bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination chemotherapy for terminal-phase chronic granulocytic leukemia: cancer and leukemia group B studies
Authors: Coleman M , Silver RT , Pajak TF , Cavalli F , Rai KR , Kostinas JE , Glidewell O , Holland JF
Published: October 2019

A 34% response was obtained in 202 evaluable patients in the terminal phase of chronic granulocytic leukemia using combinations of hydroxyurea, 6-mercaptopurine, and corticosteroids. Twelve percent of responses were complete and 22% partial. Overall median survival was 12 wk. A 30 wk median survival for responding patients was statistically superior to the 7-wk survival for nonresponders (p less than 0.001). Response was inversely correlated with toxicity. No responses were obtained in patients sustaining both severe infectious and bleeding complications. No benefit could be demonstrated from the addition of vincristine in induction and daunorubicin for consolidation. Although the response frequency and duration of survival with this combination chemotherapy were generally superior to those previously reported by our group, the terminal phase of chronic granulocytic leukemia still remains a formidable and generally refractory disease.
Characterization by immunoperoxidase of the lymphocytes with bundle- shaped tubular (BST) inclusions in human normal peripheral blood
Authors: Appay MD , Bariety J , Bretton R
Published: October 2019

In six normal subjects, no surface immunoglobulins were detected on blood lymphocytes containing bundle-shaped tubular (BST) inclusions, after incubation with anti-human IgM peroxidase-labeled Fab'2 fragments. These Fab'2 fragments from pepsin-digested sheep anti-human immunoglobulins revealed human mu kappa, and lambda chains. These results suggest that the BST inclusions do not belong to B lymphocytes but belong to T cells and/or a third lymphocyte population, including K cells and precursors of T and B cells.
Combination chemotherapy of adult acute lymphoblastic leukemia with randomized central nervous system prophylaxis
Authors: Omura GA , Moffitt S , Vogler WR , Salter MM
Published: October 2019

Although major progress has been made in the treatment of childhood leukemia, the optimal chemotherapy of acute lymphoblastic leukemia (ALL) in adults has been unclear. In addition, the value of central nervous system prophylaxis (CNS-P) in adults has been assumed, but not established in a systematic fashion. The Southeastern Cancer Study Group has completed a prospective study in which the use of vincristine plus low-dose methotrexate and high-dose prednisone in adult acute lymphoblastic leukemia has produced an 80% (79/99) complete remission rate in patients age 15 yr and over. Younger patients had a significantly higher remission rate but no increase in remission duration. This induction regimen was associated with minimal toxicity. Random assignment to CNS-P or to no prophylaxis, after a multidrug consolidation regimen, has demonstrated a significant prolongation of CNS relapse-free interval (p=0.008) in favor of CNS-P. CNS-P did not improve hematologic remission duration or survival. All complete remitters were maintained on mercaptopurine, methotrexate, and cyclophosphamide with pulses of prednisone and vincristine; the median time from remission to either hematologic or CNS relapse was 19.3 mo after CNS-P, and survival for these patients was 26.1 mo. We conclude that our current induction regimen is highly effective in adult ALL and that CNS-P prophylaxis is indicated in such patients.
Glucose-6-phosphate dehydrogenase variants: reexamination of G6PD Chicago and Cornell and a new variant (G6PD Pea Ridge) resembling G6PD Chicago
Authors: Fairbanks VF , Nepo AG , Beutler E , Dickson ER , Honig G
Published: October 2019

Two large and unrelated families were investigated for hereditary nonspherocytic hemolytic anemia associated with deficiency of erythrocyte glucose-6-phosphate dehydrogenase (G6PD). In both families, the kinetic and electrophoretic features of the G6PD variants resembled those of G6PD Chicago. Further investigation revealed that members of one of these families previously had been characterized as having the G6PD variants Chicago and Cornell. However, it is clear that each of these terms has been applied to the same variant in this single large kindred. In the second family, we describe a newly identified variant with unique characteristics, which we have designated G6PD Pea Ridge. G6PD Pea Ridge resembles G6PD Chicago but differs in electrophoretic mobility and in a few kinetic parameters. It exhibits an unusually high Ki for NADPH and thus appears to be insensitive to product inhibition. As other cases previously considered to be the Chicago variant become more fully characterized, this probably will be shown to be a heterogeneous group of variants.
Biosynthesis of hemoglobin F Malta-I in culture by adult circulating erythropoietic precursors
Authors: Kidoguchi K , Ogawa M , Karam JD , Schneider RG , Carpentieri U
Published: October 2019

By using a methylcellulose clonal assay, we cultured peripheral blood erythropoietic precursors (BFU-E) from an adult couple whose child had HbF Malta-I(gamma 117 His leads to Arg), a G gamma variant, and measured the synthetic rates of HbA, HbF, and HbF Malta-I. Hemoglobin was labeled with 14C-amino acid in culture, separated by slab gel isoelectric focusing technique, and quantitated by autoradiographic or fluorographic method. Culture of BFU-E from both parents revealed significant HbF biosynthesis. HbF Malta-I was present in culture of the father's cells and comprised about 24% of total HbF. When we analyzed Hb biosynthesis in individual bursts, all bursts contained HbA and HbF in varying ratios. The frequency distribution of the individual bursts differing in percentages of HbF biosynthesis approached normal distribution. While the relative ratio of HbF Malta-I to total HbF biosynthesis in individual bursts also revealed significant variation, its frequency distribution did not show a normal distribution. There was a positive correlation between the ratios of HbF/Hb and HbF Malta- I/HbF in individual bursts.
Focus-forming ability and surface markers of hamster-human malignant lymphoma hybrids
Authors: Price GB , Sturgeon JF , Till JE
Published: October 2019

We have examined the properties of hybrid cells formed by polyethylene glycol-mediated fusion of the GRC+L-73 line of Chinese hamster ovary (CHO) cells with peripheral blood cells from patients with chronic lymphocytic leukemia (CLL) or with bone marrow cells from patients with malignant lymphoma. The results indicate that hybrid cells can be detected by their ability to form “foci” of characteristic morphology in the presence of a monolayer of parental CHO cells and that clones isolated from such foci express aspects of the differentiation status, as detected by immunologic markers, of the human parental cells.
Activation of the guinea pig granulocyte NAD(P)H-dependent superoxide generating enzyme: localization in a plasma membrane enriched particle and kinetics of activation
Authors: Cohen HJ , Chovaniec ME , Davies WA
Published: October 2019

The subcellular localization, kinetics of activation, and substrate specificity of the guinea pig granulocyte superoxide (O2-) generating system was investigated. Membrane-enriched particles (podosomes) were made from granulocytes by mild sonication and differential centrifugation. These podosomes are enriched threefold for known plasma membrane markers, 5′-nucleotidase, and adenylate cyclase. Podosomes made from resting granulocytes have very little NAD(P)H-dependent O2- production. Podosomes made from cells stimulated with digitonin are equally enriched for membrane markers but have a 15- to 20-fold increase in NAD(P)H-dependent O2- production. The KmAPP for NADPH is one-tenth that for NADH, but the Vmax is the same. The kinetics of digitonin-stimulated whole-cell O2- production parallel the changes in enzyme activity in these podosomes. Temperature affects both the rate and extent of activation of this enzyme. The pH optimum for the enzyme, the pH optimum for activation, and the pH optimum for whole-cell O2- production are all 7.5. Enzyme activity is increased if the cells are treated with glucose and cyanide, inhibited in cells treated with 2- deoxyglucose (2-DOG), and requires the presence of calcium for activation. These effects are similar to those found for granulocyte O2- production. Thus, the granulocyte O2- generating enzyme system is located on a fraction enriched for plasma membrane markers, and the kinetics of granulocyte production are directly related to the rate and amount of activation of this enzyme.
The pharmacologic effects of PGE1 on murine lymphocytes
Authors: Winkelstein A , Kelley VE
Published: October 2019

Although PGE1, in pharmacologic quantities, possesses significant in vivo immune-modulating activities, its effects on different lymphoid populations have not been defined. In the present study, lymphocyte numbers, turnover rates, and functional activities were assessed in Swiss-Webster mice receiving PGE1, 200 microgram twice daily, for up to 14 days. The most pronounced cellular alterations were observed in the thymus. After 2 wk, the number of theta-positive cells decreased by 81%. Total splenic cellularity was concomitantly reduced by 28%. This was primarily due to a loss of B lymphocytes; the number of these cells decreased by 40%. Bone marrow lymphocytes were also decreased by PGE1 administration. By contrast, peripheral blood lymphocytes and splenic T cells were not significantly altered. Similar changes in lymphocyte numbers were observed in adrenalectomized mice, indicating that depletion was not due to a corticosteroid effect. In normal mice, PGE1 reduced the in vivo incorporation of 3HTdr in both the thymus and the spleen by approximately 50%; this finding, in conjunction with histologic and cytologic observations, suggests a decrease in intrinsic rates of lymphopoiesis. Residual splenocytes were not impaired in their in vitro responses to three polyclonal mitogens: PHA, Con-A, and endotoxin. Studies in cortisol-treated mice showed that PGE1 caused a decrease in both steroid-sensitive and steroid-resistant thymocytes and splenocytes.
Neoplastic human T-cells capable of responding to multiple human alloantigens
Authors: Rubenfeld MR , Edelson RL , Lofstrom LM , Berger CL , Warburton D
Published: October 2019

Monoclonally-derived neoplastic T-cells from a patient with cutaneous T- cell lymphoma respond to multiple human HLA-D antigens in mixed lymphocyte culture. The implications of this phenomenon relevant to normal T-cell function and to malignancy are discussed.
Differential regulation of spleen cell-mediated eosinophil and neutrophil-macrophage production
Authors: Bartelmez SH , Dodge WH , Bass DA
Published: October 2019

Nonadherent spleen cells of mice infected with Trichinella spiralis released growth stimulatory factors (GSFs) in vitro when challenged with excretory/secretory products of muscle stage larvae. The assay of GSF was based on proliferation of normal, nonadherent syngeneic marrow cells in liquid tube cultures. Media conditioned for 1 day by challenged spleen cells stimulated eosinophil production but failed to stimulate production of other cell types. In contrast, media conditioned for 5 days supported eosinophil, neutrophil, and macrophage production. The kinetics of cell production were also different. Eosinophil production started within 1 day, reached a peak at day 2, and was down to control levels by day 4. In contrast, neutrophil/macrophage production began between 2 and 4 days and reached a peak at 6--8 days. The short duration of eosinophil production was evidently due to depletion of growth-factor-responsive cells.
Heterogeneity of cell lineages in L3 leukemias
Authors: Koziner B , Mertelsmann R , Andreeff M , Arlin Z , Hansen H , De Harven E , McKenzie S , Gee T , Good RA , Clarkson B
Published: October 2019

Five cases of adult leukemia with L3 morphology in bone marrow were studied for the presence of immunologic, metabolic, and enzymatic markers. Among the five patients, there were four males and female. Median age was 66 with a range of 16–80 yr. Median survival was only 5 mo. Serum lactate dehydrogenase (LDH) levels, 3H-thymidine labeling indices, and DNA/RNA content of the L3 lymphoblasts were markedly elevated. B-cell markers were found in three cases, two exhibiting surface membrane IgM-lambda, and one IgG-K. Terminal deoxynucleotidyl transferase (TdT) enzymatic activity was consistently low in this group. In one case, the L3 lymphoblasts displayed only surface Fc receptors demonstrated by the binding of aggregated IgG. TdT activity was found to be significantly increased. In another instance, the lymphoblasts formed spontaneous rosettes with sheep erythrocytes and exhibited paranuclear staining with acid phosphatase. TdT activity was found to be low. Although most of the L3 leukemias are neoplasias of B lymphocytes, other lineages may also express this morphology.
Plasma blood group glycosyltransferase activities after bone marrow transplantation
Authors: Yoshida A , Schmidt GM , Blume KG , Beutler E
Published: October 2019

Human blood groups (ABO) are known to be determined by the terminal glycosyl residues attached to common carbohydrate chains of the red cell surface. N-acetylgalactosaminyltransferase (A-enzyme) in blood group A persons and galactosyltransferase (B-enzyme) in blood group B persons are responsible for producing A and B substances on the red cell surface, with both enzymes absent in blood group O persons. The plasma transferase (A - and B-) activity was assayed after the complete replacement of the bone marrow of patients with acute leukemia or aplastic anemia by transplantation bone marrow from donors with ABO blood group differing from the recipient. The patient's blood type completely changed from the recipient's type to the donor's type. However, the A- and B-enzyme activities of the patients changed only slightly after bone marrow transplantation. The results indicate that most of the A- and B-enzymes in the circulatory plasma is not derived from the bone marrow, lymphoid, or macrophage tissue. Other tissues must be the primary source of the enzymes in plasma.
A unique surface marker profile in T-cell acute lymphocytic leukemia
Authors: Richie ER , Sullivan MP , van Eys J
Published: October 2019

A 5-yr-old girl with acute lymphocytic leukemia presented with moderate hepatomegaly, marked splenomegaly, but no evidence of a mediastinal mass. The peripheral blood white count was 270 x 10(9)/liter with 99% leukemic cells. Surface marker analysis showed the lymphoblasts to be E- rosette negative and complement receptor positive. The patient's leukemic cells were unreactive with anti-p23,30, which detects Ia-like antigens, and strongly reactive with A99 anti-T-cell serum, which reacts with normal human thymocytes and peripheral blood T cells. The percentage of leukemic cells bearing complement receptors diminished during relapse. The leukemic cells obtained at diagnosis and during relapse were nonreactive to mitogens and alloantigens and failed to stimulate proliferation of normal lymphocytes in mixed lymphocyte culture. There was no evidence for active suppression of normal lymphocyte reactivity mediated by the leukemic cells. The surface marker and functional profile of these leukemic cells is consistent with that of an early stage in T-cell maturation.
Flow cytometry of DNA content in human bone marrow: a critical reappraisal
Authors: Dosik GM , Barlogie B , Gohde W , Johnston D , Tekell JL , Drewinko B
Published: October 2019

Because cytokinetic studies of the human bone marrow aspirate as a prognostic factor and as a monitor of drug perturbation are frequently inconsistent, we investigated reproducibility of DNA distribution measured by flow cytometry of DNA content in patients with morphologically normal bone marrow. In 15 patients, correlation was noted between DNA distributions simultaneously obtained on right and left iliac crest bone marrow aspirates (r = .588), although considerable variation in individuals was encountered. Much better reproducibility (r = .879) was achieved using bilateral core biopsy of bone marrow in these same patients. In 60 samples, comparison of DNA distribution between bone marrow aspirate and simultaneously obtained biopsy revealed higher relative proportions of S and G2 + M phase cells in biopsies (p less than 0.001), suggesting peripheral blood contamination of aspirate material. Brisk shaking of biopsy specimens in saline expelled a representative sample in the supernatant that could be subjected to simultaneous cytomorphological and cytokinetic analysis. To improve reproducibility of DNA content determinations in normal human bone marrow, bone marrow biopsy should be utilized.
Recurrent acute hepatitis following the use of factor VIII concentrates
Authors: Myers TJ , Tembrevilla-Zubiri CL , Klatsky AU , Rickles FR
Published: October 2019

During a 3-yr period, a patient with hemophilia A experienced 5 episodes of acute hepatitis within 7–16 days following 5 separate infusions of factor VIII (FVIII) concentrates. Although the exact mechanism of the recurrent hepatitis remains unclear, these episodes most likely represented repeated allergic reactions to an antigenic protein derived from the FVIII concentrates. Although no evidence was found for a specific humoral immune response to FVIII in the circulation of the patient, an isolated cellular immune response was suggested by the finding of in vitro lymphocyte stimulation in response to the FVIII concentrate. This unusual type of posttransfusion hepatitis must be added to the list of adverse responses to FVIII concentrates.
Myeloma bone marrow acid phosphatase staining: a correlative study of 38 patients
Authors: Bataille R , Durie BG , Sany J , Salmon SE
Published: October 2019

Acid phosphatase (AP) activity of plasma cells was studied in 38 patients with multiple myeloma (MM). The average activity per cell was strong (mean score = 2.42; maximum score = 4) and the percentage of positive cells was greater than 90% in over 71% of patients. The average AP activity per cell was higher prior to treatment (3.06 +/- 0.53) compared to relapse (2.48 +/- 0.77) and remission (1.81 +/- 1.02 (p less than 0.05 and p less than 0.01, respectively). In correlation of AP activity with clinical features at the time of the study, the only significant difference was between kappa and lambda subtype. Patients with lambda MM had a higher average AP activity per cell in remission (2.71 +/- 0.43) as opposed to kappa MM (1.17 +/- 1.06, p less than 0.05 for difference). AP activity was not significantly correlated with degree of bone involvement. However, activity seemed to be a good marker of disease activity.
Heterogeneity of T-cell lymphoblastic malignancies
Authors: Nadler LM , Reinherz EL , Weinstein HJ , D'Orsi CJ , Schlossman SF
Published: October 2019

To determine the T-cell lineage of the malignant lymphoblast in lymphoblastic lymphoma, tumor cells from nine patients were phenotyped employing a T-cell subset specific heteroantisera, TH2. The normal human peripheral blood T-cell compartment is composed of 80% TH2- negative and 20% TH2-positive T cells, as defined by reactivity with subset specific heteroantisera. Human suppressor cells are TH2 reactive, whereas helper cells are TH2 unreactive. Tumor cells from the majority of patients with lymphoblastic lymphoma were TH2 reactive in contrast to the lack of reactivity previously described in the majority of patients with T-cell acute lymphoblastic leukemia. Comparative clinical studies, including disease presentation and course, were correlated with the presence of the TH2 antigen on the tumor cell. These results provide evidence to support the notion of heterogeneity in the T-lymphoblastic malignancies and suggest that lymphoblastic lymphoma and T-cell acute lymphoblastic leukemia are probably not a single disease process.
Prothrombin Houston: a dysprothrombin identifiable by crossed immunoelectrofocusing and abnormal Echis carinatus venom activation
Authors: Weinger RS , Rudy C , Moake JL , Olson JD , Cimo PL
Published: October 2019

A 72-yr-old male with a lifelong history of easy bruisability and posttraumatic bleeding had a prolonged prothrombin time and activated partial thromboplastin time. His plasma Stypven, Taipan, and Echis carinatus venom clotting times were prolonged. The presence of a dysprothrombin was confirmed by the discrepancy between plasma prothrombin coagulant activity and prothrombin antigen levels. His plasma prothrombin was capable of being completely absorbed onto and then eluted from barium sulfate. Crossed immunoelectrophoresis of his plasma prothrombin, and normal plasma prothrombin, into agarose containing rabbit anti-human factor II antibody were similar. Crossed immunoelectrofocusing, a procedure combining isoelectric focusing in disc gels with electroimmunoassay in the second dimension, demonstrated that the patient's prothrombin antigen was more basic than normal. The eluate from barium sulfate absorbtion of patient plasma, when reacted with Echis carinatus venom (which directly cleaves prothrombin to thrombin) clotted purified fibrinogen at a rate slower than normal plasma eluate. SDS-slab gel electrophoresis revealed that the prothrombin present in the patient's eluate was cleaved by Echis carinatus venom. These studies suggest that the coagulopathy of prothrombin Houston results from the generation of a dysfunctional thrombin.
Phytohemagglutinin-stimulated normal human peripheral blood lymphocytes in folate-depleted medium: an in vitro model for megaloblastic hemopoiesis
Authors: Hayman RJ , Van Der Weyden MB
Published: October 2019

Normal human peripheral blood lymphocytes cultured with phytohemagglutinin in folate-free RPMI 1640 medium supplemented with normal human serum exhibit megaloblastic maturation. These changes are accompanied by a decrease in intracellular folate content, and when compared to folate-replete cells, reveal increased 3H-thymidine incorporation into DNA together with a decreased inhibitory effect of deoxyuridine on 3H-thymidine incorporation. This in vitro system of cellular folate deficiency is a convenient model for analysis of biochemical events accompanying megaloblastic maturation.
Severe platelet dysfunction in hairy cell leukemia with improvement after splenectomy
Authors: Rosove MH , Naeim F , Harwig S , Zighelboim J
Published: October 2019

A patient with hairy cell leukemia developed purpura not attributable to thrombocytopenia. We found markedly reduced platelet aggregation responses and malondialdehyde production, decreased serotonin uptake, and depleted dense granule contents. Ultrastructural studies showed that most platelets had few or nor granules. All of the clinical and laboratory studies of platelet function and morphology improved after splenectomy. These findings indicate that qualitative defects in platelet function occurring in hairy cell leukemia may cause clinically important bleeding and that the bleeding diathesis may be ameliorated by splenectomy.
Explanation for apparent hypoxemia associated with extreme leukocytosis: leukocytic oxygen consumption
Authors: Chillar RK , Belman MJ , Farbstein M
Published: October 2019

We investigated the hypoxemia associated with extreme leukocytosis in leukemic patients. In vitro experiments showed that the rate of decrease in the partial pressure of oxygen in the blood samples from such patients was proportional to the white cell count. In the presence of normal white cell count no drop in PO2 was observed. We conclude that a low arterial oxygen tension in the presence of extreme leukocytosis reflects oxygen consumption by leukocytes rather than true hypoxemia. Both normal as well as leukemic leukocytes appear to exhibit this phenomenon.
Biochemical characterization of a leukemia-associated inhibitor (LAI) suppressing normal granulopoiesis in vitro
Authors: Olofsson T , Olsson I
Published: October 2019

Low-density (less than 1.077 g/ml) marrow or blood cells from patients with acute or chronic leukemia release a high molecular weight substance called “leukemia-associated inhibitor” (LAI) that reduces the fraction of normal marrow CFU-c in S-phase as measured with the 3H-TdR suicide technique. LAI from conditioned media or 3M KCl extracts of subcellular fractions behaved homogeneously on gel chromatography, showing an apparent molecular weight greater than 500,000. However, ion- exchange chromatography and isoelectric focusing indicated considerable charge heterogeneity for LAI molecules. Results from SDS-polyacrylamide gel electrophoresis indicated that the biologic activity resides in a subunit of 150,000–170,000 daltons. The findings of marked affinity for Con-A-Sepharose, marked susceptibility to mild periodate treatment, partial susceptibility to protease digestion, and relative resistance to heating suggest that LAI is a glycoprotein. Data from radiolabeling of cell surface components and sucrose density gradient centrifugation are consistent with LAI being a peripheral cell membrane glycoprotein, which may suppress normal granulopoiesis in leukemia.
Inaccuracies associated with the automated measurement of mean cell hemoglobin concentration in dehydrated cells
Authors: Mohandas N , Clark MR , Kissinger S , Bayer C , Shohet SB
Published: October 2019

Because of discrepancies between electronically and manually measured values of mean cell hemoglobin concentration (MCHC) encountered in studies of pathologic red cells, we studied the effect of cell water content on MCHC measurements by both methods. A series of red cell samples with varying water contents (54%-164% normal) were prepared from normal cells using the antibiotic nystatin. MCHC was then measured, using the microhematocrit centrifuge and three different electronic cell counters in common laboratory use. For MCHC values above 36 g/dl as measured by the spun hematocrit method, all three electronic counters under estimmated the MCHC, with increasing error as the true MCHC increased. For MCHC values below 30 g/dl, the values from two conductivity based instruments agreed with those from the spun hematocrit method, whereas one instrument based on light scattering overestimated the MCHC. These results indicate that inaccuracies in the measured mean cell volume (MCV) of dehydrated or otherwise undeformable cells may lead to spurious values for MCHC when electronic cell counters are used.
Phagocytic plasma cells in a patient with multiple myeloma
Authors: Ludwig H , Pavelka M
Published: October 2019

A female patient with IgG multiple myeloma and phagocytosing plasma cells is presented. Electron microscopical investigation showed an unusually large number of small mitochondria in the myeloma cells. In 21%, intracytoplasmic incorporation of one or more red cells or occasionally of erythroblasts or cells of the myeloid series were found. Uptake of platelets was seen rarely only. Studies of the in vitro phagocytic activity of myeloma cells did not reveal phagocytosis of opsonized bacteria or of latex particles by the malignant plasma cells.
Effects of lipid A and liposomes containing lipid A on platelet and fibrinogen production in rabbits
Authors: Ramsey RB , Hamner MB , Alving BM , Finlayson JS , Alving CR , Evatt BL
Published: October 2019

The effect of the lipid A moiety of endotoxin on platelet and fibrinogen production was studied in rabbits. Lipid A was infused intravenously in doses ranging from 1 to 100 micrograms/kg body mass; 18 hr later, selenomethionine-75Se was injected intravenously and its incorporation into fibrinogen and platelets determined. Lipid A in saline stimulated fibrinogen and platelet production, but the dose required was 50--100 times that required for an intact endotoxin. Although lipid A solubilized in triethylamine (TEA) was at least 60 times more active in the Limulus amebocyte lysate assay than was lipid A suspended in saline, the sensitivity of platelet and fibrinogen production to solubilized lipid A was increased only twofold. Incorporation of lipid A into liposomes had no effect on its Limulus activity. Lipid A in liposomes continued to stimulate platelet, but not fibrinogen, production. Leukopenia that was induced by lipid A in TEA did not occur when rabbits received the same dose of lipid A in liposomes. Lipid A, like intact endotoxin, can stimulate platelet and fibrinogen production and induce leukopenia but the doses required are high. The low solubility of lipid A in aqueous solutions may be only one factor that determines its biologic activity.
Chromosome marker evidence for the bipotentiality of BFU-E
Authors: McLeod DL , Shreeve MM , Axelrad AA
Published: October 2019

When mouse bone marrow cells are seeded in agar cultures containing erythropoietin or pokeweed mitogen stimulated spleen cell conditioned medium plus erythropoietin, megakaryocytes are found mixed with erythroid cells in approximately 40% of the erythropoietic bursts that develop in the cultures. Chromosome spreads of C-metaphases in such “megaerythro bursts” were prepared and stained in situ with a modification of the C-banding technique. In cultures seeded with mixtures of male and female cells, metaphases from individual megaerythro bursts were shown to be either all male of all female but not both. Moreover, tetraploid C-metaphases of megakaryocytes were found to be of the same sex as diploid C-metaphases of erythroid cells in the same megaerythro burst. These results provide evidence that in the mouse, a bipotential progenitor cell exists that has the capacity to give rise to cells of both the megakaryocytic and the erythrocytic lines of differentiation.
Human myeloid leukemia cell lines: a review
Authors: Koeffler HP , Golde DW
Published: October 2019

Several human acute myeloid leukemia cell lines were recently established. These lines provide model systems to study the control of differentiation in human myelogenous leukemia and, in a broader framework, the controls of normal myeloid development. The K562 line is composed of undifferentiated blast cells that are rich in glycophorin and may be induced to produce fetal and embryonic hemoglobin in the presence of hemin. The KG-1 cell line is composed predominantly of myeloblasts and promyelocytes. A unique characteristic of the KG-1 cells is their almost complete dependence on colony-stimulating factor for proliferation in soft-gel culture. The HL-60 is a promyelocytic leukemia cell line. In the presence of DMSO, the cells mature into granulocytes. Both the KG-1 and HL-60 cells differentiate into nondividing mononuclear phagocytes when exposed to phorbol esters. Investigations with these cell lines, and selected variants should provide important insights into the cell biology and perhaps therapy of human leukemia.
Congenital dysgranulopoietic neutropenia: clinical, serologic, ultrastructural, and in vitro proliferative characteristics
Authors: Parmley RT , Crist WM , Ragab AH , Boxer LA , Malluh A , Lui VK , Darby CP
Published: October 2019

Six children with severe congenital neutropenia and repeated life- threatening infections were investigated by examining clinical features and myeloid cell ultrastructure, cytochemistry, and in vitro proliferation. Despite the presence of neutropenia, normal numbers of colony-forming cells (CFC) were present in blood and marrow specimens, and colony-stimulating activities (CSA) from blood cells and serum were normal or slightly increased in all patients. In vitro maturation of the progenitors to neutrophils was also uniformly present in the colonies. No patients had demonstrable antineutrophil antibodies or serum inhibitors of myelopoiesis. Serum lysozyme levels were normal. Ultrastructural and cytochemical studies of directly sampled marrow cells revealed several abnormalities in most neutrophilic myeloid cells from each of the patients consistent with an intrinsic myeloid precursor cell defect. These included (1) the defective synthesis or degeneration of primary granules, (2) an absence or marked decrease of secondary granules in the few late neutrophils observed in the bone marrow, and (3) the presence of autophagy. Phagocytosis of intact myeloid cells with subsequent degeneration was not observed; however, neutrophil debris was evident in phagocytic vacuoles of marrow macrophages. Our demonstration of ultrastructurally dysmorphic neutrophilic granulocytes, intramedullary cell lysis, normal stem cell numbers, and negative serology is comparable to similar observations of erythroid cells from patients with congenital dyserythropoietic anemia. We therefore hypothesize that the dysgranulopoiesis in these children results in neutropenia and propose the descriptive name congenital dysgranulopoietic neutropenia.
Result of attempted hematopoietic reconstitution using isologous, peripheral blood mononuclear cells: a case report
Authors: Abrams RA , Glaubiger D , Appelbaum FR , Deisseroth AB
Published: October 2019

In order to test the effect of peripheral blood mononuclear cell infusions on hematopoietic recovery in man we intensively leukapheresed a normal identical twin and obtained 9.8 x 10(10) peripheral blood mononuclear cells containing 4 x 10(5) CFU-C. These isologous cells were infused into his identical twin brother who had received 150 rad of total body irradiation and intensive combination chemotherapy as adjuvant therapy for Ewing's sarcoma. When compared to other patients receiving similar treatment, leukocyte recovery was accelerated by 3–4 wk, and occurred at a rate comparable to that induced by infusion of autologous cryopreserved marrow. Recovery of granulocytes, monocytes and platelets was not accelerated. The low number of CFU-C present in the preparation used ((one-eighth the number of CFU-C we usually obtain from bone marrow autograft collections) may have led to the pattern of hematopoietic recovery we observed in this patient.
Inhibition of adenosine deaminase activity results in cytotoxicity to T lymphoblasts in vivo
Authors: Mitchell BS , Koller CA , Heyn R
Published: October 2019

We have treated a patient with refractory T-cell acute lymphoblastic leukemia with 2′-deoxycoformycin, a potent inhibitor of the enzyme adenosine deaminase. Inhibition of adenosine deaminase activity resulted in (1) an abrupt rise in plasma deoxyadenosine, but not adenosine, concentrations; (2) accumulation of deoxyadenosine triphosphate by lymphoblasts; (3) inhibition of the enzyme S- adenoylhomocysteine hydrolase; and (4) rapid lysis of the leukemic cells. The patient died suddenly 3 days after therapy was discontinued, and postmortem examination revealed a complete absence of leukemic cells in all organs. Pharmacologic inhibition of adenosine deaminase activity can result in the lysis of T lymphoblasts in vivo, and this effect appears to be mediated by deoxyadenosine.
Immunodepletion of human plasma factor VIII
Authors: Ofosu F , Cassidy K , Blajchman MA , Hirsh J
Published: October 2019

Affinity chromatography of human cryosupernatants on anti-human factor VIII-Sepharose yielded a plasma devoid of detectable factor VIIIC, VIIIR:Ag, and VIIIR:WF activities. This plasma was indistinguishable from severe congenital hemophilic plasma when used as substrate in factor VIII coagulant assays.
Detection of factor IX antibodies by radioimmunoassay: effect of calcium on antibody-factor IX interaction
Authors: Lewis RM , Reisner HM , Chung KS , Roberts HR
Published: October 2019

A radioimmunoassay for alloantibodies (inhibitors) and heteroantibodies to human factor IX has been developed using radioiodinated human factor IX and formalin-fixed, heat-killed Staphylococcus aureus cells (Staph A). Staph A was used as a solid-phase adsorbent for immune complexes. The assay is specific, shows excellent correlation with factor IX coagulant neutralization assays in detecting alloantibodies (r = 0.98), and is 60 times more sensitive. The Staph A method allows rapid separation of immune complexes (within 10 min of addition) and binds immunoglobulin with equivalent efficiency in the presence and absence of calcium. These characteristics have made the Staph A binding method useful for observing the Ca++ effect on the antigenicity of factor IX as detected by hetero- and alloantibodies. All antisera investigated showed some increase in antibody titer when measured in the presence of Ca++. One particular alloantibody showed the greatest increase in titer (> twofold). The reversibility of the calcium effect by excess EDTA indicates that it was not caused by Ca++-dependent proteolysis of the factor IX molecule. The Staph A procedure can also be used as a sensitive competitive radioimmunoassay for human factor IX using alloantibody. The assay could detect factor IX antigen to a dilution of 1:1280 of normal plasma and correctly classified hemophilia B plasmas as cross-reacting material positive or negative.
Antigen--antibody complexes related to the baboon endogenous virus in humans with acute lymphoblastic leukemia--hand mirror variant (ALL-HMC)
Authors: Stass SA , Phillips TM , Weislow OS , Perlin E , Schumacher HR
Published: October 2019

Hand mirror cells are a morphological configuration that are seen in immunologically stimulated lymphocytes and can be induced by antigen-- antibody complexes. Therefore, the bone marrow and peripheral blood plasma of two patients with acute lymphoblastic leukemia--hand mirror variant were evaluated for the presence of antigen--antibody complexes. Both patients had antigen--antibody complexes in the bone marrow plasma and not in the peripheral blood plasma as determined by double counter- current immunoelectrophoresis. The antigen moiety of these complexes appears immunologically related to components of the baboon endogenous virus (BaEV), and the antibody moiety also appears related to structural components of the BaEV. Bone marrow plasmas from patients without leukemia were evaluated for the presence of antigen--antibody complexes and found to be negative. The antigen--antibody complexes may account for the presence of hand mirror cells in the bone marrow of patients with acute lymphoblastic leukemia--hand mirror variant.
Calcium distribution within human erythrocytes
Authors: Schrier SL , Johnson M , Junga I , Krueger J
Published: October 2019

In order to study 45Ca distribution within erythrocytes, a method was devised that had minimal deleterious effects on the treated erythrocytes. It was observed that newly introduced 45Ca was predominantly recoverable from the cytosol and exchanged relatively slowly with membrane-associated Ca. Younger erythrocytes appeared to have relatively more 45Ca in membrane-associated sites. Erythrocytes from patients with sickle cell anemia had significantly more 45Ca in membrane-associated sites than did normal controls or patients with reticuloctosis due to a variety of disorders. There are theoretical reasons for considering the possibility that the distribution of 45Ca between cytosol and membrane-associated sites could modulate some of the properties of the erythrocyte membrane.
Calcium distribution within human erythrocytes during endocytosis
Authors: Schrier SL , Johnson M , Junga I , Krueger J
Published: October 2019

In order to study 45Ca movements within erythrocytes, a method was devised that had minimal deleterious effect on the treated erythrocytes. Agents that induce endocytosis in intact erythrocytes (primaquine, vinblastine, and chlorpromazine) caused a prompt movement of 45Ca from cytosol to membrane-associated sites. This drug-induced movement of 45Ca to membrane sites was blocked by depleting erythrocytes of adenosine triphosphate (ATP) or by incubating them with known inhibitors of endocytosis, NaF of N-ethylmaleimide (NEM). It appears that endocytosis in intact human erythrocytes involves the movement and redistribution of 45Ca from cytosol to membrane-associated sites. Therefore, in the erythrocyte, as in perhaps other cells, movement of Ca from one site to another may modulate important cellular biologic functions.
Intrasplenic microcirculation in rats with acute hemolytic anemia
Authors: Chen LT
Published: October 2019

Intrasplenic microcirculation in rats with acute hemolytic anemia has been studied by means of the microsphere method. Alteration in the intrasplenic microcirculation was observed in the anemic rats. The open circulation was reduced from 98% in the normal rats to 67% in the anemic rats, while the closed circulation was increased from 2% in the normal rats to 33% in the anemic ones. The reduction in the open circulation in the anemic rats appears to be attributed to the congestion in the splenic cords as a result of the retardation of the passage of damaged red blood cells. Restoration of the open circulation in rats on the first day of full recovery from anemia seems to be associated with a decrease in the congestion in the splenic cords.
The 14q+ chromosome in pre-B-ALL
Authors: Kaneko Y , Rowley JD , Check I , Variakojis D , Moohr JW
Published: October 2019

A child who had acute lymphoblastic leukemia (ALL) associated with an 8;14 chromosome translocation and with a pre-B phenotype is described. The leukemic cells were determined to be pre-B-cells on the basis of intracytoplasmic mu-chain immunoglobulin (cIgM+) and the common-ALL antigen, lack of receptors for sheep erythrocytes, and lack of surface immunoglobulin. The 8;14 translocation is frequently found in patients with Burkitt's lymphoma and in most patients with B-cell ALL and is known to carry a poor prognosis. Thus far, no karyotypes have been reported for patients with pre-B-ALL. The present case indicates that a 14q+ chromosome may provide a proliferative advantage not only to cells with a B-cell phenotype, but also to pre-B-cells. The short survival of our patient also suggests that the 14q+ abnormality and the pre-B phenotype may signal a poor prognosis.
The cytoskeleton in Chediak-Higashi syndrome fibroblasts
Authors: Ostlund RE Jr , Tucker RW , Leung JT , Okun N , Williamson JR
Published: October 2019

The Chediak-Higashi syndrome (CHS) trait is expressed in cultured human skin fibroblasts as an abnormal perinuclear concentration of moderately enlarged lysosomes. The cytoskeleton of CHS fibroblasts appears intact. Microtubules are normal in number and morphology, as assessed by colchicine binding studies, antitubulin immunofluorescence, and electron microscopy. Deformability by shear force is unaltered and microfilaments are abundant. However, CHS lysosomes appear to interact abnormally with the cytoskeleton, since the perinculear aggregation partially disperses after depolymerization of cell microtubules with colchicine. These results suggest that CHS is associated with a defect of either the lysosomal membrane itself or of lysosomal membrane- microtubule interaction.
Heterotropic splenic autotransplantation in the prevention of Haemophilus influenza meningitis and fatal sepsis in Sprague-Dawley rats
Authors: Moxon ER , Schwartz AD
Published: October 2019

It has been suggested that autotransplantation of splenic tissue following trauma may result in splenic implanta that protect the human host from severe infection with encapsulated bacteria. To test this hypothesis, Sprague-Dawley rats underwent sham operation, splenectomy, or splenectomy followed by autotransplantation of splenic fragments into the peritoneal cavity. Three months later, they were inoculated intranasally with H. influenzae b. The incidence and severity of bacteremia and meningitis were determined subsequently in 15 randomly selected rats from each group. Splenosis did not appear to confer significant protection against bloodstream dissemination. However, significantly more (p = 0.005) asplenic rats (13/15) developed meningitis than did splenosed rats (6/15). None of the rats with normal splenic tissue developed CNS infection. Thus, the occurrence of meningitis was reduced in autotransplanted rats as compared to asplenic rats. Ten remaining rats from each group were followed for 3 wk after inoculation and the number of deaths was recorded. All sham-operated and autotransplanted rats survived, whereas 7 of 10 asplenic rats died (p = 0.003). These studies indicate that surgically created splenosis offers the potential for reducing the risk of life-threatening sepsis.
Relationship between in vitro colony-forming ability and expression of Ia-like antigen of acute nonlymphocytic leukemia (ANLL) cells
Authors: Hiraoka A , Yamagishi M , Ohkubo T , Yoshida Y , Uchino H
Published: October 2019

In vitro colony-forming ability of untreated acute nonlymphocytic leukemia (ANLL) cells determined by the CFU-C assay with and without PHA presensitization, and also human Ia-like antigen of their surfaces were investigated. In vitro colony-forming ability of 32 ANLLs was classified into four types: (A) no colony growth: 16, (B) PHA-dependent colony growth: 9, (C) colony-stimulating factor (CSF) dependent colony growth: 5, and (D) CSF and PHA independent colony growth: 2. The pattern of 12 normal bone marrow cells corresponded to type C. Leukemic cells were Ia-positive in type A, negative or weakly positive in type B, and negative in type C. Colonies as seen in types B and C consisted mostly of monocytes-macrophages with myeloid cells at varyi stages of maturation up to metamyelocyte. Incubation of type A ANLL cells with anti-Ia-serum followed by PHA presensitization resulted in development of colonies in some analyzed cases with moderately positive Ia-like antigen. Correlation of in vitro colony-forming ability with the expression of human Ia-like antigen of ANLL cells indicated not only a hematologic heterogeneity of ANLL in differentiation and proliferation but also biologic significance of Ia-like antigen in reference to functional maturation of ANLL cells.
Platelet sialic acid and platelet survival after aggregation by ADP
Authors: Packham MA , Guccione MA , Kinlough-Rathbone RL , Mustard JF
Published: October 2019

Some investigators have reported recently that platelet surface sialic acid is decreased during ADP-induced aggregation, whereas others have reported an increase. Since removal of sialic acid from the platelet surface shortens platelet survival, we have determined the survival of platelets that have been aggregatad by ADP. We have also measured the amount of sialic acid in the suspending fluid of platelets after ADP- induced aggregation. ADP-induced aggregation did not cause the loss of sialic acid from rabbit platelets (which do not undergo a release reaction in response to ADP) nor from washed human platelets in a medium containing physiologic concentrations of calcium in which granule contents are not released. In a medium without added calcium, ADP caused the release of 14C-serotonin (42.5% +/- 3%) from human platelets, but less than 4% of the sialic-acid-containing material was released. It seems likely that little of the releasable sialic acid of platelets is in the dense granules or the alpha-granules. Thrombin (5 U/ml) released 90.0% +/- 3.4% of the serotonin from human platelets but only 20.6% +/- 7.4% of the total sialic-acid-containing material. Neuraminidase removed 42.3% of the total sialic acid, presumably from the platelet surface. Rabbit platelets that had been aggregated by ADP and deaggregated survived normally when returned to the circulation. This observation also provides evidence that they had not lost membrane sialic acid during aggregation and deaggregation.
IgD (kappa) "nonsecretory" multiple myeloma: report of a case
Authors: Bartoloni C , Flamini G , Logroscino C , Guidi L , Scuderi F , Gambassi G , Terranova T
Published: October 2019

A case of IgD “nonsecretory” multiple myeloma in a 46-yr-old woman is reported. Despite the presence of disseminated osteolytic lesions, both serum protein electrophoresis and serum and urine immunoelectrophoresis were normal. In addition, bone scintigraphic study was normal. Bone marrow biopsy and aspirate obtained from the left femur lytic lesion showed only myelomatous proplasmocytes; when examined by immunofluorescence with monospecifc antisera, the cytoplasm showed only the presence of delta and kappa chains, suggesting that the neoplastic plasma cells might belong to a single clone. Lymphocyte studies indicated the presence of a normal amount of both B and T cells.