bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo appearance of the ph-1 chromosome in a previously monosomic bone marrow (45,XX,-6): conversion of a myeloproliferative disorder to acute myelogenous leukemia
Authors: Kohn G , Manny N , Eldor A , Cohen MM
Published: October 2019

Bone marrow examination of a patient with a myeloproliferative disorder revealed monosomy for chromosome No. 6 (45,XX,-6). Two months later, during blastic crisis, reinvestigation of the bone marrow showed the presence of the Ph-1 chromosome in the previously aneuploid cell line (45,XX,-6,-22,+Ph-1). This case differs from those previously published in that the Ph-1 chromosome appeared de novo during the development of frank acute myelogenous leukemia.
The effect of platelet concentrate storage temperature on adenine nucleotide metabolism
Authors: Filip DJ , Eckstein JD , Sibley CA
Published: October 2019

The effect of platelet concentrate storage temperature (4 degrees C versus 22 degrees C) on platelet adenine nucleotide metabolism was studied. In general, levels of platelet ATP and ADP, the release reaction, and the metabolis nucleotide pool were best preserved for 72 hr by storage of concentrates at 4 degrees C. Storage of concentrates for 72 hr at 22 degrees C was occasionally associated with a pH decrease to less than 6.0, which is incompatible with platelet viability. When the pH fell below 6.0, there was a marked deterioration of platelet adenine nucleotide levels and the release reaction. The results for concentrates stored at 22 degrees C, with a final pH above 6.0, were not inferior to the results for those stored at 4 degrees C. The pH remained above 7.0 in all concentrates stored at 4 degrees C. The pH changes of platelet concentrates stored at 22 degrees C could not solely be attributed to platelet count, red cell count, or bacterial contamination. Storage at both temperatures was associated with conversion of ATP in the metabolic adenine nucleotide pool to hypoxanthine.
In vitro granulocyte production in patients with Hodgkin's disease and lymphocytic, histiocytic, and mixed lymphomas
Authors: Bull JM , DeVita VT , Carbone PP
Published: October 2019

The in vitro granulocyte colony formation (CFU-C) was examined in 19 untreated patients with advanced Hodgkin's disease and in 25 untreated patients with histiocytic, lymphocytic, and mixed lymphomas. The patients with Hodgkin's disease and diffuse histiocytic, lymphocytic, and mixed lymphomas produced decreased numbers of granulocyte colinies, whereas patients with nodular histiocytic, lymphocytic, and mixed histiocytic-lymphocytic lymphomas showed normal granulycote colony growth. The acute response of CFU-C to combination chemotherapy (MOPP) is described in two patients followed with sequential marrow cultures through their indiction chemotherapy. The long-term effect of MOPP chemotherapy was examined in five patients who had completed chemotherapy 1.5–6 yr priot to in vitro examination.
Metal ion contents of gel-filtered platelets from patients with storage pool disease
Authors: Lages B , Scrutton MC , Holmsen H , Day HJ , Weiss HJ
Published: October 2019

Platelets from nine patients with storage pool disease (SPD) and from ten control subjects were isolated by gel filtration into a suspension medium permitting the direct determination of platelet Mg-2+, Ca-2+, and K+ levels. The total intracellular levels of ATP and ADP, as well as the incorporation patterns of 14-C-adenine into the metabolic nucleotide pool, were also determined in these platelet suspensions. The gel-filtered platelets (GFP) from SPD patients exhibited slightly lowered levels of ATP and substantially reduced amounts of ADP, in agreement with previous studies using PRP suspensions. Diminished aggregation responses to ADP, epinephrine, and to collagen in particular, similar to those observed previously in PRP, were obtained in GFP from SPD patients. However, GFP from the patients exhibited more variable aggregation responses to addition of ADP and epinephrine than did GFP from the control subjects. Increases in the extent of radioactive hypoxanthine formation, observed previously in normal platelets as a result of isolation into the suspension medium used in these studies, were significantly reduced in the GFP from SPD patients. The levels of platelet Mg-2+ and K+ determined in GFP from the patients were not significantly different from the levels of these ions in GFP from control subjects. However, substantial reductions in platelet Ca- 2+ were found in the SPD platelets. A strong correlation was obtained between this reduction in platelet Ca-2+ and the reduction in ADP in these platelets. No such correlation was apparent between the ATP and Ca-2+ deficiencies. These results suggest that a major portion of platelet Ca-2+ may be located in the dense granules and support previous hypotheses that granular ADP and/or Ca-2+ may play a role in the release reaction. The finding of normal levels of platelet Mg-2+ and K+ in SPD platelets, however, suggests that these latter ions are not located in the dense granules.
The factors controlling stem cell recirculation. i. Migration of hemopoietic stem cells in adrenalectomized mice
Authors: Khaitov RM , Petrov RV , Moroz BB , Bezin GI
Published: October 2019

The influence of bilateral adrenalectomy on hemopoietic stem cell (CFU) migration in mice has been studied. Formation of endogenous spleen colonies in lethally irradiated, leg-shielded mice was sharply increased by prior adrenalectomy, and this increase was not dependent on the volume of shielded bone marrow. Adrenalectomy was shown to increase endogenous spleen colony formation in sublethally irradiated mice as well. However, it had no affect on formation of spleen colonies in lethally irradiated mice injected with syngeneic bone marrow. The CFU content of murine bone marrow decreased acutely after removal of the adrenals, and this decrease was accompanied by a concomitant increase in the peripheral blood and splenic CFU. Thus, adrenalectomy appeared to have no affect on the splenic plating efficiency or proliferative rate of hemopoietic stem cells, but it did result in increased migration of stem cells from the bone marrow to the blood, and thence to the spleen. It is concluded that the adrenal steroids may be of physiologic importance in the regulation of ehmopoietic stem cell migration.
In vitro production of erythropoietin by mouse fetal liver
Authors: Zucali JR , Stevens V , Mirand EA
Published: October 2019

Mouse fetal liver tissue has been cultured and shown to produce and release into the culture medium an erythropoietically active substance for up to 30 days of culture. Since this substance can be completely neutralized by an antiserum to erythropoietin and shows a dose-- response relationship in the plethoric mouse assay, it is suggested that the culture medium contains erythropoietin, a hormone important in the regulation of erythropoiesis. Using this procedure, we have obtained the equivalent of about 20.7 unites of erythropoietin from five T-flasks (75 sq cm) over the 30-day culture period.
Clinical staging of chronic lymphocytic leukemia
Authors: Rai KR , Sawitsky A , Cronkite EP , Chanana AD , Levy RN , Pasternack BS
Published: October 2019

A method of clinical staging of chronic lymphocytic leukemia (CLL) has been proposed which is based on the concept that CLL is a disease of progressive accumulation of nonfunctioning lymphocytes: stage O, bone marrow and blood lymphocytosis only; stage 1, lymphocytosis with enlarged nodes; stage II, lymphocytosis with enlarged spleen or liver or both; stage III, lymphocytosis with anemia; and stage IV:lymphocytosis with thrombocytopenia. Analysis of 125 patients. in the present series showed the following median survival times (in months) from diagnosis: stage 0, is greater than 150; stage I 101; stage II, 71; stage III, 19; stage IV, 19, The median survival for the entire series was 71 mo. The prognostic significance of the stage remained even after adjustment was made for age and sex. However, both sex and age were shown to be poor predictors of survival after adjustment for stage. The method of staging proved to be a reliable predictor of survival whether used at diagnosis or during the course of the disease. The proposed staging system was an equally accurate indicator for survival when applied to two other previously published studies of large series of patients.
The effect of carbon monoxide on red cell life span in sickle cell disease
Authors: Beutler E
Published: October 2019

Carbon monoxide at a concentration of 1000–2000 ppm was administered to sickle cell disease patients. In each of two patients, one 51Cr red cell survival study was carried out before CO administration, and a second study was initiated a few days before CO administration was started. In both, significant prolongation of red cell survival was observed, suggesting that the rheologic properties of sickle cells were favorably influenced in vivo. The administration of carbon monoxide is not recommended as a treatment for sickle cell disease. However, further trials would seem to be justified if conducted under carefully controlled conditions.
Complement-sensitive red cells in aplastic anemia
Authors: Ben-Bassat I , Brok-Simoni F , Ramot B
Published: October 2019

In view of the clinical association of aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH), the complement-dependent lysis of the youngest red cells of AA patients was studied. A complement-sensitive population of young red cells was found in five of six patients with AA. These cells were rapidly cleared from the circulation and were undetectable in the oldest cell fraction. Such cells were not found in normal controls or in a variety of hematologic disorders, with the exception of PNH. This study suggests that in most patients with AA, even without any clinical manifestations of PNH, there is a population of dyserythropoietic, short-lived complement- sensitive cells.
Heterogeneity of human circulating anticoagulants against antihemophilic factor (factor VIII)
Authors: Poon MC , Wine AC , Ratnoff OD , Bernier GM
Published: October 2019

The heterogeneity of human circulating anticoagulants against antihemophilic factor (AHF, factor VIII) observed in seven patients, both with and without classic hemophilia, was investigated by neutralization of their activity with antiserums directed to whole IgG and to lambda and kappa light chains. All seven anticoagulants were immunoglobulins. Six appeared to contain both kinds of light chains, although the dual light chain composition of two of these could be demonstrated only at high concentration of antiserum. In one circulating anticoagulant, light chain specificity could not be demonstrated with small amounts of antiserum, and with larger amounts, only lambda light chain specificity was revealed. Whether or not this circulating anticoagulant really contained a single light chain type could not be ascertained with our technique. The evidence presented suggested that circulating anticoagulant antibodies against AHF are polyclonal in nature.
BCG in the treatment of acute lymphocytic leukemia
Authors: Heyn RM , Joo P , Karon M , Nesbit M , Shore N , Breslow N , Weiner J , Reed A , Hammond D
Published: October 2019

Children with acute lymphocytic leukemia, who were in remission after induction with prednisone and vincristine and consolidation with intravenous methotrexate, were randomized into three groups receiving (1) no further therapy, (2) BCG, and (3) chemotherapy with biweekly methotrexate and monthly prednisone and vincristine. Children continuing in remission after 8 mo on chemotherapy in group 3 were rerandomized into three similar groups, i.e., no therapy, BCG, and chemotherapy. In the primary randomization, the median duration of remission was identical in the groups receiving no therapy or BCG, (4 and 4.3 mo respectively), and both were significantly less than the median duration of remission on chemotherapy which had not been reached prior to secondary randomization at 8 mo. Results of secondary randomization were similar to those of primary randomization. As used in this study, BCG was ineffective in prolonging drug-induced remissions either early in remission or when the leukemic cell population might have been further reduced after 8 mo of maintenance chemotherapy.
Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. I. Distribution and cellularity of the bone marrow in normal dogs
Authors: Calvo W , Fliedner TM , Herbst EW , Fache I
Published: October 2019

Marrow cellularity in adult beagles (1–2 yr old) is highest in centrally located bones, with values between 8000 and 12,000 nucleated cells per sq mm. It decreases gradually towards the peripheral parts of the body, reaching values below 1000 per sq mm in bones distal to the elbow and knee. The first tail segment always contains some active marrow. The fifth segment has only stromal elements. In spongy bones fat cells appear to be distributed at random among the blood-forming elements. In the middle part of the femur the fatty marrow predominates in the center of the cylinder, while the subendosteal area is very cellular. The proximal and distal ends of the femur are more cellular than the middle. The small standard deviation of the cellularity in the spongy bones of the trunk and in the proximal and middle part of the humerus makes these sites areas of choice for quantitative studies of marrow regeneration. The large variations in cellularity of the marrow in the radius and tibia of young adult dogs make these sites unsuitable for such studies. The distribution of active and fatty marrow in dogs is similar to that of humans. The differential count of active marrow is quite constant between different dogs and in the various sites of each animal.
Acute monoblastic leukemia: diagnosis and treatment of ten cases
Authors: McKenna RW , Bloomfield CD , Dick F , Nesbit ME , Brunning RD
Published: October 2019

During a large clinicopathologic study of acute nonlymphocytic leukemia (ANLL), ten patients were identified in whom the leukemic blasts demonstrated striking morphologic and cytochemical similarities and who seemed to form a specific subgroup of ANLL. The patients' leukemic blasts were studied in routine blood and bone marrow preparations and by cytochemical and ultrastructural techniques. In routine smears, the blasts showed no clear evidence of differentiation. Cytochemically, the blasts exhibited strongly positive nonspecific esterase activity, which was completely inhibited by incubation with sodium fluoride, and were myeloperoxidase and sudan black B negative. Ultrastructural features of the blasts were similar to those described for monocytic leukemias. Striking clinical features included the occurrence primarily in young patients, the high frequency of lymphadenopathy at presentation, and the high incidence of post-treatment disseminated intravascular coagulation. Complete remissions were frequently initially obtained with duanorubicin in combination with various other agents and later in the disease with VP16–213. Based on the cytochemical and ultrastructural features, we concluded that this form of ANLL was a variety of acute monocytic leukemia. Recognition of the entity is important for optimal therapy.
Hairy cell leukemia: functional, immunologic, kinetic, and ultrastructural characterization
Authors: Debusscher L , Bernheim JL , Collard-Ronge E , Govaerts A , Hooghe R , Lejeune FJ , Zeicher M , Stryckmans PA
Published: October 2019

A diagnosis of hairy cell leukemia was made by optic microscopy, phase- contrast microscopy, electron microscopy, scanning microscopy, and histochemistry of the abnormal blood cells. In vivo these cells were found to have a half-time in the blood of approximately 150 hr. In vitro they had the capacity to adhere firmly to plastic, making it possible to obtain a pure population of hairy cells. Neither T-rosette formation nor phytohemagglutinin (PHA) transformation could be demonstrated in these cells. On the other hand, the presence of immunoglobulins on the surface of the hairy cells (HC) by immunofluorescence, and the synthesis and secretion by these cells of IgM type lambda-chains shown by radioimmunodiffusion, were in favor of their B-type lymphocyte origin. Similarities to chronic lymphocytic leukemia were apparent.
DNA-metabolizing enzymes in normal human lymphoid cells. VI. Induction of DNA polymerases alpha, beta, and gamma following stimulation with phytohemagglutinin
Authors: Mayer RJ , Smith RG , Gallo RC
Published: October 2019

At least three distinct DNA polymerases, named alpha, beta, and gamma, have been isolated from normal mammalian cells. The function of these enzymes in regard to DNA replication and repair remains unclear. Stimulation of blood lymphocytes with the plant mitogen phytohemagglutinin (PHA), is known to increase total DNA polymerase activity. In this study, we measured the change of each of these activities as lymphocytes intered a mitotic cycle. Aliquots of a pool of normal human blood lymphocytes were incubated with PHA for 0, 24, 48, and 72 hr, respectively, and the various DNA polymerase activities quantitated at each point. No significant DNA polymerase activity was detected in unstimulated cells. Low levels of polymerase beta were found at 24 hr. The average DNA content per cell doubled between 24 and 48 hr, and during this interval all three DNA polymerases increased to easily detectable levels. By far the greatest fractional increase in activity of all three polymerases was seen between 48 and 72 hr, after the average doubling of cellular DNA. In summary, these blood lymphocytes lack significant levels of DNA polymerases; stimulation with PHA induces all three of the major DNA polymerase species. In both these respects, these cells differ from other proliferating mammalian cell systems. The possible significance of this difference is discussed.
Treatment of life-threatening hemorrhage due to acquired factor VIII inhibitor
Authors: Pintado T , Taswell HF , Bowie EJ
Published: October 2019

An otherwise healthy elderly man developed massive, life-threatening, sublingual bleeding associated with an idiopathic factor VIII inhibitor. The patient was treated wtih cyclophosphamide, steroids, factor VIII concentrates, and repeated plasmapheresis (including three times with NCI-IBM blood-cell separator). Rapid clinical and laboratory improvement occurred, with complete disappearance of the inhibitor. The patient has remained well, without evidence of an inhibitor, for 8 mo. The possible role of each of the therapeutic measures in the disappearance of the inhibitor and the possible pathogenetic mechanism of this disorder are discussed. A high mortality rate and a striking incidence of sublingual hematoma have been observed in cases in the literature.
Treatment of acute lymphoblastic leukemia in adolescents and a-dults: A retrospective study of 41 patients (1970-1973)
Authors: Willemze R , Hillen H , Hartgrink-Groeneveld CA , Haanen C
Published: October 2019

During the period from January 1970 until December 1973, therapy was started in 41 previously untreated adolescents and adults with acute lymphoblastic leukemia. Induction therapy was started with vincristine and prednisone in all patients, resulting in complete remission in 19 and death due to infection during the first month in one case. After 3 wk on these two drugs, the addition of daunorubicin was required in the remaining 21 patients. Fifteen of these obtained remission, one died during induction therapy, and five patients were unresponsive to this therapy, as well as to all subsequent induction schemes. The overall remission rate was 83%. Significantly higher initial leukocyte counts were found in the group treated with vincristine, prednisone, and daunorubicin. Meningeal leukemia prophylaxis, by either periodic methotrexate injections given intrathecally or a combination of cranial irradiation and intrathecally administrated methotrexate, was administered in 29 therapy responders. The median duration of complete remission obtained with various maintenance therapy schemes was 13 mo. No differences were seen in the results obtained in patients between 14 and 20 yr of age and older patients. Twenty-two patients relapsed within 2–37 mo. Relapses were confined to the central nervous system in two cases, to the bone marrow in 18, and to the bone marrow and CNS simultaneously in two. A second remission was obtained in 17 cases (77%). The median survival time of the whole group was 27 mo, as compared with 32 mo for therapy responders and 7 mo for the nonresponders. The percentage and duration of remission and the survival time in our group of adolescents and adults were comparable to those currently being achieved in other centers, but not as good as those reported for children treated with the same protocol.
Globin chain synthesis in HbD (Punjab)-beta-thalassemia
Authors: Rieder RF
Published: October 2019

A 23-yr-old man of Greek-Italian ancestry with mild anemia was found to be heterozygous for HbD (Punjab) beta121 glu leads to gin and beta- thalassemia. HbA was not detected upon electrophoresis of the subject's hemolysate, and no synthesis of betaA globin was demonstrated after incubation of peripheral blood or bone marrow with 3H-leucine. The thalassemia gene was thus of the betao variety. The betaD/alpha synthesis ratios were almost equally unbalanced in the blood and bone marrow: 0.53 and 0.61, respectively. The mother of the propositus had beta-thalassemia trait. In peripheral blood the betaA/alpha synthesis ratio was 0.38. The mutant betaD gene thus appeared potentially capable of directing the synthesis of globin chains as efficiently as a normal betaA gene. The mildness of the HbD-betao-thalassemia syndrome appeared to be due to the maintenance of a relatively high total beta/alpha synthesis ratio in the presence of a physiologically neutral structural mutation.
Hybrid erythrocytes for membrane studies in sickle cell disease
Authors: Clark MR , Shohet SB
Published: October 2019

A hybrid erythrocyte model for membrane studies in sickle cell disease has been developed. The model consists of normal red cell membranes containing hemoglobin S and sickle cell membranes containing hemoglobin A. In hybrids, complete hemoglobin exchange has been achieved together with restoration of low membrane permeability to potassium. Normal membranes containing HbS sickle upon deoxygenation and assume the characteristic appearance of irreversibly sickled cells (ISC) after prolonged anoxia. It is suggested that the hybrid model will be useful in defining further the process of ISC formation and in studying the influence of sickle hemoglobin upon the function of the surrounding membrane.
Study of a kindred with hereditary spherocytosis and glyceraldehyde-3- phosphate dehydrogenase deficiency
Authors: McCann SR , Finkel B , Cadman S , Allen DW
Published: October 2019

A patient with hereditary spherocytosis (HS) was found to have glyceraldehyde-3-phosphate dehydrogenase (G3PD) deficiency by electrophoresis of the isolated red cell membranes on polyacrylamide gels with sodium dodecyl sulfate (PAGE SDS) as demonstrated by a diminished band 6 (G3PD) and confirmed by specific enzyme assay. Thirteen members of his family were studied: four were normal, two had HS alone, three had G3PD deficiency alone, and four had both HS and G3PD deficiency. G3PD deficient kindred members were probably heterozygous, since their red cell enzyme, while qualitatively normal, was present in half normal amounts. The G3PD deficiency alone was asymptomatic, and there was no evidence that the combination of HS with G3PD deficiency increased the clinical severity of the disease. However, G3PD deficiency, when combined with HS, was associated with an increase in protein band 4.5 on PAGE SDS. This band was also increased by incubation of normal red cells without glucose, and appeared to be a protein absorbed to the membrane as a consequence of metabolic stress. Hence, red cells with the combined abnormalities of both HS and G3PD deficiency showed signs of the exceptional metabolic stress to which they were exposed.
Red cell calcium leak in congenital hemolytic anemia with extreme microcytosis
Authors: Wiley JS , Gill FM
Published: October 2019

A child with congenital hemolytic anemia, extreme microcytosis and bizarre red cell morphology has been studied. Splenectomy at the age of 21 mo greatly improved the hemolytic anemia, although red cell morphology was unchanged. Aniso- and poikilocytosis were marked on a stained smear, and there were many small hyperchromatic cells of irregular shape. The MCV of 25 cu mu was very low and the MCHC was normal. Osmotic fragility of fresh blood was increased, and postsplenectomy blood showed a fraction of extremely fragile cells. Concentration and fluxes of Na+ and K+ were normal, except K+ efflux, which was stimulated by external Ca2+. Inward Ca2+ movement into the patient's red cells was elevated three- to fourfold above red cells of the same mean age. Red cell Ca2+ concentration was raised 2.5 times normal and most of the Ca2+ was localized in the stroma. Red cell lipid, sialic acid, and ouabain-binding sites, all per milliliter of cells, were increased by 16%-23%, and, since these substances estimate the amount of membrane, it was likely that Ca2+ content per unit of membrane area was at least twice normal. Deformability of the cells, as judged by their filterability was markedly impaired. It was concluded that the red cell membrane was defective, and an increased membrane Ca2+ content was associated with reduced deformability, hemolysis, and distorted red cell morphology in this syndrome.
Chronic myelogenous leukemia presenting in the blastic phase and its association with a 45 XO Ph1 karyotype
Authors: Nigam R , Dosik H
Published: October 2019

A 58-yr-old male patient presented in the blastic phase of chronic myelogenous leukemia (CML). Cytogenetic studies revealed a 45 XO Ph1 chromosome pattern in bone marrow cells during a short remission and again in the blastic phase of the disease. The patient expired 8 mo following diagnosis. The blastic phase of CML can stimulate acute myelogenous leukemia (AML) clinically and hematologically; CML can be differentiated by the presence of the Ph1 chromosome and the stigmata of CML. Absence of the Y chromosome from the bone marrow in CML is a recently described finding. Previous reports indicating the prevention of the blastic phase in patients with this karyotype could not be confirmed by our or other recently reported cases.
Evidence that Fitzgerald factor counteracts inhibition by kaolin or ellagic acid of the amidolytic properties of a plasma kallikrein
Authors: Ratnoff OD , Saito H
Published: October 2019

Fitzgerald trait, an asymptomatic disorder, is associated with abnormalities of surface-mediated plasma reactions, including coagulation via the intrinsic pathway, augmentation of the clot- promoting properties of factor VII, kaolin-mediated fibrinolysis, kinin generation, and enhancement of vascular permeability by diluted plasma (PF/Dil). These abnormalities can be corrected by Fitzgerald factor, an agent probably identical with high molecular weight kininogen found in normal, but not Fitzgerald-trait plasma. Our preparations of Fitzgerald factor possessed a second property. Amidolysis of alpha-N-benzoyl-L- proline-L-phenylalanine-L-arginine-pnitroanilide by a plasma kallikrein (activated Fletcher factor) was inhibited by kaolin or solutions of ellagic acid. Addition of preparations of Fitzgerald factor to kaolin or to solutions of ellagic acid counteracted their inhibitory properties. The action of these preparations was duplicated by solutions of cytochrome C or IgG, suggesting that these agents may inhibit the negative charges of kaolin or ellagic acid. Fitzgerald factor enhanced amidolysis of both normal and Fitzgerald-trait plasmas exposed to kaolin, effects not duplicated by cytochrome C or IgG. Whether or not the two properties of our preparations of Fitzgerald factor are related to the same agent is not yet certain. The relationship between these observations and the biologic role of Fitzgerald factor remains to be investigated.
Increased erythropoietin production in anephric rats with hyperplasia of the reticuloendothelial system induced by colloidal carbon or zymosan
Authors: Peschle C , Marone G , Genovese A , Rappaport IA , Condorelli M
Published: October 2019

Adult rats were subjected sequentially to (1) administration of colloidal carbon, zymosan, or gadolinium; (2) subtotal hepatectomy, bilateral nephrectomy, or sham operation; and (3) a 6-hr bout of hypoxia, starting 1 hr or 24 hr after the operation. Control animals received the respective vehicles. The erythropoietin (Ep) activity was assayed in exhypoxic polycythemic mice on the basis of 48-hr per cent RBC(-59) Fe incorporation values. Ep levels in serum of anephric rats primed with either colloidal carbon or zymosan were considerably more elevated than in control animals. This potentiating effect was observed in rats subjected to hypoxia starting either 1 or 24 hr after nephrectomy. On the other hand, gadolinium did not enhance the extrarenal Ep response to hypoxia. It is emphasized that both colloidal carbon and zymosan induced marked hyperplasia of the hepatic and splenic reticuloendothelial system (RES), while gadolinium did not induce this effect. A strict correlation was thus established between potentiation of extrarenal Ep production and hyperplasia of the RES. It is therefore tentatively concluded that the RES is a source of extrarenal Ep. Additionally, since the liver plays a prominent role in extrarenal Ep production, Kupffer cells may represent a major source for Ep in the anephric rat. Finally, it is of interest that both colloidal carbon and zymosan did not potentiate the Ep response to hypoxia in sham-operated or subtotally hepatectomized rats.
Cryoprotective agents as inducers of erythroleukemic cell differentiation in vitro
Authors: Preisler HD , Christoff G , Taylor E
Published: October 2019

The ability of families of compounds with known and potential cryoprotective properties to induce the differentiation of Friend leukemia cells in vitro was studied. For each agent, both the proportion of differentiated cells in the culture and the total amount of heme/10(7) cells were determined. Within each family of compounds there was a direct correlation between a compound's cryoprotective ability, its ability to donate electron pairs for hydrogen bonding (basicity), and its ability to induce differentiation. While individual agents differed with respect to the proportion of cells which were induced to differentiate, the biology of the process of differentiation appeared to be similar, regardless of the agent used. A cell line which was unresponsive to DMSO was responsive to other inducers, suggesting that this DMSO-resistant cell line differed from its parent DMSO- responsive cell line either in its metabolism of the inducers or in the ability of the inducers to enter the cell. Alternatively, there may be more than one mechanism involved in the chemical induction of differentiation.
Isolation of variant lymphoma cells with reduced growth requirements for extracellular calcium and magnesium and enhanced oncogenicity
Authors: Brennan JK , Lichtman MA , Chamberlain JK , Leblond P
Published: October 2019

By exposing an established cell line of malignant mouse lymphocytic cells (L5178Y) to a culture environment low in calcium and magnesium, we have isolated and maintained in continuous culture a variant population with reduced growth requirements for the cations. The variant cells are larger, have enhanced aggregability, tend to form dispersed colonies in semisolid medium, and have increased oncogenicity. Variants and their progenitors share similar morphology, maximum proliferative rate, and stability of phenotype. The significance of these findings is discussed and an analogy suggested between the selective influence of calcium and magnesium deprivation in vitro and the evolution of thymic dysplasias in divalent cation- deprived rodents.
Explanation for the apparent lack of ouabain inhibition of pyruvate production in hemolysates: the "backward" PGK reaction
Authors: Chillar RK , Beutler E
Published: October 2019

The concept that ouabain-sensitive membrane (Na+ + K+)-ATPase-generated adenosine diphosphate (ADP) preferentially serves as the substrate for the phosphoglycerate kinase (PGK) step of erythrocyte glycolysis has been reexamined. Membrane ATPase readily provides ADP for and utilizes ATP generated in the pyruvate kinase (PK) step and is ouabain sensitive. Earlier reports in the literature, which have suggested that in hemolysates the ATPase reaction facilitating the PK reaction is ouabain-insensitive, are reinterpreted: in crude hemolysates ADP generated in the “backward” PGK reaction can account for these data. We conclude that there is no convincing evidence of selective linkage of (Na+ + K+)-ATPase with the PGK reaction.
Platelet to leukocyte adherence phenomena associated with thrombocytopenia
Authors: Greipp PR , Gralnick HR
Published: October 2019

Two patients developed thrombocytopenia associated with an in vitro platelet to leukocyte adherence phenomenon (PLAP). In one patient, whole serum, intact plasma, and the IgG fraction of the serum could induce the PLAP of normal platelets in normal whole blood or buffy coat preparations. Passage of serum over a Sepharose column coupled with antihuman IgG resulted in the loss of all the PLAP activity. Activity could not be recovered from the whole serum or the IgG fraction of serum of the second patient; however, the PLAP was transferred to her newborn infant. In both patients, an unusual pulmonary illness accompanied the PLAP and thrombocytopenia.
Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. II. Distribution and cellularity of the marrow in irradiated and transfused animals
Authors: Calvo W , Fliedner TM , Herbst E , Hugl E , Bruch C
Published: October 2019

Dogs were given transfusions of cryopreserved autologous mononuclear blood leukocytes after 1200 roentgens (R) (midline dose) whole-body x- irradiation. Bone marrow repopulation was studied by means of histomorphological methods at days 9 and 10 after transfusion of an average of 3 X 10(9), 7 X 10(9), 13 X 10(9), and 31 X 10(9) cells. The return of marrow cellularity to normal values was related to the number of cells transfused. With low cell doses (3 X 10(9) and 7 X 10(9)), the marrow regeneration at 10 days was focal. There were groups of cells (colonies) showing either erythropoiesis, myelopoiesis, or megakaryocytopoiesis in the osteal niches of the trabecular bones. Frequently such niches were seen showing complete cellular recovery next to niches with complete aplasia. With higher cell doses, all niches showed hemopoietic regeneration, and the cellularity approached normal values. No hemopoietic regeneration was observed in those skeletal parts that do not show hemopoiesis, even under normal circumstances.
In vitro colony-forming cells in the marrow of leukemic and preleukemic mice
Authors: Hays EF , Craddock CG , Haskett D , Newell M
Published: October 2019

In vitro colony-forming cells (CFUc) were evaluated in preleukemic and leukemic AK mice. Increased concentrations of CFUc were found in normal appearing marrow of superinfected animals 2–3 wk prior to the onset of lymphoma. CFUc were present in marrows of mice with virus-accelerated, spontaneous, and transplanted lymphoma. CFUc concentration was often increased in mice with advanced disease and marrow replacement by lymphoblasts. When calculated on the basis of CFUc per normal marrow cells, this increase was marked. The colonies developed only in the presence of added colony-stimulating activity (CSA) and had the morphologic features of colonies from normal marrow. Leukemic cells did not form colonies. Lymphoma cells, from virus accelerated, spontaneous and transplanted lymphoma, did not produce CSA in feeder layers or conditioned medium. Leukemic and nonleukemic AK bone were found to produce similar small amounts of CSA. These studies showed that the preleukemic state as well as marrow replacement by lymphoblasts resulted in increased marrow CFUc's. No evidence for increased local production of CSA by lymphoblasts or the marrow microenvironment was found to account for this.
Mechanism of dilutional anemia in massive splenomegaly
Authors: Hess CE , Ayers CR , Sandusky WR , Carpenter MA , Wetzel RA , Mohler DN
Published: October 2019

Twenty patients with anemia and massive splenomegaly were studied in order to elucidate the mechanism by which splenomegaly results in plasma volume expansion. In 18 patients, increased plasma volume accounted for most of the anemia. Fourteen patients had an exaggerated renin response to standing, mean 1967 +/- 613 (SE) ng angiotensin ll/100 ml plasma (p less than 0.05). The mean resting forearm blood flow was increased 3.47 +/- 0.32 (SE) ml/100 ml forearm tissue (p less than 0.001). The venous capacitance was normal, as contrasted to a marked decrease in venous capacitance in patients with anemia of comparable degree without splenomegaly. Cardiac indices were increased in 10 of 11 patients (range 4.1–8.1 liters/min/sq m). In nine of ten patients oxygen consumption was increased (range 147–231 ml/min/sq m). Splenectomy was performed on 14 patients. Splenic blood flow was elevated in four of four patients (range 750–2000 ml/min). Splenic A-V oxygen difference was exaggerated in seven of seven patients and in three of three patients splenic indocyanine-green dye dilution curve failed to show an early peak suggestive of A-V shunting in the spleen. Free portal pressure was elevated in 12 of 12 patients and decreased immediately after splenectomy. The intravascular albumin mass decreased in ten patients, was unchanged in three at 2–4 mo after splenectomy, and was accompanied by a rise in the plasma albumin concentration in nine. These data suggest that a flow-induced portal hypertension with expansion of the portal vascular space is an important early hemodynamic change. This finding, together with a decreased peripheral resistance, probably results in a decrease in effective intravascular volume, resulting in stimulation of the renin-angiotensin-aldosterone system and other renal hemodynamic changes necessary for salt and water retention. Splenectomy usually accomplishes a complete reversal of these abnormalities and correction of the anemia.
Abnormal parachloromercuriphenylsulfonate-sensitive cation channel in the erythrocytes of hereditary spherocytosis
Authors: Kitao T , Hattori K , Takeshita M
Published: October 2019

The erythrocytes of hereditary spherocytosis (HS) demonstrate an increased inward movement of sodium ions, an alteration which has been proposed as the primary defect leading to cell destruction. Parachloromercuriphenylsulfonate (PCMBS), an agent reacting with sulfhydryl groups of the membrane, increases the cation permeability of normal red cells, but does so to a much lesser extent in the HS red cells. On the other hand, pronase that is specific for amino groups of the membrane increases cation permeability and decreases anion permeability equally in normal and HS red cells. It may be postulated that a decreased number of sulfhydryl sites or a mutation of proteins in the PCMBS-sensitive cation channels of the HS cell membrane result in this hyposensitivity to PCMBS.
Preferential involvement of chromosomes no. 8 and no. 21 in acute leukemia and preleukemia
Authors: Yamada K , Furusawa S
Published: October 2019

Chromosome analyses were performed by a direct method on bone marrow cells of 147 patients with acute leukemia and preleukemia; in 53 chromosomally abnormal cell lines were found. Chromosome abnormalities due to structural alterations were observed in 48% of the aneuploid patients. Using the ASG banding technique, the exact identification of the abnormal chromosomes was successfully made in 22 aneuploid patients. Even though variability between patients existed in the chromosome changes; the nonrandom occurrence of some chromosome abnormalities was revealed, involving most frequently chromosomes No. 8 and No. 21. Abnormalities of chromosome No. 22 were not encountered, contrasting sharply with the frequent involvement of this chromosome in chronic myelogenous leukemia. The significance of the preferential involvement of No. 8 and No. 21 chromosomes is discussed in relation to leukemogenesis.
Chromosomal banding patterns in acute nonlymphocytic leukemia
Authors: Rowley JD , Potter D
Published: October 2019

Bone marrow chromosomes obtained from 50 of 55 consecutive adult patients with acute nonlymphocytic leukemia were analyzed with quinacrine fluorescence. Twenty-five patients showed a normal karyotype and 25 an abnormal karyotype on the initial samples available for analysis. Among the 25 patients with abnormalities, the marrow cells contained 48 chromosomes in one case, 47 in two, 46 in ten, 45 in nine, 43 in two, and 42 chromosomes in one case. Seven of the ten patients with 46 chromosomes had abnormalities, primarily balanced translocations, that were not detected with the standard Giemsa stains. The analysis of all of the data available revealed the presence of nonrandom chromosome changes such as the addition of No. 8, the loss of No. 7, and a gain or loss of one No. 21. the most frequent structural rearrangement was the translocation between the long arm of No. 8 and No. 21, which may also be associated with the loss of a sex chromosome. Chromosomal abnormalities decreased or disappeared during remission; the same abnormality recurred in relapse. Chemotherapy did not appear to produce a stable clone of aberrant cells. Evolution of the karyotype occurred in eight patients, in five of whom an additional No. 8 was observed. This pattern of chromosomal evolution in patients with acute leukemia was very similar to that observed in patients with chronic myelogenous leukemia in the blast phase.
Isolation and in vitro differentiation of human erythroid precursor cells
Authors: Kim HC , Marks PA , Rifking RA , Maniatis GM , Bank A
Published: October 2019

There is decreased beta-globin production in beta-thalassemic reticulocytes and nucleated erythroid cells. In this study, we have examined whether unbalanced globin synthesis is expressed at all stages of human erythroid cell maturation. In order to determine the pattern of globin synthesis in early erythroid cells during erythroid cell maturation, an in vitro culture system using human bone marrow erythroid precursor cells has been developed. Early erythroid precursor cells (proerythroblasts and basophilic erythroblasts) have been isolated from nonthalassemic and thalassemic human bone marrows by lysing more mature erythroid cells, using complement and a rabbit antiserum prepared against normal human red cells. In the presence of erythropoietin, differentiation and proliferation of erythroid cells in demonstrable in liquid suspension culture for 24–48 hr, as determined by morphological criteria and by an increase in globin synthesis. The ratio of alpha- to beta-globin chain synthesis in nonthalassemic cells in approximately 1 at all stages of erythroid cell differentiation during culture. In cells from four patients with homozygous beta- thalassemia there is decreased beta-globin synthesis compared to alpha- globin synthesis, both in early erythroid precursor cells and during their maturation in culture. These findings indicate that unbalanced globin chain synthesis is expressed at all stages of red cell maturation in homozygous beta-thalassemia.
Trisomy 8 in the bone marrow associated with high red cell glutathione reductase activity
Authors: de la Chapelle A , Vuopio P , Icen A
Published: October 2019

In a series of 841 patients with hematologic disorders, 10 individuals were found to have an extra C group chromosome in their bone marrow cells. In two the extra chromosome was not identified, but in the remaining eight it was No. 8. Four of these ten patients had leukemia, and the others had cytopenias or other probably preleukemic conditions. The mean value for glutathione reductase activity in the red cells of four patients with trisomy 8 was significantly higher (2980 +/- 940 mumoles/min/liter of erythrocytes) than in normal controls (1930 +/- 360) or in any of five different control groups of patients with hematologic disorders. The extent of enzyme activation as a result of preincubation with exogenous flavin adenine dinucleotide was similar in the erythrocytes of all groups. The reasons for the high values of red cell glutathione reductase activity in patients with trisomy 8 are discussed in the light of the proposed assignment of the gene for that enzyme to chromosome 8.
The effect of experimental hematoma on serum levels of fibrinogen- related antigen
Authors: Cade J , Regoeczi E , Hirsh J , Buchanan M
Published: October 2019

The effect of experimental hematomas on serum levels of fibrinogen- related antigen (FRA) was studied in rabbits. Homologous blood used for production of hematomas was mixed with 131I-fibrinogen, and the measurement of FRA was made using a radioactive technique (representing FRA from hematoma) and immunologically (representing total FRA). Total body radiation of animals bearing hematomas containing 131I-fibrinogen decayed slowly (mean t 1/2 = 189 hr) over the first 2–3 days and then rapidly (mean t 1/2 = 43 hr) during the subsequent days. Serum FRA levels measured immunologically rose transiently from 4 to 11 mug/ml during the slow phase of hematoma resolution, and returned to baseline levels during the rapid phase of resolution. The appearance of a small amount of protein-bound radioactivity in the blood of animals with hematomas paralleled the time course of the changes in immunologically determined FRA, but, even at its peak, circulating levels only averaged 0.36% of the administered tracer. From these observations, it seemed unlikely that the dissolution of fibrin which may form as the result of bleeding into tissues would significatnly contribute to levels of circulating FRA.
Chemotherapy of the blastic phase of chronic granulocytic leukemia: hypodiploidy and response to therapy
Authors: Canellos GP , DeVita VT , Whang-Peng J , Chabner BA , Schein PS , Young RC
Published: October 2019

Thirty-two patients in the blastic phase of Philadelphia chromosome- positive chronic granulocytic leukemia (CGL) were studied in a prospective randomized trial in which vincristine--prednisone (19 patients) was compared with cytosine arabinoside--6-thioguanine (13 patients). Seven remissions (37%), including two complete remissions, were achieved in the vincristine--prednisone group. Three of the five with predominant hypodiploid blast cell lines treated with vincristine-- prednisone had complete or partial remissions. Both complete remitters presented with hypodiploidy consisting of 44 chromosomes. Four patients (30%) who were treated with cytosine arabinoside--6-thioguanine responded with one complete remission. The median survival of the responders was 8 mo, as compared to 1--2 mo for the nonresponders. Crossover to the opposite regimen as secondary therapy following refractoriness or resistance resulted in only 3 partial responses out of 21 treated. All three had previously responded to vincristine-- prednisone. Of the 32 cases, 14 had an elective splenectomy during the chronic phase of the disease. Prior splenectomy did not influence the response to chemotherapy, as all three complete remitters occurred in the nonsplenectomized group. Similarly, survival in the blastic phase was not affected by prior splenectomy.