoffbrand A. V. , Tripp Edith , Houlihan Catherine M. , Scott J. M.
Published: October 2019

Pteroyltriglutamate shows little abiility (between 1% and 5%), compared to pteroylmonoglutamate (folic acid), to enter human marrow cells and to act as a coenzyme in intracellular DNA synthesis. This was shown by comparing the effectiveness of these two forms of the vitamin at stimulating folate-dependent pyrimidine incorporation into DNA in vitro in the bone marrow cells and lymphocytes of patients with megaloblastic anemia. It, therefore, appears that human hemopoietic cells (like Streptococcus fecalis rather than Lactobacillus casei) are unable to take up efficiently polyglutamyl forms of folate. The suggestion that polyglutamyl analogues of the antifolates might be more effective chemotherapeutic agents than corresponding monoglutamates, while biochemically possible, would appear to be precluded because of failure of transport of these compounds into human hemopoietic cells.
The Effect of Periodic Mixing on the Preservation of 2,3-Diphosphoglycerate (2,3-DPG) Levels in Stored Blood
Authors: Wood L. A. , Beutler E.
Published: October 2019

Blood from six donors was stored in two experimental blood preservatives, CPD-adenine-sodium ascorbate and bicarbonate-adenine-glucose-phosphate-mannitol. Control aliquots were stored in CPD-adenine and ACD-adenine preservatives. Half of each donor’s blood was stored without mixing and half was mixed vigororously 5 days each week. Glucose, ATP, and 2,3-DPG levels were measured at various times during storage in both the mixed and unmixed bags. Mixed bags maintained higher levels of glucose, ATP, and 2,3-DPG throughout storage. Frequent mixing was shown to be essential for the maintenance of 2,3-DPG with these preservatives.
Hodgkin’s Disease in Childhood
Authors: Young Robert C. , DeVita Vincent T. , Johnson Ralph E.
Published: October 2019

Thirty-eight children with Hodgkin’s disease have been treated over the past 8 yr with either intensive radiotherapy or combination chemotherapy (MOPP), depending on their initial stage. The median survival of the entire group of children has not yet been reached, as 63% are still alive, but it will be in excess of 58 mo. Median survivals by stage are as follows: stage I, greater than 46 mo; stage II, greater than 46 mo; stage III, 35 mo; and stage IV, 26.7 mo. Although the numbers of children are small, these results appear significantly superior to published reports utilizing less intensive radiotherapy and single-agent chemotherapy and suggest that intensive radiotherapy for localized disease and combination chemotherapy for advanced disease may, at present, be the preferred forms of therapy for Hodgkin’s disease in childhood.
Platelet Production in Experimental Iron Deficiency Anemia
Authors: Choi Sun I , Simone Joseph V.
Published: October 2019

Abnormal platelet counts have been observed in patients with iron deficiency anemia. To study this relationship, rats were made iron deficient, and platelet production was estimated by radiosulfate incorporation into platelets. With progressive iron deficiency anemia, both platelet counts and the rate of platelet production increased significantly. Platelet survival was normal. Injection of iron was followed by a fall in platelet counts and platelet production to normal levels within 72 hr, at which time stainable iron had appeared in the bone marrow. An inverse relationship between platelet counts and hematocrit was also seen. It appears that platelet homeostasis in iron deficiency anemia is influenced by the duration and severity of anemia.
Gm Allotype Preference in Erythrocyte IgG Antibodies of Patients With Autoimmune Hemolytic Anemia
Authors: Litwin S. D. , Balaban S. , Eyster M. E.
Published: October 2019

IgG antibodies were isolated from erythrocytes of five patients with autoimmune hemolytic anemia (AHA) and one case of hemolytic anemia of unknown etiology. All six persons were heterozygous for human IgG1 allotypes, and thus their serum immunoglobulins were Gm (a+f+). Quantitative analysis of the antibody preparations disclosed that three patients contained only the Gm(a) allotype; the remaining samples showed a predominance of Gm(a) in comparison to the Gm(f) allele. It was concluded that erythrocyte antibodies of patients with AHA are often restricted in respect to their Gm genetic characters with a preference for the Gm(a) allotype. In a second group of experiments, serums from three cases of hemolytic anemia were incubated with Rh+ erythrocytes from a healthy donor. Subsequently, the red cell IgG coat was eluted and analyzed. One sample had only Gm(a+) antibody; a second case showed Gm(a) predominance. The last antibody preparation varied from a disproportionately high Gm(a) concentration to equal allotype concentrations, depending on the antibody/antigen ratio used during the sensitization of the erythrocytes. The latter data suggested that allelic expression was influenced by the immunologic characteristics of the antibody subpopulation tested. No association could be demonstrated between the Ig allotypes and either the Rh specificity of the eluate, or the presence of complement coating on erythrocytes. These findings are similar to a previous report from this laboratory that noted a preference for the Gm(a) allotype in many isoantibodies with Rh specificity. The data suggest an association between certain erythrocyte antibodies and Ig allotypes.
Methyldopa: Physicochemical Characterization of the Erythrocyte Autoantibody
Authors: Wenz Barry , Lalezari Parviz
Published: October 2019

A modification of the Polybrene technique for red blood cell antibody characterization has been employed to differentiate the panhemagglutinins arising during methyldopa administration from those accompanying other disease states. Dissociation characteristics of methyldopa-associated antigen-antibody complexes were determined by temperature gradient dissociation technique. Data obtained by this technique for cell-bound antibody were found to distinguish this antibody from those accompanying systemic lupus erythematosus (SLE) and Pronestyl therapy. Graphic data derived from temperature gradient dissociation curves at varying antibody concentrations were obtained for the methyldopa-induced serum antibodies. Results obtained with samples from all six patients were found to be relatively uniform in relation to each other, and different from similarly derived results for red cell antibodies accompanying idiopathic autoimmune hemolytic anemia and Hodgkin’s disease. By means of these procedures, as well as standard blood banking techniques, distinguishing features are described that permit in vitro segregation of these distinct groups of red cell autoantibodies.
Thrombotic Thrombocytopenic Purpura— Coagulation Parameters in Twelve Patients
Authors: Jaffe Eric A. , Nachman Ralph L. , Merskey Clarence
Published: October 2019

Twelve patients with thrombotic thrombocytopenic purpura have been studied with emphasis on the changes in blood coagulation and the occurrence of disseminated intravascular coagulation (DIC). No coagulation abnormalities were found in six patients. Minimal abnormalities were present in three patients and major abnormalities compatible with DIC were present in three patients. There was little temporal relationship between the coagulation abnormalities and the clinical pathological course except for the extent of hemolysis. In addition, heparin administration in four patients had no effect on the course of the disease. Intravascular coagulation does not appear to be a primary factor in the pathogenesis of thrombotic thrombocytopenic purpura and the changes suggestive of DIC, when present, may well result from, rather than cause, the hemolytic anemia.
The Effect of Cold on Platelets. III. Adenine Nucleotide Metabolism After Brief Storage at Cold Temperature
Authors: Kattlove Herman E. , Mormino Dorothy
Published: October 2019

The effect of cold on platelet adenine nucleotide (PAN) metabolism was studied. Spontaneous aggregation which occurs when chilled platelet-rich plasma (PRP) is simultaneously warmed and stirred was not accompanied by the changes in adenine nucleotides associated with the release reaction. Connective tissue caused the release of the same amount of ADP and conversion of equal amounts of ATP to IMP and hypoxanthine in cold-stored platelets as it did in room temperature stored platelets. However, cold did have an important effect on PAN. In PRP stored at cold (0° C, 3° C) temperatures and warmed up to 37° C in the presence of 3H adenine, there was an increase in the conversion of adenine to its metabolites and ultimately to hypoxanthine as compared to PRP stored at warmer temperatures. This effect could not be prevented by ouabain, prostaglandin E1, antibody to immunoglobulin M or adenosine.
Effect of Platelets Stored at 22° C for 24 Hours in Patients With Acute Leukemia
Authors: Vallejos C. S. , Freireich E. J. , Brittin G. M. , de Jongh D. S.
Published: October 2019

We have compared the ability of transfused platelets that were fresh or stored for 24 hr at room temperature (22° C) to increase the platelet counts of thrombocytopenic patients with acute leukemia. Increments in the recipients’ platelet counts after transfusion of stored platelets were substantially smaller and shorter-lived than those given by fresh platelets. This was the case even in patients who responded consistently to fresh platelets.
Pokeweed Mitogen Response of Lymphocytes in Chronic Lymphocytic Leukemia: A Fine Structural Study
Authors: Cohnen Georg , Douglas Steven D. , König Erika , Brittinger Günter
Published: October 2019

The in vitro response of lymphocytes from patients with chronic lymphocytic leukemia (CLL) to pokeweed mitogen (PWM) was diminished and/or delayed. Electron microscopy of PWM stimulated CLL lymphocytes revealed both PHA-type blast cells and plasmacytoid cells. Some PHA-type blast cells were indistinguishable from corresponding normal cells. However, many transformed cells had a reduced cell, cytoplasmic, and nuclear area in comparison to transformed lymphocytes from normal individuals. In 7- and 9-day cultures, 5-10% of the cells present were plasmacytoid. No ultrastructural differences were observed between the plasmacytoid cells in PWM stimulated cultures of normal and CLL lymphocytes. The findings support the concept that the circulating lymphocyte population in CLL is comprised predominantly of abnormal cells, in addition to a small number of normal T and B lymphocytes.
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

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

"Properties of the Platelet Retention (von Willebrand) Factor and Its Similarity to the Antihemophilic Factor (AHF)" by Harvey J. Weiss, John Rogers, and Harvey Brand (pp. 809-815).

On page 811, Table 1, the second and third lines from the bottom were reversed. "37°C, 2 hr" should go with "25% platelet retention;" "4°C, 18 hr" should go with "88% platelet retention."
Hematopoiesis Versus Osteogenesis in Ectopic Bone Marrow Transplants
Authors: Meck R. A. , Haley J. E. , Brecher G.
Published: October 2019

Dispersed and intact marrow fragments have been implanted in the omentum and subcutaneous fat of irradiated and nonirradiated hosts. Osteogenesis and hemopoiesis in varying proportions were observed at 10 and 35 days. The subcutaneous site favored osteogenesis, the omental site and host irradiation prior to transplant resulted in predominance of hemopoiesis. In dispersed and recompacted marrow grafts, only hemopoiesis developed. Differentiation was predominantly granulocytic. Osteogenesis is not an obligatory prerequisite of hemopoiesis in extramedullary sites.
Globin Messenger RNA in Hemoglobin H Disease
Authors: Benz Edward J. , Swerdlow Paul S. , Forget Bernard G.
Published: October 2019

Functional messenger RNA (mRNA) for human globin synthesis was isolated from reticulocytes of each of two patients with hemoglobin H disease. The RNA was tested for its capacity to direct globin synthesis in a messenger RNA-dependent cell-free system derived from Krebs Type II mouse ascites tumor cells. In each case, hemoglobin H disease mRNA directed the synthesis of a great excess of β-globin chains relative to α-globin chains of hemoglobin A. The β/α synthetic ratios obtained in the cell-free system at saturating concentrations of mRNA were >22 and >15, respectively, for the two hemoglobin H disease mRNA preparations, whereas the β/α synthetic ratios obtained by incubation of intact reticulocytes from these same patients were 2.6 and 2.8, respectively. The β/α synthetic ratio obtained in the cell-free system did not vary when lower concentrations of hemoglobin H disease mRNA were used. A marked decrease in the amount of functional α-globin-chain mRNA relative to β-chain mRNA is therefore associated with the decreased α-chain synthesis observed in hemoglobin H disease. This decrease in α-chain-specific mRNA activity is greater than expected from the β/α synthetic ratio of intact reticulocytes in hemoglobin H disease.
Abnormalities of Megakaryocytes in Sl/Sld Mice
Authors: Ebbe Shirley , Phalen Elizabeth , Stohlman Frederick
Published: October 2019

Megakaryocytopoiesis was evaluated in Sl/Sld mice and their heterozygous and homozygous normal (+/+) littermates. Sl/Sld mice had a normal concentration of blood platelets which were of normal size. Numbers of megakaryocytes in bone marrow and spleen were reduced, but individual megakaryocytes were larger than normal.