bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preferential involvement of chromosomes no. 8 and no. 21 in acute leukemia and preleukemia
Authors: Yamada K , Furusawa S 
Published: October 2019

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
Evaluation of the role of in vivo proteolysis (fibrinogenolysis) in prolonging the thrombin time of human umbilical cord fibrinogen
Authors: Galanakis DK , Mosesson MW 
Published: October 2019

Abstract
These studies have been directed at evaluating the role played by proteolysis (fibrinogenolysis) in vivo in prolonging the thrombin time of human umbilical cord (“fetal”) fibrinogen. The aggregation rate of cord fibrin compared with that from adult plasma is always delayed when the reaction is carried out under conditions of relatively high ionic strength (e.g., 0.29); this difference is not apparent at relatively low ionic strength (e.g., 0.09). In addition, as assessed by turbidimetric techniques, the maximum absorbance attained by cord fibrin is considerably less than that attained by adult fibrin. Coagulable fibrinogen catabolites (i.e., fraction I-5) are present in cord plasma and, like their counterparts from adult plasma, lack various portions of the COOH-terminal region of the A alpha chain. However, their presence in plasma does not explain the behavioral differences between cord and adult fibrin. Moreover, differences revealed by turbidimetric comparison of cord and adult fibrin from plasma fraction I-2 persist in fibrin from fraction I-5; it therefore appears that the COOH-terminal region of the A alpha chain does not contain the structure(s) accounting for the unique behavior of “fetal” fibrinogen.
Effect of heterologous antibody on human platelets
Authors: Colman RW , Schreiber AD 
Published: October 2019

Abstract
The effect of heterologous anti-human platelet antibody on human platelet function was examined in the presence and absence of whole plasma as an in vitro model for antibody-induced immune damage to cells. Heterologous IgG anti-human platelet antibody mediated platelet aggregation and released serotonin from both platelets in plasma and from platelets isolated by gel filtration and increased the availability of platelet acid phosphatase in a dose-response fashion. Anti-platelet antibody failed to release beta-glucuronidase (lysosomal enzyme marker) or cause lactic dehydrogenase loss (cytolysis). The effect of the antiplatelet antibody on platelets proceeded in the absence of complement. The active molecule in the anti-platelet antiserum was isolated in the IgG fraction and all three indi cators of platelet injury were mediated by purified monomeric IgG. Thrombin was not required for the antibody-mediated effects, as three thrombin inhibitors failed to block the reaction. EDTA was an effective inhibitor, suggesting a cation requirement; however, as little as 38 muM calcium was sufficient for effective platelet aggregation and release. The inability of acetylsalicylic acid to inhibit the effect of the antiplatelet antibody suggests that heterologous antibody (IgG) induced platelet alteration proceeds by a different mechanism than that mediated by ADP and epinephrine and does not involve endogenous platelet prostaglandin synthesis.
Kappa and lambda light chain disease: survival rates and clinical manifestations
Authors: Shustik C , Bergsagel DE , Pruzanski W 
Published: October 2019

Abstract
Ninety-seven patients with light chain disease (LCD) were studied. The median survival from diagnosis was 30 mo for 52 patients with kappa-LCD and 10 mo for 45 patients with lambda-LCD (p less than 0.0007). A lower proportion of kappa-LCD patients (15.7%) than lambda-LCD patients (42.2%) died within the first 6 mo after diagnosis. The survival of the remaining patients with kappa-LCD was still much longer than of those with lambda-LCD (p = 0.022). The shorter survival of lambda-LCD patients could not be ascribed to an increased incidence of recognized manifestations indicating a poor prognosis (e.g., anemia, hypercalcemia, azotemia, low albumin, the extent of osteolytic lesions, or proteinuria), the incidence of amyloidosis, the clinical stage of the disease at diagnosis, or the response to treatment, and remains unexplained. A comparison of the clinical manifestations of LCD with those of other myelomas revealed some differences. LCD patients were slightly younger than IgA and IgG patients but older than IgD patients. A 1:1 ratio of males to females was similar to the ratios in IgA and IgG myeloma, but differed from the 3:1 ratio reported for IgD myeloma. Plasma-cell leukemia developed in 7/97 LCD patients, an incidence that was higher than has been reported in other myelomas. The initial BUN was more than or equal to 30 mg/100 ml in 54 of 95 LCD patients, an incidence that was higher than has been reported for IgA and IgG myeloma, but lower than the incidence in IgD myeloma. The incidence of amyloidosis in LCD (23 of 97 patients) was similar to that reported for IgA and IgG myeloma, but less than the incidence in IgD myeloma.
Evidence that functional subunits of antihemophilic factor (Factor VIII) are linked by noncovalent bonds
Authors: Poon MC , Ratnoff OD 
Published: October 2019

Abstract
Partially purified human antihemophilic factor (AHF, factor VIII), when treated with high concentrations of salt, has been shown to dissociate into two components: one, of relatively low molecular weight, possesses procoagulant activity, and the other, of higher molecular weight, forms precipitates with heterologous antiserum against AHF and supports ristocetin-induced platelet aggregation. The ease of separation suggests that the two components in the native state might be held together by noncovalent bonds. Earlier observations do not exclude the possibility that the subunits may be covalently bonded in nature but might be severed by plasma proteolytic enzymes during laboratory manipulation. The issue was examined by preparing partially purified AHF from fresh human plasma in the presence of protease inhibitors, including benzamidine, soybean trypsin inhibitor, epsilon-aminocaproic acid, heparin, and hirudin. Under these conditons, gel filtration in the presence of 0.25 M calcium chloride and 0.001 M benzamidine resulted in its separation into two components, having properties identical to those separated in the absence of these protease inhibitors. The inhibitor mixture blocked generation and action of streptokinase- and kaolin-activated plasmin from plasma, and protected both plasma AHF and partially purified AHF from the action of thrombin. Surface-induced activation of PTA (factor XI) was partially inhibited, and that of Christmas factor (factor IX) was completely inhibited. This observation provides further evidence that in the native state the high- and low-molecular-weight components of preparations of antihemophilic factor are held together by noncovalent bonds.
Immunosuppressive therapy of Factor VIII inhibitors
Authors: Hultin MB , Shapiro SS , Bowman HS , Gill FM , Andrews AT , Martinez J , Eyster EM , Sherwood WC 
Published: October 2019

Abstract
Immunosuppressive therapy was used in seven hemophiliac and three nonhemophiliac patients with factor VIII inhibiors. Permanent disappearance of the inhibitor occurred in three hemophiliac and two nonhemophiliac patients following treatment with cyclophosphamide and factor VIII. Critical factors influencing the response to therapy may include both the titer and duration of the inhibitor and the degree of intervening factor VIII exposure prior to immunosuppressive therapy. Two severe hemophiliacs with low titer inhibitors that disappeared without specific therapy are also reported.
Further characterization of the circulating cell in chronic lymphocytic leukemia
Authors: Schultz EF , Davis S , Rubin AD 
Published: October 2019

Abstract
Peripheral lymphocytes from normal individuals and from patients with chronic lymphocytic leukemia (CLL) were cultured in vitro for 1–7 days. The growth response to phytohemagglutinin (PHA) was quantitated by the incorporation of tritiated uridine into RNA nucleotide during a 2-hr pulse with the radioisotope. While the maximum response in PHA- stimulated normal cultures appeared at 2–3 days, CLL cultures required 5–7 days to develop their maximal response, which was 50%-60% of the normal magnitude. Dilution of the number of normally reactive lymphocytes by culturing them with totally unreactive, mitomycin- treated cells produced a normal 72-hr maximal response, no matter what proportion of unreactive cells was included in the PHA-stimulated cultures. In addition, the response of peripheral lymphocytes from patients with myeloblastic leukemia, where large numbers of unreactive myeloblasts diluted the normal small lymphocytes, a depressed reaction occurred at the anticipated 2–3 days. Nylon fiber-adherent lymphocytes consisting of 85% immunoglobulin (Ig)-bearing cells responded minimally to PHA, but showed no evidence of a delay. When isolated from CLL patients, both fiber-adherent cells (Ig-bearing) as well as non-fiber- adherent (sheep erythrocyterosetting) cells responded to PHA in a delayed fashion. Similarly, a case of CLL, in which 93.5% of the circulating lymphocytes bore sheep red blood cell receptors, showed its peak response to PHA at 7 days. Therefore, using surface marker criteria considered characteristic of normal T cells and B cells, the delayed response to PHA on the part of CLL lymphocytes was independent of thymic or nonthymic origin.
A diffusible stimulator of eosinophilopoiesis produced by lymphoid cells as demonstrated with diffusion chambers
Authors: Miller AM , McGarry MP 
Published: October 2019

Abstract
Previous experiments have indicated that eosinophilopoiesis is stimulated in lymphoid cell-dependent eosinophil responses to certain antigens. In order to study if the potential for this stimulation of eosinophilopoiesis is a function of lymphoid cells and can be expressed on challenge with the eosinophilia-inducing antigen, the diffusion chamber technique for the culture in vivo of murine hemopoietic cells has been modified. A quadrachamber diffusion assembly allows for the simultaneous maintenance in the same host of four cell populations, pairs of which are separated by a cell-impermeable Millipore diffusion membrane of defined porosity. Spleen cells for chambers were from normal mice and mice primed with tetanus toxoid; secondary challenge induces eosinophilia. These spleen cells were placed transfilter from isogeneic bone marrow cells and cultured in vivo for 6 days in normal mice that received tetanus toxoidintraperitoneally following chamber- assembly implant. The marrow cell transfilter from spleen cells of primed-donor origin exhibited significantly greater eosinophilopoiesis than contiguous-chamber marrow transfilter from normal spleen cells. Such stimulated eosinophilopoiesis was independent of total chamber marrow cellularity. The data indicated that antigen-stimulated lymphoid cells may be the source of an eosinophilopoietic factor.
Evidence for early recruitment of granulocyte precursors during high- dose methotrexate infusions in mice
Authors: Pinedo HM , Chabner BA , Zaharko DS , Bull JM 
Published: October 2019

Abstract
The effects of constant exposure to high concentrations of methotrexate in vivo on the committed stem cell (CFU-C) were studied by in vitro culture of mouse bone marrow. Bone marrow samples were obstained from animals receiving a continuous infusion, and were cultured in a methotrexate-free semisolid gel system. The effects of methotrexate infusion on the pluripotent stem cell population (CFU-S) were studied as well. Constant exposure to 10(-5) M methotrexate produced a rapid decrease in total nucleated cells per femur, reaching 35% of control at 12 hr and remaining at approximately this level throughout 48 hr of drug infusion. A decrease in the number of both CFU-C and CFU-S per femur was observed, which paralleled the drop in nucleated cells during the first 24 hr. However, in contrast to an additional drop in the number of CFU-S, an increase of CFU-C number per femur was observed from 24 to 48 hr. These data indicated a self-limited cell kill of nucleated bone marrow cells, and suggested recruitment of CFU-C from the CFU-S pool between 24 and 48 hr of infusion despite continued methotrexate infusion.
Granulopoiesis in chronic myeloid leukemia. II. serial cloning of blood and bone marrow cells in agar culture
Authors: Olofsson T , Olsson I 
Published: October 2019

Abstract
Colony-forming cells (CFC) and CFC in S-phase were assayed in chronic myeloid leukemia (CML). A correlation was found between leukocyte counts and CFC of blood, suggesting that the leukocytosis of CML depended on expansion of the committed granulopoietic stem cell compartment. Serial studies performed in four cases demonstrated a decrease of the CFC in S-phase during early stages of developing leukocytosis, which was consistent with the operation of growth control mechanisms. During later stages, serial studies revealed that sudden increments of CFC S-phase coincided with rapidly growing leukocytosis, which was consistent with leukemic cell populations escaping growth control. H-thymidine labeling indices for differentiated precursor cells showed slight variations not coinciding with variations of the CFC S-phase fraction. Cyclic oscillations of the white cell count were observed in one case. The white cell count and the fraction of CFC in S- phase displayed a direct relationship, indicating that the occurence of cycles was not likely to be due to a negative feedback mechanism elaborated by mature granulocytes. In another case, marked cycling of the CFC S-phase fraction was found without distinct oscillations of the white cell count. The present work has emphasized the necessity for serial assays of parameters of cell kinetics in vitro in CML since changing relationships were found between stem cell and differentiated cell kinetics during different phases of the disease.
Factors which affect erythropoiesis in partially nephrectomized and sham-operated rats
Authors: Anagnostou A , Vercellotti G , Barone J , Fried W 
Published: October 2019

Abstract
Current concepts of the pathogenesis of anemia in uremic animals are derived mainly from the results of studies performed either in vitro or in bilaterally nephrectomized animals. These data may not be applicable to the situation which exists in more chronically uremic animals. In 1932, Chanutin and Ferris showed that removal of five-sixths of the renal mass caused rats to become uremic and to remain so for a prolonged period of time. Rats made uremic in this manner were utilized as models for studying the pathogenesis of the anemia of uremia. Removeal of five-sixths of the renal mass of rats caused their BUNs to rise to over 100 mg/100 ml and to remain at this level for over 3 wk. The hematocrits of these uremic rats fell from 42% to approximately 30% in 3 wk. Erythropoietin (Ep) production immediately fell to a barely detectable level postoperatively and did not increase significantly in 3 wk, although the renal remnant hypertrophied. Extrarenal Ep production also remained at a low level and did not increase during the 3-wk observation period. The response of plethoric uremic rats to 2 units of Ep was as great (in some experiments greater) as that of sham- operated ones. A surprising finding was that plethoric uremic rats, injected with saline rather than with Ep, incorporated more 59Fe into their red blood cells than did sham-operated ones. This finding suggested that in uremic rats erythropoiesis was less markedly suppressed by plethora than it was in non-uremic rats.