bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic bone marrow transplantation for patients with acute nonlymphocytic leukemia
Authors: Dinsmore R , Kirkpatrick D , Flomenberg N , Gulati S , Kapoor N , Brochstein J , Shank B , Reid A , Groshen S , O'Reilly RJ 
Published: October 2019

Abstract
Seventy patients with acute nonlymphocytic leukemia (ANLL) underwent allogeneic bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide. Thirty patients underwent transplantation in first remission, 11 in second remission, 3 in third remission, and 26 in relapse. At a median follow-up of 30 mo, 17 of those in first remission and 7 of those in second remission survive in continuous remission, compared to 1 in third remission and 3 in relapse. The 3-yr Kaplan-Meier probability of disease-free survival among the various groups was 55% (+/- 9.2%) for the first remission transplants, 64% (+/- 14.5%) for second remission, 33% (+/- 20%) in third remission, and 10.3% (+/- 6.3%) in the relapse group. Statistical analysis showed a similar survival in the first and second remission groups that was significantly better than that seen in the third remission and relapse groups (p less than 0.01). The improved survival seen in the early remission groups was due to a significant decrease in the incidence of relapse posttransplant (p less than 0.01). These results confirm observations that a significant number of patients transplanted in first remission may achieve extended disease-free survival and document similar results for patients transplanted in second remission.
Human malignancy-associated nucleolar antigen as a marker for tumor cells in patients with acute leukemia
Authors: Davis FM , Hittelman WN , McCredie KB , Keating MJ , Vellekoop L , Rao PN 
Published: October 2019

Abstract
Tumor burden in adult patients with acute leukemia is assessed using the percentage of blast cells in the bone marrow or blood. It is clear, however, that not all blast cells are leukemic cells, especially during rapid marrow regeneration. Similarly, some leukemia cell lines have been shown to differentiate in vitro, and the same process also occurs in vivo. Therefore, the leukemic burden may be due to more differentiated cells as well as to blast cells. The purpose of this study was to investigate whether the human malignancy-associated nucleolar antigen (HMNA) could be used as a marker for leukemic cells and to examine its potential as a diagnostic tool. The proportion of HMNA-positive cells in the bone marrow of patients with acute leukemia was determined by indirect immunofluorescence with antibodies to HMNA and was compared with the differential counts routinely made in the clinic laboratory. The percentages of HMNA-positive cells among the nucleated cells in the marrow of 72 patients with clinical evidence of leukemia were significantly higher (range 9%-98%, median 83%) than those observed for nonleukemic individuals (range less than 0.05%-2.5%, median 1%) or for fractions of marrow cells from normal volunteers enriched for normal early progenitor cells (less than or equal to 2%). Patients with leukemia in remission had a lower percentage of HMNA- positive cells (range 0%-83%, median 3%). The percentage of HMNA- positive cells increased as patients approached relapse. Although the percentage of HMNA-positive cells was related to the percentage of blast cells in the bone marrow of the patients with leukemia, some partially differentiated cells were also HMNA-positive in some specimens, and some blastic cells were HMNA-negative in other specimens. These studies indicate the potential usefulness of HMNA as a marker for leukemic cells.
Serologic and biochemical studies of a previously unclassified blood type B variant
Authors: Wheeler DA , Nelson JM , Shulman IA , Okamoto M , Dave V , Yoshida A 
Published: October 2019

Abstract
The designation B4 is proposed for a weak variant of type B blood found in a Salvadorian woman and her two daughters. The red cells were weakly agglutinated by anti-B and anti-A,B; the serum contained anti-B; and the saliva contained H but not B substance. Biochemical studies of the serum showed that the enzyme specified by the variant B gene had low activity and low affinity for both sugar donor and acceptor.
Effects of neuraminidase on the regulation of erythropoiesis
Authors: LaRussa VF , Sieber F , Sensenbrenner LL , Sharkis SJ 
Published: October 2019

Abstract
In this article, we present evidence that sialic acid-containing surface components play a role in the regulation of erythropoiesis. A 1- hr exposure of mouse bone marrow cells to high concentrations of neuraminidase reduced erythroid colony formation. Coculture of 10(6) untreated thymocytes with neuraminidase-treated bone marrow cells restored erythroid colony growth. Neuraminidase-treated thymocytes retained their ability to suppress erythroid colony formation by untreated marrow cells, but lost their ability to enhance erythroid colony formation. Continuous exposure to low concentrations of neuraminidase enhanced erythroid bone marrow cell colony growth in response to a suboptimal dose of erythropoietin.
Prognostic discrimination in "good-risk" chronic granulocytic leukemia
Authors: Sokal JE , Cox EB , Baccarani M , Tura S , Gomez GA , Robertson JE , Tso CY , Braun TJ , Clarkson BD , Cervantes F 
Published: October 2019

Abstract
The prognostic significance of disease features recorded at the time of diagnosis was examined among 813 patients with Philadelphia chromosome- positive, nonblastic chronic granulocytic leukemia (CGL) collected from six European and American series. The survival pattern for this population was typical of “good-risk” patients, and median survival was 47 mo. There were multiple interrelationships among different disease features, which led to highly significant correlations with survival for some that had no primary prognostic significance, such as hematocrit. Multivariable regression analysis indicated that spleen size and the percentage of circulating blasts were the most important prognostic indicators. These features, and age, behaved as continuous variables with progressively unfavorable import at higher values. The platelet count did not influence survival significantly at values below 700 X 10(9)/liter but was increasingly unfavorable above this level. Basophils plus eosinophils over 15%, more than 5% marrow blasts, and karyotypic abnormalities in addition to the Ph1 were also significant unfavorable signs. The Cox model, generated with four variables representing percent blasts, spleen size, platelet count, and age, provided a useful representation of risk status in this population, with good fit between predicted and observed survival over more than a twofold survival range. A hazard function derived from half of the patient population successfully segregated the remainder into three groups with significantly different survival patterns. We conclude that it should be possible to identify a lower risk group of patients with a 2-yr survival of 90%, subsequent risk averaging somewhat less than 20%/yr and median survival of 5 yr, an intermediate group, and a high- risk group with a 2-yr survival of 65%, followed by a death rate of about 35%/yr and median survival of 2.5 yr.
T lymphocyte-mediated graft--antigraft reactivity during graft-versus- host reaction in vitro
Authors: von Melchner H , Hoffken K 
Published: October 2019

Abstract
Spleen organ cultures were prepared from lethally irradiated mice that had been injected with allogeneic bone marrow, with or without lymph node cells. These cultures were used in the analysis of graft-versus- host reactions (GVHR) in vitro. It was found that donor-derived T lymphocytes, which had been grown in an allogeneic spleen, prevented hemopoietic progenitor cells (colony-forming cells, CFC) of the recipient from differentiating in agar cultures. Furthermore, these lymphocytes were found to inhibit growth and differentiation of CFCs of the same donor. This graft-antigraft reactivity was not abolished by monoclonal anti-Thy-1 plus complement (C'), in contrast to the conventional GVHR. This indicates that the graft-versus-graft reaction depends on “de novo” generation of mature T lymphocyte effector cells from transplanted graft precursors.
Complement-dependent killing of human hematopoietic progenitor cells with noncomplement-fixing monoclonal antibodies in an antiglobulin assay
Authors: Fitchen JH , Russo C , Ferrone S 
Published: October 2019

Abstract
A complement (C)-dependent antiglobulin assay was utilized to determine the reactivity of non-C-fixing monoclonal antibodies (MoAb) with human granulocyte-macrophage progenitor cells (CFU-GM). The variables of the assay were analyzed with non-C-fixing MoAb against Ia antigens, including CR11–462, which recognizes the same (or spatially close) determinant identified by the C-fixing anti-Ia MoAb Q5/13. The sensitivity of the antiglobulin assay was influenced by dilutions of anti-mouse Ig xenoantiserum and of rabbit C. Five non-C-fixing MoAb to Ia antigens, seven non-C-fixing MoAb to HLA-A,B antigens, and one non-C- fixing MoAb to beta 2-microglobulin induced marked inhibition of human CFU-GM in the antiglobulin assay. The activity of non-C-fixing MoAb in the antiglobulin assay was comparable to that of C-fixing anti-Ia and anti-HLA-A,B MoAb in the standard cytotoxicity assay. In addition, the cytotoxic effect of dilute C-fixing anti-Ia MoAb was enhanced when the antiglobulin technique was employed. The results of this study indicate that the antiglobulin assay is a rapid and simple technique for the characterization of antigens on human hematopoietic progenitors. Our data also indicate that Ia antigens are expressed on most CFU-GM and that the conflicting results in the literature (that is, those suggesting that Ia antigens are expressed on a smaller proportion of CFU-GM) may reflect differences in the cytolytic activity of the MoAb and rabbit C used.
A new method for the detection of Lesch-Nyhan heterozygotes by peripheral blood T cell culture using T cell growth factor
Authors: Kamatani N , Yamanaka H , Nishioka K , Nakamura T , Nakano K , Tanimoto K , Mizuno T , Nishida Y 
Published: October 2019

Abstract
Thioguanine-resistant T lymphoblast populations were selectively amplified using T cell growth factor in the cultures of peripheral blood T cells from four Lesch-Nyhan heterozygotes. Although Lesch-Nyhan T lymphoblasts were all thioguanine-resistant, none of the cultures from 13 control subjects yielded the growth of such defective cell populations. These data provide direct evidence for the existence of a small percentage (5%–40%) of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficient T cells in the heterozygotes, but not in normal individuals. Conversely, culture of the T lymphoblasts with azaserine plus hypoxanthine permitted the growth of the other part of the cell population that was enzyme positive. The low percentages of HGPRT-negative cells among T cells in heterozygotes suggest that the presence of this enzyme is beneficial for differentiation of lymphocytes of T cell linkage. Considering the ease and the reliability, culture of the peripheral T cells with thioguanine and T cell growth factor is very likely of practical use for detecting Lesch-Nyhan syndrome carriers among predisposed females.
Heavy chain immunoglobulin gene rearrangement in acute nonlymphocytic leukemia
Authors: Rovigatti U , Mirro J , Kitchingman G , Dahl G , Ochs J , Murphy S , Stass S 
Published: October 2019

Abstract
Samples of leukemic cell DNA from 14 children with acute nonlymphocytic leukemia (ANLL) and 4 human myeloid leukemia cell lines were analyzed for rearrangement in the heavy chain region of the immunoglobulin gene. The diagnosis of ANLL was confirmed in all patients by morphological, cytochemical, and immunologic studies. By restriction endonuclease digestion and hybridization with cloned heavy chain immunoglobulin gene probes for the constant (Cmu) and joining (JH) regions, the DNA of 2 patients and 1 cell line (ML-1) was found to contain rearrangements. The DNA from the remaining 12 patients and 3 cell lines was not rearranged (germline configuration). Both patients with apparent immunoglobulin gene rearrangement achieved complete remission on therapy for ANLL. Immunoglobulin gene rearrangement in phenotypically defined ANLL suggests (1) that such changes may not be limited to lymphoid leukemia of B cell lineage, or (2) that, in some patients, the leukemic transforming event may involve stem cells capable of both B cell and myeloid differentiation.
Lethal graft-versus-host disease: modification with allogeneic cultured donor cells
Authors: Mauch P , Lipton JM , Hamilton B , Obbagy J , Kudisch M , Nathan D , Hellman S 
Published: October 2019

Abstract
The use of the bone marrow culture technique was studied as a means to prepare donor marrow for bone marrow transplantation to avoid lethal graft-versus-host disease (GVHD). Preliminary experiments demonstrated the rapid loss of theta-positive cells in such cultures, so that theta- positive cells were not detected after 6 days. Initial experiments in C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in place of hind limb marrow for transplantation. However, hemoglobin typing of recipient animals revealed only short-term donor engraftment, with competitive repopulation of recipient marrow occurring. Subsequent experiments were done in 1,200-rad prepared recipients, with long-term donor engraftment demonstrated. The majority of 1,200-rad prepared animals receiving cultured allogeneic cells died of GVHD, but animals receiving 28-day cultured cells had an improved 90- day survival and a delay in GVHD development over animals receiving hind limb marrow or marrow from shorter times in culture. In addition, animals receiving anti-theta-treated, 3-day nonadherent cells had an improved survival (44%) over animals receiving anti-theta-treated hind limb marrow (20%). These experiments demonstrate modest benefit for the use of cultured cells in bone marrow transplantation across major H-2 histocompatibility complex differences.
Cytogenetic studies of early myeloid progenitor compartments in Ph1- positive chronic myeloid leukemia. II. Long-term culture reveals the persistence of Ph1-negative progenitors in treated as well as newly diagnosed patients
Authors: Dube ID , Kalousek DK , Coulombel L , Gupta CM , Eaves CJ , Eaves AC 
Published: October 2019

Abstract
We recently showed that long-term marrow cultures can be used to demonstrate the presence of Philadelphia (Ph1) negative progenitors in patients with newly diagnosed Ph1-positive chronic myeloid leukemia (CML). We now report results for 6 chronic phase patients studied 5–83 mo postdiagnosis and an additional 3 newly diagnosed patients. Marrow metaphases were exclusively Ph1-positive. Clonogenic assays revealed a minor population of Ph1-negative progenitors in 3 cases (1 treated, 2 untreated). Long-term marrow culture adherent layers contained Ph1- negative progenitors in 6 cases (3 treated, 3 untreated). Whenever this occurred, the Ph1-negative population had become the only one detectable within 3–4 wk, and this was always associated with a rapid decline of the Ph1-positive population. For 2 of the 3 cases where Ph1- negative progenitors were not detected, there was a similar rapid decline in the Ph1-positive population in culture. In the other case, Ph1-positive progenitors were maintained at levels typically seen in normal long-term marrow cultures. These results suggest that chromosomally normal stem cells may persist for a considerable period in the marrow of some, but perhaps not all, patients with CML, even in the face of maintenance chemotherapy. In addition, they provide new evidence of heterogeneity in this disease, as shown by the variable ability of Ph1-positive progenitor populations to be maintained in vitro.
An immunotoxin with therapeutic potential in T cell leukemia: WT1-ricin A
Authors: Myers CD , Thorpe PE , Ross WC , Cumber AJ , Katz FE , Tax W , Greaves MF 
Published: October 2019

Abstract
A conjugate of the monoclonal antibody WT1 and ricin A-chain was studied for its suitability for purging marrow of leukemic T cells for autologous transplantation in T cell acute lymphocytic leukemia (T- ALL). The conjugate was powerfully cytotoxic to the human T-ALL cell line, GH1, which expresses the WT1 antigen at a high density. Treatment of the cells with the conjugate at 10(-11) M reduced their rate of protein synthesis by 50%, and the inclusion of 6 mM ammonium chloride in the cultures enhanced the potency of cytotoxic effect by 10–100- fold. Clonogenic assays indicated that less than 0.1% of GH1 cells survived 3-hr exposure to the conjugate in ammonium chloride. WT1 alone did not react with multipotent (CFU-GEMM) hematopoietic progenitors in normal human bone marrow, as measured by fluorescence-activated cell sorting. Under conditions giving maximal killing of GH1 cells, there was no toxicity to multipotential progenitors in normal human marrow.
Glucose-6-phosphate-dehydrogenase-deficient erythrocytes have an impaired shape recovery mechanism
Authors: Alhanaty E , Snyder M , Sheetz MP 
Published: October 2019

Abstract
In the human erythrocyte, the maintenance of the biconcave disc shape is important for cell viability as well as cell function. Previous studies have indicated the involvement of the hexose monophosphate shunt in the recovery of discoid shape after perturbation of echinocytic agents. In glucose-6-phosphate-dehydrogenase-deficient (Gd- ) erythrocytes, the shunt activity is significantly decreased; thus, it might be expected that the shape recovery rate of Gd- erythrocytes would be decreased. We show here that shape recovery rates in the presence of the shunt stimulator methylene blue are as much as fivefold lower in Gd- erythrocytes. We also show that the protease inhibitor, N- alpha-tosyl-1-phenylalanine-chloromethyl ketone, has no effect on shape recovery in Gd-, whereas it increases normal cell shape recovery rates by 10–30-fold at 50 microM and causes cupping at 200 microM (see companion article by Alhanaty et al.). These changes are not due to reticulocytosis, as other hemolytic disorders do not show such changes. Further, both chronic hemolyzing Gd and A Gd variants show similar abnormal shape recovery behavior, whereas the extent of hemolysis is quite different between variants. Thus, the activity of the hexose monophosphate shunt appears to have a dramatic effect on the rate of reversal of echinocytosis. The lack of shunt activity of Gd cells would necessarily impair their ability to recover normal shape after perturbation.
Clinical relevance of immunologic phenotype in diffuse large cell lymphoma
Authors: Horning SJ , Doggett RS , Warnke RA , Dorfman RF , Cox RS , Levy R 
Published: October 2019

Abstract
The immunologic phenotypes of 78 diffuse large cell lymphomas were determined by an immunoperoxidase technique using a panel of monoclonal antibodies. The phenotypes were correlated with clinical and morphological parameters by univariate and multivariate analysis. Forty- one lymphomas (53%) expressed immunoglobulin (Ig+). Of the 37 cases that did not express immunoglobulin (Ig-), 9 expressed T cell antigens. Although the T cell phenotypes were antigenically heterogeneous, all cases represented mature T cell phenotypes. The majority of the remaining 28 cases expressed the B cell-associated antigen, B1. At 5 yr, actuarial survival for the Ig- patients was 63%, compared with 15% for the Ig+ patients. A significantly greater proportion of patients with Ig+ lymphomas were over the age of 65 at diagnosis. All of the 9 patients with marrow involvement were Ig+. Multiple factors were analyzed by the Cox regression procedure for their impact on survival, including antigenic profile, histologic grade, morphological classification, and numerous clinical parameters previously recognized to be of prognostic significance. In this analysis, stage, age greater than 65 yr, systemic symptoms, and marrow involvement had the greatest influence on survival. The survival difference between Ig- and Ig+ patients is explained by a higher proportion of Ig+ patients with these unfavorable prognostic factors. With our current immunologic methods, retrospective cell phenotyping analysis has not provided independent prognostic significance in diffuse large cell lymphoma. A prospective evaluation of similarly treated patients is needed to characterize the influence of phenotype fully and to determine its potential usefulness for therapy.
Demonstration of in situ fibrin degradation in pathologic thrombi
Authors: Francis CW , Markham RE Jr , Marder VJ 
Published: October 2019

Abstract
Fibrin prepared from 15 pathologic thrombi was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine the extent and pattern of fibrinolysis that occurs in vivo. Two groups of patients could be distinguished on the basis of the polypeptide chain composition of fibrin in their thrombi. Those patients who presented with acute vascular obstruction, either arterial or venous, showed a minimal degree of fibrin degradation, with a dominance of intact, undegraded crosslinked gamma-gamma dimers. On the other hand, patients with long-standing symptoms associated with chronic aortic aneurysms had thrombi containing extensively degraded fibrin. Thrombi in large aortic aneurysms were dissected into concentric layers that showed different degrees of fibrinolysis. The luminal surface consisted of fresh, red thrombus and contained undegraded crosslinked fibrin similar to that found in patients with acute occlusive disease. Deeper layers of the thrombus showed gamma-gamma chain degradation throughout, indicating that this portion was undergoing active thrombolysis. The findings demonstrate that the variability in the pathophysiologic balance between coagulation and fibrinolysis is reflected in vivo by the polypeptide chain composition of crosslinked fibrin in thrombi. The results support the hypothesis of a dynamic equilibrium between clotting and lysis, but indicate that the balance between these two processes may be distinctly different in separate areas of a single clot.
The detection of human T cell leukemia virus proviral DNA and its application for classification and diagnosis of T cell malignancy
Authors: Yamaguchi K , Seiki M , Yoshida M , Nishimura H , Kawano F , Takatsuki K 
Published: October 2019

Abstract
Adult T cell leukemia virus (HTLV or ATLV) proviral DNA integrated in the cellular DNA was examined by a modified Southern blotting method in the peripheral blood mononuclear cells and/or lymph node cells from 61 patients with adult T cell leukemia (ATL) and other hematologic diseases. Serum antibodies against ATL-associated antigens (ATLA) were also examined. The presence of human T cell leukemia virus (HTLV) proviral DNA was confirmed in all 20 patients with overt ATL and in 3 patients with T cell malignant lymphoma, who were seropositive but did not show clinical features characteristic of prototypic ATL. However, it was not detected in 6 antibody-positive healthy individuals and 8 seropositive patients with various hematologic disorders. Thus, the detection of proviral DNA by the method described here seems to be useful for the diagnosis of ATL in the endemic area and may provide a powerful tool for the classification of T cell malignancies.
Immunologic injury to vascular endothelial cells: effects on release of prostacyclin
Authors: Goldsmith JC , McCormick JJ 
Published: October 2019

Abstract
Prostacyclin is released from cultured and ex vivo bovine vascular endothelium following sublethal immunologic injury by a heterologous antibody to endothelial cells developed in rabbits. This release was dependent on calcium and complement and was not enhanced by the presence of platelets. Prostacyclin release was diminished 1–2 hr after the injury, but recovered fully following reculture of the endothelial cells for 72 hr.