bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herpes zoster infection after autologous bone marrow transplantation
Authors: Schuchter LM , Wingard JR , Piantadosi S , Burns WH , Santos GW , Saral R 
Published: October 2019

Abstract
One hundred fifty-three patients who underwent autologous bone marrow transplant (ABMT) were studied retrospectively to determine the frequency, outcome, and risk-factors associated with varicella-zoster infections (VZV). Forty-three patients (28%) developed VZV infection after transplant. The median onset of infection was the fifth month, with 91% of cases occurring within the first year. Thirty-three patients (77%) had localized herpes zoster, and ten patients (23%) had varicella. Cutaneous dissemination developed in 15% of patients and probable visceral dissemination developed in 5%. Overall morbidity was 25% and included scarring, alopecia, postherpetic neuralgia, and neurologic dysfunction. There were no deaths from VZV infection. The majority of patients (79%) were treated with intravenous (IV) acyclovir. The only significant risk factor associated with VZV infection was the underlying disease. VZV infection occurred most frequently in patients with Hodgkin's and non-Hodgkin's lymphoma (46%) as compared with patients with leukemia (23%) or solid tumors (9%) (P less than .002). The frequency of VZV infection in ABMT patients appears to be comparable to that reported for allogeneic BMT patients and other immunocompromised patients.
Stimulation of nonclonal hematopoiesis and suppression of the neoplastic clone after treatment with recombinant human granulocyte- macrophage colony-stimulating factor in a patient with therapy-related myelodysplastic syndrome
Authors: Vadhan-Raj S , Broxmeyer HE , Spitzer G , LeMaistre A , Hultman S , Ventura G , Tigaud JD , Cork MA , Trujillo JM , Gutterman JU 
Published: October 2019

Abstract
A complete hematologic remission was achieved in a patient with therapy- related preleukemia and transfusion-dependent pancytopenia after treatment with recombinant human granulocyte-macrophage colony- stimulating factor (GM-CSF). The patient remained in remission for nearly 1 year despite the discontinuation of GM-CSF treatment. Several lines of evidence suggest that normal hematopoiesis was restored after GM-CSF treatment. First, the cytogenetic anomaly, which was present before GM-CSF, completely disappeared after three cycles of treatment. Cytogenetic conversion was documented by conventional karyotypic evaluation of mitotic bone marrow cell preparations as well as by premature chromosome condensation analysis of the nonmitotic cells of bone marrow and peripheral blood. Second, the growth pattern and cycle status of bone marrow granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells were found to be normal during remission. Third, X chromosome-linked restriction fragment length polymorphism- methylation analysis of DNA from mononuclear cells (greater than 80% lymphocytes) and mature myeloid elements showed a polyclonal pattern. These findings suggest that restoration of hematopoiesis in this patient after GM-CSF treatment may have resulted from suppression of the abnormal clone and a selective growth advantage of normal elements.
A two-step timed sequential treatment for acute myelocytic leukemia
Authors: Geller RB , Burke PJ , Karp JE , Humphrey RL , Braine HG , Tucker RW , Fox MG , Zahurak M , Morrell L , Hall KL 
Published: October 2019

Abstract
Since 1980, adults with acute myelocytic leukemia (AML) have been treated on two clinical studies using intensive timed sequential therapy. All patients ages 16 to 80, including those with secondary AML (SAML) and those with AML preceded by a hematologic disorder (AHD), were treated, regardless of medical complications at the time of diagnosis. The first study combined high doses of cytarabine (ara-C, AC) and daunorubicin (DRN, D) in sequence (Ac2-D-Ac) and resulted in a complete remission rate of 55%. A group of these patients selected by functional status was able to receive a second course of therapy in remission, which resulted in a disease-free survival (DFS) of greater than 40% at 7 years. Because of toxicity in that study, 114 patients were entered on a second trial initiated 4 years ago, using a less aggressive first course, with amsacrine, to achieve a stable remission (Ac2-D-Amsa). This first treatment was followed by a more intensive second course (Ac6-D-Ac). With this two-step approach, a higher complete remission (CR) rate (76% for de novo AML and 54% for SAML-AHD) was achieved, and more patients were able to receive the second course of therapy. At the current median follow-up of 26 months, the median duration of DFS and overall survival are 11 and 14 months for patients with de novo AML. Age less than or equal to 55 is the most significant prognostic factor for both prolonged DFS and overall survival, with median durations of 17 and 18 months, respectively, for these younger patients. Patients with SAML-AHD remain relatively refractory to treatment despite aggressive chemotherapy, with median durations of DFS and overall survival of 9 months and 5 months, respectively.
Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]
Authors: Beelen DW , Quabeck K , Graeven U , Sayer HG , Mahmoud HK , Schaefer UW 
Published: October 2019

Abstract
The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).
Granulocyte-macrophage colony-stimulating factor and interleukin-3 mRNAs are produced by a small fraction of blood mononuclear cells
Authors: Wimperis JZ , Niemeyer CM , Sieff CA , Mathey-Prevot B , Nathan DG , Arceci RJ 
Published: October 2019

Abstract
Northern blot analysis has identified granulocyte macrophage colony stimulating factor (GM-CSF) mRNA in monocytes and both GM-CSF and interleukin-3 (IL-3) mRNA in lymphocytes. However, these results have not addressed whether all cells or a subset of the population is capable of hematopoietic growth factor (HGF) production. To resolve this question, we applied in situ hybridization of radiolabeled antisense RNA probes to centrifuged preparations of total blood mononuclear cells (BMCs) and fractionated lymphocyte subpopulations. Without stimulation, no circulating cells expressed detectable levels of GM-CSF or IL-3 mRNA. On stimulation of BMCs with phorbol myristate acetate (PMA) and phytohemagglutinin or PMA and the calcium ionophore ionomycin, approximately 5% expressed GM-CSF mRNA and approximately 1% IL-3 mRNA. Control sense probes produced no labeled cells. To determine the subsets of lymphocytes capable of GM-CSF and IL-3 expression, BMCs were fractionated by FACS into CD8+ and CD4+ lymphocyte subsets and CD16+ (NK) cells. The unfractionated cells and cell fractions were then stimulated with PMA and ionomycin. Results demonstrated that 3% to 5% of the CD16+, CD8+, and CD4+ lymphocytes produced GM-CSF mRNA. However, the number of IL-3 mRNA-positive cells in the FACS-sorted subsets was greatly reduced (0.02% to 0.05%) as compared with the unseparated cells (1%). Treatment of BMCs with high-dose interleukin-2 (IL-2) for 1 week followed by PMA plus ionomycin resulted in a lymphocyte population in which 50% and 3% of cells expressed GM-CSF and IL-3 mRNA, respectively. Thus, GM-CSF and IL-3 mRNA expression in T cells and NK cells is restricted to a small fraction of cells that can be greatly expanded by IL-2 stimulation. These results suggest a possible physiologic mechanism for increasing HGF production by circulating lymphocytes.
Lactoferrin decreases monocyte-induced fibroblast production of myeloid colony-stimulating activity by suppressing monocyte release of interleukin-1
Authors: Zucali JR , Broxmeyer HE , Levy D , Morse C 
Published: October 2019

Abstract
Lactoferrin (Lf) is a negative regulator of myelopoiesis which operates by suppressing the release from mononuclear phagocytes of GM colony- stimulating factor (GM-CSF) or monokines which can then induce the release of GM-CSA from accessory cells. In this study, endotoxin- depleted, purified iron-saturated human Lf was assessed for its effect on the production of interleukin-1 by cultured monocytes and their subsequent effect on colony-stimulating factor release from cultured fibroblasts. Monocytes were grown with or without Lf and Lf that had previously been incubated with monoclonal anti-Lf. The monocyte- conditioned medium was then either assayed for the presence of interleukin-1 (IL-1) with an enzyme-linked immunosorbent assay or for its ability to stimulate fibroblasts to release growth factors for CFU- GM, BFU-E, or CFU-Mix colonies. In the presence of Lf (10(-7) or 10(-8) mol/L), GM colony-stimulating activity (GM-CSA) was suppressed by 31% to 73%, whereas stimulating activities for BFU-E and CFU-mix colony formation were suppressed by 93% to 100%. Antibody to Lf completely abrogated the suppressive effects observed with Lf, whereas antibody to IL-1 ablated the induction by monocyte-conditioned medium of CSA release by fibroblasts. Lf at 10(-7) and 10(-8) mol/L also reduced IL-1 synthesis by cultured monocytes from 60% to 77%. The inhibitory effects of Lf were only observed when Lf was added before adherence of the monocytes for culture. If Lf was added at the time of adherence or after adherence, no suppression was observed. We conclude that the inhibition of GM-CSA production/release by Lf is mediated through inhibition of the synthesis/release of IL-1 by mononuclear phagocytes. This inhibition of IL-1 prevents accessory cells from producing and/or releasing GM-CSA.
Regulation of megakaryocyte development by interleukin-6
Authors: Lotem J , Shabo Y , Sachs L 
Published: October 2019

Abstract
Megakaryocytes develop in densely seeded normal mouse bone marrow (BM) cells cultured in agar or in liquid medium. This formation of megakaryocytes is enhanced by the myeloid differentiation-inducing protein MGI-2, which we have shown to be interleukin-6 (IL-6). Monoclonal antibody (MoAb) that specifically neutralizes mouse IL-6 but not human IL-6 inhibited megakaryocyte development in cells cultured either with or without the addition of mouse IL-6 but did not inhibit megakaryocyte development induced by human IL-6. This MoAb to mouse IL- 6 that does not neutralize mouse IL-3 also inhibited mouse IL-3-induced megakaryocyte development. Antibody to mouse GM-CSF did not inhibit the formation of megakaryocytes. The results show that the induction of megakaryocyte development by IL-3 is due to the production of IL-6 in the BM cultures. The present experiments demonstrate a new property of IL-6 and indicate that IL-6 is a regulatory protein of normal megakaryocyte development.
Pharmacodynamics and pharmacokinetics of dermatan sulfate in humans
Authors: Dol F , Houin G , Rostin M , Montastruc JL , Dupouy D , Gianese F , Sie P , Boneu B 
Published: October 2019

Abstract
Dermatan sulfate (DS), a catalyst of the thrombin-heparin cofactor II interaction, has antithrombotic activity and is devoid of significant hemorrhagic risk in several animal models. We investigated the pharmacodynamic and pharmacokinetic properties of DS in humans. DS was injected in single bolus intravenous injections of four increasing doses (0.5, 1, 1.5, 2 mg/kg) to six healthy volunteers. The resulting anticoagulant activities were assessed by the activated partial thromboplastin time (APTT) and the thrombin clotting time (TCT). There were dose-dependent prolongations of the APTT and TCT, and the anticoagulant activities disappeared in less than three hours. The pharmacokinetic parameters were calculated from the plasma concentrations of DS measured with a new chromogenic assay. The volume of distribution was approximately 1.8 times greater than the theoretical plasma volume and was independent of dose. In contrast, the clearance decreased with dose and the terminal half-life ranged from 0.45 +/- 0.08 hours at 0.5 mg/kg to 0.72 +/- 0.11 hours (mean +/- SD) at 2 mg/kg. The bioavailabilities of subcutaneous (SC) and intramuscular (IM) administration relative to those of intravenous administration were determined in 12 other volunteers. The respective bioavailabilities were 24.7% +/- 12.9% and 12.4% +/- 9.2% for SC and IM administration. There was no detectable change in the APTT and the TCT when the volunteers were injected with 1.5 mg/kg SC or IM. In addition, the pharmacokinetic parameters derived from plasma concentrations of DS showed considerable interindividual variations by the two later routes of administration. Peak concentrations were noted 2.7 +/- 1.3 hours after SC injection and 4.3 +/- 4.9 hours after IM injection. The average peak concentrations were 0.7 +/- 0.3 and 0.4 +/- 0.2 mg/L after SC and IM injections, respectively. The half-lives of DS were 7.9 +/- 6.5 hours (SC) and 6.3 +/- 7.4 hours (IM). No adverse reaction to DS was recorded during this study.
Initiation of the extrinsic pathway of coagulation by human and rabbit alveolar macrophages: a kinetic study
Authors: McGee MP , Wallin R , Wheeler FB , Rothberger H 
Published: October 2019

Abstract
We examined assembly and expression of the factor X activating complex on human and rabbit alveolar macrophages. Kinetic parameters of the factor X activating reaction were determined by functional titrations of factors VII and X with macrophage tissue factor (TF) added. We found rapid activation of factor X to Xa on alveolar macrophage surfaces. Detection of rapid factor Xa formation on macrophages required addition of exogenous factors VII and X. At plasma concentrations of the purified factors, factor Xa was formed on freshly isolated macrophages at approximately 5.4 pmol/min/10(6) cells. After macrophage maturation in culture for 20 hours with LPS (endotoxin) added, the factor X activation rate was increased two- to sixfold. The km' (apparent km) of TF-factor VII enzymatic complexes assembled on alveolar macrophages for factor X were (258 +/- 55 and 475 +/- 264 nmol/L for human and rabbit cells, respectively). The km' did not change during macrophage maturation in culture, but V'max (apparent Vmax) was consistently increased. The K1/2 of human factor VII (concentrations giving half maximal rates of factor X activation) for the interaction with human and rabbit alveolar macrophage TF were 0.191 +/- 0.096 and 1.7 +/- 0.7 etamol/L, respectively. The K1/2 were not significantly changed after maturation, whereas rates of Xa formation at saturation with factor VII were increased. The fast rates of factor X activation observed at physiologic concentrations of plasma-derived factors VII and X indicate that TF on alveolar macrophages is likely to provide sites for binding of factor VII and activation of factor X in vivo during clotting reactions associated with alveolar edema and inflammation.
An arginine to cysteine amino acid substitution at a critical thrombin cleavage site in a dysfunctional factor VIII molecule
Authors: Shima M , Ware J , Yoshioka A , Fukui H , Fulcher CA 
Published: October 2019

Abstract
We have analyzed the factor VIII (FVIII) protein and the nucleotide sequence around two thrombin cleavage sites, at arginine 372 in the FVIII heavy chain and arginine 1689 in the FVIII light chain in a naturally occurring dysfunctional FVIII variant, FVIII Okayama. The patient was a 42-year-old hemophiliac with a FVIII coagulant activity of 0.03 U/mL and a FVIII antigen level of 0.8 U/mL. The patient's FVIII was not thrombin activatable to levels seen in normal plasma. Immunoblotting of partially purified FVIII Okayama and normal FVIII showed that thrombin cleavage of the 92 kilodalton (Kd) heavy chain was impaired in the mutant protein. The patient's genomic DNA was amplified using the polymerase chain reaction with two sets of synthetic oligonucleotide primers spanning amino acid residues 319 to 400 and 1630 to 1720. Sequence analysis of the amplified DNA fragments revealed a cytosine to thymine transition, converting an arginine to a cysteine codon at residue 372. No abnormality was found in the FVIII light chain region analyzed. The patient's hemophilic brother and carrier mother revealed the same mutation. We conclude that the pathogenesis of hemophilia A in this patient is probably due to an arginine to cysteine substitution at a thrombin cleavage site in the FVIII heavy chain.
Prevalence of human T-cell leukemia/lymphoma virus (HTLV) type II infection among high-risk individuals: type-specific identification of HTLVs by polymerase chain reaction
Authors: Ehrlich GD , Glaser JB , LaVigne K , Quan D , Mildvan D , Sninsky JJ , Kwok S , Papsidero L , Poiesz BJ 
Published: October 2019

Abstract
The extent of human T-cell leukemia/lymphoma virus type II (HTLV-II) infection and its rate of spread have been difficult to determine owing to the serological cross-reactivity between HTLV-I and HTLV-II. The present study overcame this problem by directly detecting type-specific proviral sequences by means of the polymerase chain reaction (PCR) and liquid hybridization. Screening was performed on a cohort of primarily white intravenous drug abusers (IVDAs), and individuals of other behaviorally defined risk groups from the New York City area. Eleven percent (19 of 169) of the individuals in these high-risk groups were determined by PCR to have HTLV-II proviral infections. One of these patients displayed an exfoliative erythrodermatitis. Thirteen of the 19 subjects were positive in an HTLV-II enzyme-linked immunosorbent assay (ELISA). The remaining six individuals, although negative in the HTLV- II ELISA, were confirmed as HTLV-II positive by analyzing their DNA with a second HTLV-II-specific primer detector system. Four additional individuals were reactive in the HTLV-II ELISA but were PCR-negative for HTLV-II. PCR analysis for HTLV-I revealed that all four were positive for that virus. Thirty-seven percent (seven of 19) of the HTLV- II PCR-positive subjects were also PCR-positive for HTLV-I, and 84% (16 of 19) of the HTLV-II positive individuals were infected with human immunodeficiency virus (HIV-1). Six individuals were triply infected with HTLV-I, HTLV-II, and HIV-1.
Granulocyte- and granulocyte-macrophage colony-stimulating factors enhance neutrophil cytotoxicity toward HIV-infected cells
Authors: Baldwin GC , Fuller ND , Roberts RL , Ho DD , Golde DW 
Published: October 2019

Abstract
Although the control of retroviral disease in animal systems often involves antibody-dependent cell-mediated cytotoxicity (ADCC), the role of cytotoxic function in human retroviral disorders is uncertain. The ability of the neutrophil to kill HIV-infected targets directed by antiviral antibody was examined. Neutrophils from patients with AIDS killed HIV-infected MOLT-3A cells in a manner equivalent to neutrophils obtained from normal volunteers. Both granulocyte- and granulocyte- macrophage colony-stimulating factors (G-CSF and GM-CSF) markedly augmented the cytotoxic function. Studies done with fractionated human antisera revealed that ADCC to HIV-infected cells was mediated only by antibody to the env glycoprotein. ADCC in this system was not dependent on oxidative metabolism because neutrophils from patients with chronic granulomatous disease (CGD) were capable of CSF-augmented cytotoxicity. Although ADCC can be mediated by various classes of lymphocytes and mononuclear phagocytes, such cells may be infected by HIV. Because the neutrophil apparently is not productively infected by the virus, it is an ideal cell to focus on with regard to cytotoxic function in AIDS patients. The findings regarding neutrophil ADCC in AIDS are clinically relevant because the availability of CSFs now permits therapeutic regulation of neutrophils in AIDS patients, and presumably natural antibody may be useful in targeting HIV-infected cells for neutrophil cytotoxicity in vivo.
BER-H2: a new anti-Ki-1 (CD30) monoclonal antibody directed at a formol- resistant epitope
Authors: Schwarting R , Gerdes J , Durkop H , Falini B , Pileri S , Stein H 
Published: October 2019

Abstract
The production and characterization of a monoclonal antibody (MoAb) designated Ber-H2, directed against a new epitope of the Ki-1 (CD30) antigen, are described. In comparison with the formerly reported Ki-1 MoAb whose reactivity with Hodgkin and Reed-Sternberg (H-RS) cells in frozen tissue sections is well-documented, the Ber-H2 MoAb showed new, important features: the labeling intensity of the Ber-H2 MoAb was much stronger, and the number of positively labeled cells was higher. Most important, however, was that the Ber-H2 MoAb could be applied in routinely processed, formaldehyde-fixed, paraffin-embedded tissue sections. Therefore, it was possible to investigate an unprecedented number of tumors received as frozen or formaldehyde-fixed material for expression of the CD30 antigen. Beside Hodgkin's disease, the Ber-H2 MoAb labeled a variable number of cells in lymphomatoid papulosis, peripheral T-cell lymphomas, and angoimmunoblastic lymphadenopathy. Among B-cell non-Hodgkin's lymphomas (NHLs), some cases containing large centroblast-like or immunoblast-like cells or displaying plasma- cellular differentiation were positive. This finding was in keeping with the reactivity of the Ber-H2 MoAb with activated B-cell blasts and a subpopulation of plasma cells in paraffin sections of normal lymphoid tissue. The diagnostic value of the Ber-H2 MoAb was most significant for a group of anaplastic large-cell (ALC) lymphomas (formerly frequently referred to as malignant histiocytosis or regressive atypical histiocytosis), of which more than 50 cases could be investigated, owing to applicability in paraffin sections. Although about one third of these ALC lymphomas did not express the leukocyte common (CD45) antigen, they were consistently reactive with the Ber-H2 MoAb in both frozen and paraffin-embedded tissue sections. Using the Ber-H2 MoAb, these Ki-1 lymphomas could be easily distinguished from other nonlymphoid anaplastic large-cell tumors.