bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model of intramedullary hematopoietic microenvironments based on stereologic study of the distribution of endocloned marrow colonies
Authors: Lambertsen RH , Weiss L 
Published: October 2019

Abstract
Hematopoietic colonies were studied in the marrow of alternate fraction- irradiated mice by light microscopic stereology to investigate the microenvironmental organization of marrow. Separate analyses of the relative colony cell density of undifferentiated, granulocytic, erythrocytic, and macrophage colonies in four marrow zones were carried out at 3, 4, and 5 days postirradiation (PI) for all colonies, all periarterial colonies, and all non-periarterial colonies. The results demonstrate a differential colony cell distribution that does not appear to be due to a preferential distribution of certain colony types around arteries. Undifferentiated colony cells showed a consistent predilection for endosteal and periarterial regions, with the majority of colony cells occurring along bone. Erythrocytic colony cells proliferated initially in intermediate and central marrow zones and along arteries. Granulocytic colony cells occurred in all areas at 3 days PI, but increased in density along bone thereafter. Macrophage colony cells occurred in all zones at 4 days PI, but at 5 days were concentrated in subosteal and central regions. Macrophage colonies also occurred periarterially. To explain these findings and the organization of normal bone marrow, we present a detailed model of the microenvironmental organization of intramedullary hematopoiesis. This model portrays the stroma as engendering distinct microenvironments for stem cell replication, stem cell commitment, and early progenitor cell proliferation.
Ph1-positive acute lymphoblastic leukemia with a 14q+ chromosome abnormality
Authors: Maekawa T , Sonoda Y , Taniwaki M , Misawa S , Abe T , Takino T 
Published: October 2019

Abstract
A 13-yr-old Japanese female with acute lymphoblastic leukemia (ALL) that was associated with a Philadelphia chromosome (Ph1) as well as a 14q+ chromosome abnormality is reported. The cell surface phenotype of leukemic cells was determined to be non-T, non-B ALL on the basis of positive Ia-like antigen, terminal deoxynucleotidyl transferase activity, and lack of receptors for sheep erythrocytes, surface immunoglobulin, or intracytoplasmic mu-chain immunoglobulin. The combination of both a Ph1 and a 14q+ has not been reported previously in patients with ALL.
Refractory dysmyelopoietic anemia and acute leukemia
Authors: Rosenthal DS , Moloney WC 
Published: October 2019

Abstract
One hundred and seventeen consecutive patients with refractory dysmyelopoietic anemia (RDA) were followed and studied over 6 yr. All RDA cases had at least two marrow cell lines involved with dysplasia and usually all three. Morphologically, the series could be divided into 55 cases that had primarily “erythroid” hyperplasia and 62 cases with primarily “myeloid” dysplasia. There was a significantly higher number of acute leukemias in the myeloid group, 21/62 (33.9%), than in the erythroid group, 7/55 (12.7%). Of the 117 cases, 64 had marrow culture studies performed using implanted diffusion chambers (DC) in an irradiated rat host. There was a highly statistically significant correlation between the development of leukemia and abnormal growth in DC during the RDA stage.
The availability of therapeutic hydroxocobalamin to cells
Authors: Hall CA , Begley JA , Green-Colligan PD 
Published: October 2019

Abstract
Hydroxocobalamin (OH-Cbl), when used to treat vitamin B12 deficiency, is better retained by the body than is cyanocobalamin (CN-Cbl), but the availability to cells has not been studied systematically. In a series of experiments, we compared the uptake and internalization of OH-Cbl and CN-Cbl bound to transcobalamin II (TCII) by a human cell model, the HeLa cell. TCII-OH-Cbl was: (1) taken up in larger amounts per unit time, (2) the greater uptake was not a consequence of more effective attachment to receptors of TCII-Cbl nor to a more rapid regeneration of receptors, (3) the difference was expressed during the phase of internalization of TCII-Cbl, (4) with CN-Cbl, the stages of binding to receptors plus internalization were more readily reversed, and (5) larger amounts of OH-Cbl were internalized and converted to active coenzyme forms of Cbl. When injected into a healthy person, 200 micrograms of OH-Cbl was better retained in the circulation than 200 micrograms of CN-Cbl. When added in vitro in equivalent amounts, more OH-Cbl was bound to nonspecific plasma proteins. This greater and broader binding neither enhanced nor interfered with the uptake of Cbl by cells, which was determined by the amount of Cbl bound physiologically to TCII. It was concluded that OH-Cbl is a more efficient form of treatment of the common types of Cbl deficiency, principally because of the better retention, which requires less frequent injections, but also because of greater availability to cells.
Therapy of severe aplastic anemia with anti-human thymocyte globulin and androgens: the effect of HLA-haploidentical marrow infusion
Authors: Doney K , Dahlberg SJ , Monroe D , Storb R , Buckner CD , Thomas ED 
Published: October 2019

Abstract
Fifty-four patients with severe aplastic anemia were treated with horse anti-human thymocyte globulin (ATG) and androgens. Thirty of these patients also received an infusion of HLA-haploidentical marrow cells. Only those patients having evidence of hematologic recovery within 3 mo after ATG therapy were considered responders to the immunosuppressive regimen. Of 53 patients evaluable for response, 21 had complete or partial responses and 7 had minimal improvement by defined criteria. The remaining patients did not respond or died. Factors correlated with response to therapy included a short duration of aplasia and a high admission granulocyte count. Thirty-six patients (66.7%) are surviving between 18 and 43 mo, and 18 have died. Deaths were due to hemorrhage and/or infection. Short duration of aplasia and high granulocyte counts also correlated with survival, as did younger age. Four patients with complete or partial responses had a recurrence of severe aplasia 6–17 mo after their first course of ATG. Three of these patients were retreated with ATG (and oxymetholone in two cases). All three had second responses to therapy, but two of the three have had second relapses. The fourth patient responded to oxymetholone alone, but died after a second relapse. Mismatched marrow infusion had no effect on the incidence of response or survival.
Regulation of normal human blood neutrophilic, macrophagic, and eosinophilic committed stem cell proliferation by autologous blood T lymphocyte subsets
Authors: Chikkappa G , Phillips PG 
Published: October 2019

Abstract
The influence of T lymphocyte (T cell) subsets on the proliferation of the blood neutrophilic, macrophagic, and eosinophilic cluster and colony (aggregate) forming cells (CFC) was evaluated. The T cells and the CFC-enriched B-null cells (mononuclear cells depleted of monocytes and T cells) and null cells (B-null) cells depleted of B lymphocytes) were separated from the blood of normal individuals. The population enriched for OKT4 (T4 cells) monoclonal antibody-binding T helper/inducer cells and for OKT8 (T8 cells) monoclonal antibody- binding T suppressor/cytotoxic cells were separated from the T cells or mononuclear cells depleted of monocytes by negative enrichment using an immunoadherence “panning” method. These separated cell populations were cultured separately, and the B-null or null cells were cocultured with the T, T4, and T8 cells in agar medium in the presence and absence of an exogenous source of colony-stimulating activity (CSA). The cultures were evaluated at day 14. The B-null and null cells, but not the T cells or subsets, contained CFC. The number of CFC proliferated from the B-null or null cells increased significantly (p less than 0.001) in cocultures with unseparated T and T8 cells in a dose-dependent manner. The T4 cells neither promoted nor inhibited the CFC growth. The T8 population was a better promoter (p less than 0.01) of CFC growth than the unseparated T cells. This suggests that the CFC promoting effect of the unseparated T cells is probably due to the influence of the T8 subset present within the T cells. The proportion of the neutrophilic, macrophagic, and eosinophilic CFC that proliferated in these cultures was comparable under the influence of the T and T8 cells. The results of these studies indicate that the T8 population, which is the suppressor in the classical immune system, promotes the growth of the blood CFC. We speculate that the T cells are involved in the regulation of granulopoiesis in vivo.
A novel phospholipid in irreversibly sickled cells: evidence for in vivo peroxidative membrane damage in sickle cell disease
Authors: Jain SK , Shohet SB 
Published: October 2019

Abstract
In individuals with sickle cell disease, a variable number of irreversibly sickled cells (ISC) is present that may contribute to the pathophysiology of sickle cell anemia. The present study was undertaken to determine the possible role of membrane lipid peroxidation in the genesis of ISC. After 24 hr of simple aerobic incubation, sickle cells accumulated 2–3 times more malonyldialdehyde (MDA), an end product of lipid peroxidation, than normal cells. To assess the possibility of peroxidative damage in ISC in vivo, ISC were separated from sickle blood using Stractan density gradients. Lipid extracts of the untreated ISC-enriched fraction of sickle blood showed significant fluorescence and contained a novel phospholipid:MDA adduct that was not seen in control cells. Taken together, these observations suggest that ISC have previously undergone lipid peroxidative damage and the accumulation of MDA in vivo.
Autoantibodies against the platelet glycoprotein IIb/IIIa complex in patients with chronic ITP
Authors: Woods VL Jr , Oh EH , Mason D , McMillan R 
Published: October 2019

Abstract
Chronic idiopathic thrombocytopenic purpura (ITP) is caused by an antibody reactive with platelet-associated antigens. The present studies provide direct evidence that some patients with chronic ITP have autoantibodies against the platelet glycoprotein (GP) IIb/IIIa complex. Microtiter wells, coated with a monoclonal antibody (2G12) specific for GPIIb/GPIIIa were reacted with GPIIb/GPIIIa contained in a platelet extract. Control wells containing the same antibody were reacted with a cell extract containing no GPIIb/GPIIIa. After washing, the wells were reacted with patient or control plasma, and IgG binding was detected using 125I-Fab2-anti-human IgG. Assay values were expressed as binding ratios (cpm GPIIb/GPIIIa wells/cpm control wells). Plasma from 5 of 56 patients with chronic ITP had ratios (1.36–3.14) greater than 3 standard deviations above the mean (+/- SD) of control plasmas--0.93 +/- 0.12. Elevated values were also noted in two patients with anti-P1A1 antibody (ratios greater than 30) and in one patient with Hodgkin's disease and an ITP-like syndrome (ratio 1.53). Normal values were noted in 34 patients with a variety of immune and nonimmune diseases. Plasma from two of the positive ITP patients was reacted with 125I-surface-labeled platelets and, after solubilization, the IgG and bound antigen were precipitated with Staph-A. Autoradiographs from SDS- PAGE electrophoresis of the Staph-A-bound proteins shows two radioactive bands consistent in size with GPIIb and GPIIIa.
Characterization of glucocorticoid receptors in animal lymphoblastic disease: correlation with response to single-agent glucocorticoid treatment
Authors: Bell R , Cotter S , Lillquist A , Sallan S , McCaffrey R 
Published: October 2019

Abstract
The clinical significance of initial DEAE chromatography of glucocorticoid binders in lymphoblastic disease was evaluated in an animal model. Domestic cats and dogs with lymphoblastic disease were treated with prednisone, 2 mg/kg/day, for 14 days, and the outcome of therapy was correlated with DEAE chromatograms of glucocorticoid binders, using 3H-triamcinolone as ligand. Six of 30 animals had a single-peak low-salt binder species, similar to that seen in a subset of human leukemia, and none of these responded. Of the 29 animals with chromatograms identical to normal tissues, 6 had a complete response and another 11 a partial response. This distribution of responders is statistically significant (p = 0.02). Thus, the leukemia-associated single-peak DEAE species appears to be associated with glucocorticoid resistance, as defined by clinical responsiveness. In contrast, the two- peak normal pattern is a necessary, but insufficient, criterion for defining responsive disease.
Evidence that platelet density depends on the alpha-granule content in platelets
Authors: van Oost BA , Timmermans AP , Sixma JJ 
Published: October 2019

Abstract
The relation between platelet buoyant density and beta-thromboglobulin (beta-TG), a marker for platelet alpha-granule content, was assessed by three independent approaches. (1) Platelets were separated on iso- osmolar discontinuous Stractan density gradients into five fractions, ranging in density from 1.061 g/ml to 1.091 g/ml (20 degrees C). The beta-TG content (mean +/- SD, n = 17) increased with the platelet density from 27.8 +/- 8.6 micrograms beta-TG/10(9) cells (20% less- dense platelets) up to 65.6 +/- 15.5 micrograms beta-TG/10(9) cells (15% most-dense platelets). (2) Activation of platelets in platelet- rich plasma with thrombin, adenosine diphosphate, collagen, or epinephrine resulted in a decreased density of the platelets. This was only seen when there was simultaneous secretion of beta-TG. (3) The less-dense and the more-dense platelet fractions, after isolation by density gradient centrifugation, were separately treated with thrombin. After complete degranulation, the density distribution of the originally less-dense and more-dense platelets were identical and were much narrower than the density distribution of resting platelets.
Monoclonal antibodies differentiating between monocytic and nonmonocytic variants of AML
Authors: Linch DC , Allen C , Beverley PC , Bynoe AG , Scott CS , Hogg N 
Published: October 2019

Abstract
Blast cells from 70 cases of acute myeloid leukemia (AML), with a preponderance of monocytic variants (M4 and M5), were stained with a panel of 10 monoclonal antibodies (MoAb) that react with normal myeloid cells. Two McAb, UCHMI and UCHALF, stained cells from nearly every case of M4 and M5 leukemia, but not cells from cases of M1/M2 leukemia. Two other antibodies, E11 and UC45, were also specific for the monocytic leukemias, but stained cells from a lesser proportion of cases. The antibodies TG1, OKM1, Smo, DA2, 28, and 5.5 stained a differing proportion of cases in both the M1/M2 and M4/M5 subtypes. Routine morphology and alpha-naphthyl acetate esterase (ANAE) staining were largely in agreement with the antibody findings, though the interpretation of the fluoride sensitivity of ANAE was apparently misleading in 10% of cases. It is concluded that these antibodies, particularly UCHMI and UCHALF, will be of considerable value in the more precise subtyping of AML and that some of this panel of antibodies will be valuable tools for the investigation of normal monocytic differentiation.
Increased tissue factor activity of monocytes/macrophages isolated from canine renal allografts
Authors: Rothberger H , Barringer M , Meredith J 
Published: October 2019

Abstract
Kidney allografting was performed in a group of ten beagles, and viable leukocytes infiltrating the transplanted organs were isolated during episodes of acute rejection 5 or 6 days postoperatively. These infiltrate populations, consisting predominantly of lymphocytes and monocytes/macrophages, were found to have significantly increased amounts of procoagulant activity relative to control leukocytes isolated from circulating blood and lymph. Using nonspecific esterase staining in an agar microclot assay, procoagulant activity in the infiltrate leukocytes was found to reside in monocytes/macrophages rather than other coisolated cell types. By contrast, control monocytes from blood had no activity in this microclot assay. Procoagulant activity in the infiltrate cells was characterized as tissue factor. Increased amounts of this activator of the extrinsic pathway, as found in infiltrate monocytes/macrophages, may initiate clotting reactions and fibrin deposition within allografts.
Chronic myelomonocytic leukemia according to FAB classification: analysis of 35 cases
Authors: Solal-Celigny P , Desaint B , Herrera A , Chastang C , Amar M , Vroclans M , Brousse N , Mancilla F , Renoux M , Bernard JF 
Published: October 2019

Abstract
Thirty-five patients who fulfilled the FAB diagnosis criteria of chronic myelomonocytic leukemia (CMML), i.e., myelodysplastic features, monocytosis over 10(9)/liter, bone marrow monocyte infiltration, blast cells less than 5% in the peripheral blood and less than 30% in the bone marrow, are analyzed. CMML appears as an entity distinct from myelodysplastic and myeloproliferative disorders. Splenomegaly, anemia, thrombocytopenia, leukocytosis with monocytes and granulocytic cells in all stages of development, increased blood and urine lysozyme levels without renal failure, and polyclonal hyperimmunoglobulinemia are its main clinical and biologic features. With conventional cytotoxic drugs (6-mercaptopurine, hydroxyurea), the prognosis of CMML appears poor (median survival 475 days). None of the clinical hematologic or biologic parameters tested had a significant effect on prognosis. As other chemotherapy trials seemed necessary, we recently administered small doses of cytosine-arabinoside (ARA-C) to six patients over several consecutive days and obtained a complete remission in four. These preliminary results must be confirmed by larger series using the diagnostic criteria proposed by the FAB cooperative group.
A functional assay of protein C in human plasma
Authors: Sala N , Owen WG , Collen D 
Published: October 2019

Abstract
A three-step spectrophotometric assay was developed for measuring functional protein C (PC) in human plasma. The assay is based on: (1) adsorption of citrated platelet-poor plasma on barium citrate and elution of the vitamin K-dependent factors with EDTA; (2) activation of PC by incubation of the mixture of vitamin K-dependent factors with a complex of thrombin and its endothelial cell cofactor, thrombomodulin; (3) addition of antithrombin III and heparin to the system to inhibit thrombin and other coagulation enzymes generated during incubation and measurement of the activated PC with a synthetic (chromogenic) substrate. The assay appears to be specific for PC because: (a) PC- depleted plasma (by immunoadsorption) is inactive; (b) addition of purified PC to PC-depleted plasma reconstitutes its activity; and (c) no enzymatic activity is generated in the absence of the thrombin- thrombomodulin complex. Mixtures of a normal plasma pool with PC- depleted plasma yielded an amount of enzymatic activity proportional to the fraction of normal plasma. Using this as a standard curve, the amount of PC in the plasma of 23 normal subjects was 97% +/- 15%. The within-assay coefficient of variation was 3.5% and the between-assay coefficient 6.5%. A linear correlation (r = 0.86) was found between PC as measured with the functional assay and with a radioimmunoassay. In 3 patients with congenital PC deficiency, the functional PC level was 37% +/- 9% and the antigen level 64% +/- 11%. It is concluded that the present assay may be used for reliable and accurate estimation of activatable PC in human plasma.
Cellular and molecular mechanisms of the bone marrow sparing effects of the glucose chloroethylnitrosourea chlorozotocin
Authors: Byrne P , Tew K , Jemionek J , MacVittie T , Erickson L , Schein P 
Published: October 2019

Abstract
1,(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and other chloroethylnitrosourea anticancer agents in clinical use produce severe and cumulative bone marrow toxicity. Chlorozotocin, a glucose analogue, has demonstrated reduced hematologic toxicity while retaining full antitumor activity. The biochemical-pharmacologic properties of chlorozotocin and CCNU were compared in human bone marrow. After a 2-hr incubation with a 0.1-mM drug concentration, total cellular uptake of chlorozotocin in whole marrow was 2.47 +/- 0.80 pmole/10(4) cells and was not significantly different compared to the uptake of 1.94 +/- 0.53 pmole/10(4) cells with CCNU. The quantitative alkylation of bone marrow DNA by chlorozotocin, 22.8 +/- 1.2 pmole/mg DNA, was equivalent to that produced by CCNU, 22.9 +/- 0.5 pmole/mg DNA. Bone marrow was separated into 14 fractions by centrifugal elutriation. CCNU uptake was found to be greater than that of chlorozotocin in 3 fractions that were primarily composed of lymphocytes, monocytes, and normoblasts. Chlorozotocin uptake was greater than CCNU in 6 fractions that contained primarily mature and immature myeloid cells as well as the highest CFU-GM activity. The two drugs produced a comparable degree of DNA strand breakage and DNA-protein cross-linking as measured by alkaline elution of pooled fractions of elutriated bone marrow. DNA interstrand crosslinking was not found with either drug. The most significant finding of this study is the differences in the site of drug alkylation by chlorozotocin and CCNU in bone marrow chromatin. Endonuclease digestions with MCN, DNase I, and DNase II showed nonrandom alkylation of specific regions of chromatin by the two drugs: CCNU demonstrated a preferential binding to the transcriptionally active regions of chromatin, whereas chlorozotocin predominantly alkylated the transcriptionally inactive regions. These data suggest that the lethal damage of nitrosourea alkylation in human bone marrow is principally expressed in transcriptionally active regions of chromatin.
Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice
Authors: Hagiwara M , Chen IL , McGonigle R , Beckman B , Kasten FH , Fisher JW 
Published: October 2019

Abstract
The present studies report erythropoietin (Ep) production in primary cultures of a human renal carcinoma from a patient with erythrocytosis that has been serially transplanted to BALB/c nude mice. The levels of erythropoietin in the culture media were estimated using the exhypoxic polycythemic mouse assay (EHPCMA), fetal mouse liver erythroid colony- forming technique (FMLC), and a radioimmunoassay (RIA). The spent culture media of the exponentially growing cells contained less than 10 mU/ml of Ep measured by RIA. However, after the cells became confluent, Ep levels (RIA) in the spent media showed a marked increase to approximately 300 mU/ml. Ep levels estimated using the FMLC and EHPCMA were approximately 2/3 and 1/10, respectively, of those measured by RIA. Rabbit antiserum to highly purified human urinary Ep (70,400 U/mg protein) was utilized for immunocytochemical (peroxidase-antiperoxidase method) localization of Ep in the cultured cells. Very few of the cells in exponential growth exhibited Ep-like immunoreactivity, whereas intense Ep-like immunoreactivity was observed in the cytoplasm of the cells maintained in culture for a prolonged period after reaching confluency. The most intense staining was observed in some of the cells forming domes. The domes developed after the cells reached confluency, and their numbers increased with increasing time in confluent culture, in parallel with the increase in Ep levels in the spent media. This primary cell culture system of a renal cell carcinoma maintained in nude mice, which produces immunologically and biologically active Ep, may provide a useful model for studies of the mechanism of Ep production.