bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome
Authors: Weisdorf D , Haake R , Blazar B , Miller W , McGlave P , Ramsay N , Kersey J , Filipovich A 
Published: October 2019

Abstract
We have analyzed the long term outcome of 197 patients who were treated for grade II to IV acute graft-versus-host disease (GVHD) following histocompatible allogeneic bone marrow transplantation (BMT). Of 469 recipients of sibling donor allografts performed at our center between January, 1979 and October, 1987, 197 patients (42%) developed greater than or equal to grade II acute GVHD at a median of 38 days (range 9 to 98 days) post-BMT. After treatment with corticosteroids (n = 160) or other immunosuppressive therapies (n = 37), 72 patients (41% +/- 8%; 95% confidence interval [CI]) achieved complete and continuing resolution of acute GVHD after a median of 21 days of therapy. Sixty- one patients required additional immunosuppressive therapy with high dose methylprednisolone, antithymocyte globulin (ATG)/steroids, or other therapies because of refractory or progressive symptoms of acute GVHD. Seven of these 61 patients eventually obtained complete and continuing remission after 13 to 57 days (median 50) of secondary treatment. The overall rate of chronic GVHD was 70% +/- 16%; 95% CI following grade II to IV acute GVHD. Twenty-five of the 197 patients never developed chronic GVHD, resulting in a Kaplan-Meier projection of 30% +/- 8% (95% CI) cure of moderate/severe acute GVHD. Analysis of clinical features associated with complete response (CR) to acute GVHD therapy identified more favorable responses to therapy in patients without either liver or skin involvement, patients with acute lymphoblastic leukemia, and donor/recipient pairs other than male patients with female donors. Older recipient age was not associated with more resistance to GVHD treatment. CR to GVHD treatment was associated with significantly better 5-year survival: 51% +/- 14% versus 32% +/- 11% for patients with therapy resistant acute GVHD (P = .004). GVHD was a major contributing cause of death in 49 of the 90 patients who died and was often complicated by infection or interstitial pneumonitis. Control of acute GVHD through immunosuppressive therapy did not affect the risk of leukemic relapse after transplantation.
The treatment of progressive non-Hodgkin's lymphoma with intensive chemoradiotherapy and autologous marrow transplantation
Authors: Phillips GL , Fay JW , Herzig RH , Lazarus HM , Wolff SN , Lin HS , Shina DC , Glasgow GP , Griffith RC , Lamb CW 
Published: October 2019

Abstract
Intensive chemoradiotherapy, with or without additional local radiotherapy, and unpurged autologous marrow transplantation was given to 68 patients with progressive non-Hodgkin's lymphoma. Responses were attained in 44 patients (65%, 95% confidence intervals [CI], 52% to 76%), including 37 who achieved complete responses. Fifteen patients (22%, 95% C.I. 13% to 34%) remain free of disease (including 11 continuously) at a median of 5.3 (range 3.1 to 9.1) years later. Higher Karnofsky scores (P less than .01, Mann-Whitney U test) and the absence of a history of prior radiotherapy (P = .02, chi 2 test) were associated with achievement of complete plus partial responses. Higher Karnofsky scores (P less than .01, Mann-Whitney U test) and less resistant disease status at transplantation (P = .04, chi 2 test) were significant when calculations were limited to complete responses. Karnofsky scores were also associated with the probability of freedom from progression (P = .02, log-rank) for responding patients. Also, Karnofsky scores and the absence of prior radiotherapy (P less than .01 and P = .01, respectively, log-rank) were associated with improved survival. Progressive lymphoma was the chief cause of failure; progression usually occurred less than 6 months after transplantation, most often at the sites of active disease before the transplant. However, five patients (including four with high-grade non-Hodgkin's lymphoma) suffered hematogenous patterns of relapse; four of these five patients had no prior history of marrow involvement. Other causes of mortality included interstitial pneumonitis, sepsis, hemorrhage and renal failure. Intensive chemoradiotherapy and autologous marrow transplantation produces durable remissions in some patients with progressive non-Hodgkin's lymphoma. Since such therapy is more effective when given to patients with signs of less advanced disease, earlier treatment would be the simplest way to produce improved results. However, improved conditioning regimens will also be needed, and measures to reduce occult lymphoma stem cell contamination with the autograft may also be required to increase the likelihood of cure in some patients.
In vivo hematologic effects of recombinant human macrophage colony- stimulating factor
Authors: Ulich TR , del Castillo J , Watson LR , Yin SM , Garnick MB 
Published: October 2019

Abstract
Macrophage colony-stimulating factor (recombinant human M-CSF) given as a single intravenous injection to Lewis rats induces a dose-dependent peripheral monocytosis, neutrophilia, and lymphopenia. The monocytosis peaks at 28 to 32 hours with a seven- to eightfold increase in the number of circulating monocytes and promonocytes. The peripheral monocytosis is accompanied by a slight increase in marrow blasts, promonocytes, and monocytes. A monocytopenia reaching a nadir at 15 minutes precedes the monocytosis, suggesting that M-CSF activates circulating monocytes and causes intravascular margination. The M-CSF- induced neutrophilia and lymphopenia are relatively mild in magnitude, are observed between 2 and 16 hours after injection, and are no longer evident at later time-points. The monocytosis was at least partially inhibited by dexamethasone. M-CSF-induced monocytosis most likely reflects a direct effect of M-CSF on marrow monocyte precursor proliferation, maturation, and release, whereas the neutrophilia and lymphopenia may reflect indirect effects mediated by the known ability of M-CSF to cause the release of other cytokines.
Human granulocyte colony-stimulating factor: biologic activities and receptor characterization on hematopoietic cells and small cell lung cancer cell lines
Authors: Avalos BR , Gasson JC , Hedvat C , Quan SG , Baldwin GC , Weisbart RH , Williams RE , Golde DW , DiPersio JF 
Published: October 2019

Abstract
Human granulocyte colony-stimulating factor (G-CSF) is a regulatory glycoprotein that stimulates the production of neutrophilic granulocytes from committed hematopoietic progenitor cells both in vitro and in vivo. In this report, we show that biosynthetic (recombinant) human G-CSF enhances colony formation by normal human bone marrow and the human myeloid leukemic cell lines, HL-60 and KG-1, as well as nonhematopoietic small cell lung cancer lines, H128 and H69. G-CSF also modulates multiple differentiated functions of human neutrophils, including enhanced oxidative metabolism in response to f- Met-Leu-Phe (f-MLP), increased antibody-dependent cell-mediated cytotoxicity (ADCC), and augmented arachidonic acid release in response to ionophore and chemotactic agents. These effects are all maximal at a concentration of 100 to 500 pmol/L. Using 125I-labeled recombinant human G-CSF, high affinity binding sites were identified on human neutrophils, the myeloid leukemia cell lines KG-1 and HL-60, and the small cell carcinoma cell lines, H128 and H69. G-CSF receptor numbers ranged between 138 and 285 sites per cell with a kd of 77 to 140 pmol/L, consistent with the concentrations of G-CSF that elicit biologic responses in vitro. Decreased specific binding of 125l-G-CSF by human neutrophils was consistently observed in the presence of excess unlabeled human granulocyte-macrophage colony-stimulating factor (GM-CSF), suggesting competition or down modulation by GM-CSF of the G- CSF receptor.
von Willebrand factor competes with fibrin for occupancy of GPIIb:IIIa on thrombin-stimulated platelets
Authors: Hantgan RR , Nichols WL , Ruggeri ZM 
Published: October 2019

Abstract
We have investigated two major questions related to the molecular basis of interactions between the three-dimensional fibrin network and thrombin-stimulated human platelets. First, what are the roles played by glycoproteins (GP) Ib and IIb:IIIa in linking the fibrin clot tightly to the platelet surface? Second, does von Willebrand factor (vWF) modulate the extent of platelet-fibrin interactions? Quantitative fluorescence microscopy (microfluorimetry) has been used to determine the quantity of fluorescein-labeled fibrin bound to the surface of thrombin-stimulated, gel-filtered platelets (the supernatants of which contained small quantities of vWF) in the presence/absence of receptor- specific and vWF-specific monoclonal antibodies (MoAbs), as well as exogenous vWF. A MoAb specific for the GPIIb:IIIa complex exhibited a concentration-dependent inhibition of fibrin binding, whereas a MoAb specific for GPIb was ineffective in this regard. Similarly, a MoAb that recognizes the N-terminal region of vWF involved in GPIb binding did not influence fibrin binding. In contrast, a MoAb that binds to a C- terminal region of vWF involved in GPIIb:IIIa recognition caused a specific, concentration-dependent increase in the quantity of platelet- bound fibrin. We also found that exogenous vWF caused a concentration- dependent decrease in fibrin binding. These results support the hypothesis that vWF and fibrin, both of which are multimeric adhesive ligands, compete for occupancy of the GPIIb:IIIa complex on thrombin- stimulated platelets.
B8.7 antigen is present on B-cell precursor acute lymphocytic leukemia. Correlation with the low molecular weight B-cell growth factor responsiveness of these cells
Authors: Leprince C , Blumenfeld N , Flandrin G , Galanaud P , Sigaux F , Richard Y 
Published: October 2019

Abstract
The purpose of this study was to analyze the expression of B8.7 antigen and its implication in the low molecular weight B-Cell growth factor (LMW BCGF) proliferative pathway at the early stages of the human B- cell differentiation. After an overnight incubation in culture medium of B-cell precursor acute lymphoblastic leukemias (ALL), we demonstrated the presence of B8.7 antigen in 18 of 25 cases (72%). Such an incubation also induced a significant increase in the LMW BCGF responsiveness of ALL cells (P less than 0.03). In addition, we showed a significant correlation between B8.7 expression and the ability of pre-B ALL cells to respond to LMW BCGF. As previously described for normal B cells, the anti-B8.7 monoclonal antibody inhibited the LMW BCGF-dependent proliferation of pre-B ALL cells in a dose-dependent manner. These data indicate that B8.7 antigen is expressed and may be functionally related to the LMW BCGF pathway at the pre-B cell stages of differentiation. These results also suggest that human B-cell precursor ALL are not only phenotypically similar to their normal B lymphocyte counterparts, but are also sensitive to the same immunoregulatory cytokines that control normal cell growth.
Differential effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in children with severe congenital neutropenia
Authors: Welte K , Zeidler C , Reiter A , Muller W , Odenwald E , Souza L , Riehm H 
Published: October 2019

Abstract
Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia secondary to a maturational arrest at the level of promyelocytes. We treated five patients with SCN with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 42 days and subsequently, between 1 and 3 months later, with rhG-CSF for 142 days. The objective was to evaluate the safety and ability of these factors to elicit a neutrophil response. rhGM-CSF was administered at a dose of 3 to 30 micrograms/kg/d (30 to 60 minutes, intravenously). In all patients, a specific, dose-dependent increase in the absolute granulocyte counts was observed. However, in four patients this increase was due to an increase in eosinophils, and in only one patient it was due to an increase in the absolute neutrophil counts (ANC). Subsequently, all patients received rhG-CSF at a dose of 3 to 15 micrograms/kg/d subcutaneously. In contrast to rhGM-CSF treatment, all five patients responded to rhG-CSF during the first 6 weeks of treatment with an increase in the ANC to above 1,000/microL. The level of ANC could be maintained during maintenance treatment. In one patient, the increase in ANC was associated with an improvement of a severe pneumonitis caused by Peptostreptococcus and resistant to antibiotic treatment. No severe bacterial infections occurred in any of the patients during CSF treatment. All patients tolerated rhGM-CSF and rhG-CSF treatment without severe side effects. These results demonstrate the beneficial effect of rhG-CSF in SCN patients.
Released adenosine diphosphate stabilizes thrombin-induced human platelet aggregates
Authors: Cattaneo M , Canciani MT , Lecchi A , Kinlough-Rathbone RL , Packham MA , Mannucci PM , Mustard JF 
Published: October 2019

Abstract
Normal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, chymotrypsin, and prostaglandin E1 (PGE1). In contrast, thrombin-induced aggregates of platelets from patients with delta-storage pool deficiency (delta-SPD), which lack releasable nucleotides, are readily deaggregated by the same combination of inhibitors. The ease with which delta-SPD platelets are deaggregated is caused by the lack of stabilizing effects of released ADP, since: (1) exogenous adenosine diphosphate (ADP) (10 mumol/L), but not serotonin (2 mumol/L), abolishes the ability of these inhibitors to deaggregate delta-SPD platelets; (2) thrombin-induced aggregates of platelets from a patient (V.R.) (whose platelets have a severe, selective impairment of sensitivity to ADP, but normal amounts of releasable nucleotides) can be readily deaggregated, and addition of ADP does not stabilize the platelet aggregates; (3) apyrase or creatine phosphate (CP)/creatine phosphokinase (CPK), added before thrombin, make control platelets more easily deaggregated by hirudin, chymotrypsin, and PGE1, and do not change the deaggregation response of delta-SPD platelets and of V.R.'s platelets. Thrombin-induced aggregation and release of beta- thromboglobulin in control, delta-SPD, and in V.R.'s platelets was similar and not inhibited by apyrase or CP/CPK. The stabilizing effect of ADP on platelet aggregates is specific, since epinephrine in the presence of apyrase to remove traces of released ADP does not stabilize the aggregates of control, delta-SPD, or of V.R.'s platelets. Because epinephrine increases fibrinogen binding to thrombin-stimulated platelets to a greater extent than ADP, but does not stabilize the aggregates, it is unlikely that the additional fibrinogen binding sites induced by ADP have a major role in inhibiting deaggregation by the combination of inhibitors.
Clonal growth of murine pre-B colony-forming cells and their targeted infection by a retroviral vector: dependence on interleukin-7
Authors: Williams DE , Namen AE , Mochizuki DY , Overell RW 
Published: October 2019

Abstract
The cDNA for interleukin-7 (IL-7) was recently isolated from a stromal cell line derived from a long-term B-lymphoid culture. We report that purified recombinant murine IL-7 can promote the clonal growth in semi- solid culture of a subpopulation of cells expressing the B220 surface antigen from normal murine bone marrow. These colony-forming cells (CFC- Pre-B) give rise to colonies of 20 to 1,000 cells after 7 days in culture. Morphologic examination of cells within the colonies showed a characteristic lymphoid morphology, and histochemical examination demonstrated an absence of markers associated with granulocyte, macrophage, eosinophil, or megakaryocyte differentiation, as well as an absence of hemoglobinization (indicative or erythroid differentiation). IL-7 was found to specifically enhance the infection of CFC-Pre-B but not CFU-GM when the cytokine was present during a 48-hour co- cultivation period between irradiated, retrovirus-producing psi 2 clones and normal mouse bone marrow cells. In contrast, IL-3 enhanced the infection of CFU-GM but not CFC-Pre-B. Thymidine suiciding studies suggest that this targeted infection is due to specific induction of cycling of CFC-Pre-B by IL-7 and CFU-GM by IL-3. These data demonstrate that IL-7 can target retroviral infection into a specific subpopulation of early B-lymphoid cells (CFC-Pre-B), and that IL-7 cannot directly promote the in vitro clonal growth of myeloid committed progenitor cells (ie, CFU-GM).
T lymphocytes from invaded lymph nodes in patients with B-cell-derived non-Hodgkin's lymphoma: reactivity toward the malignant clone
Authors: Jacob MC , Piccinni MP , Bonnefoix T , Sotto MF , Couderc P , Bensa JC , Sotto JJ 
Published: October 2019

Abstract
Tumor-infiltrating T lymphocytes (TIL-T) are always present in B-cell- derived non-Hodgkin's lymphoma (NHL). In this investigation, we explored the possibility that collaboration might exist between these cells. TIL-T were isolated from 39 lymph nodes of patients with NHL. In most of the cases, few of them (less than 10%) possessed surface activation receptors CD25 or OKT9. In 80% of the cases, they proliferated in response to recombinant interleukin-2 (rIL-2), but the degree of proliferation was often low as compared with control populations. The influence of irradiated autologous malignant cells on the TIL-T proliferation in response to rIL-2 (40 U/mL) was also investigated: in 38% of the cases, this proliferation was not modified (group O), and in 41% it was higher (group +) and in 21% it was lower (group -). The mechanism of this immune response (specific or not) is not elucidated at present. The definition of these groups was statistically correlated with different parameters of the disease: (1) percentage of TIL-T was higher in group + (44% +/- 17%) than in group O (31% +/- 18%) and group - (24% +/- 15%); (2) B-cell proliferation in centrofollicular lymphomas was more frequently nodular or nodular and diffuse in group + (83%) and O (55%) than in group - (0%); (3) low- grade malignancies in the Working Formulation were more frequent in group + (75%) than in group O (60%) or group - (12%); (4) favorable prognosis evaluated with the Grenoble cytologic classification was more frequent in group + and O (87%) than in group - (12%); (5) actuarial survival curves showed a significantly better prognosis for patients in group +.
N-ras gene point mutations in childhood acute lymphocytic leukemia correlate with a poor prognosis
Authors: Lubbert M , Mirro J Jr , Miller CW , Kahan J , Isaac G , Kitchingman G , Mertelsmann R , Herrmann F , McCormick F , Koeffler HP 
Published: October 2019

Abstract
Ras genes can be altered by point mutations at critical portions of their coding regions to acquire transforming ability in vitro. These point mutations have been detected in a variety of human malignancies. However, their relevance for the clinical and biologic behavior of the subgroups of patients exhibiting these mutations in unclear. We analyzed 100 patients with childhood acute lymphocytic leukemias (ALLs) for point mutations of exons 1 and 2 of all three ras genes (H-ras, K- ras, and N-ras) by polymerase chain reaction and a combination of oligonucleotide hybridization and direct DNA sequencing. A 6% incidence of N-ras gene mutations was detected, all of which occurred at different nucleotides of codons 12 or 13 of N-ras. When correlating presence of ras mutations with the clinical and biologic features and the clinical outcome of these cases, a significantly higher risk for hematologic relapse (P = .01) and a trend toward a lower rate of complete remission (P = .07) was noted. The two groups did not differ in any of the known high-risk factors of ALL. These results suggest that presence of an N-ras mutation in children with ALL may be an independent predictor for worse clinical outcome and therefore may have therapeutic implications; further studies to confirm these findings are required because of the small number of patients with N-ras mutations.
Alpha-granule pool of glycoprotein IIb-IIIa in normal and pathologic platelets and megakaryocytes
Authors: Cramer EM , Savidge GF , Vainchenker W , Berndt MC , Pidard D , Caen JP , Masse JM , Breton-Gorius J 
Published: October 2019

Abstract
Using an immunogold staining technique and electron microscopy, we investigated the localization of the alpha-granule pool of glycoprotein (GP) IIb-IIIa in normal platelets and maturing megakaryocytes (MK), in pathologic platelets from a patient with type I Glanzmann's thrombasthenia (GT), and from three patients with the gray platelet syndrome (GPS). In normal resting platelets, GPIIb-IIIa was observed on the plasmatic side of the plasma membrane, the open canicular system (OCS) membranes, and along the internal face of the alpha-granule membrane. This location was found with three monospecific polyclonal antibodies: one anti-GPIIb-IIIa antibody, the second specific for GPIIb, and the third specific for GPIIIa. After thrombin stimulation, the alpha-granule labeling disappeared whereas membrane labeling increased. Platelets from GT did not display labeling on plasma membranes, OCS membranes, or alpha-granule membranes. Platelets from the three patients with GPS displayed intense labeling of the plasma membrane and the OCS membrane, as well as the abnormal small alpha- granules and along the inside of large vacuoles (which contain the granule membrane protein [GMP]-140). In cultured immature MK from normal progenitors, both peptide components of GPIIb-IIIa appeared in the Golgi saccules and vesicles, and in the small precursors of alpha- granules, labeling both their membranes and their matrix. It was then observed only on the membrane of the mature MK alpha-granules, although labeling was less consistent than on the platelet granules. The MK plasma membrane and demarcation membrane system also displayed GPIIb- IIIa labeling. In conclusion, this study demonstrates that GPIIb-IIIa is present on the internal face of the alpha-granule membranes of platelets (where it appears early during MK maturation) as well as in the abnormal alpha-granules of gray platelets; it is absent from GT type I platelets.