bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukemic relapse 5 1/2 years after allogeneic bone marrow transplantation
Authors: Oliff A , Ramu NP , Poplack D
Published: October 2019

A 13-yr-old male with acute myelogenous leukemia was treated with various chemotherapy regimens for 3 1/2 yr and then underwent an allogeneic bone marrow transplantation. The donor marrow was successfully engrafted, and the patient remained in remission free of all chemotherapy. Then, 5 1/2 yr later, he developed an extramedullary relapse with a chloroma of his maxillary sinus. This case illustrates the need for prolonged followup of transplant recipients and suggest that statements proposing cure as a result of this procedure may be premature.
32P and acute leukemia: development of leukemia in a patient with hemoglobin Yakima
Authors: Bagby GC Jr , Richert-Boe K , Koler RD
Published: October 2019

In 1954 a then 31-yr-old male was found to have erythrocytosis. Over the ensuing decade he received 72 mCi32P. In 1964 his daughters were found to have erythrocytosis. Further investigation led to the discovery of hemoglobin Yakima, a variant with high oxygen affinity. He received no further therapy and was well until 1975, when he developed the preleukemic syndrome. Within 12 mo. he developed acute nonlymphocytic leukemia accompanied by fetal erythropoiesis. Because the inital discovery of this type of hemoglobinopathy came 27 yr after the introduction of 32P for use in the treatment of polycythemia vera, and because there are now known to be more than 39 different high- oxygen-affinity hemoglobins, we anticipate that more patients such as ours have been exposed to 32P. The exposed population should be cosely followed, since this will likely permit assessment of the risk of 32P- induced leukemia in a nonneoplastic condition.
Leukocyte-platelet interactions in a murine model of Chediak-Higashi syndrome
Authors: Kaplan SS , Boggs SS , Nardi MA , Basford RE , Holland JM
Published: October 2019

Chediak-Higashi (CH) syndrome, a genetic disease affecting man and other animals, is partially characterized by defective platelets that lack serotonin and dense bodies and by impaired leukocyte function where chemotaxis, degranulation, and bacterial killing are decreased. The effects of normal platelets containing serotonin and of reagent serotonin on the subnormal microbicidal activity of CH leukocytes were evaluated. The peripheral blood leukocytes of the beige mouse, an animal model with CH syndrome, were used with Staphylococcus aureus as the bacterial challenge. Addition of as few as two normal platelets/leukocyte resulted in normal levels of microbicidal activity of CH leukocytes. A similar normalization of leukocyte function was seen when 1-100-micrometer serotonin was added to the incubation mixture. Based on this work and work of others, a plausible explanation for these observations is that normal platelets interact with CH leukocytes, releasing serotonin, which results in reversal of the CH leukocyte defect in bacterial killing.
Myeloproliferative syndromes: a unique presentation of chronic myelogenous leukemia (CML) as a primary tumor of bone
Authors: Longo DL , Whang-Peng J , Jaffe E , Triche TJ , Young RC
Published: October 2019

A 45-yr-old female presented with a rapidly enlarging bony tumor that was eventually identified as a Philadelphia chromosome (Ph1)-positive myeloproliferative disorder with extramedullary blastic transformation. This transformation occurred in the absence of demonstrable chronic or acute leukemic phase. She had no history of a chronic or prodromal illness in spite of a bone marrow biopsy showing myelofibrosis and liver biopsy documenting extramedullary hematopoiesis. This case represents a unique constellation of features of the myeloproliferative syndrome in which the diagnosis was obscure until special stains of the bony tumor and cytogenetic studies were performed.
Postmitotic marrow neutrophils and neutrophil mobilization in man: role of the spleen
Authors: Deubelbeiss KA , Roth P
Published: October 2019

The relationship between postmitotic marrow neutrophils (PMMN) and neutrophil increment in blood after an intravenous dose of 3 mg hydrocortisone/kg was studied in patients with normal-sized spleens and compared with splenectomized and splenomegalic patients. PMMN were quantified from the ferrokinetic measurement of the normoblast number and the PMMN/normoblast ratio in bone marrow biopsy sections. In 12 control patients with normal PMMN the increment was 3.50 +/- 1.13 X 10(9) neutrophils/liter. An excellent correlation was found between the number of PMMN and the maximal neutrophil increment (y = 826x - 1021, r = 0.93, p less than 0.001) among 24 patients with normal spleen size and a wide range of marrow cellularity. Significantly higher responses were observed in 10 splenectomized patients (y = 872x + 1429, r = 0.92, p less than 0.001). The two regression lines were shown to be parallel, indicating a diminution of the response by 2.5 X 10(9) neutrophils/liter in the presence of a normal spleen. In 11 hypersplenic patients the responses were further reduced and more variable. Peak neutrophilia occurred after median values of 2, 3, and 4 hr in the hypersplenic, the control, and the splenectomized group, respectively. These studies indicate that allowing for the different response curves neutrophil increments may be used as an index of PMMN in patients with normal spleen size and in splenectomized patients. They further suggest sequestration of the prematurely released cells by the spleen.
Autoimmune cytotoxic granulocyte antibodies in normal persons and various diseases
Authors: Drew SI , Terasaki PI
Published: October 2019

Of 400 female and 58 normal nonommunized male sera approximately 10% were cytotoxic for a panel of allogeneic granulocytes. Sera with strong alloreactivity were also autoreactive, which emphasized the large autoimmune component of most alloantisera against granulocytes. The cytotoxic granulocyte autoantibodies were complement dependent, of the IgM class, and exhibited optimum cytotoxic activity in vitro at 5 degrees C precomplement incubation temperatures with papain-treated cells. The sera were unreactive with autologous or allogeneic B and T lymphocytes, monocytes, and red blood cells but were cytotoxic for adult and cord granulocytes, eosinophils, and chronic myeloid leukemia cells. Granulocyte autoantibodies were present in 53% of sera from 57 patients with systemic lupus erythematosus (p less than 0.00002) but were not found in increased frequency in the sera of patients with 28 other diseases. We conclude that a single tissue-specific antigenic determinant(s) called “G” may be present on granulocytes and is the target of naturally occurring autoantibodies.
Hemoglobin E trait reexamined: a cause of microcytosis and erythrocytosis
Authors: Fairbanks VF , Gilchrist GS , Brimhall B , Jereb JA , Goldston EC
Published: October 2019

The current Indochinese resettlement program in the United States has resulted in an increase in the number of persons with hemoglobin E trait. American physicians should be aware of the hematologic expressions of this innocuous condition. The hematologic manifestations of 21 persons with hemoglobin E trait were evaluated. The subjects were of Tai-dam, Vietnamese, Chinese, Laotian, and European origin. These studies showed uniform hematologic manifestations in hemoglobin E trait, characterized by slight microcytosis, by morphologic features resembling those of thalassemia minor, and often by increased erythrocyte count. Hemoglobin instability also was confirmed.
Controlling the production of blood cells
Authors: Cline MJ , Golde DW
Published: October 2019

The development since 1966 of a technology for growing stem cells in vitro has provided new insights into the controls of blood cell production. Hematopoietic hormones have been purified and important cellular interactions in hematopoiesis have been defined.
Prostacyclin (prostaglandin I2, PGI2) inhibits platelet adhesion and thrombus formation on subendothelium
Authors: Weiss HJ , Turitto VT
Published: October 2019

Prostaglandin I2 (prostacyclin, PGI2), a substance synthesized in the wall of blood vessels, has been previously shown to inhibit the aggregation of platelets in stirred platelet-rich plasma. We used a method in which segments of deendothelialized rabbit aorta are perfused at arterial shear rates with human blood and found that both platelet adhesion and thrombus formation on subendothelium was inhibited in blood containing 10 nM PGI2. PGI2 appears to reduce adhesion by inhibiting platelet spreading. These findings suggest that PGI2 could regulate the deposition of platelets on vascular surfaces.
In vitro platelet abnormality in adenosine deaminase deficiency and severe combined immunodeficiency
Authors: Lee CH , Evans SP , Rozenberg MC , Bagnara AS , Ziegler JB , Van der Weyden MB
Published: October 2019

The platelets of an infant with severe combined immune deficiency and adenosine deaminase deficiency showed markedly diminished responses to ADP-induced aggregation in vitro. This abnormality was corrected by the addition of purified adenosine deaminase in vitro. Exogenous adenosine added to platelet-rich plasma caused markedly prolonged inhibition of ADP-induced aggregation. This was shown by isotopic studies to be due to slow clearance of adenosine and hence persistence of this nucleoside. Direct assay for adenosine deaminiase in plasma and platelet lysates of the patient confirmed the very low activity of this enzyme. Raised cAMP levels were demonstrated in his platelets. The deranged adenosine metabolism and raised cAMP in the platelets of this child with severe combined immunodeficiency may explain the altered response to ADP. Despite the in vitro platelet aggregation abnormality, the patient had no clinical evidence of impaired hemostasis.
Human myeloid progenitor cells expressing HLA antigens
Authors: Fitchen JH , Cline MJ
Published: October 2019

Marrow cells of known HLA type were incubated with HLA antiserum plus complement and then plated in soft agar. Colony formation was consistently inhibited by appropriate HLA antisera. Mixing experiments excluded an indirect effect on CFU-C by lysis of mature leukocytes. We conclude that human CFU-C express HLA antigens.
Salicylate blockade of granulocyte adherence and the inflammatory response to experimental peritonitis
Authors: Spagnuolo PJ , Ellner JJ
Published: October 2019

Aspirin profoundly inhibited the in vitro augmentation of human and mouse granulocyte adherence to nylon fiber induced by the bacterial products Escherichia coli endotoxin and Staphylococcus aureus culture filtrate. Granulocytes obtained from normal volunteers during the 48 hr following ingestion of aspirin did not respond normally to endotoxin stimulation. Furthermore, pretreatment of mice with sodium salicylate prior to intraperitoneal infection with Streptococcus pneumoniae impaired granulocyte exudation and resulted in uncontrolled bacteremia and greater lethality of infection.
Genetic control of F cells in human adults
Authors: Zago MA , Wood WG , Clegg JB , Weatherall DJ , O'Sullivan M , Gunson H
Published: October 2019

Hb F levels were determined on samples from 750 normal blood donors. Six individuals (0.8%) had Hb F levels in excess of 1.1%, the upper end of the continuous distribution. Eight individuals at the upper end and 7 individuals at the lower end of the range were selected for family studies. These studies revealed that the control of Hb F levels in adults, as judged by the more sensitive F-cell technique, has a major genetic component. Structural analysis of the Hb F in several cases demonstrated that both G gamma and A gamma chains were present, but in variable proportions. These results are discussed in light of current concepts of adult F-cell production.
Increased circulating neutrophils with surface receptor activity for immunoglobulin G in polycythemia vera and myeloid metaplasia
Authors: Gilbert HS , Goldberg R , Ward L
Published: October 2019

Reports of heterogeneity of IgG receptor activity of normal circulating neutrophils prompted measurements in myeloproliferative disease to determine if dysplasia of the hematic stem cell resulted in an abnormality of this membrane property. IgG receptors were assayed by rosette formation in suspension with human Rh-positive erythrocytes sensitized with high-titer Rh antiserum. IgG receptors were detected on 19 +/- 1.6% (mean +/- SEM) of neutrophils from 45 normal subjects. A significant increase in IgG-receptor-bearing neutrophils was found in polycythemia vera (PV) and myeloid metaplasia (MyM), with values of 70 +/- 3.6% and 69.7 +/- 4.3%, respectively. Normal values were observed in polycythemic states not due to myeloproliferative disease and in chronic myelocytic leukemia. Rosette-forming neutrophils were increased to 52.3 +/- 3.7% in infection and inflammatory disease, but this value was significantly lower than those in PV and MyM. Increased IgG receptors in PV and MyM may be related to the activated state of the neutrophil and may result from an intrinsic cellular abnormality of the proliferating clone or from altered bone marrow release. Quantitation of neutrophil IgG receptors may be of value in the differential diagnosis of PV and MyM and may offer insights into the derangement of hematopoiesis that underlies these myeloproliferative disorders.
Factor VII Padua 2: another factor VII abnormality with defective ox brain thromboplastin activation and a complex hereditary pattern
Authors: Girolami A , Cattarozzi G , Dal Bo Zanon R , Toffanin F
Published: October 2019

A new factor VII abnormality is presented. The propositus was a 9-yr- old child who presented a mild bleeding tendency characterized by epistaxis and easy bruising. The parents were not consanguineous, but they came from the same area. The laboratory features were mild prolongation of prothrombin time and P.P. test and normal partial thromboplastin and Stypven cephalin clotting times. The Thrombotest was moderately prolonged. Factor VII was 40%-50% of normal using rabbit or human brain thromboplastin, but only 13%-24% using ox brain thromboplastin. Factor VII cross-reacting material (CRM) was about 50% of normal. The father, a paternal aunt, and a paternal cousin showed similar clinical and laboratory findings. The brother of the propositus, the mother, and other members of her family showed about 50% factor VII activity and CRM and were considered to be heterozygotes for true factor VII deficiency. Similar findings were also present in the father and in the brother of the affected cousin. The defect in the propositus seems to consist of a double heterozygosity between abnormal factor VII and heterozygous factor VII true deficiency. The factor VII abnormality appears to consist of abnormal reactivity toward ox brain tissue thromboplastins and appears to be different from previously described factor VII abnormalities. The name factor VII Paudua2 is proposed for this condition.
Shifts in expression of cell membrane phenotypes in childhood lymphoid malignancies at relapse
Authors: Borella L , Casper JT , Lauer SJ
Published: October 2019

To determine if cell membrane phenotypes change under the selective pressures of therapy we have conducted a prospective study of 54 children with lymphoid malignancies of T-like, B-like, common, and null cell types. Membrane phenotypes were determined at diagnosis in all patients and again 1–24 mo later in 18 children who either failed induction therapy or had one or more relapses. In 7 patients the cells tested were from relapse sites different than those of the original diagnoses. The data indicate that at relapse most children with lymphoid neoplasias had the same cell membrane phenotype as established at diagnosis, and suggest that the site of relapse did not affect the expression of cell surface markers. However, there were three exceptions: (1) a child initially diagnosed as having null cell acute lymphocytic leukemia had 90% T-antigen-positive blasts in her second- relapse bone marrow; (2) only membrane IgM was present on relapse blasts from a B-cell lymphoma that had both membrane IgM and IgD before initiation of treatment; (3) at diagnosis, bone marrow blasts from a child with T-like leukemia expressed both T antigen and E receptors, but at relapse, bone marrow and pleural fluid cells expressed only T antigens. We postulate that these phenotype shifts may be due to selective effects of therapy on cells at different stages of differentiattion.
Surface immunoglobulin density on human peripheral blood mononuclear cells
Authors: Slease RB , Wistar R Jr , Scher I
Published: October 2019

The densities of surface immunoglobulin (slg) on peripheral blood mononuclear cells (PBM) of normals and patients with chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (LCL), and hairy cell leukemia (HCL) were analyzed using the fluorescence- activated cell sorter (FACS). PBM were labeled with fluorescein conjugates of F(ab')2 fragments of affinity chromatography-purified anti-Fab or class-specific anti-mu, anti-delta, anti-gamma, or anti- alpha. Histograms of relative cell fluorescence, rems of relative cell fluorescence, reflecting slg density, were prepared with the FACS. Anti- Fab-labeled normal PBM demonstrated a homogeneous low-density peak that when separated by the FACS and analyzed cytochemically consisted predominantly of monocytes, whereas brighter-staining cells were predominantly lymphocytes. Anti-mu and anti-delta labeled 9.0% and 8.5% of normal PBM, respectively, the slg+ cells being virtually all lymphocytes. Cells labeled by anti-gamma exhibited low homogeneous slg density and consisted of more than 80% monocytes. No normal or leukemic PBM were labeled by anti-alpha. All slg-positive cells (less than 5% monocytes) from 12 of 13 patients with CLL had very low homogeneous densities of slg and bore slgM, Whereas cells from 9 of 13 and 2 of 13 patients bore slgD and slgG, respectively. Similarly, PBM from 2 patients with HCL exhibited low and homogeneous densities of algM, slgD, and slgG, whereas those from a third patient bore only slgG. By contrast, the density of slgM and PBM derived from 3 patients with LCL was very high; slgD and slgG densities varied from very high to undetectable in these patients. The different homogeneous densities of slg on peripheral blood lymphocytes from patients with CLL, HCL, and LCL suggest that these diseases represent malignant transformation of different B-lymphocyte subpopulations.
Release of platelet fibronectin (cold-insoluble globulin) from alpha granules induced by thrombin or collagen; lack of requirement for plasma fibronectin in ADP-induced platelet aggregation
Authors: Zucker MB , Mosesson MW , Broekman MJ , Kaplan KL
Published: October 2019

Platelets lysed with Triton X-100 contain 3.44 +/- 1.27 (SD) microgram of fibronectin (cold-insoluble globulin) per 10(9) platelets. Fibronectin was partially released from washed whole platelets by collagen or thrombin, and its release by collagen was inhibited by aspirin. Analysis of subcellular fractions obtained by density-gradient centrifugation of disrupted platelets indicated that fibronectin was contained in the alpha granules. Fibrinogen depleted of fibronectin (less than 2 microgram/mg) supported ADP-induced aggregation as effectively as fibrinogen contaminated with this protein, thus reinforcing the generally held view that fibrinogen itself is the necessary protein cofactor in this reaction.
Two cases of carcinoma of the lung characterized by a bone marrow agar culture pattern resembling acute myeloid leukemia
Authors: McCarthy JH , Sullivan JR , Ungar B , Metcalf D
Published: October 2019

In vitro agar culture patterns of bone marrow cells in acute myeloid leukemia may show several growth patterns, including cultures where no colonies or clusters develop, cultures with varying numbers of clusters and no colonies, or colony and cluster formation with an extremely high ratio of clusters to colonies. Twelve cases of carcinoma of the lung are described, of which two show an in vitro growth pattern of cluster formation alone, characteristic of that seen in acute myeloid leukemia. The remaining ten patients showed slightly reduced colony numbers compared to normal.
Clonal growth of metastatic carcinoma of bronchus in bone marrow culture
Authors: Francis GE , Broadbent JE , Johnson N , Hoffbrand AV
Published: October 2019

Bone marrow cells from a 35-yr-old male with small cell anaplastic carcinoma of the bronchus and bone marrow metastases were cultured in semisolid agar. Numerous small clones grew in the cultures, with a similar gross appearance to clones produced by cell from a proportion of patients with acute myeloid leukemia. Examination of the cells from these clones by electron microscopy revealed marked differences between these cells and cells grown in cultures from normal and acute myeloid leukemia marrow. This suggests that metastatic cells of the anaplastic carcinoma of the bronchus grew in clones in the agar culture system.
Lithium and granulocytopenia during induction therapy of acute myelogenous leukemia
Authors: Stein RS , Flexner JM , Graber SE
Published: October 2019

Twenty-seven patients receiving a standard cytosine arabinoside and daunorubicin regimen as induction of reinduction therapy of acute myelogenous leukemia were randomly assigned to receive lithium carbonate, 300 mg t.i.d., or no lithium. Treatment groups were comparable with respect to age and baseline granulocyte counts. All patients developed granulocyte nadirs below 100/cu mm. By actuarial analysis, the median duration of granulocytopenia, less than 1000/cu mm, was 16.0 days in the lithium group and 24.6 days in the no-lithium group, p = 0.013. The median duration of granulocytes less than 500/cu mm also favored the lithium group but only approached statistical significance: 14.0 days versus 20.5 days, p = 0.054. Lithium levels between 0.5 and 1.0 meq/liter were easily maintained in 11 of 12 patients receiving lithium, 300 mg t.i.d., and toxicity directly attributable to lithium was not observed. Despite the shortened duration of neutropenia, the incidence of infections and the rate of remission were not affected.
Membrane receptors and their redistribution in lymphoproliferative disorders
Authors: Naeim F , Bergmann K , Gatti RA
Published: October 2019

Lymphoid cells from 20 patients with lymphoproliferative disorders, including chronic lymphocytic leukemia, hairy cell leukemia, Sezary syndrome, lymphoma, and lymphadenitis, were studied for redistribution of surface membrane immunoglobulins (SmIg) and concanavalin A (Con-A) receptors. Fluorescein-labeled polyvalent goat anti-human immunoglobulin and fluoresceinated concanavalin A were used as ligands. Results were similar with both ligands. The highest percentage of capping of ligand-membrane receptors was noted in mononuclear cells from patients with “hairy” cell leukemia: from 24% to 90%. These cells showed moderate to marked fluorescein activity and were able to cap within 15 min at 4 degrees C. Chronic lymphocytic leukemia cells showed a weak fluorescein stain with a very low percentage of cells (0%--16%) capping. Lymph node cells from patients with lymphoma demonstrated moderate to strong fluorescein activity with only an average of 3% of the cells capping; while lymphoid cells from patients with lymphaedenitis showed an average of 27.5% capping and moderate fluorescein activity. Capping of Con-A receptors in mononuclear cells from patients with Sezary syndrome was poor (0%--14%) with moderate fluorescein intensity. This report demonstrates difference in density and mobility of binding sites for SmIg and Con-A on the surface membrane of lymphoid cells from various subclasses of lymphoproliferative disorders. These differences may assist in the differential diagnosis and classification of these conditions.
Fetal erythropoiesis and hemoglobin ontogeny in tail-short (Ts/+) mutant mice
Authors: Brotherton TW , Chui DH , McFarland EC , Russell ES
Published: October 2019

Mutant Ts/+ fetuses are developmentally retarded as compared to normal +/+ littermates. Mutant fetuses have less total hemoglobin than do normal fetuses of the same gestational age. However, when compared to +/+ fetuses of similar body weight, Ts/+ fetuses have the appropriate amount of total hemoglobin, suggesting that the apparent anemia observed in mutant fetuses is most likely the result of delay in growth and development. Changes in proportions of embryonic hemoglobins during fetal development are similar in Ts/+ and +/+ fetuses at day 12 and later of gestation. Moreover, adult hemoglobin is detected in circulating primitive nucleated erythrocytes in the developmentally retarded Ts/+ mutant fetuses at about the same chronologic age as their +/+ normal littermates.
Megakaryocyte colony formation from human bone marrow precursors
Authors: Vainchenker W , Bouguet J , Guichard J , Breton-Gorius J
Published: October 2019

We report the growth in plasma clot culture of megakaryocyte colonies from adult bone marrow cells with the use of four different sources of erythropoietin (Ep) as the stimulating factor. A major proportion of the megakaryocyte colonies (75%) were pure, while the others were mixed, involving erythroblasts and megakaryocytes. Ultrastructural studies have shown that the maturation of megakaryocytes was essentially normal and that platelet shedding occurred. Megakaryocyte colony formation required a large number of plated cells (greater than 3 X 10(5)/ml). In the absence of erythropoietin, rare spontaneous megakaryocyte colonies could be observed, while no erythroid colonies were present. However, erythropoietin induced a fivefold increase in the total number of colonies. These data suggest that erythropoietin is involved in the differentiation of human megakaryocytes, but that it does not act alone, since another factor related to the number of seeded cells appears essential for the formation of human megakaryocyte colonies.
Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics
Authors: Hittelman WN , Broussard LC , McCredie K
Published: October 2019

The phenomenon of premature chromosome condensation (PCC) was used to compare the bone marrow proliferation characteristics of 163 patients with various forms of leukemia prior to the initiation of new therapy. The proliferative potential index (PPI, or fraction of G1 cells in late G1 phase) and the fraction of cells in S phase was determined and compared to the type of disease and the bone marrow blast infiltrate for each patient. Previously untreated patients with acute leukemia exhibited an average PPI value three times that of normal bone marrow (37.5% for acute myeloblastic leukemia [AML], acute monomyeloblastic leukemia [AMML], or acute promyelocytic leukemia [APML] and 42% for acute lymphocytic leukemia [ALL] or acute undifferentiated leukemia [AUL]). Untreated chronic myelogenous leukemia (CML) patients showed intermediate PPI values (25.2%), whereas CML patients with controlled disease exhibited nearly normal PPI values (14.6%). On the other hand, blastic-phase CML patients exhibited PPI values closer to that observed in patients with acute leukemia (35.4%). Seven patients with chronic lymphocytic leukemia (CLL) exhibited even higher PPI values. No correlations were observed between PPI values, fraction of cells in S phase, and marrow blast infiltrate. For untreated acute disease patients, PPI values were prognostic for response only at low and high PPI values. These results suggest that the PCC-determined proliferative potential is a biologic reflection of the degree of malignancy within the bone marrow.
Comparison of fibrinogen association with normal and thrombasthenic platelets on exposure to ADP or chymotrypsin
Authors: Mustard JF , Kinlough-Rathbone RL , Packham MA , Perry DW , Harfenist EJ , Pai KR
Published: October 2019

Although 125I-fibrinogen becomes associated with washed platelets from normal human subjects during ADP-induced shape change and aggregation, 125I-fibrinogen did not become associated with washed plateletes from a thrombasthenic subject during ADP-induced shape change and the platelets did not aggregate. Platelets from control and thrombasthenic subjects were treated with chymotrypsin, which is known to degrade platelet membrane glycoproteins. More 125I-fibrinogen became associated with chymotrypsin-pretreated platelets from normal subejcts than with untreated platelets, and fibrinogen caused the enzyme-treated platelets to aggregate. 125I-fibrinogen did not become associated with chymotrypsin-pretreated thromobasthenic platelets, and fibrinogen did not aggregate them. Thus, there appears to be a defect in thrombasthenic platelets that prevents the association of fibrinogen with them.
Thrombocytosis-induced suppression of small acetylcholinesterase- positive cells in bone marrow of rats
Authors: Long MW , Henry RL
Published: October 2019

Transfusion of platelet concentrates was used to establish a thrombocytosis of approximately three times normal platelet levels in male rats. This thrombocytosis resulted in a rebound thrombocytopenia to 60% of normal counts. Examination of the small acetylcholinesterase (ACh-E) positive cells of the marrow at this time showed a reduction to 50% of normal levels without significant changes in control animals. A second group of experiments indicated that this suppression developed as early as the third day posttransfusion, persisted until day 7, and returned to baseline levels by day 9. Incorporation of 75SeM indicated that the reduction in platelet count was due to decreased platelet production. Little or no changes were observed in the hematocrit or WBC. This evidence supports the hypothesis that these cells are early cells in the megakaryocytic series. They are the earliest cells of the series seen to be affected by thrombocytosis. Feedback control by platelets or platelet extracts of this cell population may represent one level of regulation of megakaryopoiesis.
Effect of prothrombin complex concentrates on factor VIII inhibitor levels
Authors: Kasper CK
Published: October 2019

Factor VIII inhibitor levels were measured on 261 occasions in 76 hemophilia-A inhibitor patients before and after prothrombin complex concentrate infusion at 13 treatment centers. A rise in inhibitor level to at least twice the pretreatment value occurred in 35 treatment episodes (13.5%), in 27 patients (36%). In 16 patients (21%), such an anamnestic immune response occurred with the first treatment. Factors predisposing to anamnestic responses may include patient idiosyncrasy, low pretreatment inhibitor levels, and exposure to concentrate over several days.
Molecular basis of hemoglobin-H disease in the Mediterranean population
Authors: Kan YW , Dozy AM , Stamatoyannopoulos G , Hadjiminas MG , Zachariades Z , Furbetta M , Cao A
Published: October 2019

We investigated the molecular basis of hemoglobin-H disease by hybridization and restriction endonuclease mapping of the DNA in the Mediterranean populations. Of the 12 patients studied from Cyprus and Sardinia, 8 had the typical deletion defect with a single remaining alpha-globin gene. The nondeletion type of alpha-thalassemia was found in 3, and a “dysfunctional” gene in one. We conclude that the predominant cause of alpha-thalassemia in these populations is gene deletion.
Dual B and T markers in acute and chronic lymphocytic leukemia
Authors: Foon KA , Billing RJ , Terasaki PI
Published: October 2019

Leukemic cells from 20 patients with chronic lymphocytic leukemia (CLL) and 60 patients with acute lymphocytic leukemia (ALL) were studied for T- and B-lymphocyte cell surface membrane markers. B-cell markers included surface membrane immunoglobulin, erythrocyte-antibody complement rosette formation, and B-cell (a-like or HLA-DR) antigens detected by a B-cell antiserum. T-cell markers included spontaneous sheep red blood cell rosette formation and a cytotoxic reaction to a specific T-cell antiserum. Seven patients with CLL and two with ALL had dual B and T markers. We propose that dual B- and T-cell markers are more common in CLL and ALL patients than previously reported. With newer and more sensitive tests for identification of B and T cells, this observation may be recognized more frequently.
Platelet production after administration of antiplatelet serum and 5- fluorouracil
Authors: Radley JM , Hodgson GS , Levin J
Published: October 2019

Although 5-fluorouracil induces relatively minimal thrombocytopenia in mice compared with antiplatelet serum, the ensuing rebound thrombocytosis is much greater. It also occurs several days later. Administration of 5-fluorouracil 24 hr after antiplatelet serum suppresses the increase in platelets produced by antiplatelet serum while the subsequent thrombocytosis is indistinguishable from that produced by 5-fluorouracil alone. It is concluded that the thrombocytosis that occurs after 5-fluorouracil originates from a class of primitive stem cells, or early megakaryocyte precursors, which are not killed by the drug. Thrombocytosis occurring after antiplatelet serum is derived from more mature precursor cells, which are sensitive to 5-fluorouracil.
Immunologic characterization of a granulocytic leukemia of inbred strain 13 guinea pigs: presence of Ia-positive myeloblasts
Authors: Clement LT , Hu C , Shevach EM , Green I
Published: October 2019

Membrane markers expressed by a transplantable granulocytic leukemia induced in inbred strain 13 guinea pigs by N-nitroso-N-butylurea have been investigated by serologic and immunochemical methods. Although the leukemic myeloblasts have no detectable surface immunoglobulin or Fc receptors, they have been found to synthesize and express membrane antigens encoded for by the I-region of the major histocompatibility complex. Despite the presence of Ia antigens, these cells do not stimulate allogeneic T lymphocytes in the mixed lymphocyte reaction nor are they able to present soluble antigen to immune T cells. The presence of Ia antigens on immature myeloid cells suggests that these proteins may be important in cellular functions beyond those identified in the cellular immune system.
Thymidine as a chemotherapeutic agent: sensitivity of normal human marrow, peripheral blood T cells, and acute nonlymphocytic leukemia
Authors: Howell SB , Taetle R , Mendelsohn J
Published: October 2019

Normal marrow granulocyte (CFU-GM) and peripheral blood T-lymphocyte (CFU-TL) colony-forming cells were studied for their sensitivity to high concentrations of thymidine (dThd) and compared to leukemic CFU from patients with acute nonlymphocytic leukemia (ANLL). The sensitivity of two ANLL cell lines was also assessed. dThd was toxic to both CFU-GM and CFU-TL at concentrations above 10(-5) M when cultured under conditions where dThd exposure was analogous to that used in clinical trials. There was little variation in the fractional colony survival between marrow samples, and the sensitivity of CFU-GM closely approximated that of CFU-TL. Thymine was not toxic at up to 10(-3) M. In liquid culture, T cells in G0 at the start of exposure were able to proliferate in the presence of 10(-3) M dThd, whereas T cells already proliferating in response to phytohemagglutinin (PHA) at the start of dThd exposure were killed. Leukemic CFU demonstrated marked variability in dThd sensitivity; blasts from some patients were resistant to dThd, while others were greater than 100-fold more sensitive than normal CFU- GM.
Fatal graft-versus-host disease following blood transfusion in Hodgkin's disease documented by HLA typing
Authors: Dinsmore RE , Straus DJ , Pollack MS , Woodruff JM , Garrett TJ , Young CW , Clarkson BD , Dupont B
Published: October 2019

Fatal graft-versus-host disease (GVHD) developed in a patient with Hodgkin's disease treated with combined chemotherapy and radiotherapy following the transfusion of 2 U of packed red blood cells. Clinical features of the GVHD included the development of exfoliative dermatitis, progressive hepatic dysfunction, aplastic anemia, and finally progressive fatal pneumonia. GVHD was documented by skin biopsy and chimerism by HLA typing. The HLA phenotype of the patient's skin fibroblasts [A3, Bw44 (w4)/A2, B15 (w4)] was appropriate for parental haplotypes and probably represented her true HLA phenotype. Lymphocytes from the patient (peripheral blood and lymph node biopsy) were of a different HLA phenotype (A3; Bw35, w38, w4, w6; Cw4), which was inappropriate for parental HLA haplotypes but identical to the HLA phenotype of one of the blood donors. The HLA-DR typing of the patient's family and of the blood donor demonstrated that the patient and the donor probably were HLA-DR identical (DRw5/DRw6), although no B lymphocytes could be obtained from the patient for direct DR typing. We are currently irradiating all blood products administered to patients with Hodgkin's disease receiving intensive treatment. Further observations will be necessary to determine whether transfusions to other cancer patients with immunodeficiency states should be restricted to irradiated blood products.
A murine model system for the study of the human leukemia-associated inhibitory activity
Authors: Marcelletti J , Furmanski P
Published: October 2019

Mice inoculated with the RFV strain of Friend virus develop an erythroleukemia that spontaneously regresses. Bone marrow cells from leukemic mice produce a factor that inhibits colony formation in agar by normal CFU-Cs. CFU-Cs from leukemic animals are resistant to the factor. Bone marrow cells from some mice whose leukemia has regressed continue to produce the factor, and CFU-Cs from some regressed mice retain resistance to the factor. These observations dupllicate findings reported for patients with acute leukemias and those with leukemia in remission. The RFV system thus serves as an accurate experimental model for the study of hematopoietic cell interactions and the proliferative advantage of neoplastic cells in human leukemias.
Philadelphia chromosome positive childhood acute lymphoblastic leukemia
Authors: Priest JR , Robison LL , McKenna RW , Lindquist LL , Warkentin PI , LeBien TW , Woods WG , Kersey JH , Coccia PF , Nesbit ME Jr
Published: October 2019

In a 3-yr period, the Philadelphia chromosome (Ph1) was found in 4 of 43 children with acute lymphoblastic leukemia (ALL) in whom chromosomes were studied at diagnosis. The clinical, morphological, cytochemical, and immunologic findings in the Ph1-positive (PH1+) CASES WERE CONsistent with typical childhood ALL, indicating that identification of cases requires chromosome studies. A review of all reported cases of Ph1 + childhood ALL shows that Ph1 + patients are older and have higher initial platelet and white blood cell counts (WBC) than most children with ALL. However, a life table comparison between the reported cases of Ph1 + ALL in children and randomly selected age-, sex-, and WBC- matched controls with ALL shows the duration of first marrow remission to be significantly shorter (p less than 0.02) for the Ph1 + cases Ph1 + ALL is a distinct subtype of childhood ALL that is not rare and can be identified only by cytogenetic studies. The prognosis is poor. Cytogenetic studies should be done prospectively in a large group of children with ALL to define further the subgroup of patients and to confirm the findings of this retrospective analysis.
Chlorpromazine inhibition of granulocyte superoxide production
Authors: Cohen HJ , Chovaniec ME , Ellis SE
Published: October 2019

Superoxide production by granulocytes is a result of the activation of an NAD(P)H-dependent oxidase present in the plasma membrane. Chlorpromazine (5–50 muM) prolongs the time necessary to activation of the superoxide generating system and inhibits the extent of activation. When chlorpromazine is added after activation, there is an inhibition of further superoxide production. These effects are seen with digitonin, phorbol myristate acetate, and opsonized zymosan stimulated guinea pig and human granulocytes. Other phenothiazines (1–20 muM) and tetracaine (0.1–1.0 muM) produce similar effects. Lidocaine (1–10 mM) inhibits superoxide production but has no effect on the rate of activation. The effect of chlorpromazine on the rate of activation is reversible, but its effect on extent of activation is unaffected by extensive washing. Incubation of granulocytes with chlorpromazine results in decreased activation of the plasma membrane superoxide generating NADPH oxidase. Chlorpromazine also competes with NADPH for the membrane oxidase. These data and previously published results provide the basis of a model for the activation of the superoxide generating system.
In vitro interactions of PGE and cAMP with murine and human erythroid precursors
Authors: Rossi GB , Migliaccio AR , Migliaccio G , Lettieri F , Di Rosa M , Peschle C , Mastroberardino G
Published: October 2019

Addition of prostaglandins of the E series (PGE1, PGE2) in methylcellulose cultures of murine marrow results in a dose-dependent inhibition of the cloning efficiency of both BFU-E and CFU-C. However, CFU-E growth is unaffected. The inhibitory action of PGE is progressively overcome by increasing amounts of colony-stimulating factor (CSF), and with some limitations, also of erythropoietin (Ep). Addition of PGF2 alpha' associated or not with indomethacin, does not exert any significant effect on these hemopoietic precursors. In an attempt to unvail the mechanism(s) underlying these phenomena, dibutyryl-cyclic AMP (db-cAMP), theophylline (an inhibitor of phosphodiesterase), or theophylline + PGE were plated at various concentrations. Both db-cAMP and theophylline induce an inhibitory influence on both BFU-E and CFU-C growth, which mimicks that by PGEs; additionally, theophylline potentiates the inhibitory action of PGE1. In all these studies, the CFU-E number was not significantly modified. PGE action on BFU-E proliferation is clearly species-dependent, since PGE1 addition to human marrow methylcellulose cultures induces a significant enhancement of the number of both BFU-E and CFU-E derived colonies. This action was abolished upon removal of adherent cells, thus suggesting that PGE1 evokes a release of factor(s) enhancing human erythroid colony growth by adherent cells.
Hemoglobin Ohio (beta 142 Ala replaced by): a new abnormal hemoglobin with high oxygen affinity and erythrocytosis
Authors: Moo-Penn WF , Schneider RG , Shih T , Jones RT , Govindarajan S , Govindarajan PG , Patchen LC
Published: October 2019

Hemoglobin Ohio [beta 142 (H20) Ala replaced by Asp] was found in three members of a white family, all of whom showed erythrocytosis. The variant hemoglobin has a high oxygen affinity, a reduced Bohr effect, and diminished cooperativity. The functional abnormalities of Hb Ohio are explained by the proximity of the substituent beta 142 residue, both to beta 143 His, which is involved in the DPG binding site of hemoglobin, and to the critical C terminal region of the beta chain, which participates in the stabilization of the deoxy (T) conformation.
An undifferentiated variant derived from the human acute myelogenous leukemia cell line (KG-1)
Authors: Koeffler HP , Billing R , Lusis AJ , Sparkes R , Golde DW
Published: October 2019

A variant subline (KG-1a) of the human acute myelogenous leukemia (AML) cell line (KG-1) has been isolated. The cells retain the same constitutive markers as the parent line, including HLA antigens, isoenzymes, and karyotype. The cells from the subline are morphologically and histochemically undifferentiated blast cells, while the parent cells and several of its clones are at the myeloblast and promyelocyte stages of development. The variant cells do not respond to colony-stimulating factor (CSF), and they do not express the human la antigen, nor a recently characterized AML antigen. The parent KG-1 cells are stimulated to proliferate in the presence of CSF and the cells express the la and AML antigen. Variant AML cell lines, such as KG-1a, will be useful in vitro models for investigating cellular response to CSF and for studying antigen expression in leukemic cells.
Restoration of nonclonal hematopoiesis in chronic myelogenous leukemia (CML) following a chemotherapy-induced loss of the Ph1 chromosome
Authors: Singer JW , Arlin ZA , Najfeld V , Adamson JW , Kempin SJ , Clarkson BD , Fialkow PJ
Published: October 2019

After intensive chemotherapy, marrow cells of some patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) become partially or completely Ph1-negative. However, without a second marker for the neoplastic clone, it could not be determined if these Ph1-negative cells arose from normal progenitors or were still members of an abnormal clone. In the present study, a patient with Ph1- positive CML, also heterozygous for glucose-6-phosphate dehydrogenase (G6PD), was studied before and after intensive chemotherapy. Prior to treatment only G6PD type B was detected in the patient's red cells, platelets, and granulocytes, and all unstimulated marrow metaphases had Ph1. After four cycles of chemotherapy, 76% of marrow cells were Ph1- negative, and approximately 80% of the granulocytes were nonclonal by G6PD analysis. Thus, the frequency of nonclonal cells by G6PD analysis correlated closely with that of the Ph1-negative cells. The data indicate that intensive chemotherapy can restore nonclonal and presumably non-neoplastic hematopoiesis in CML.
T lymphocytes expressing human Ia-like antigens in infectious mononucleosis (IM)
Authors: Tatsumi E , Kimura K , Takiuchi Y , Fukuhara S , Shirakawa S , Uchino H , Morikawa S , Minowada J
Published: October 2019

In six patients with Epstein-Barr virus (EBV) induced infectious mononucleosis (IM) and in two patients with IM-like syndrome, peripheral blood lymphocytes in the acute and convalescent phase were tested for human la-like antigens as well as other cell surface markers. The major population of T lymphocytes in the acute phase showed la-like antigens, as detected by indirect immunofluorescence with heteroantisera, and the number of la-like antigen-positive T lymphocytes decreased with convalescence. The crossabsorption study indicated that the amount of la-like antigen on the surface of IM T cells was less than that of Raji cells.
Cellular phenotypes of normal and leukemic hemopoietic cells determined by analysis with selected antibody combinations
Authors: Janossy G , Bollum FJ , Bradstock KF , Ashley J
Published: October 2019

Individual leukemic cells and the corresponding rare normal cell types in nonleukemic bone marrow were analyzed with various combinations of antisera (labeled with different fluorochromes: TRITC and FITC). Double staining for membrane Ia-like molecules (TRITC) and nuclear terminal transferase (FITC) was a very useful combination that distinguished common non-T, non-B ALL (Ia+,TdT+) and thymic ALL (Ia-,TdT+) from the rare cases of B ALL (Ia+,TdT-) and from AML (frequently Ia+, TdT-; in some cases Ia-, TdT-). Additional antisera (such as anti-ALL, anti- HuTLA, anti-immunoglobulin reagents, etc.) confirmed the diagnosis and further characterized the leukemic blasts. Ia+,TdT+ cells could be observed in low numbers in normal and nonleukemic regenerating marrow and were probably normal precursor cells; this reagent combinations was, therefore, not useful for monitoring residual non-T, non-B ALL blasts in treated patients. Other marker combinations detecting pre-B ALL blasts (double staining for cytoplasmic IgM and nuclear TdT) and Thy-ALL blasts (HuTLA+,TdT+) were, however, virtually leukemia specific in the bone marrow and could be used to effectively monitor residual leukemic cells throughout the disease. These combined single-cell assays are not only economical and informative but are also important for assessing the heterogeneity of leukemia and for standardizing new mouse or rat monoclonal antibodies for diagnosis.