bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of chronic lymphocytic leukemia with properties characteristic of natural killer cells
Authors: Itoh K , Tsuchikawa K , Awataguchi T , Shiiba K , Kumagai K
Published: October 2019

A case of chronic lymphocytic leukemia that consisted of a homogeneous population of cells that had properties similar to those described for natural killer (NK) cells is presented. These leukemic cells had a morphology of large granular lymphocytes (LGL) and receptors for sheep erythrocytes (ER) and for the Fc portion of IgG (Fc gamma-R). They expressed pan-T antigens OKT3 and Leu-4, but neither helper/inducer T- cell differentiation antigens OKT4 and Leu-3a nor cytotoxic/suppressor T-antigens OKT8 and Leu-2a. HNK 1 antigen, which can be expressed on human NK cells, could be detected on almost all leukemic cells (LGL), whereas a myeloid differentiation antigen, OKM1, which can be expressed on macrophages, granulocytes, and NK cells, was not detected. Thus, it was concluded that the leukemia cells had a characteristic profile of the surface markers: ER+, Fc gamma-R+, HNK-1+, OKT3+, Leu-4+, OKT4-, OKT8-, Leu-3a, Leu-2a, and OKM1-. Although freshly isolated leukemic cells showed no cytotoxicity on NK targets, after incubation at 37 degrees C, the cells did show a potent cytotoxicity on targets of erythroleukemic cell, T cell, and monocyte (but not B cell) origins. When the cells were incubated at 37 degrees C, interferon (IFN gamma) was spontaneously produced in the culture fluids. Treatment with anti- HNK-1 and complement completely abrogated expression of NK activity and interferon production of the patient's lymphocytes in culture. These characteristic features of surface markers and functions strongly suggest the possibility that the leukemia cells of this case are of NK cell origin. The relationship between this case and chronic lymphocytic leukemia of T-cell origin is discussed.
Suppression of mouse myelopoiesis by administration of human lactoferrin in vivo and the comparative action of human transferrin
Authors: Gentile P , Broxmeyer HE
Published: October 2019

Purified human lactoferrin was assessed for its influence in vivo in untreated mice and in mice undergoing rebound myelopoiesis after sublethal dosages of Cytoxan. Fully iron-saturated lactoferrin suppressed the numbers of granulocytes and monocytes per femur, the numbers of granulocyte-macrophage progenitor cells (CFU-GM) per femur and spleen, and decreased the cycle status of femoral and splenic CFU- GM. These effects were detected after administration of lactoferrin i.v. or i.p. into untreated and Cytoxan-treated mice. The suppressive effects on cellularity and numbers of CFU-GM per femur were apparent to a greater degree in mice treated with Cytoxan, and the i.v. route appeared preferable to the i.p. route. Heat-treated lactoferrin, inactive in vitro, was inactive in vivo, but iron-depleted (apo-) lactoferrin, inactive in vitro, was active in vivo, suggesting that the apo-lactoferrin acquired the iron in vivo that was necessary to change it into an active form. Titration of the effects of lactoferrin in Cytoxan-treated mice demonstrated a plateau curve of suppression of nucleated cells and CFU-GM per femur with dosages ranging from 100 micrograms to 10(-4) micrograms lactoferrin per mouse, with loss of activity at 10(-5) micrograms. The suppressive effect of lactoferrin on cycle status of CFU-GM required concentrations of 10 micrograms or higher. The effects of lactoferrin were reversible with time, with the suppressive influence on cycling status being lost before that on numbers of CFU-GM per femur. Purified human transferrin was also assessed for its influence in mice undergoing rebound myelopoiesis. Transferrin decreased the nucleated cellularity and the number of CFU- GM per femur and per spleen, but had little or no influence on the cycling status of CFU-GM and differed in its temporal effect on myelopoiesis from that of lactoferrin. These results suggest that lactoferrin and transferrin suppress the number of progenitor cells moving into the CFU-GM compartment and lactoferrin suppresses the cycling status of cells within the CFU-GM compartment. These effects are probably mediated by an action on the production of factors necessary for movement of cells into, and cell cycling within, the CFU- GM compartment.
Proliferation of human malignant hematopoietic cells in immunodeficient mice: suppression by antibody to pluripotent K-562 leukemia cells involves direct cytolysis and effector cells
Authors: Lozzio BB , Machado EA , Mitchell J , Lozzio CB , Wust CJ , Golde DW
Published: October 2019

Six human hematopoetic cell lines were successfully heterotransplanted into athymic (nude) and asplenic-athymic (lasat) neonatal mice. The tumors arising from leukemia and lymphoma cells could then be serially transplanted into adult nude mice. Seven days after the fourth serial mouse passage, each mouse was treated with goat immune gamma globulin against K-562 cells. One control group was treated similarly, but with nonimmune (normal) gamma globulin, while another control group was not treated. The goat gamma globulin was not toxic for nude and lasat mice, and the immune, but not the normal, gamma globulin suppressed local subcutaneous growth of myelosarcomas, lymphosarcomas, and Burkitt lymphoma cells. On the other hand, the growth of lung, breast, and prostatic carcinomas and a melanoma of human origin were not altered by the immune gamma globulin. Since suppression of cell growth occurred equally well in decomplemented mice, a complement-mediated cytotoxicity apparently cannot be considered as responsible for the abrogation. The Fab fragment of the immunoglobulin did not suppress the growth of the myelosarcomas. We conclude that antibody suppression of the in vivo proliferation was specific for malignant hematopoietic cells and that the Fc portion of IgG is necessary for in vivo cytolysis of leukemia cells. The most probable mechanisms are direct antibody cytolysis and antibody-dependent macrophage-mediated cytotoxicity.
Purification of two heparin-binding proteins from porcine platelets and their homology with human secreted platelet proteins
Authors: Rucinski B , Poggi A , James P , Holt JC , Niewiarowski S
Published: October 2019

Two heparin-neutralizing proteins secreted by thrombin-stimulated platelets were purified to homogeneity by means of heparin-agarose affinity chromatography. These proteins, termed porcine platelet basic protein (PBP) and porcine platelet factor 4 (PF4), were eluted from a heparin-agarose column at 0.6–0.9 M NaCl and at 1–1.4 M NaCl, respectively. The molecular weight of porcine platelet basic protein was 7,000–7,700 daltons, as estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and amino acid analysis. The isoelectric point of this protein was at pH 9.0. The amino acid composition of porcine platelet basic protein resembled that of human low affinity platelet factor 4 (LA-PF4), except that the porcine protein did not contain tyrosine. The molecular weight of porcine platelet factor 4 ranged from 10,000 (estimated from amino acid analysis) to 14,000 (estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis). The amino acid compositions of human platelet factor 4 and of porcine platelet factor 4 were similar. Monospecific antibodies against porcine platelet factor 4 and porcine platelet basic protein were raised in rabbits. Competitive radioimmunoassay demonstrated a low but significant immunologic cross-reactivity between human and porcine platelet factor 4, and between porcine platelet basic protein and a group of human secreted platelet proteins that bind to heparin with low affinity (beta-thromboglobulin [beta TG] and low affinity platelet factor 4). Experiments with direct immuno- precipitation of 125I-labeled antigens suggested that all four proteins investigated (human platelet factor 4, porcine platelet factor 4, human low affinity platelet factor 4 or human beta-thromboglobulin, and porcine platelet basic protein) share common antigenic determinants. However, there was a higher degree of immunologic cross-reactivity between heterologous antigens with similar heparin binding affinity (human platelet factor 4 and porcine platelet factor 4) than between heterologous antigens with different binding affinity (human platelet factor 4 and porcine platelet basic protein). In conclusion, our finding suggests a significant structural homology among the four proteins.
The ontogeny of terminal deoxynucleotidyl transferase positive cells in the human fetus
Authors: Bodger MP , Janossy G , Bollum FJ , Burford GD , Hoffbrand AV
Published: October 2019

he ontogeny of cells containing the enzyme terminal deoxynucleotidyl transferase (TdT) in human fetal liver, bone marrow, and thymus has been studied using a highly specific antiserum to TdT together with monoclonal antiprecursor cell antibodies in double and triple marker immunofluorescence. TdT+ cells were first observed in fetal liver at 12 wk of gestation and accounted for 55% of the lymphoid-like cells isolated after Ficoll-Hypaque separation. TdT+ cells were first observed in the bone marrow 16 wk after gestation. Like TdT+ cells in normal infant bone marrow, the majority of TdT+ cells in fetal liver and bone marrow expressed both BA-1 and RFB-1 antigens. This suggests that fetal TdT+ cells include progenitors of the B lineage (BA-1+) and perhaps of thymocytes (RFB-1+). Nevertheless, TdT was not observed in fetal thymocytes until after 20 wk of gestation, although thymic blasts and the majority of thymocytes were strongly RFB-1+ from 12 wk of gestation. These results clearly show that fetal thymus is first populated by TdT, RFB-1+, BA-1 cells, but does not exclude the fact that a second “wave” of TdT+ prothymocytes, possibly bone marrow derived, also exists.
Direct radioimmune detection in human plasma of the association between factor VIII procoagulant protein and von Willebrand factor, and the interaction of von Willebrand factor-bound procoagulant VIII with platelets
Authors: Moake JL , Weinstein MJ , Troll JH , Chute LE , Colannino NM
Published: October 2019

The predominant procoagulant factor VIII (VIII:C) form in normal human plasma containing various combinations of anticoagulants and serine/cysteine protease inhibitors is a protein with mol wt 2.6 +/- 0.2 X 10(5). This protein can be detected by 125I-anti-VIII:C Fab binding and gel electrophoresis in the presence and absence of sodium dodecylsulfate (SDS) and is distinct from the subunit of factor VIII/von Willebrand factor (VIII:vWF) multimers. No larger VIII:C form is present in plasma from patients with severe congenital deficiencies of each of the coagulation factors, other than VIII:C. The mol wt approximately 2.6 X 10(5) VIII:C form is, therefore, likely to be the in vivo procoagulant form of VIII:C, rather than a partially proteolyzed, partially activated derivative of a larger precursor. About 60% of this procoagulant mol wt approximately 2.6 X 10(5) VIII:C form in plasma is present in noncovalent complexes with larger VIII:vWF multimers, which attach reversibly to platelet surfaces in the presence of ristocetin. This VIII:vWF-bound protein of mol wt approximately 2.6 X 10(5) may be the plasma procoagulant form of VIII:C which, after proteolytic activation, accelerates the IXa-mediated cleavage and activation of X postulated to occur on platelet surfaces.
Antigenic analysis of hematopoiesis. I. Expression of the My-1 granulocyte surface antigen on human marrow cells and leukemic cell lines
Authors: Strauss LC , Stuart RK , Civin CI
Published: October 2019

Five monoclonal antibodies that identify the My-1 human granulocyte surface antigen were not reactive with other peripheral blood cells. These antibodies effected complement-dependent cytolysis of a large fraction of normal human marrow leukocytes. This My-1-positive marrow cell population consisted of morphologically identifiable granulocytic precursor cells. Colony-forming cells of the granulocyte-monocyte lineage (CFC-GM) did not express My-1, suggesting that the My-1 antigen is expressed later in normal granulocytic maturation. However, these antibodies did react with myeloid leukemic cell lines. The significance and potential utility of these probes for the understanding of granulopoietic differentiation is discussed.
Eosinophil activation by colony-stimulating factor in man: metabolic effects and analysis by flow cytometry
Authors: Vadas MA , Varigos G , Nicola N , Pincus S , Dessein A , Metcalf D , Battye FL
Published: October 2019

Substantial increases in the killing capacity of human eosinophils after in vitro incubation with human placental conditioned medium (HPCM), a standard source of colony-stimulating factor (CSF), have recently been described. In this article, the interaction between HPCM and purified human eosinophils is analyzed by flow cytometry and by effects on iodination, superoxide production, and protein synthesis. HPCM increased the intensity of natural eosinophil autofluorescence (aFlu) (460 nm) after the absorption of ultraviolet light (360 nm) in a manner that was both time and dose dependent. Measured in arbitrary units, eosinophil aFlu was 72 +/- 7.3 (arithmetic mean +/- SEM) and 121 +/- 3.2 after 18-hr incubations in the absence or presence of HPCM, respectively. The activity in HPCM responsible for these changes cochromatographed on Ultrogel AcA44 columns with CSF and with the less hydrophobic variant of CSF (CSF-alpha) on phenyl Sepharose. Mouse spleen, but not mouse lung, conditioned medium was also active on human eosinophils in this assay. Both CSF-alpha and mouse spleen conditioned medium also contain eosinophil colony-stimulating activity (CSA), whereas inactive CSFs with no effect on mature eosinophils, CSF-beta, and mouse lung conditioned medium also lack eosinophil CSA. CSF-alpha stimulated superoxide production of resting eosinophils (from 0.03 +/- 0.03 to 0.47 +/- 0.08 nmole cytochrome-c reduced/10(5) eosinophils) and of eosinophils incubated with preopsonized zymosan (from 0.15 +/- 0.06 to 0.73 +/- 0.07). It also stimulated iodination by resting eosinophils (from 0.76 +/- 0.16 to 2.60 +/- 0.72 nmoles l/10(7) eosinophils/hr) and of eosinophils incubated with preopsonized zymosan (from 7.52 +/- 2.08 to 29.8 +/- 1.32). In contrast, CSF-beta was inactive in these assays. CSF-alpha also stimulated, between 2- and 15-fold, the new protein synthesis of eosinophils. Thus, substances that stimulate the differentiation of progenitor cells into eosinophils also interact with peripheral mature eosinophils, and the activation of postmitotic cells may be a physiologic role of CSF-like molecules.
Restoration of normal hematopoiesis by bone marrow ablation and allogeneic marrow transplantation in a case of Hodgkin's disease therapy-related preleukemia
Authors: Gyger M , Perreault C , Boileau J , Aymard JP , Bonny Y , Lacombe M , Lavallee R , d'Angelo G , Tawil E
Published: October 2019

Therapy-related leukemias are generally preceded by a preleukemic phase of several months duration, characterized by pancytopenia, abnormal bone marrow findings, and nonrandom chromosomal abnormalities in almost all cases. No specific therapeutic guidelines are recommended in this preleukemic phase or any other type of preleukemia; aggressive combination chemotherapy is usually withheld until the full expression of leukemia. A 22-yr-old man with therapy-related preleukemia following treatment of Hodgkin's disease received as primary treatment ablative chemotherapy followed by marrow transplantation from his histocompatible sister. At day 316, the patient is still in complete bone marrow recovery with a normal donor karyotype. In the light of the very poor results obtained with conventional chemotherapy regimens once the leukemic phase is established, we suggest that bone marrow transplantation, if undertaken before leukemic conversion, may be the treatment of choice in young adults with therapy-related preleukemia.
Stem cells in normal and leukemic hemopoiesis (Henry Stratton Lecture, 1982)
Authors: McCulloch EA
Published: October 2019

This paper deals with three themes: (1) the nature of differentiation in normal and leukemic processes, (2) stochastic and deterministic control mechanisms that affect differentiation, and (3) the nature of the events that separate self-renewing stem cells from their committed descendants. These all impinge on both myelopoietic and lymphopoietic leukemias. The view is advanced that differentiation continues in these diseases, but new programs are assembled abnormally but with normal components.
Development of pluripotent hematopoietic progenitor cells in the human fetus
Authors: Hann IM , Bodger MP , Hoffbrand AV
Published: October 2019

Pluripotent hematopoietic progenitor cells (CFU-GEMM), myeloid progenitor cells (CFU-GM), and erythroid progenitors (BFU-E) were studied in midtrimester human fetuses using the mixed colony assay. All three progenitor cell populations were detected at high levels in the fetal liver from 12 to 23 wk of gestation. Stem cells were first observed in the bone marrow at 15–16 wk of gestation, although bone marrow cultures from earlier fetuses showed heavy growths of stromal cells. Spleen cultures first showed growth of stem cells at 18–19 wk, but fetal thymus showed no hematopoietic activity. Peripheral blood from four fetuses aged 13, 18, 20, and 21 wk showed very high levels of all 3 progenitor cells. The results demonstrate that hematopoietic development in the human fetus parallels that of the mouse. The observation that stromal cell development in the bone marrow precedes the appearance of hematopoietic progenitor cells suggests that they may be closely involved in stem cell growth.
Malignant lymphoma, mixed cell type, diffuse
Authors: Nathwani BN , Metter GE , Gams RA , Bartolucci AA , Hartsock RJ , Neiman RS , Byrne GE Jr , Barcos M , Kim H , Rappaport H
Published: October 2019

This retrospective study of diffuse mixed (DM) cell lymphoma was undertaken as a collaborative study between the Repository Center for Lymphoma Clinical Studies and four cooperative oncology groups (CALGB, ECOG, SECSG, SWOG), and was based on 62 patients from the files of the Repository Center. We wanted to ascertain whether there were any significant clinical differences among the various morphological subtypes of this lymphoma. All patients were treated according to different protocols of the Cooperative Oncology Groups sponsored by the National Cancer Institute. In 16 patients (26%), the malignant lymphoma (ML) had morphological features consistent with follicular center cell origin (FCC); in 34 patients (55%), the ML did not have features of follicular center cell type (non-FCC), but had morphology described for peripheral T-cell-derived ML. In 8 of the patients (13%), no agreement could be reached by the 7 histopathologists who participated in the study, and these were classified as unresolved; the remaining 4 (6%) were unclassifiable. We compared the survival times of the 16 patients having the morphological features of the FCC subtype with the survival times of the 34 patients with the non-FCC subtype and found that patients with FCC lived longer (p = 0.07 Cox's regression). In the FCC group, all patients who had complete remissions (CR) were alive; however, their survival times were similar to those who had a partial or no response (p = 0.32). In contrast, in the non-FCC group, the median survival was 20 mo, and patients with a CR had a significantly longer survival than did incomplete responders (p = 0.003). According to these results the non-FCC diffuse mixed cell lymphoma appears to be a high-grade malignant lymphoma, whereas the FCC type is not.
The delta beta crossover region in Lepore boston hemoglobinopathy is restricted to a 59 base pairs region around the 5' splice junction of the large globin gene intervening sequence
Authors: Mavilio F , Giampaolo A , Care A , Sposi NM , Marinucci M
Published: October 2019

Genomic DNA from a hemoglobin (Hb) Lepore Boston (delta 87 Gln beta 116 His) homozygote of Southern Italian origin has been studied in order to map the fusion point between the delta and beta genes. An Ava II restriction endonuclease recognition sequence, located 12 base pairs (bp) downstream from the 5′ end of the beta gene large intervening sequence, has been taken as marker of the beta-like portion of the fusion gene. This site was present even in the delta beta gene, allowing the localization of the crossover area to a 59-bp region extending from the first nucleotide of the Leu codon in position 88 to the 11th nucleotide of the large intervening sequence. The analysis of the DNA restriction polymorphisms in the gamma delta beta globin gene region provides evidence that a single mutational event originated the Lepore delta beta genes, at least in the Italian population.
Acute megakaryoblastic leukemia in early childhood
Authors: Chan WC , Brynes RK , Kim TH , Verras A , Schick C , Green RJ , Ragab AH
Published: October 2019

Two girls, each less than 2 yr of age, developed acute megakaryoblastic leukemia (malignant myelosclerosis). Both presented with anemia, severe thrombocytopenia, and a low percentage of blasts in their peripheral blood. Their marrow showed marked reticulin fibrosis with an increase in blasts and immature megakaryocytes. The blasts stained negatively for myeloperoxidase and Sudan Black B, but showed acid phosphatase (ACP) and alpha-naphthyl acetate esterase (ANAE) activity inhibitable by sodium fluoride. They were identified as megakaryoblasts by the platelet peroxidase reaction. Cytogenetic studies showed multiple chromosomal abnormalities in both cases. Chemotherapy with vincristine, prednisone, and L-asparaginase was without effect, while daunorubicin and cytosine arabinoside induced a complete remission in one case. The second case responded to a combination of cytosine arabinoside, daunorubicin, and 6-thioguanine. This article documents that acute megakaryoblastic leukemia occurs in early childhood and describes its clinical, pathologic, and cytogenetic features. Previous reports of childhood “myelofibrosis” are reviewed, and their possible relationship with acute megakaryoblastic leukemia is discussed.
Generation of procoagulant activity by mononuclear phagocytes: a possible mechanism contributing to blood clotting activation within malignant tissues
Authors: Lorenzet R , Peri G , Locati D , Allavena P , Colucci M , Semeraro N , Mantovani A , Donati MB
Published: October 2019

This study investigated the procoagulant activity (PCA) of mononuclear phagocytes from rabbits bearing the V2 carcinoma. Macrophages harvested from either intraperitoneally or subcutaneously growing tumors were found to express a very strong procoagulant activity as compared with peritoneal macrophages and circulating mononuclear cells from the same animals. On the other hand, when incubated with or without endotoxin in short-term cultures, circulating mononuclear cells from tumor-bearing animals generated significantly more procoagulant activity than those from control animals. In all instances, procoagulant activity was identified as tissue factor by using assay systems with plasmas selectively deficient in the various clotting factors. These results indicate that, besides cancer cells, mononuclear phagocytes might also play an important role in the activation of blood coagulation and in the deposition of fibrin at the host-tumor interface.
Activation of factor XII by dextran sulfate: the basis for an assay of factor XII
Authors: Tankersley DL , Alving BM , Finlayson JS
Published: October 2019

A system was developed for studying the activation of factor XII (Hageman factor) in the presence of dextran sulfate (DS). Salient features of the system included low ionic strength (0.08), low concentration of factor XII (approximately 1/10,000 that in normal plasma), and an excess of exogenous prekallikrein (PK). In this system, factor XII was rapidly converted to the 80,000 molecular weight (mol wt) form of factor XIIa (alpha-factor-XIIa). Once formed, the factor XIIa converted PK to kallikrein at a rate that was proportional to the amount of factor XII originally present in the incubation mixture. This system was used to construct a simple sensitive assay for factor XII in plasma and other biologic samples. The kallikrein produced was measured spectrophotometrically with the chromogenic substrate (H-D-Pro-Phe-Arg- p-nitroanilide (S-2302). This assay was shown to be independent of the high molecular weight kininogen and the PK content of the sample being analyzed. The measurements obtained were consistent with fundamental enzymologic principles and, if desired, could be processed with a simple calculator program to achieve linear standard curves. When applied to the quantitation of factor XII in plasma, the assay yielded values in close agreement with those determined by coagulant assay or by radial immunodiffusion.
Delayed alloimmunization using random single donor platelet transfusions: a prospective study in thrombocytopenic patients with acute leukemia
Authors: Gmur J , von Felten A , Osterwalder B , Honegger H , Hormann A , Sauter C , Deubelbeiss K , Berchtold W , Metaxas M , Scali G , Frick PG
Published: October 2019

A randomized study was performed in 54 thrombocytopenic patients with acute leukemia. Alloimmunization of recipients of random multiple-donor platelet concentrates (MD group) was compared to that of patients receiving random single-donor platelets (SD group). In the SD patients, formation of alloantibodies (mostly anti-HLA) occurred less frequently (p less than 0.002), after a longer time period (p less than 0.002), and after a higher number of transfusions (p less than 0.005) as compared to MD patients. SD patients also became refractory to random platelets less frequently (p less than 0.005), after a longer time period, and after a higher number of transfusions (p less than 0.02). In SD patients, the increments after the first and the last transfusion were in the same range, whereas in MD patients, the 1-hr (p less than 0.001) and the 24-hr (p less than 0.025) increments decreased from the first to the last transfusion. Thus, the use of random SD platelet transfusions postponed alloimmunization.
Clonal chromosome abnormalities in patients with Waldenstrom's and CLL- associated macroglobulinemia: significance of trisomy 12
Authors: Han T , Sadamori N , Takeuchi J , Ozer H , Henderson ES , Bhargava A , Fitzpatrick J , Sandberg AA
Published: October 2019

We performed cytogenetic analyses by Q- and G-banding techniques of unstimulated or B-mitogen-stimulated spleen, bone marrow, and peripheral blood cells from six patients with malignant macroglobulinemia [two with Waldenstrom's macroglobulinemia (WM) and four with chronic lymphocytic leukemia associated macroglobulinemia (CLL-M)]. Normal karyotypes were obtained in two of the treated patients (one with WM in remission and the other with CLL-M in relapse). An extra chromosome 12 (trisomy 12) was observed in all four untreated patients. In patient no. 2 (K.R.) and no. 3 (F.G.) with CLL- M, an abnormal karyotype, with trisomy 12 as the only abnormality, was identified. In patient no. 1 (C.C.) with WM, there were two clonal chromosome changes, identified: 47, XX, -9, +12, plus marker chromosome and 48, XX, -9, +12, plus both marker and minute chromosomes. In patient no. 4 (R.M.) with CLL-M, a minute chromosome with or without loss of a G-group chromosome was seen in some metaphases without trisomy 12, in addition to metaphases with trisomy 12 alone. Each of the four untreated patients with WM or CLL-M had clonal chromosome abnormalities, suggesting that chromosome changes may be more frequently associated with WM or CLL-M than with typical CLL without macroglobulinemia. These observations also suggest that trisomy 12 may be the primary karyotypic change in malignant macroglobulinemia, whereas the appearance of the minute or marker chromosome as well as the loss of G-group chromosomes or chromosome no. 9 may be secondary karyotypic changes resulting from clonal evolution in these malignancies.
Erythroid blast crisis in chronic myelogenous leukemia
Authors: Ekblom M , Borgstrom G , von Willebrand E , Gahmberg CG , Vuopio P , Andersson LC
Published: October 2019

Blood or bone marrow specimens from 22 patients with chronic myelogenous leukemia in blast crisis were studied for the surface expression of glycophorin-A, a marker for early erythroid differentiation. The leukemic blasts were stained with rabbit anti- glycophorin-A antiserum. The glycophorin-A molecules detected by the rabbit antiserum were identified by polyacrylamide slab gel electrophoresis of the immunoprecipitates from the membrane lysates of surface-labeled blasts. Blasts expressing surface glycophorin-A were found in 9 of the 22 patients. In 4 patients, almost all blasts were glycophorin-A positive, and in 5 patients, less than half of the blast population expressed glycophorin-A. The present study shows that when glycophorin-A is used as a marker for erythroid blasts, involvement of the erythroid lineage during blast crisis of chronic myelogenous leukemia seems to occur more frequently than previously recognized.
Comparison of chemotherapy with immunotherapy for maintenance of acute lymphoblastic leukemia in children and adults
Authors: Stryckmans PA , Otten J , Delbeke MJ , Suciu S , Fiere D , Bury J , Solbu G , Benoit Y
Published: October 2019

Two hundred and seventeen patients, 1–50 yr old, with acute lymphoblastic leukemia in complete remission were randomized to receive a 1-yr consolidation chemotherapy of either type P, comprising 7 different drugs, or type M, consisting of methotrexate interspersed with prednisone and vincristine. Thereafter, they were randomized a second time to receive a 4-yr maintenance of either chemotherapy or immunotherapy, comprised of allogeneic blasts and bacillus Calmette- Guerin (BCG). Consolidation P caused more toxicity than consolidation M. However, comparison between the consolidation therapies P and M showed no significant difference, neither for disease-free interval nor for duration of survival. Chemotherapy showed more lethal toxicity in adults than in children. Comparison between chemotherapy (C) and immunotherapy (I) as maintenance treatment showed a significant (p = 0.016) superiority of C for disease-free interval (DFI). The difference was even more pronounced (p = 0.009) in the group with less than 8 g/dl of hemoglobin (Hb) at diagnosis before therapy. On the other hand, for patients with more than 8 g/dl Hb at diagnosis, presumably those with T- ALL, no difference in DFI was seen. No difference has been seen so far between maintenance therapies I and C concerning the duration of survival. The patients who were receiving maintenance I when they relapsed and who were consequently retreated by chemotherapy, survived longer from relapse than those patients retreated for relapse while receiving maintenance C.
The chlorinating potential of the human monocyte
Authors: Lampert MB , Weiss SJ
Published: October 2019

Human monocytes incubated with phorbol myristate acetate (PMA) or opsonized zymosan particles can chlorinate the beta-amino acid taurine to its monochloramine derivative. Taurine monochloramine can then be quantitated by its ability to oxidize 5-thio-2-nitrobenzoic acid to its disulfide or by its characteristic absorption peak at 252 nm. Stimulated, but not resting, monocytes chlorinated taurine by a process dependent on time, cell concentration, and pH. The formation of taurine chloramine by stimulated monocytes could be inhibited by catalase, azide, or cyanide, was unaffected by superoxide dismutase, and was stimulated by exogenous myeloperoxidase. Thus, taurine chloramine generation by human monocytes appeared dependent on both H2O2 and myeloperoxidase. Compared to human neutrophils, the monocyte could generate similar amounts of chloramine when stimulated with phorbol myristate acetate, but far less if opsonized zymosan particles were used as the trigger. Based on the known ability of the H2O2- myeloperoxidase-Cl- system to generate free HOCl, it would seem that this oxidant is the most likely species responsible for the monocyte- mediated chlorination reactions. Thus, we have used a simple quantitative assay to demonstrate the ability of the human monocyte to generate large quantities of a highly reactive and toxic oxygen metabolite.
Amino-sugars enhance recognition and phagocytosis of particles by human neutrophils
Authors: Doolittle RL , Packman CH , Lichtman MA
Published: October 2019

Neutrophils were examined for their ability to recognize and ingest beads coated with amino-derivatives of glucose, mannose, and galactose. Radioactive or fluorescent beads coated with any of the three sugars were ingested to an extent three times that observed with albumin- coated beads. Enhancement of ingestion of sugar-coated beads was much more evident when examined by electron micrographic studies. Inclusion of glucose or mannose in the medium with glucose- or mannose-coated beads caused a dose-dependent reduction of ingestion to control levels, but ingestion of galactose-coated beads was poorly inhibited. Similarly, galactose or fucose (6-deoxy-galactose) markedly inhibited ingestion of galactose-coated beads, but caused only a slight decrease in ingestion of glucose- or mannose-coated beads. Thus, neutrophils possess carbohydrate-binding membrane structures that can mediate recognition and ingestion of sugar-coated beads. Such carbohydrate recognition systems may underlie certain interactions of neutrophils and other surfaces.
Human erythroleukemia cell line (HEL) undergoes a drastic macrophage- like shift with TPA
Authors: Papayannopoulou T , Nakamoto B , Yokochi T , Chait A , Kannagi R
Published: October 2019

We investigated the effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the human erythroleukemia cell line, HEL, and found that TPA addition (10(-6)-10(-8) M) to HEL cell cultures induces morphological, functional, and biochemical changes in HEL cells that are characteristic for macrophage-like cells. Apart from the drastic changes in morphology, the cells greatly enhance their phagocytic ability and acquire receptors for binding and degradation of chemically modified lipoproteins. At the biochemical level, a newly synthesized 85K glycoprotein is observed, and the cells are unresponsive to inducers of globin synthesis. Comparative observations with K562 cells indicate that TPA inhibits, as in HEL cells, spontaneous and induced globin synthesis, but induces minimal macrophage-like properties in these cells. The results with HEL cells are interpreted to indicate that TPA uncovers a latent monocyte-like phenotype in these cells.
A variant of von Willebrand's disease characterized by recessive inheritance and missing triplet structure of von Willebrand factor multimers
Authors: Mannucci PM , Lombardi R , Pareti FI , Solinas S , Mazzucconi MG , Mariani G
Published: October 2019

A 10-yr-old girl had bleeding symptoms of moderate severity; her mother and maternal aunt had milder bleeding symptoms, and other members of the kindred were asymptomatic. In the child, factor VIII coagulant activity (VIII:C) and von Willebrand factor antigen (vWF:Ag) were normal, ristocetin cofactor very low, and the bleeding time (BT) markedly prolonged. These values were normal in the rest of the kindred, but the mother and maternal aunt had prolonged BT and a high VIII:C/vWF:Ag ratio. Crossed immunoelectrophoresis (CIE) showed a vWF:Ag peak migrating more anodally in the propositus, two distinct peaks, one migrating anodally, in the father, paternal uncle, and grandmother, and normal peaks in the rest of the kindred. In the propositus, analysis of vWF multimers in plasma on 1.6% sodium dodecyl sulfate (SDS) agarose revealed that there were no larger multimers and there was a relative increase of the smallest multimer. This relative increase was also seen in her relatives with a double peak on CIE. Using gels of smaller porosity, each multimer of the propositus's plasma consisted of a single band, instead of the repeating triplet seen in normal and von Willebrand's disease varients types IIA and IIB. The abnormalities found in the propositus are tentatively interpreted as being due to double heterozygosity for two different genes. The defective gene carried by the father affects the triplet structure of vWF multimers, whereas a prolonged BT and a high VII:C/vWF:Ag ratio are the only phenotypic expressions of the defective gene of the mother. The findings of aberrant triplet structure in congenital vWD strengthen the view that this structure is an intrinsic feature of the normal vWF molecule.
Histidine-rich glycoprotein is present in human platelets and is released following thrombin stimulation
Authors: Leung LL , Harpel PC , Nachman RL , Rabellino EM
Published: October 2019

Histidine-rich glycoprotein, and alpha 2-glycoprotein in human plasma, has been shown to interact with heparin, with the high-affinity lysine- binding site of plasminogen, with divalent cations, and is associated with the rosette formation between erythrocytes and lymphocytes. A specific enzyme-linked immunosorbent assay for histidine-rich glycoprotein has been developed and used to demonstrate that histidine- rich glycoprotein is present in human platelets. Histidine-rich glycoprotein was detected and quantified in detergent extracts of washed human platelets, with a mean level of 371 ng/10(9) platelets. Plasma histidine-rich glycoprotein, either in the platelet suspending medium or on the surface of the platelets, accounted for less than 3.4% of the detectable platelet histidine-rich glycoprotein. Histidine-rich glycoprotein was also demonstrated in human bone marrow megakaryocytes by immunofluorescence. The extent of histidine-rich glycoprotein release from platelets was dependent on the thrombin dose and correlated directly with the extent of serotonin release. The platelet and plasma histidine-rich glycoprotein were similar by immunochemical analysis. Anti-histidine-rich glycoprotein IgG did not inhibit platelet aggregation. Histidine-rich glycoprotein released by platelets following thrombin stimulation may play a significant role in modulating inflammatory events in the microenvironment of the platelet plug.
A granulocyte reactive monoclonal antibody, 1G10, identifies the Gal beta 1-4 (Fuc alpha 1-3)GlcNAc (X determinant) expressed in HL-60 cells on both glycolipid and glycoprotein molecules
Authors: Urdal DL , Brentnall TA , Bernstein ID , Hakomori SI
Published: October 2019

1G10, a monoclonal IgM antibody that identifies a differentiation antigen on human granulocytes and a subpopulation of monocytes, was found to react specifically with glycosphingolipids bearing the Gal beta 1–4(Fuc alpha 1–3)GlcNAc hapten (X determinant). This carbohydrate determinant was found on both glycolipid and glycoprotein molecules isolated from HL-60 cells (a promyelocytic leukemia cell line). Thus, this highly conserved carbohydrate-defined determinant previously described on mouse embryonic and mouse and human carcinoma cells is also expressed as a tissue-specific differentiation antigen on normal human granulocytes.
Erythropoietin production by a human testicular germ cell line
Authors: Ascensao JL , Gaylis F , Bronson D , Fraley EE , Zanjani ED
Published: October 2019

An established human testis germ cell line (1411-H) was found to produce significant amounts of erythropoietin (Ep), the primary regulator of erythropoiesis. Media conditioned by the 1411-H cells stimulated erythropoiesis both in vivo and in vitro. This activity was neutralized by anti-Ep. This continuous cell line provides a unique model for the study of the mechanisms of control of Ep biogenesis.
Regulatory mechanism of granulopoiesis in the bone marrow of CSF- producing tumor-bearing nude mice
Authors: Motoyoshi K , Suda T , Takaku F , Miura Y
Published: October 2019

The regulatory mechanism of differentiation of granulocyte and macrophage precursor cells (G/M CFU-C) in bone marrow and spleen obtained from nude mice bearing colony-stimulating factor (CSF) producing tumor (G-mice), which developed marked granulocytosis, was studied. In these mice, granulopoiesis is enhanced in the spleen, but suppressed in bone marrow. Coculture of G-mouse bone marrow cells with splenic cells of control nude mice (C-mice) and of G-mice resulted in 68% and 62%, respectively, more colonies than expected, while coculture of C-mouse bone marrow cells with these two sources of cell fractions resulted in only 2% and 11% more colonies. In the double-layer agar culture system, bone marrow and splenic cells of C- and G-mice produced a maximal number of colonies containing adequate amounts of human urinary CSF in the upper layer when C-mouse bone marrow cells were added to the lower layer, while these four sources of cells produced a moderate or minimal number of colonies when splenic cells of C- and G- mice or G-mouse bone marrow cells were added to the lower layer. Morphological examination of colonies formed in the upper layer revealed that addition of C-mouse bone marrow cells or irradiated G- mouse bone marrow cells to the lower layer resulted in a massive increment in the number of colonies with pure granulocytes and granulocyte and macrophage mixed (G + G/M) colonies formed by G-mouse bone marrow cells in the upper layer. However, the addition of irradiated C-mouse bone marrow cells or G-mouse bone marrow cells before irradiation to the lower layer did not change G + G/M colony formation by G-mouse bone marrow cells in the upper layer. We could reproduce these findings with conditioned media obtained from 3-day liquid cultures of these cell fractions. This suggests that a diffusible factor may be necessary for inhibition of G + G/M colony formation in G-mouse bone marrow cells. The fine mechanism of such inhibition remains to be clarified.
Adult hemoglobins are synthesized in murine fetal hepatic erythropoietic cells
Authors: Wong PM , Chung SW , White JS , Reicheld SM , Patterson M , Clarke BJ , Chui DH
Published: October 2019

The hemoglobins present in murine fetal hepatic erythroblasts on days 12–15 of gestation were studied by biochemical and immunocytologic techniques. In addition, fetal hepatic hemopoietic progenitor cells obtained from normal and mutant f/f mouse fetuses on days 11–13 of gestation were cultured in vitro with added erythropoietin and adult spleen cell conditioned medium to form large erythroid colonies. In all instances, adult hemoglobin synthesis was detected in the fetal hepatic erythroblasts and in the erythroid cell cultures in vitro. The tumor promoter, 12-O-tetradecanoylphorbol 13-acetate, enhanced the fetal hepatic erythroid colony growth in vitro, but did not alter the hemoglobin phenotypic expression.
Immunohistologic study of bone marrow involvement in B-chronic lymphocytic leukemia
Authors: Pizzolo G , Chilosi M , Ambrosetti A , Semenzato G , Fiore-Donati L , Perona G
Published: October 2019

Bone marrow trephine biopsies from 17 patients with B-chronic lymphocytic leukemia (B-CLL) were studied by immunohistologic techniques in order to investigate the cellular phenotypes of both neoplastic (B-lymphoid) and reactive (T-lymphoid) infiltrates. For this purpose, several heteroantisera and monoclonal antibodies against human Ig isotypes, HLA-DR antigens, and T-cell subpopulations were used in immunofluorescence. The findings were analyzed in relationship to the histologic pattern of involvement, as well as to the immunologic data of cell suspensions from peripheral blood. In all cases, the dominant lymphoid population within the bone marrow infiltrates showed identical phenotypic characteristics of B-CLL cells from the blood (HLA-DR+, mu +, most frequently delta +, kappa +, or lambda +, and weakly RFA-1+). The infiltration by these malignant B cells was diffuse in 5 cases and nodular plus interstitial in 12. The number of T cells (UCHT1+, RFA-1+, mu) was variable (5%-25%) in the different samples, but the values were high when compared to the proportion of T cells in normal bone marrow and in the blood of most patients studied. Furthermore, a clear predominance of T cells exhibiting the inducer phenotype (Leu-3+) was observed in all bone marrow samples, which is in contrast with the findings from peripheral blood, where T cells with the suppressor/cytotoxic phenotype (Leu-2+) were dominant. These data suggest a different blood and tissue distribution of inducer and suppressor/cytotoxic cells in B-CLL, which may have important pathophysiologic significance.
Allogeneic bone marrow transplantation as treatment for accelerating chronic myelogenous leukemia
Authors: McGlave PB , Arthur DC , Weisdorf D , Kim T , Goldman A , Hurd DD , Ramsay NK , Kersey JH
Published: October 2019

Sixteen patients with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) when they presented with or developed objective signs suggesting acceleration of disease. Patients have been followed for a median of 515 days (range 216–806 days). Seven patients are alive from 319 to 732 days (median 538 days). Four patients are in complete remission 501–732 days after BMT. Three patients have developed cytogenetic evidence of relapse after BMT; however, these patients are alive and not dependent on therapy and have normal activity levels at 319, 515, and 550 days following BMT. Three additional patients have developed cytogenetic and hematologic evidence of relapse after BMT, progressed to blast crisis, and died. Six patients have died of other causes. Allogeneic BMT can eradicate the abnormal clone and provide normal hematopoiesis when performed during the accelerated phase of CML; however, this approach is associated with relapse and with relatively high mortality. The long-term efficacy of this approach and the relative efficacy of transplant during acceleration rather than during the chronic phase of CML have yet to be established.
Potential role of platelets in the pathogenesis of tumor metastasis
Authors: Mehta P
Published: October 2019

Platelet activity may be involved in tumor metastasis. The tumor cells, after detachment from the primary site, adhere to vascular endothelium at distant sites and proliferate. Platelets form aggregates with tumor cells in circulation, facilitating their adhesion to the vascular endothelium. Formation of platelet-tumor cell aggregates and their sequestration in various end-organs may result in thrombocytopenia. Certain tumor cell lines directly stimulate platelet activity, some by releasing platelet-aggregating material, a urea-extractable membrane component, others by release of cathepsin, and still others by undefined mechanisms. The direct effect of platelets on tumor cells may be of pathogenic significance. For example, platelet-derived factors stimulate growth of some tumors, whereas others increase vascular permeability and thus facilitate migration of tumor cells across the vessel wall. Lack of these platelet factors, as in thrombocytopenic animals, may indeed inhibit tumor metastasis. Arachidonic acid metabolism in platelets and the vessel walls may contribute to metastatic process. In particular, thromboxane A2 and prostacyclin generation capabilities appear to be important in modulating platelet- tumor cell deposition and growth. To alter the metastatic process, several preliminary trials of platelet-inhibitory agents have been performed. However, the results of these trials have been equivocal, perhaps related to nonspecific effects of these agents on arachidonic acid metabolism. Studies directed at specific pathways of platelet- vessel wall interaction on some tumors appear promising. These newer agents may be of therapeutic value in man.