bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing erythrocyte populations in juvenile chronic myelocytic leukemia: evidence for disordered regulation
Authors: Dover GJ , Boyer SH , Zinkham WH , Kazazian HH Jr , Pinney DJ , Sigler A
Published: October 2019

Fetal and adult erythrocyte characteristics were studied serially in a 30-mo-old female with juvenile chronic myelocytic leukemia. On presentation the erythrocytes exhibited predominantly fetal characteristics as indicated by 69% hemoglobin F (HbF), 1.1% hemoglobin A2 (HbA2), absent I antigen, and fetal levels of the erythrocyte enzymes, carbonic anhydrase I and II, glucose-6-phosphate dehydrogenase, hexokinase, pyruvate kinase, and lactate dehydrogenase; 100% of the erythrocytes present contained HbF. However, Orskov-Jacobs- Stewart hemolysis demonstrated that at least one adult characteristic was present. Seven months later HbF was 17%; I antigen and carbonic anhydrase I had increased to adult levels. The number of cells containing HbF had decreased to 30%. Further studies indicated that at least three new populations of red cells were present after 7 mo which had not previously been detected. Two of these populations exhibited a mixture of both fetal and adult characteristics. Such findings suggested that an ongoing disturbance of regulatory mechanisms was responsible for the variable expression of fetal versus adult erythrocyte characteristics.
Multiple myeloma: quantitative staging and assessment of response with a programmable pocket calculator
Authors: Salmon SE , Wampler SB
Published: October 2019

Studies of M-component synthesis and metabolism, as well as clinical staging of multiple myeloma, have provided the basis for calculation of the total body tumor cell number and quantitation of response to treatment. Many of the calculations involved have been complex and have previously required the availability of a computer. The advent of programmable pocket calculators has permitted simplification of these programs for general clinical and investigative applications in studies of myeloma and related monoclonal gammopathies. In this paper we have included the background information and a clinical example of the use of the programmable calculator, as well as the logic steps and the calculator programs themselves, for several of the most useful programs for clinical staging and quantitation of response to therapy in IgG myeloma.
Proliferation of diffusion chamber colony-forming units (CFUD) in cultures of normal human bone marrow in diffusion chambers in mice
Authors: Jacobsen N
Published: October 2019

Normal human bone marrow contains cells capable of forming colonies of hemopoietic cells in fibrin clots in diffusion chambers implanted intraperitoneally (i.p.) into irradiated mice. The present paper describes the proliferation of such colony-forming units (CFUD) in cultures in vivo. Cells harvested from diffusion chambers after 1–14 days of culture in 450-R irradiated mice contained CFUD, which formed neutrophilic, eosinophilic, or megakaryocytic colonies when tested by secondary culture in fibrin clot chambers. When bone marrow was precultured in irradiated mice at a concentration of 10(6) cells per chamber, an initial fall in the number of neutrophilic CFUD was observed. This decrease was followed by an increase to a maximum at day 2, and then a secondary decrease. The number of neutrophilic CFUD recovered after 2 days of preculture in irradiated mice varied between 60% and 250% of the number present before preculture. Preculture in nonirradiated mice resulted in a significantly lower recovery of neutrophilic CFUD. In vitro treatment of bone marrow cells with hydroxyurea (OHU) after 2 days of preculture in irradiated mice resulted in a 68% +/- 5% reduction in the number of neutrophilic CFUD. In contrast, OHU had no similar effect on precultures from nonirradiated mice. Both the recovery and sensitivity to OHU of eosinophilic CFUD were independent of host irradiation. Similarly, no effect of host irradiation on the recovery or the 3H-thymidine (3HTdR) labeling index of morphologically recognizable granulocytic cells was observed at day 2. The data suggest an effect of humoral host factor(s) on the proliferation of early precursor cells, which are or become committed to differentiate into the neutrophilic pathway in diffusion chambers.
Intraerythrocytic adaptation (2,3 DPG,P50) in thalassemia minor
Authors: Pearson HA , Motoyama E , Genel M , Kramer M , Zigas CJ
Published: October 2019

P50 and 2,3 DPG content of erythrocytes were determined in 25 patients with heterozygous beta thalassemia minor to assess the adaptive mechanisms to anemia. 2,3 DPG levels were appropriately elevated for the degree of anemia. However, P50 values were not proportionately increased. No correlations were noted between hemoglobin level, 2,3 DPG, or P50 and the presence of symptomatic complaints of fatigue or weakness in these heterozygous patients.
Effects of ascorbic acid on glucose-6-phosphate dehydrogenase-deficient erythrocytes: studies in an animal model
Authors: Udomratn T , Steinberg MH , Campbell GD Jr , Oelshlegel FJ Jr
Published: October 2019

There is little information available concerning the possible effects of ascorbic acid on glucose-6-phosphate dehydrogenase (G-6-PD) - deficient erythrocytes. We therefore studied the survival of G-6-PD- deficient cells, incubated with ascorbic acid, in rats with partial reticuloendothelial and complement blockade. Animals were pretreated with ethyl palmitate and cobra venom factor. They were then transfused with 51Cr-labeled erythrocytes which had been incubated in the presence or absence of ascorbic acid. G-6-PD-deficient cells, incubated with ascorbic acid, had impaired survival when compared to that of controls. G-6-PD-deficient cells, in the absence of ascorbic acid, had survival times equal to those of normal control erythrocytes. At the concentrations used, ascorbic acid did not appear to alter the survival of normal cells. Ascorbic acid causes premature loss of G-6-PD- deficient human erythrocytes in this rat model. On the basis of previous clinical and experimental observations, as well as this study, caution should be used when administering ascorbic acid in large doses to individuals who might be G-6-PD deficient.
Techniques for demonstration of the specificity of circulating anticoagulants against antihemophilic factor (factor VIII), with studies of two cases possibly related to diphenylhydantoin therapy
Authors: Poon MC , Saito H , Ratnoff OD , Forman WB , Wisnieski J
Published: October 2019

Circulating anticoagulants against antihemophilic factor (AHF, factor VIII) sometimes seem to inactivate other clotting factors as well. Measurements of the concentration of clotting factors in highly diluted plasma, or after neutralization of the anticoagulant with purified AHF, have demonstrated the specific nature of the anticoagulant in a patient under treatment with diphenylhydantoin. A second case in a patient treated with this agent, and with penicillin, an agent previously associated with the evolution of circulating anticoagulants, is also described.
Blood viscosity in Waldenstrom macroglobulinemia
Authors: MacKenzie MR , Lee TK
Published: October 2019

Patients with Waldenstrom macroglobulinemia were studied for the presence or absence of the hyperviscosity syndrome, the relative serum viscosity value, and the calculated whole blood viscosity to identify a level at which symptoms occurred. The majority of symptomatic patients had whole blood viscosity values above 8.0 centipoises. There was a direct correlation between whole blood viscosity and relative serum viscosity, r = 0.75. One patient with central nervous system abnormalities was identified as having a high whole blood viscosity but a low serum viscosity. It was concluded that the vast majority of patients with the hyperviscosity syndrome will be identified by measuring the relative serum viscosity. In patients with central nervous system findings and a low serum viscosity, the whole blood viscosity should be determined either by direct measurement or by calculation.
One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation
Authors: Thomas ED , Buckner CD , Banaji M , Clift RA , Fefer A , Flournoy N , Goodell BW , Hickman RO , Lerner KG , Neiman PE , Sale GE , Sanders JE , Singer J , Stevens M , Storb R , Weiden PL
Published: October 2019

One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3–17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1–4 1/2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). Four patients are alive 1 1/2 - 3 1/2 yr after grafting but have had a relapse of their leukemia. Of 93 evaluable patients, 19 did not develop GVHD and 24 developed very mild GVHD. Fifty patients developed moderate to severe GVHD, and 40 of these were treated with antithymocyte globulin. Interstitial pneumonia occurred in 54 patients and was the primary cause of death in 34. Interstitial pneumonia often occurred in association with GVHD and the most common etiologic agent was cytomegalovirus. A total of 31 patients have had a relapse of leukemia. There was no definite correlation between relapse of leukemia and the presence or absence of GVHD. The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA- matched sibling marrow donor.
Ph1-positive childhood leukemias: spectrum of lymphoid-myeloid expressions
Authors: Forman EN , Padre-Mendoza T , Smith PS , Barker BE , Farnes P
Published: October 2019

Two children presented with Ph1-positive leukemia, confirmed by Giemsa banding as 22q-. One child showed an initial presentation characteristic of acute lymphoblastic leukemia, followed by development of chronic myelocytic leukemia 2 yr later. A second child presented in blast crisis. Both patients showed blast cells possessing both lymphoid and myeloid characteristics, as demonstrated by histochemical, biochemical, or surface receptor properties of each cell series. The evidence provided supports the assumption of mixed lymphoid-myeloid properties of blast cells in chronic myelocytic leukemia in children. Detailed study of the leukemic cells may aid in the understanding of complex stem cell relationships and suggest more effective therapeutic approaches.
Systemic mastocytosis in a patient with polycythemia vera treated with radioactive phosphorus
Authors: Eagan JW Jr , Baughman KL , Miller S , Conley CL , Eggleston JC
Published: October 2019

Systemic mastocytosis occurred as a fatal event in a patient with long- standing polycythemia vera. The patient had been treated over the course of 21 yr with radioactive phosphorus. Possible relationships between mastocytosis and polycythemia vera, and also between mastocytosis and treatment with ionizing radiation, are discussed. Histopathologic and electron microscopic findings are illustrated. Difficulties in establishing the diagnosis of mast cell disease in this setting are also described.
Evidence for differentiation of human leukemic blood cells in diffusion chamber culture
Authors: Hoelzer D , Kurrle E , Schmucker H , Harriss EB
Published: October 2019

Peripheral blood cells of 21 patients with different forms of acute leukemia were cultured in diffusion chambers (5 x 10(5) cells/chamber) implanted intraperitoneally in 650 R preirradiated host mice over a period of up to 21 days. In patients with acute myeloid leukemia (AML), acute erythroleukemia (AEL), or acute myelomonocytic leukemia (AMMoL), the total number of cells which developed during this culture period exceeded the implanted value and also the values for normal peripheral blood cells from ten controls. In acute undifferentiated leukemia (AUL), two out of six patients showed considerable growth whereas the others, and also two patients with acute lymphoid leukemia (ALL), had poor growth. Differential counts revealed that the rise in total cells was due mainly to proliferation of blast cells and formation of granulopoietic cells. The latter exceeded the numbers from normal peripheral blood cells in 9 out of 13 patients with AML, AEL, or AMMoL and in 2 out of 6 patients with ALL. The production of granulopoiesis was not restricted to proliferating cells, but included mature cells which were of abnormal morphology in some cases. From the amount of granulopoiesis and the time of its development it was assumed that they were at least partly derived from leukemic blast cells. Chromosome analyses to decide whether the granulopoietic cells were of leukemic or normal cell origin are in progress.
Leukemic reticuloendotheliosis: "hairy cell leukemia," functional and structural features of the abnormal cell in a patient with profound leukocytosis
Authors: Boldt DH , Speckart SF , MacDermott RP , Nash GS , Valeski JE
Published: October 2019

The development of profound leukocytosis in a patient with leukemic reticuloendotheliosis (LRE) enabled us to obtain purified LRE cells for the investigation of their structural and functional characteristics. The LRE cells of our patient bore surface immunoglobulin and had complement receptors but did not bear Fc receptors and did not form rosettes with sheep erythrocytes. By electron microscopy, the cells were observed to contain typical ribosome lamella structures and to phagocytize both 0.81 micron latex particles and complement-coated zymosan particles. They were adherent to both glass and nylon wool fibers. The mitogenic response to erythroagglutinating phytohemagglutinin was normal to magnitude but delayed chronologically. The binding of 125I-labeled plant lectins was used to characterize the surface topography of LRE cells. Results of these studies indicated that the LRE cell surface differed significantly from the surface of normal T and B lymphocytes and chronic lymphatic leukemia cells. The LRE cells were capable of both stimulating and responding in a one-way mixed lymphocyte culture. However, the LRE cells were not active as effector cells of either cell-mediated lympholysis, a T cell function, or antibody-dependent cellular cytotoxicity, a null cell function. In contrast, they were effector cells of lectin-induced cellular cytotoxicity showing that they did possess the capacity to function as cytotoxic effector cells. These data indicated that the LRE cells in our patient had surface and functional characteristics of both lymphocytes and monocytes.
Factor V activity of platelets: evidence for an activated factor V molecule and for a platelet activator
Authors: Osterud B , Rapaport SI , Lavine KK
Published: October 2019

This study was prompted by the observation that fresh platelet suspensions--prepared by gel filtration or albumin density gradient centrifugation--possessed only minimal factor V activity, whereas frozen-and-thawed platelet suspensions possessed striking factor V activity. Results of experiments with fresh suspensions suggested that unaltered platelets did not bind plasma factor V. The factor V activity of frozen-and-thawed platelet suspensions was markedly diminished after exposure to a factor V antibody, was not activated by thrombin, and was not associated with an increase in factor V antigen over that found in fresh platelet suspensions. Consequently, disruption by freezing and thawing must have resulted in the appearance of small amounts of an activated factor V molecule in platelet suspensions. Disrupted platelets were shown to activate native factor V, but an interaction between a platelet activator and traces of native factor V in fresh suspensions could not be demonstrated to account for the full activity of frozen-and-thawed suspensions. Apparently, therefore, platelets also contained an activated factor V molecule. Adding collagen, but not adenosine 5′-diphosphate to fresh platelet suspensions increased their factor V activity. Release of an activated platelet factor V molecule after exposure to collagen could represent a physiologically significant early step in hemostasis.
Demonstration of granulopoietic factor(s) in the plasma of nude mice transplanted with a human lung cancer and in the tumor tissue
Authors: Asano S , Urabe A , Okabe T , Sato N , Kondo Y
Published: October 2019

A human lung cancer (OTUK-tumor) was transplanted serially to nude mice, which invariably developed a marked neutrophilia. In order to analyze this phenomenon, in vitro agar culture studies were carried out. A three- to fourfold increase of colony-forming units in culture was observed in the femurs of these nude mice. Moreover, the plasma of nude mice bearing this tumor, as well as the tumor extract, had a significantly higher colony-stimulating activity on mouse bone marrow cells than appropriate controls. This activity had the property to stimulate granulocyte and/or mixed cell type colonies rather than mononuclear cells. This activity was also demonstrated, in a dose- dependent way, on normal human bone marrow cells. These findings indicated that the OTUK-tumor produced human granulopoietic colony- stimulating activity, which may have stimulated granulopoiesis in vivo as well.
Health of the intensively treated hemophiliac, with special reference to abnormal liver chemistries and splenomegaly
Authors: Levine PH , McVerry BA , Attock B , Dormandy KM
Published: October 2019

Liver function abnormalities have been noted in intensively treated hemophiliacs, and have led to less aggressive application of pooled plasma products by some physicians. In a prospective study, liver function was abnormal in 68 of 98 hemophiliacs. The abnormalities of hepatic function tended to persist over a 1-yr study period. There was no correlation between these abnormalities and the age of the patient, the presence of hepatitis-associated antigen or antibody, the presence or absence of splenomegaly (which was found in 26 of 98 patients), the number of infusions of plasma products, the type of hemophilia, or the type of product infused. Titers of antibodies to cytomegalovirus were generally higher in hemophilic patients than in a control group of healthy volunteers. These abnormalities did not suggest that a less aggressive infusion regimen was indicated for the hemophiliac, but did suggest the need for careful long-term observation of such patients.
Parallel tubular arrays in severe combined immunodeficiency disease: an ultrastructural study of peripheral blood lymphocytes
Authors: Payne CM , Jones JF , Sieber OF Jr , Fulginiti VA
Published: October 2019

The ultrastructure of the lymphocytes from three children with severe combined immunodeficiency disease (SCID) is described. Parallel tubular arrays (PTA) were found in a large percentage of circulating lymphocytes (53%, 41%, and 13%) in three SCID patients when compared to age-matched controls. The size of these inclusions was quite variable, with some attaining a length of 1.7 micrometer. They contained a tubular substructure with a diameter of 36--44 nm. The PTA were mostly located in the centriolar and Golgi regions of the cytoplasm, and were sometimes membrane bound. A centriolar origin of the inclusion was suggested. A second inclusion, the tubuloreticular structure, was found in only 1.4% of the circulating lymphocytes from one SCID patient. The origin of the PTA and its occurrence in severe combined immunodeficiency disease are discussed.
Comparative studies on monotypic IgM lambda and IgG kappa from an individual patient. IV. Immunofluorescent evidence for a common clonal synthesis
Authors: Hopper JE
Published: October 2019

Previous studies have presented evidence of shared idiotypic antigenic determinants located within the variable (VH) region of the heavy chains of monotypic IgMlambda and IgGkappa isolated from the serum of an individual patient, Bro, with Waldenstrom macroglobulinemia. Comparative N-terminal VH sequence analyses have demonstrated that the respective micron and gamma chains belong to separate VH subgroups. The entire VH sequence of the Bro micron chain has been reported, but the VH sequence of the Bro gamma chain still awaits completion. We report the results of an immunofluorescent analysis of cytoplasmic Ig of lymphoid cells isolated from the patient's peripheral blood and bone marrow. Between 6% and 9% of the cytoplasmic Ig-positive lymphoid cells exhibited fluorescent evidence for the dual presence of kappa and lambda chains are well as micron and gamma chains. These results strongly suggest that the idiotypically related Bro IgMlambda and IgGkappa paraproteins are derived from a common clonal origin. Moreover, these findings extend the results of a previous study that has demonstrated the dual presence of IgGkappa and IgGlambda paraproteins within individual myeloma plasma cells. Collectively, these studies suggest that a single neoplastic lymphoid clone may not necessarily be restricted to the synthesis of Ig proteins of the identical light chain class. These findings may have a broad implication for the understanding of surface and cytoplasmic Ig markers of neoplastic lymphoid cells in certain other lymphoproliferative disorders.
Reversal of granulocyte adherence to nylon fibers using local anesthetic agents: possible application to filtration leukapheresis
Authors: Schiffer CA , Sanel FT , Young VB , Aisner J
Published: October 2019

The effects of the cationic anesthetic agents tetracaine and lidocaine on granulocyte function, morphology, and adherence to nylon fibers were studied in an attempt to improve current methods of granulocyte collection by filtration leukapheresis (FL). When dissolved in acid- citrate-dextrose (ACD) plasma, these drugs significantly increased granulocyte elution from the fibers in a dose-related fashion. Granulocytes exposed to tetracaine and lidocaine remained more than 95% viable, retained normal bactericidal capacity after the drugs were washed from the cells, and had preserved membrane integrity, as evidenced by the normal ultrastructural appearance of tetracaine- exposed cells and an absence of leakage of lysozyme or lactic dehydrogenase. Granulocytes eluted with the anesthetic agents were rounded in shape with a reduction in the number of filopodial cytoplasmic projections and a relative absence of cytoplasmic vacuolization when compared to granulocytes eluted with ACD plasma alone. Dose-related inhibition of phagocytosis and adherence, which was largely reversible after washing the granulocytes, was noted. Greater than 95% of the lidocaine could be removed from the eluate with a single centrifugation and resuspension, indicating that granulocytes prepared by FL with anesthetic-enhanced elution could be potentially transfusable.
Divergent patterns of marrow cell suspension culture growth in the myeloid leukemias: correlation of in vitro findings with clinical features
Authors: Elias L , Greenberg P
Published: October 2019

Cellular recovery, maturation, and colony-forming cell (CFC) generation patterns of bone marrow cells from 23 patients with acute, subacute, and chronic myeloid leukemia (AML, SML, and CML) were studied using liquid and agar culture techniques. Increased recovery of proliferative myeloid cells from liquid culture was noted in 6 of 8 AML patients at diagnosis or relapse and 5 of 7 untreated SML patients. Patients with either AML or SML with rapid clinical progression exhibited greater recovery of cells in vitro with less maturation than patients with more stable disease. Studies from 3 patients with CML showed normal to increased cellular recovery with normal maturation. Three of 4 studies of AML patients followed sequentially in apparent remission, but with impending relapse, exhibited increased numbers of myeloblasts and promyelocytes, whereas 28 of 32 studies performed during stable remission were normal. The normally observed increase in CFC during liquid culture was absent in most leukemic marrow samples studied (3 of 4 AML, 4 of 6 SML, and 2 of 3 CML). Persistent low recovery of CFC during AML remission was associated in 3 patients with short remission duration. These studies indicated the potential utility of these techniques for the clinical evaluation of patients with myeloid leukemia and for studying factors involved in the progression of these diseases.
Platelet-associated IgG in immune thrombocytopenic purpura
Authors: Luiken GA , McMillan R , Lightsey AL , Gordon P , Zevely S , Schulman I , Gribble TJ , Longmire RL
Published: October 2019

A method for the measurement of immunoglobulin G associated with gel- filtered platelets is described and finding in 70 control subjects and 37 patients with immune thrombocytopenic purpura (ITP) are reported. Control platelet-associated IgG (PAIgG) levels (nanograms IgG per 10(9) platelets) averaged (+/-SD) 1231+/-424; samples studied after 24 and 48 hr remained within the control range. PAIgG values of 19 adult and 12 childhood patients with chronic ITP averaged 4711+/-3025 and 4923+/- 3955, respectively, and differed significantly from controls (p less than 0.001). There was an inverse correlation between PAIgG values and the chronic ITP patient's platelet count. Six patients with childhood acute ITP had PAIgG levels ranging from 5588 to 56,250 and appeared to represent a different statistical population from those with chronic ITP. In chronic ITP patients responding to splenectomy, there was an immediate normalization of PAIgG levels; however, a certain percentage of patients studied several months after splenectomy evidenced elevated PAIgG levels in association with normal platelet counts. These data showed that the direct measurement of platelet associated antibody is a useful technique in the diagnosis and follow-up of patients with chronic ITP. Preliminary studies in patients with acute ITP have suggested that this method may be useful in differentiating acute and chronic childhood ITP.
Autooxidation as a basis for altered function by polymorphonuclear leukocytes
Authors: Baehner RL , Boxer LA , Allen JM , Davis J
Published: October 2019

To investigate the possibility that human polymorphonuclear leukocytes (PMN) elaborate sufficient amounts of hydrogen peroxide (H2O2) and other radicals of reduced oxygen to be autotoxic and retard directed cell movement and phagocytosis, the rate of ingestion of opsonized lipopolysaccharide-paraffin oil particles and movement through Nuclepore filters were studied. Ingestion rates were increased under anaerobic conditions and in normal aerobic conditions in the presence of extracellular catalase but not superoxide dismutase (SOD) or scavengers of singlet oxygen or hydroxyl radicals. Conversely, ingestion rates were decreased when cells were exposed to H2O2 or a superoxide anion (O2-)-H2O2 generating system of xanthine-xanthine oxidase. Catalase, but not SOD, prevented the effect and also enhanced the directed movement of PMN in normal aerobic conditions. PMN from volunteers administered 1600 U/day of the membrane lipid antioxidant alpha-tocopherol were hyperphagocytic but killed Staphylococcus aureus 502A less effectively than controls, suggesting that less H2O2 was available to damage PMN or kill bacteria. H2O2-dependent stimulation of the hexose monophosphate shunt, H2O2 release from phaogytizing PMN, and fluoresceinated concanavalin A cap formation promoted by H2O2 damage to microtubules were all diminished, but the release of O2- from phagocytizing PMN was not diminished in the vitamin E group. These results support the hypothesis that directed movement and phagocytosis by PMN are attenuated by autooxidative damage to the cell membrane by endogenously derived H2O2 and that the administration in vivo of vitamin E may prevent this damage by scavenging H2O2.
Metabolic crowding effect in suspension of cultured lymphocytes
Authors: Sand T , Condie R , Rosenberg A
Published: October 2019

We studied the respiration and glucose utilization of suspensions of cultured lymphocytes. Respiration was measured by a couloximetric method using closed systems without a gas-suspension interface. The sensitivity of the method allowed measurements during a time interval of less than 1 hr. We found that the respiration of lymphocytes was strongly density dependent over the range of 10(8)-10(3) cells/ml. Oxygen utilization per cell increased 100-fold with 1000-fold dilution of the cell suspension. Glucose utilization showed little density dependence. We showed that the phenomenon was not due to nutrient depletion, pH shifts, accumulation of lactic acid, nor damage of cells during the dilution. Since in our experiments a gas-liquid interface was absent, the previously suggested explanation of gas diffusion as a limiting factor has been excluded. The experiment was best explained by regulation of respiration by humoral factors produced by the cell suspension.
Plasmapheresis in the treatment of thrombotic thrombocytopenic purpura
Authors: Bukowski RM , King JW , Hewlett JS
Published: October 2019

Two patients with thrombotic thrombocytopenic purpura (TTP) have recovered completely after intensive plasmapheresis. The mechanisms responsible for the improvement in these instances are most likely related to the removal of an inciting or damaging agent. The possibility that this agent may be an immune complex is discussed. Plasmapheresis appears to be useful therapy for some patients with this syndrome.
Combination intrathecal therapy for meningeal leukemia: two versus three drugs
Authors: Sullivan MP , Moon TE , Trueworthy R , Vietti TJ , Humphrey GB , Komp D
Published: October 2019

The comparative effectiveness of intrathecal (IT) combination chemotherapy using two agents, methotrexate (MTX) and hydrocortisone (HDC), and three agents, MTX, HDC, and cytosine arabinoside (CA), in treating meningeal leukemia was determined in a randomized Southwest Oncology Group study. Following central nervous system (CNS) remission induction the same regimen was used for periodic maintenance until CNS relapse supervened. Complete CNS remission was achieved in 100% of 43 children given two-agent therapy and in 96% of 48 children given three- agent therapy. Length of CNS remission for two-agent therapy was 1-150+ wk, median 47.2 wk; for three-agent therapy, remissions were 1-190+ wk, median 64.6 wk. Differences in length of remission curves were not of statistical significance (p=0.71). Toxicity of combination IT chemotherapy in the two- and three-agent regimens was reduced compared to that of IT MTX alone for CNS remission induction and maintenance. The additive effects of the IT drug combinations have been less than expected. The cytocidal activity of these agents when administered simultaneously of sequentially is not fully understood. Further studies are clearly indicated to determine optimum doses, schedules, and sequences for the chemotherapeutic agents which can be given intrathecally in combination.
Ultrastructural, cytochemical, and membrane surface marker characteristics of the atypical lymphocytes in infectious mononucleosis
Authors: McKenna RW , Parkin J , Gajl-Peczalska KJ , Kersey JH , Brunning RD
Published: October 2019

Atypical lymphocytes from nine young adults with acute infectious mononucleosis (IM) were studied for morphologic, ultrastructural, cytochemical, and membrane surface marker characteristics. There was an absolute increase in T lymphocytes in the patients. Atypical lymphocytes accounted for 83%-96% of the lymphocyte population. These lymphocytes contained cytoplasmic inclusions which ranged in size from 1000 to 6000 A, were usually membrane bound, and consisted of parallel arrays of microtubulelike structures. The inclusions, which have been referred to as parallel tubular arrays (PTA), were found in 15%-75% of the lymphocytes from the IM patients. Ultrastructural cytochemical methods demonstrated acid phosphatase activity within many of the membrane-bound PTA. The function of the PTA is unknown. Since they were observed only in the lymphocytes which appeared to correspond to the atypical lymphocytes on light microscopy, the majority of which typed as T cells, there appears to be an association between PTA and T lymphocytes. It is possible that PTA identify a specific subset of T lymphocytes which is expanded in IM. Alternatively, PTA may be a transient finding in lymphocytes appearing only in certain biologic states of the cell such as during T-lymphocyte activation.
Source of hydrogen peroxide and of chemiluminescence observed in activated human platelet preparations
Authors: Krinsky NI , Scoon KL , Hardin JC , Levine PH
Published: October 2019

Human platelet suspensions can be observed to produce small amounts of H2O2 (0.04 nmoles H2O2/min/2.5 X 10(5) cells/cu mm) and measurable chemiluminescence when exposed to target particles for phagocytosis, such as latex spherules. Both H2O2 production and chemiluminescence are characteristic of phagocytosing polymorphonuclear leukocytes (PMN) and analysis of the purified platelets indicates contamination by PMN at the level of 0.2%. The amount of H2O2 produced and the chemiluminescence observed can be duplicated by adding latex spheres to a preparation of PMN at a concentration equivalent to the contaminant in the platelet preparations. We conclude that the H2O2 produced and chemiluminescence observed from activated platelets is due to the presence of small amounts of contaminating PMN. These studies emphasize the importance of controlling for PMN contamination in studies of platelet biochemistry and physiology.
Comparison of polymerization of ancrod and thrombin fibrin monomers
Authors: Spellman GG Jr , Macoviak JA , Gralnick HR
Published: October 2019

The polymerization of thrombin and ancrod fibrin monomers was studied with a standardized technique that evaluated turbidity changes and protein incorporation into the clot. Ancrod fibrin monomers were found to polymerize more slowly and form less turbid clots (at identical protein concentrations). Changes in ionic strength and pH influences ancrod fibrin monomer polymerization to a greater extent than thrombin fibrin monomer polymerization. Benzyltriethylammonium chloride was shown to be a potent inhibitor of fibrin monomer polymerization, with a greater inhibitory effect on ancrod fibrin monomers than on thrombin fibrin monomers. The differences between ancrod and thrombin fibrin may play a role in the infrequent thrombotic complications reported with ancrod therapy.
Treatment of hypoplastic anemia in mice with placental transplants
Authors: Dancis J , Jansen V , Brown GF , Gorstein F , Balis ME
Published: October 2019

A genetic mutation in mice (W/Wv) causes an autosomal recessive disease characterized by hypoplastic anemia which lasts throughout life. Double- dominant W/Wv anemic mice were sublethally irradiated to facilitate repopulation of marrow with transplanted cells and were injected intravenously with suspensions of 5–10 million placental cells of 15 days gestation derived from normal, isogeneic donors. Red cell counts fell promptly after irradiation and then rose progressively over a period of weeks, reaching normal levels of the nonmutant. Mean corpuscular volume and hemoglobin electrophoresis patterns of red cells in recipient W/Wv mice resembled those of normal donor animals. The therapeutic effect lasted for the duration of the observation period, in some instances over 9 mo. W/Wv mice that were administered Hanks' solution or fetal blood, instead of placental transplants, remained anemic. Late gestation placentas (18 days) were also ineffective.
Properties of a factor increasing monocytopoiesis (FIM) occurring in serum during the early phase of an inflammatory reaction
Authors: van Waarde D , Hulsing-Hesselink E , van Furth R
Published: October 2019

A factor increasing monocytopoiesis (FIM) has been demonstrated during the onset of an acute inflammatory reaction caused by an intraperitoneal injection of polystyrene latex particles. It is protein in nature, does not contain a carbohydrate moiety essential for its function, and is very probably not a glycoprotein. The molecular weight of FIM lies between 18,000 and 24,000 daltons (determined with both ultrafiltration membranes and gel filtration on Sephadex G100). The monocytosis induced by FIM is dose dependent. FIM is thermolabile, having a half-time of about 20 min at 37 degrees C in serum; temperature inactivation can be delayed by the addition of epsilon- aminocaproic acid, the half-time at 37 degrees C then being about 45 min. In vitro treatment of normal murine blood with the inducers of the inflammatory reaction does not result in FIM activity in the serum. FIM dose not have chemotactic activity toward macrophages, is not a clotting factor, is not a biologically active fragment of the complement system, and has no colony-stimulating or-enhancing activity in the vitro bone marrow colony assay. On the basis of these results, a mechanism is postulated for the humoral regulation of monocytopoiesis.
Eosinophil and neutrophil colony-forming cells in culture
Authors: Dao C , Metcalf D , Bilski-Pasquier G
Published: October 2019

Clusters of cells obtained from a short-term culture of human bone marrow cells in methylcellulose were transplanted in cell-free plates containing conditioned medium. Of 2559 transplants, 439 gave small clusters, 223 gave large clusters, and 70 gave colonies. A better cloning efficiency was achieved from 4-day-old clusters, from aggregates containing 3 cells or more, and from large cells rather than from small cells. Cytocentrifugation could be performed on 215 large clusters or colonies. The population consisted of pure neutrophils in 36.3% and of pure macrophages in 36.8%. A mixture of neutrophils and macrophages was found in 23.2%, thus indicating that these two cell lines originated from the same committed cell (G-CFC). Eosinophils were found in 8 (3.7%) clusters as a pure population, and were never mixed with either neutrophils or macrophages in the other 207 clusters. Despite the small number of eosinophil colonies, one could suggest that using the in vitro technique the committed eosinophil colony-forming cells could be distinguished from the G-CFC.
Selective increase of potassium permeability in red blood cells exposed to acetylphenylhydrazine
Authors: Orringer EP , Parker JC
Published: October 2019

Normal human red blood cells, when exposed briefly to acetylphenylhydrazine (APH), acquire Heinz bodies and a propensity for net ion and water loss upon subsequent incubation in an APH-free medium of physiologic sodium and potassium (K) content. The cells can be protected from APH damage by previous deoxygenation. The ion and water loss depend on the presence of a K gradient from cell to medium. In contradistinction to some other types of membrane perturbation in which K permeability is increased, the APH effect is not dependent on calcium. The meaning of these observations is discussed in relation to the vulnerability of the K permeability barrier.
Progenitor cells in canine cyclic hematopoiesis
Authors: Dunn CD , Jones JB , Jolly JD , Lange RD
Published: October 2019

Granulocytic (colony-forming units in culture, or CFU-c) and erythrocytic (erythropoietin-responsive cells, or ERC) progenitor cells in canine cyclic hematopoiesis (CH) have been shown to fluctuate over the cycle and in the same phases as one another. The ERC cycle is preceded by 3 or 4 days by a rise in serum erythroid-stimulating activity and is followed by a reticulocytosis. During the cycle CFU-c show a differential sensitivity to two sera, one normal and one containing elevated amounts of colony-stimulating activity. The proliferation rate of CFU-c also fluctuates from well above normal to considerably less than normal over the cycle. These results are discussed in the light of present knowledge of the pathogenesis of canine CH. We suggest that these results support the contention that CH is a disorder of hemopoietic stem cells and that the cycling of humoral factors and peripheral blood cells may follow as a consequence.
Development of hematopoietic spleen colonies in nonirradiated genetically normal mice
Authors: Kitamura Y , Tamai M , Miyano Y , Shimada M
Published: October 2019

The question as to whether prior irradiation or injection of cytotoxic drugs is essential for the development of spleen colonies was examined in genetically normal mice. Mixtures of lymph node and bone marrow cells from C57BL mice were injected into (C57BL X CBA-T6T6) F1 hybrid mice without pretreatment. Hematopoietic nodules were observed in the spleens of F1 hybrid mice killed 18 days after injection. The average number of nodules increased linearly with increased numbers of injected bone marrow cells. Hematopoietic stem cells (CFU-S) and dividing cells in the nodules were shown to be of C57BL origin. Histologic examination showed that erythroid cell colonies predominated over granulocytic cell colonies. These results suggest that any kind of treatment that causes the depletion of CFU-S in the spleen of hosts would provide a suitable environment for the production of colonies by transplanted CFU-S.
Effects of porcine plasmin on the coagulation and fibrinolytic systems in humans
Authors: Hedner U , Johansson L , Nilsson IM
Published: October 2019

Pig plasmin (Lysofibrin) was given to 11 patients with phlebographically verified venous thrombosis, 2 of whom were treated two and three times, respectively. The effect on coagulation and fibrinolytic parameters was studied. The platelet count, Owren's P&P (prothrombin plus factors VII and X), plasminogen, factor XIII, and antithrombin III did not change during the treatment. All patients developed a proteolytic activity demonstrable on both unheated and heated fibrin plates. The fibrinogen decreased successively to very low levels, and parallel to this an increase in fibrin/fibrinogen degradation products was found. The factor VIII and factor V activities decreased immediately after each Lysofibrin infusion but normalized rapidly again. The factor VIII molecule, however, retained its reactivity to rabbit antiserum against factor VIII. Immediately after the plasmin infusion a decrease of both alpha2-macroglobulin (alpha2-M) and the rapidly reacting alpha2-antiplasmin was observed. alpha2-M decreased successively and in several of the patients values were unmeasurable for a period of some days. A complex formation between pig plasmin and the alpha2-antiplasmin was demonstrated in crossed immunoelectrophoresis. The complexes were rapidly cleared from the circulation. No interaction between the pig plasmin and the inhibitor of the plasminogen activation, alpha1-antitrypsin or inter-alpha- inhibitor, was found.
Proliferative state of normal in vitro colony-forming cells during development of L5222 rat leukemia and their reaction to chemotherapy
Authors: Harriss EB , Hoelzer D
Published: October 2019

In the experimental rat leukemia, L5222, the decrease of normal in vitro colony-forming cells (CFU-C) after chemotherapy with daunomycin is much less than in nonleukemic controls. The leukemia is therefore used here to test the hypothesis that in leukemia the CFU-C are expelled from the active cell cycle to a resting state and are thereby less sensitive to cycle-dependent chemotherapeutic agents. The L5222 leukemia has the advantage that the leukemic blast cells do not form colonies in agar culture so that normal CFU-C can be assessed under leukemic conditions. To compare the proportions of CFU-C in the S-phase in normal and leukemic rats, two S-phase-specific agents, 3H-thymidine and hydroxyurea, were used to kill proliferating bone marrow cells. Following treatment with 3H-thymidine in vitro, about 41% of the CFU-C were killed in normal and about 25% in leukemic bone marrow. Hydroxyurea administered in vivo resulted in the death of about 33% and 26%, respectively. The results indicate that fewer normal CFU-C are in S-phase in the L5222 leukemia, which might help to explain how enough normal stem cells survive chemotherapy to regenerate the bone marrow.
Hypoprothrombinemia: case report
Authors: Montgomery RR , Otsuka A , Hathaway WE
Published: October 2019

A patient with a significant history of spontaneous and posttraumatic bleeding was found to have hypoprothrombinemia. His prothrombin (factor II) activity by clotting assay was 9.5% and his factor II antigen was 5%. Crossed immunoelectrophoresis and sucrose density gradient ultracentrifugation of the patient's plasma showed his prothrombin to be qualitatively indistinguishable from normal prothrombin by these techniques.
Defective iron uptake and globin synthesis by erythroid cells in the anemia of the Belgrade laboratory rat
Authors: Edwards JA , Garrick LM , Hoke JE
Published: October 2019

Erythroid cell iron uptake and globin synthesis were studied in the anemia of the Belgrade Laboratory rat (gene symbol, b), an autosomal recessive trait characterized by hypochromia and hyperferrinemia. Reticulocyte protein and globin synthesis, as measured in vitro by the incorporation of 3H-L-leucine, were significantly diminished in b/b animals, although no major imbalance between alpha-and beta-chain production was observed in b/b reticulocytes. The incorporation in vitro of 3H-L-methionine into marrow cell globin demonstrated no difference between b/b animals and +/? control animals in the proportion of alpha-to beta-chain production. The transfer of iron from plasma to reticulocytes, as measured in vitro by the uptake of 59Fe, was significantly decreased in b/b animals; Sephadex G 200 chromatography of b/b red cell lysates did not reveal the accumulation of 59Fe in nonhemoglobin fractions found when heme synthesis was inhibited with isoniazid. The magnitude of the reticulocyte iron-uptake defect was greater than the reticulocyte globin-synthesis defect, suggesting that the former is the primary lesion.