bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical Amyloidosis Associated With Nonthrombocytopenic Purpura and Plasmocytic Hyperplasia of the Bone Marrow
Authors: PROPP SIMON , SCHARFMAN WILLIAM B. , BEEBE RICHARD T. , WRIGHT ARTHUR W. 
Published: October 2019

Abstract
1. Two cases of chronic nonthrombocytopenic purpura of unusual distribution, associated with generalized amyloidosis and plasma cell hyperplasia of the bone marrow, are described in detail with their postmortem findings.
2. Grossly recognizable amyloid was present in the antemortem sternal marrow aspirates of both patients.
3. Skin sections in each patient revealed hemorrhages associated with marked amyloid deposition in the dermis and blood vessel walls. It is postulated that this purpura was of vascular type.
4. The diagnosis of the underlying pathology in both patients was made possible by marrow aspiration. The importance of proper use of marrow particle smears in the diagnosis of plasma cell disturbances in the bone marrow is emphasized.
5. The difficulty in differentiating plasma cell myeloma from other causes of plasma cell hyperplasia of the marrow is clearly documented in this report.
Complement in Hemolytic Disease of the Newborn
Authors: TRIANTAPHYLLOPOULOS DEMETRIOS , GREENWALT TIBOR J. 
Published: October 2019

Abstract
1. The 50 per cent complement levels in thirty-three normal newborn infants and twenty-three infants with D (Rh0)-hemolytic disease were determined.
2. No statistically significant difference in complement values was found between the two groups.
3. In vitro tests with ten anti-D (Rh0) sera demonstrated that there was no fixation of human complement.
Leukemia in Atomic Bomb Survivors
Authors: LANGE ROBERT D. , MOLONEY WILLIAM C. , YAMAWAKI TOKUSO 
Published: October 2019

Abstract
1. Observations on seventy-five established cases of leukemia occurring in people exposed to atomic bomb radiation are presented.
2. These data indicate a great increase in the incidence of leukemia among atomic bomb survivors due to a single massive exposure to ionizing radiation.
3. The leukemogenic effects of radiation are manifested equally in both sexes and at all age levels represented in this series.
4. The striking preponderance of chronic myelogenous leukemia compared to chronic lymphatic leukemia has been noted in exposed individuals but it is pointed out that chronic lymphatic leukemia is comparatively rare among the Japanese.
5. Cases of leukemia are still appearing in atomic bomb survivors. However, since 1950 there has been a steady decline in the number of cases.
Polycythemic Response in Normal Adult Rats to a Nonprotein Plasma Extract from Anemic Rabbits
Authors: BORSOOK HENRY , GRAYBIEL ASHTON , KEIGHLEY GEOFFREY , WINDSOR EMANUEL 
Published: October 2019

Abstract
Experiments are described in which a protein-free extract of plasma obtained from anemic rabbits was injected into healthy young rats. The resulting erythropoietic response was comparable to that induced by hypoxia. The findings suggest that a humoral factor was at work which was capable of disturbing the physiologic mechanisms which establish the equilibrium between red blood cell formation and destruction. The far-reaching significance of these findings is apparent.
Predictors of Long-Term Response to High-Dose Interferon Therapy in Type II Cryoglobulinemia Associated With Hepatitis C Virus Infection
Authors: Casato Milvia , Agnello Vincent , Pucillo Leopoldo P. , Knight Glenn B. , Leoni Marco , Del Vecchio Savino , Mazzilli Cristina , Antonelli Guido , Bonomo Lorenzo 
Published: October 2019

AbstractWe have prospectively studied patients with type II cryoglobulinemia since 1985 to assess the efficacy of treatment with interferon-α at cumulative doses ranging from 234 to 849 MU. In the present study we retrospectively evaluated in this cohort parameters associated with complete response to therapy in 31 consecutive patients with type II cryoglobulinemia associated with hepatitis C virus (HCV) infection. Prevalence of complete response of cryoglobulinemia (disappearance of symptoms and signs of vasculitis and decrease of cryocrit below 10% of the initial value) was 62%, with a median response duration of 33 months and a range of 3 to 100 months. Three patients were putatively cured, as they remained in complete remission for more than 5 years off therapy. Eighteen patients (58%) had liver disease evidenced by histopathology and/or raised transaminase levels. Prevalence of normalization of transaminase levels was 100%, with a median response duration of 36 months. Relapse of hypertransaminasemia occurred in 100% and 8% of patients receiving less than or greater than 621 MU, respectively. By logistic regression analysis, the only pretherapy parameter that associated significantly (P = .0393) with complete response of cryoglobulinemia was the solitary anti-C22 (HCV core) antibody pattern, which was observed in 29% of patients. Association with older age and low cryocrit approached statistical significance (P = .06), while no significant correlations were found with serum IgM levels, duration of disease, HCV genotype, NS5a gene mutations, liver histology, HLA-DR phenotype, or WA cross-idiotype. Complete responses were also associated, on univariate statistical analysis, with low pretherapy HCV viremia. Responses were accompanied by decrease of viremia, of anti-HCV antibody levels and cryocrit. The usefulness of a high dose regimen is underscored by the higher rates of sustained responses of cryoglobulinemia and transaminase levels compared with previous studies.
Pooled Normal Human Polyspecific IgM Contains Neutralizing Anti-Idiotypes to IgG Autoantibodies of Autoimmune Patients and Protects From Experimental Autoimmune Disease
Authors: Hurez Vincent , Kazatchkine Michel D. , Vassilev Tchavdar , Ramanathan Sheela , Pashov Anastas , Basuyaux Bertrand , de Kozak Yvonne , Bellon Blanche , Kaveri Srini V. 
Published: October 2019

AbstractNormal human serum contains IgM antibodies that regulate the natural autoantibody activity of IgG in autologous serum. In the present study, we show that pooled normal human IgM (IVIgM) purified from plasma of more than 2,500 healthy donors and processed in a similar fashion to that of therapeutic preparations of pooled normal human IgG (IVIg) suppresses activity of IgG autoantibodies purified from the serum of patients with autoimmune diseases in vitro. The inhibitory effect of IVIgM was greater or equivalent to that of IVIg on a molar basis. We show that IVIgM contains anti-idiotypic antibodies directed against idiotypic determinants of autoantibodies, in particular by showing that Sepharose-bound IVIgM selectively retained F(ab′)2 fragments of IgG autoantibodies. The infusion of (Lewis × Brown-Norway) F1 rats with IVIgM protected the animals against experimental autoimmune uveitis induced by immunization with the soluble retinal S antigen, as evidenced by clinical scoring and histopathological analysis. The present findings provide a rationale for considering pooled IgM for immunomodulation of autoimmune disease.
The Plasmacytoma Resistance Gene, Pctr2, Delays the Onset of Tumorigenesis and Resides in the Telomeric Region of Chromosome 4
Authors: Mock Beverly A. , Hartley Janet , Le Tissier Paul , Wax Judith S. , Potter Michael 
Published: October 2019

AbstractMouse plasmacytomas share pathogenetic features in common with both multiple myeloma and Burkitt's lymphoma in humans. Susceptibility to plasmacytoma induction by intraperitoneal pristane in mice is controlled by multiple genes. At least two of these genes reside on mouse chromosome 4 in regions of the genome sharing linkage homology with human chromosomes 9p21, 1p32, and 1p36. A series of congenic strains recombinant for regions of mouse chromosome 4 in the vicinity of the Pctr2 predisposition locus were created and typed for their tumor susceptibility/resistance phenotypes. These strains were derived by introgressively backcrossing alleles from resistant DBA/2 mice onto the susceptible BALB/cAnPt background. Six resistant and two susceptible strains were allelotyped for 10 genes and 49 random DNA markers to identify the smallest region of overlap in the resistant strains. These studies have determined that the Pctr2 locus resides in either a 500-kb interval proximal to Nppa, or in a 1- to 2-centiMorgan (cM) interval distal to Nppa. In these congenic strain analyses, the Nppa and Fv1 loci, in addition to genes within about 1 cM of these loci, have been excluded as candidates for the Pctr2 locus. A relevant locus that may reside in this interval is Rep2; it is associated with the efficiency of repairing X-ray induced DNA damage sustained during the G2 phase of the mitotic cycle. The Pctr2 locus acts in a codominant fashion. F1 hybrids between resistant and susceptible congenic strains exhibit a reduced tumor incidence and a significant delay in the onset of tumorigenesis. Identification and eventual cloning of the Pctr2 locus may assist in the identification of genes involved in many types of cancer showing aberrations in human chromosome 1p36.
Failure of Immunologic Purging in Mantle Cell Lymphoma Assessed by Polymerase Chain Reaction Detection of Minimal Residual Disease
Authors: Andersen Niels S. , Donovan John W. , Borus Joseph S. , Poor Christina M. , Neuberg Donna , Aster Jon C. , Nadler Lee M. , Freedman Arnold S. , Gribben John G. 
Published: October 2019

Abstract
To assess the clinical significance of minimal residual disease (MRD) detection by polymerase chain reaction (PCR) we analyzed samples from 26 patients with mantle cell lymphoma (MCL) who had undergone bone marrow transplantation (BMT) at the Dana-Farber Cancer Institute. The BCL-1/IgH translocation and clonally rearranged Ig heavy chain genes (IgH) provided molecular markers for detection and follow-up of MRD by polymerase chain reaction (PCR) amplification in 19 of the 26 (73%) MCL patients studied. IgH gene sequencing analysis showed somatic mutations in MCL that are characteristic of an antigen driven process suggesting that, in MCL, the final malignant transformation occurs in a mature B cell. Of the 19 patients with a PCR amplifiable marker, 17 underwent autologous, 1 an allogeneic, and 1 a syngeneic bone marrow transplantation (BMT). All patients had PCR-detectable MRD in the bone marrow (BM) at the time of BMT, irrespective of any history of histological BM involvement. In contrast to other B-cell malignancies, we found that immunological purging with complement-mediated lysis eradicated PCR-detectable MCL in only two patients. Moreover reinfusion of MRD was associated with a poor outcome. More than half of the patients undergoing autologous BMT had relapsed by the time of restaging at 2 years after autologous BMT. In four MCL patients in whom no residual lymphoma was reinfused, including the allogeneic and the syngeneic BMT, only one patient relapsed. Persistence of MRD detection after BMT was also associated with a high probability of relapse, although one patient did not have PCR-detectable MRD in peripheral blood or BM before relapse at nodal sites. We conclude that PCR amplification of disease-specific markers is a feasible and sensitive method to assess MRD and its clinical significance in patients with MCL. Moreover, PCR amplification provides a tool to evaluate modifications of purging and stem cell collection procedures that may be required for the management of this otherwise incurable disease.
Retroviral-Mediated Transfer of the Green Fluorescent Protein Gene Into Murine Hematopoietic Cells Facilitates Scoring and Selection of Transduced Progenitors In Vitro and Identification of Genetically Modified Cells In Vivo
Authors: Persons Derek A. , Allay James A. , Allay Esther R. , Smeyne Richard J. , Ashmun Richard A. , Sorrentino Brian P. , Nienhuis Arthur W. 
Published: October 2019

AbstractWe have investigated the utility of the green fluorescent protein (GFP) to serve as a marker to assess retroviral gene transfer into hematopoietic cells and as a tool to identify and enrich for cells expressing high levels of the vector-encoded transcript. GFP, by virtue of a naturally occurring chromophore encoded in its primary sequence, displays autonomous fluorescence, thus eliminating the need for antibody or cytochemical staining to detect its expression. A bicistronic murine stem cell virus (MSCV)-based retroviral vector was constructed containing the GFP cDNA and a mutant, human dihydrofolate reductase gene. High-titer, ecotropic retroviral producer cells free of replication competent virus were generated and used to transduce murine bone marrow cells by cocultivation. Within 24 hours after completion of the transduction procedure, a high proportion (40% to 70%) of the marrow cells were intensely fluorescent compared to mock-transduced cells or cells transduced with a control retrovirus. Erythroid and myeloid hematopoietic colonies derived from GFP-transduced marrow were easily scored for retroviral gene transfer by direct in situ fluorescence microscopy. Clonogenic progenitors expressing increased levels of antifolate drug resistance could be enriched from the GFP-transduced marrow population by fluorescence activated cell sorting of cells expressing high levels of GFP. In vivo, splenic hematopoietic colonies and peripheral blood cells from animals transplanted with GFP-transduced marrow displayed intense fluorescence. These results show that GFP is an excellent marker for scoring and tracking gene-modified hematopoietic cells and for allowing rapid selection and enrichment of transduced cells expressing high levels of the transgene.
CD40 Ligand Induces an Antileukemia Immune Response In Vivo
Authors: Dilloo Dagmar , Brown Michael , Roskrow Marie , Zhong Wanyung , Holladay Martha , Holden William , Brenner Malcolm 
Published: October 2019

AbstractLeukemia cells may express tumor specific antigens in association with Class I and II major histocompatability complex (MHC) molecules. However, lack of expression of conventional costimulator molecules means that these cells tend to induce specific T-cell anergy rather than activation. CD40 ligand (CD40L) is a costimulator molecule that directly activates T cells and may promote antigen presentation by CD40-expressing cells, which include professional antigen presenting cells and B-acute lymphoblastic leukemia (ALL) cells from many patients. We determined whether transgenic expression of CD40L could enhance an antileukemia immune response using a CD40+ murine lymphoblastic (A20) leukemia and a CD40− myeloblastic (WEHI-3) leukemia in a tumor treatment model. Injection of otherwise nonimmunogenic A20 cells in the presence of CD40L induced an immune response active against preexisting A20 tumor at a distant site. Moreover, concomitant local secretion of transgenic interleukin-2 (IL-2) further amplified the antileukemic response induced and increased protection against preexisting tumor. In ex vivo studies, CD40 activation of A20 cells enhances the antigen presenting potential of A20 cells by upregulating expression of B7.1 (CD80), Class I and II MHC molecules, and increases expression of fas antigens. The importance of CD40 activation to the resulting antitumor response is further emphasized by the failure of transgenic CD40L to protect against the CD40− WEHI myeloblastic leukemia. Depletion studies showed the protective effects against A20 cells to be mediated by a combination of CD4+ and CD8+ T lymphocytes and by natural killer (NK) cells. These results suggest a means by which CD40+ leukemia cells may be rendered immunogenic in vivo.
Allelotype Analysis in the Evolution of Chronic Myelocytic Leukemia
Authors: Mori Naoki , Morosetti Roberta , Lee Stephen , Spira Susanne , Ben-Yehuda Dina , Schiller Gary , Landolfi Raffaele , Mizoguchi Hideaki , Koeffler H. Phillip 
Published: October 2019

Abstract
To elucidate the genetic events that may play important roles in the progression of chronic myelocytic leukemia (CML), we performed allelotype analysis in 30 patients with CML as the disease transformed to accelerated phase or blast crisis (21 myeloid and 9 lymphoid cases). DNAs were extracted from slides of bone marrow smears or from freshly isolated bone marrow mononuclear cells. The DNAs from the same individuals in both chronic phase and either blast crisis or accelerated phase were analyzed at 82 microsatellite markers, which mapped to each of the autosomal arms except the short arms of the acrocentric chromosomes. Loss of heterozygosity (LOH) on at least one locus was observed in 21 of the 30 cases (70%) as the disease progressed. Frequent allelic loss of ≥ 20% of the informative cases was observed on chromosome arms 1p (35%), 7p (21%), 19p (20%), and 20q (29%). Allelic losses were also analyzed according to phenotypes. LOH of ≥ 20% was detected on 1p (29%), 18p (20%), and 20q (27%) in myeloid blast crisis, and on 1p (50%), 4p (25%), 7p (43%), 9p (29%), 18q (25%), 19p (43%), and 20q (33%) in lymphoid blast crisis. Serial cytogenetic information was available for most of our cases with LOH on these arms, and only one case had loss of both chromosomes 9 and 20. Fractional allelic loss, calculated for each sample as the total number of chromosomal arms lost/total number of arms with information, showed a median value of 0.06 and a mean of 0.098 (range 0 to 0.60). These results suggest that tumor suppressor genes especially on 1p, 7p, 19p, and 20q probably have an important role in the progression to blast crisis of CML.
High-Dose Chemotherapy With Autologous Bone Marrow Rescue in Children With Poor-Risk Burkitt's Lymphoma: A Report From the European Lymphoma Bone Marrow Transplantation Registry
Authors: Ladenstein Ruth , Pearce Rachel , Hartmann Olivier , Patte Catherine , Goldstone Tony , Philip Thierry 
Published: October 2019

Abstract
To evaluate the role of high-dose chemotherapy (HDC) followed by autologous bone marrow transplantation (ABMT) in children with poor-prognosis Burkitt's lymphoma, the European Lymphoma BMT registry was critically reviewed. Between February 1979 and July 1991, a selected group of 89 children (78 boys and 11 girls) were considered as ABMT candidates in 12 European cancer centers for the following reasons: poor initial response (PIR) to first-line chemotherapy in 28 patients, primary refractory disease (PRD) in nine patients, sensitive relapse (SR) in 38 patients, and resistant relapse (RR) in 14 patients. The median age at ABMT was 8.2 years (range, 2.8 to 16.2 years). Thus, this report reflects data for patients surviving the salvage attempt deemed appropriate for HDC/ABMT and who then actually underwent the transplant procedure. The median follow-up period after HDC/ABMT was 4.3 years (range, 2 to 12 years). The prognosis was dismal for PRD patients and those with RR, ie, all patients died within 1 year. The 5-year event-free survival (EFS) was 56.6% (P < .0001) for patients in partial remission (PR) and 48.7% (P = .002) for patients with SR. The toxic death rate was 11.1%. Continuous complete remissions (CRs) in 39.4% of these otherwise incurable children highlight the fact that HDC/ABMT was an effective complementary procedure after conventional-dose chemotherapy protocols used during the given period. In addition, these data show that patients with PRD or RR clearly had no advantage from this aggressive and cost-intensive procedure. It has to be considered that the need for HDC/ABMT has greatly diminished in parallel with the improvement in survival using the modern intensive pulsed CCT of current protocols. To further rescue patients failing to respond to modern protocols, new approaches appear necessary, ie, combinations of HDC with antibody-targeted therapy plus allogeneic BMT for the additional benefits of the potential graft-versus-lymphoma effect.
Peripheral Blood Progenitor Cell Mobilization Using Stem Cell Factor in Combination With Filgrastim in Breast Cancer Patients
Authors: Glaspy J.A. , Shpall E.J. , LeMaistre C.F. , Briddell R.A. , Menchaca D.M. , Turner S.A. , Lill M. , Chap L. , Jones R. , Wiers M.D. , Sheridan W.P. , McNiece I.K. 
Published: October 2019

Abstract
The safety and optimal dose and schedule of stem cell factor (SCF ) administered in combination with filgrastim for the mobilization of peripheral blood progenitor cells (PBPCs) was determined in 215 patients with high-risk breast cancer. Patients received either filgrastim alone (10 μg/kg/d for 7 days) or the combination of 10 μg/kg/d filgrastim and 5 to 30 μg/kg/d SCF for either 7, 10, or 13 days. SCF patients were premedicated with antiallergy prophylaxis. Leukapheresis was performed on the final 3 days of cytokine therapy and, after high-dose chemotherapy and infusion of PBPCs, patients received 10 μg/kg/d filgrastim until absolute neutrophil count recovery. The median number of CD34+ cells collected was greater for patients receiving the combination of filgrastim and SCF, at doses greater than 10 μg/kg/d, than for those receiving filgrastim alone (7.7 v 3.2 × 106/kg, P < .05). There were significantly (P < .05) more CD34+ cells harvested for the 20 μg/kg/d SCF (median, 7.9 × 106/kg) and 25 μg/kg/d SCF (median, 13.6 × 106/kg) 7-day combination groups than for the filgrastim alone patients (median, 3.2 × 106/kg). The duration of administration of SCF and filgrastim (7, 10, or 13 days) did not significantly affect CD34+ cell yield. Treatment groups mobilized with filgrastim alone or with the cytokine combination had similar hematopoietic engraftment and overall survival after PBPC infusion. In conclusion, the results of this study indicate that SCF therapy enhances CD34+ cell yield and is associated with manageable levels of toxicity when combined with filgrastim for PBPC mobilization. The combination of 20 μg/kg/d SCF and 10 μg/kg/d filgrastim with daily apheresis beginning on day 5 was selected as the optimal dose and schedule for the mobilization of PBPCs.
Overexpression of Human Stem Cell Factor Impairs Melanocyte, Mast Cell, and Thymocyte Development: A Role for Receptor Tyrosine Kinase-Mediated Mitogen Activated Protein Kinase Activation in Cell Differentiation
Authors: Kapur Reuben , Everett Eric T. , Uffman Josh , McAndrews-Hill Monica , Cooper Ryan , Ryder John , Vik Terry , Williams David A. 
Published: October 2019

AbstractStem cell factor (SCF) is synthesized as both soluble (S) and membrane-associated (MA) proteins. Indirect insight into the function of MA and S isoforms of SCF has come from studies performed in Steel (Sl) mutant mice. However, the physiologic role(s) of these two isoforms remain unknown. In an attempt to better understand the in vivo role of c-kit/SCF interactions on various cell lineages, transgenic mice were generated that overexpress MA isoform of human SCF (hSCF). In murine cells, hSCF behaves as an antagonist to normal SCF function, due to interference with the interaction between endogenous murine SCF and its receptor, c-kit, encoded by the dominant white spotting (W) gene. Mice expressing the hSCF transgene display a variety of phenotypic abnormalities, which are accentuated when combined with W alleles. Here we show that mice homozygous for the hSCF transgene demonstrate a coat color deficiency seen in some mice homozygous for mild W alleles. Specifically, homozygous hSCF transgenic mice (hSCF220) display a pronounced forehead blaze, with additional white spots over the cervical region, as well as a very large belly spot. Doubly heterozygous animals that carry both a mutated W allele and the hSCF transgene also display an unusual pigment defect and a dramatic reduction in the number of dermal mast cells. Furthermore, overexpression of MA hSCF in the thymus results in abnormal thymocyte differentiation and proliferation, which is associated with reduced mitogen activated protein (MAP) kinase activation. Thus, MAP kinase activation by a receptor tyrosine kinase, such as c-kit, may be critical for the differentiation of thymocytes in vivo.