bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two phases of engraftment established by serial bone marrow transplantation in mice
Authors: Jones RJ , Celano P , Sharkis SJ , Sensenbrenner LL 
Published: October 2019

Abstract
Serially transplanted bone marrow eventually fails to reconstitute lethally irradiated mice. The reasons for this loss of repopulating ability are unknown. We showed that serial bone marrow transplantation changed the ratio of hematopoietic progenitors in bone marrow. The numbers of granulocyte-macrophage colony-forming units (CFU-GM) in the bone marrow did not change with serial transplantation. Spleen CFU (CFU- S) numbers decreased with serial transfer but remained at levels which should be associated with engraftment, even on the transfers which were unsuccessful. The CFU-S, therefore, did not appear to be the cells responsible for long-term hematopoietic repopulation. The number of successful serial transfers was dependent on the size of the grafts, and prolonging the time interval between transfers reestablished the ability of the serially transplanted marrow to reconstitute lethally irradiated recipients. Serial bone marrow transplantation dissociated two phases of engraftment. The first unsustained phase was maintained with repeated serial transfer and appeared to be produced by committed progenitors. The second sustained phase was eventually lost with repeated serial transfer and was apparently due to the pluripotent stem cell.
Formation of C1s-C1-inhibitor, kallikrein-C1-inhibitor, and plasmin- alpha 2-plasmin-inhibitor complexes during cardiopulmonary bypass
Authors: Wachtfogel YT , Harpel PC , Edmunds LH Jr , Colman RW 
Published: October 2019

Abstract
Stimulation of platelets and neutrophils occurs during clinical cardiopulmonary bypass. We investigated whether the classical complement, contact, or fibrinolytic pathways are activated as potential sources of neutrophil agonists. Using enzyme-linked immunosorbent “sandwich” assays specific for C1s-C1-and kallikrein-C1- inhibitor complexes respectively, we found that there was a modest increase in plasma levels of each complex after clinical cardiopulmonary bypass was completed. The increased concentration of enzyme-inhibitor complexes reverted to baseline within 24 hours. Since these complexes are cleared in vivo, we measured their formation by assaying their plasma levels during in vitro simulated extracorporeal circulation. Over a period of two hours, C1s-C1-inhibitor complexes rose from a baseline of 2 +/- 1 nmol/L to 21 +/- 2 nmol/L, and kallikrein-C1-inhibitor complexes rose from 2 +/- 1 nmol/L to 25 +/- 5 nmol/L. However, there was no evidence of either in vivo or in vitro plasmin-alpha 2-plasmin-inhibitor complex formation. These results indicate that the pathways of classical complement and contact activation, but probably not fibrinolysis, may be associated with neutrophil activation seen during clinical cardiopulmonary bypass.
A form of protease nexin I is expressed on the platelet surface during platelet activation
Authors: Gronke RS , Knauer DJ , Veeraraghavan S , Baker JB 
Published: October 2019

Abstract
A protein that has several similarities to protease nexin I, a fibroblast thrombin and urokinase inhibitor, has been detected on platelets (Gronke RS, Bergman BL, and Baker JB: J Biol Chem 262:3030, 1987). On incubation of platelets with 125I-thrombin, this platelet protein forms complexes with 125I-thrombin that are found both in the incubation medium and, as demonstrated here, associated with purified platelet plasma membranes. The present results indicate that interaction with the platelet surface may modulate the conformation and function of this platelet form of protease nexin I (PNIp) because: (a) an antibody against protease nexin I inhibited released PNIp, but not platelet-bound PNIp from complexing 125I-thrombin, and (b) whereas PNIp extracted from platelets bound both thrombin and urokinase, platelet- bound PNIp bound only thrombin. In experiments using several different platelet isolation methods, PNIp accounted for a large fraction of the rapid high affinity binding of 125I-thrombin to platelets. However, platelets isolated and maintained in the presence of metabolic inhibitors failed to take added thrombin into 125I-thrombin-PNIp complexes. This finding suggests that PNIp is released from inside platelets during activation, and thus does not function to transmit the primary activating signal that is generated by thrombin binding to platelets.
Partial protein S gene deletion in a family with hereditary thrombophilia
Authors: Ploos van Amstel HK , Huisman MV , Reitsma PH , Wouter ten Cate J , Bertina RM 
Published: October 2019

Abstract
Familial thrombophilia, the hereditary predisposition to venous thromboembolic disease, is associated with a protein S deficiency in approximately 8% of the cases. Laboratory measurements of total protein S antigen in affected families have indicated that heterozygotes, ie, individuals carrying both a normal and a defective protein S gene, are severely at risk of developing venous thrombosis at a young age. The recent isolation of protein S cDNA has enabled us to start a search for genetic defects in the protein S gene of heterozygotes. Using Southern blotting on probands of six unrelated families with hereditary protein S deficiency, one proband was found to have a grossly abnormal gene pattern. The abnormality appears to involve at least the deletion of the middle portion of the protein S coding sequence. Family analysis showed that the defect cosegregates with the protein S deficiency. These data agree with the notion that hereditary thrombophilia associated with protein S deficiency is indeed directly the result of a defect in the protein S gene.
Characterization of antithrombins produced by active site mutagenesis of human alpha 1-antitrypsin expressed in yeast
Authors: George PM , Pemberton P , Bathurst IC , Carrell RW , Gibson HL , Rosenberg S , Hallewell RA , Barr PJ 
Published: October 2019

Abstract
Both congenital and acquired antithrombin-III (AT-III) deficiencies are amenable to replacement therapy. We describe two antithrombins produced by recombinant DNA techniques from human alpha 1-antitrypsin (alpha 1AT) cDNA in yeast. Alteration of the alpha 1AT active site, replacing methionine 358 with arginine, results in a thrombin inhibition rate similar to that of heparin-activated AT-III. Alteration of two further residues, to give a five-residue sequence identical to AT-III, does not increase this rate further. Neither antithrombin is activated by heparin; both are unglycosylated and have shorter in vivo half-lives (t1/2) than human alpha 1AT. These antithrombins should be suitable for therapeutic replacement of AT-III in cases of congenital deficiency and in conditions associated with acquired AT-III deficiency, such as disseminated intravascular coagulation.
Colony forming T lymphocyte deficit in the development of feline retrovirus induced immunodeficiency syndrome
Authors: Quackenbush SL , Mullins JI , Hoover EA 
Published: October 2019

Abstract
The identification and molecular cloning of a feline leukemia virus (FeLV) isolate (FeLV-FAIDS) that consistently produces immunodeficiency syndrome has allowed prospective investigation of events that occur in the prodromal phase of disease. Using a T-lymphocyte colony forming assay (T-CFU-Ic) we have demonstrated that a drastic depletion of circulating T-CFU-Ic prefigures the development of clinical immunodeficiency disease in inoculated cats and correlates with the appearance and replication of the FeLV-FAIDS variant genome in serially collected bone marrow samples. During the same presymptomatic time period, no significant alterations in conventional mitogen-induced lymphocyte blastogenic responses or in circulating lymphocyte numbers were evident. Thus T-CFU-Ic assay but not conventional mitogen-driven blastogenesis identified animals destined to develop immunodeficiency syndrome. The correlation among T-CFU-Ic depletion, the replication of the lymphocytopathic FeLV-FAIDS variant genome in hematopoietic and lymphoid tissues, and the onset of clinical disease, infers that ablation of a colony-forming T lymphocyte progenitor subset is important in the early pathogenesis of feline retrovirus-induced immunodeficiency syndrome.
Identification of a cellular polypeptide that distinguishes between acute lymphoblastic leukemia in infants and in older children
Authors: Hanash SM , Kuick R , Strahler J , Richardson B , Reaman G , Stoolman L , Hanson C , Nichols D , Tueche HJ 
Published: October 2019

Abstract
We analyzed the polypeptide pattern of leukemic cells of infants and older children with acute lymphoblastic leukemia (ALL), using two- dimensional polyacrylamide gel electrophoresis (PAGE). Patterns were analyzed for the occurrence of a previously detected cytosolic polypeptide, designated L3. Quantitative analysis of L3 in 12 infants and 91 older children with non-T ALL indicated lack of expression of polypeptide L3 in leukemic cells of infants which, in most cases, expressed HLA-DR and CD19 and lacked CD10. Quantitative analysis of L3 in relation to cell surface marker expression revealed that L3 was limited in its occurrence to non-T ALL and was not coordinately expressed with any of the surface markers included in the study. Among patients in the HLA-DR-positive, CD19-positive, and CD10-negative group, different levels of polypeptide L3 were observed between infants and older children. These results indicate differences in leukemic cell constituents between infants and older children with ALL and an otherwise similar cell surface marker phenotype.
Bone marrow transplantation for children with myelodysplastic syndromes
Authors: Guinan EC , Tarbell NJ , Tantravahi R , Weinstein HJ 
Published: October 2019

Abstract
Therapeutic options for children with de novo or secondary myelodysplastic syndromes (MDSs) are limited. We report the outcome of eight pediatric patients (median age 12 years, range 3 to 19 years) with myelodysplasia who underwent allogeneic bone marrow transplantation between 1984 and 1987. Two of the eight children had developed secondary myelodysplasia after alkylating agent-based combination chemotherapy. Five patients had clonal chromosomal abnormalities, including four patients with monosomy 7. Seven of eight patients engrafted. Two of these seven subsequently died of complications of acute or chronic graft-v-host disease (GVHD), and a third patient died at 21 months of pulmonary fibrosis. None of the patients have had recurrence of disease. The four surviving patients remain in complete remission at a median follow-up of 19 months (range 10 to 44 months).
Inhibition of platelet-dependent thrombus formation by human activated protein C in a primate model
Authors: Gruber A , Griffin JH , Harker LA , Hanson SR 
Published: October 2019

Abstract
The in vivo antithrombotic properties of human plasma activated protein C (APC), a natural anticoagulant enzyme, were investigated in a baboon model of thrombus formation on prosthetic vascular grafts. Infusion of 0.25 to 1.1 mg/kg/h purified, human, APC inhibited blood clotting, as measured by the activated partial thromboplastin time (APTT), and reduced vascular graft platelet deposition by 40% to 70%, as determined by the real-time scintillation camera imaging of 111In-labeled platelet deposition. APC infusion also preserved graft patency. Hemostatic plug formation remained normal, as measured by the template bleeding times. These results suggest that APC administration may produce immediate antithrombotic effects under arterial flow conditions.
von Willebrand factor biosynthesis and partitioning between constitutive and regulated pathways of secretion after thrombin stimulation
Authors: Mayadas T , Wagner DD , Simpson PJ 
Published: October 2019

Abstract
The major part of von Willebrand factor (vWf) synthesized in cultured endothelial cells is secreted constitutively without stimulation and consists of all multimeric forms of vWf. In contrast, stimulation with secretagogues such as thrombin results in the release of vWf from the storage pool, the Weibel-Palade bodies which contain only the largest, most biologically potent multimeric forms of vWf. We wished to determine whether the signal for release of vWf might also function as a signal for replenishment of the vWf by enhancing de novo biosynthesis and if replenishment of the vWf storage pool involved a diversion of newly synthesized vWf from the constitutive pathway to the regulated pathway. vWf mRNA and protein levels in unstimulated human umbilical vein endothelial cells were compared with cells that were briefly stimulated with 1 U/mL thrombin for 15 minutes and then incubated without thrombin for periods up to 72 hours. A comparison was also made between unstimulated cells and cells continuously exposed to thrombin for up to 48 hours. Thrombin stimulation, brief or continuous, had no significant effect on subsequent biosynthesis of vWf protein or vWf- specific mRNA. Since thrombin releases vWf only from the storage pool, we examined the possibility of diversion of newly synthesized vWf from the constitutive pathway to the regulated pathway. Cells were pulse- labeled, incubated for 15 minutes with and without thrombin, chased for various periods in unlabeled media, and briefly restimulated with thrombin. No significant redistribution of vWf between the two pathways was observed as a result of thrombin stimulation for the time periods tested.
Two novel point mutations correlate with an altered developmental expression of blood coagulation factor IX (hemophilia B Leyden phenotype)
Authors: Reitsma PH , Mandalaki T , Kasper CK , Bertina RM , Briet E 
Published: October 2019

Abstract
Hemophilia B Leyden is characterized by low levels of factor IX antigen and activity before the age of 15 years, whereas after puberty factor IX levels rise at a rate of about 5% per year. Two distinct point mutations (deletion of A, A----G) were identified at position +13 of the factor IX gene of a Greek and an American patient with hemophilia B Leyden. The nucleotide changes have occurred 32 basepairs downstream of a previously reported point mutation in a Dutch kindred with the same hemophilic phenotype. The results point to the importance of sequences surrounding the putative start site for the constitutive expression of the factor IX gene and to the possible significance of an imperfect direct repeat of DNA.
Myelomonocytic antigen positive multiple myeloma
Authors: Grogan TM , Durie BG , Spier CM , Richter L , Vela E 
Published: October 2019

Abstract
In a four year span, between 1983 and 1987, 215 bone marrow and cell culture samples from 125 myeloma patients were immunotyped and coexpression of myelomonocytic and plasma cell antigens occurred in 16 (13%). We employed both immunohistochemical and flow cytometry methods including coplots and double labelling. Three types of myeloma cases were found: (1) those with isolated myeloid antigen coexpression, usually Leu M1 or esterase (BE, CE) positive (11 cases); (2) those with multiple myeloid antigens (Leu M1, M3, M5, MY7, BE, CE) (four cases); and (3) one case beginning as 1 and ending as 2. Isolated myeloid antigen expression was generally associated with typical features of myeloma with survival close to the anticipated median (33 months), while multiple myeloid antigen expression was associated with more aggressive disease and shorter survival duration (median survival 16 months). The latter subgroup also had other poor prognostic factors including high labelling index and common acute lymphoblastic leukemia antigen (CALLA) positivity. Other features found overall were frequent abnormal karyotypes (seven of 12 abnormal) and coexpressed IgA (eight of 16); all IgA+ cases also coexpressed Leu M1. We conclude that there is an unusual and unexpected predilection for coexpression of myelomonocytic antigens in myeloma cells. The reasons are not immediately obvious. Whether the coexpression indicates that myeloma cells truly have latent multilineage potential or just aberrantly coexpress other hematopoietic antigens as a manifestation of malignancy remains to be explained. However, a cell line established from the bone marrow of one patient is a valuable scientific tool allowing detailed analysis of these questions.
Basophils (Bsp-1+) derive from the leukemic clone in human myeloid leukemias involving the chromosome breakpoint 9q34
Authors: Bodger MP , Morris CM , Kennedy MA , Bowen JA , Hilton JM , Fitzgerald PH 
Published: October 2019

Abstract
The monoclonal antibody (MoAb) Bsp-1 was used to purify basophilic cells from leukemic blood of five patients with Philadelphia chromosome (Ph′) positive chronic myeloid leukemia (CML) and two patients with acute myeloid leukemia (AML) characterized by the chromosomal translocation t(6;9)(p23;q34). When cultured, Bsp-1 positive cells from all CML and AML patients showed the same clonal karyotype changes observed in diagnostic buffy coat preparations, indicating that the basophilic cells were of leukemic origin. In contrast, T lymphocytes from four of five CML patients cultured in the presence of interleukin- 2 (IL-2) showed a normal karyotype and were therefore not derived from the leukemic clone. Bsp-1 staining correlated with toluidine blue- positive basophils in chronic phase CML and with toluidine blue- negative blast cells expressing an immature myeloid phenotype in blast crisis CML and AML. Chromosome in situ hybridization showed that the ABL oncogene was translocated from chromosome 9 to chromosome 22 in the CML patients but remained on chromosome 9 in the AML patients. These results indicate that the breakpoint at 9q34 in CML is 5′ of ABL, whereas the breakpoint at 9q34 in AML is 3′ of ABL. Field inversion gel electrophoresis showed that the 9q34 breakpoint was not within 200 kb 3′ of ABL in one of the AML patients, nor was there any rearrangement of the PIM oncogene locus at 6p21.
A novel translocation, t(2;5)(p23;q35), in childhood phagocytic large T- cell lymphoma mimicking malignant histiocytosis
Authors: Kaneko Y , Frizzera G , Edamura S , Maseki N , Sakurai M , Komada Y , Sakurai M , Tanaka H , Sasaki M , Suchi T 
Published: October 2019

Abstract
We report a novel chromosome translocation--t(2;5)(p23;q35) or its variant, t(2;5;13)(p23;q35;q12)--in 3 patients with peripheral T-cell lymphoma. All 3 were female children who had peripheral lymphadenopathy without organomegaly and underwent complete remission with or without chemotherapy. Their tumors were characterized histologically by predominant large cells, at times showing phagocytosis, and immunologically by peripheral T-cell phenotype and expression of Ki-1 antigen and epithelial membrane antigen (EMA). Since the same translocation has been reported in the literature in 4 patients with malignant histiocytosis (MH), and our patients had histologic features suggestive of that disease, it is likely that many tumors previously interpreted as MH are actually phagocytic large T-cell lymphoma carrying this translocation.
Monocyte long-term cultivation on microvascular endothelial cell monolayers: morphologic and phenotypic characterization and comparison with monocytes cultured on tissue culture plastic
Authors: Schumann RR , van der Bosch J , Ruller S , Ernst M , Schlaak M 
Published: October 2019

Abstract
Human monocytes were cultured on monolayers of a newly established microvascular endothelial cell strain. As compared to monocytes cultured on plastic, these endothelium-“derived” monocytes (EDM) showed distinct morphology, higher motility, and different antigen-expression pattern for several surface markers, as detected by cytofluorimetry. The MO-1- and the Leu-M1-marker were maintained on EDMs while they were lost on plastic-cultured cells. The MAX 1–26-termed markers failed to increase on EDMs, in contrast to plastic-cultured monocytes. For seven additional markers, expression after two weeks in vitro was higher on EDMs than on plastic-cultured monocytes. Functionally EDMs showed typical monocyte/macrophage behavior and were easily removable from the culture system for further experimentation. Our data suggest that monocytes cultured on microvascular endothelial cells are maintained for several weeks in a more physiologic state than monocytes cultured on plastic.
Identical nucleotide sequences of the 3'A gamma globin gene enhancer elements from four different chromosomes
Authors: Han IS , Huang HJ , Zeng YT , Lanclos KD , Huisman TH 
Published: October 2019

Abstract
We have determined the nucleotide sequence of the 2,360-bp long EcoRI fragment from four chromosomes; this fragment is located 3′ to the A gamma globin gene and is considered to contain the enhancer element identified by Bodine and Ley. The chromosomes were from an Arabian sickle cell anemia patient with high Hb F and a homozygosity for haplotype No 31 and from a black sickle cell anemia patient with low Hb F and a homozygosity for haplotype No 19. A third chromosome carried the determinant for a nondeletional hereditary persistence of fetal hemoglobin seen in a Chinese subject, and the fourth was a normal chromosome from a Yugoslavian subject. Twenty-one differences were observed when a comparison was made with the published sequence; no differences were seen between the sequences of the four different samples except for an additional mutation in the Chinese. These data make it unlikely that specific mutations within this sequence are associated with increases in G gamma and A gamma production.
Evidence that large granular lymphocytes from B-CLL patients with hypogammaglobulinemia down-regulate B-cell immunoglobulin synthesis [published erratum appears in Blood 1989 Jun;73(8):2232]
Authors: Kay NE , Perri RT 
Published: October 2019

Abstract
B-chronic lymphocytic leukemia (CLL) patients frequently suffer from moderate to severe hypogammaglobulinemia. This complication is a serious cause of morbidity and mortality in this disorder. There is recent evidence that natural killer (NK) cells modulate B-cell immunoglobin (Ig) synthesis/secretion. The authors therefore evaluated the circulating NK cells from B-CLL patients on their ability to regulate mitogen-induced B-cell Ig synthesis. Blood, NK cells (CD16+, CD3-) from three B-CLL patients with hypogammaglobulinemia were able to clearly down-regulate the pokeweed mitogen (PWM)-induced-B-cell Ig secretion. In contrast, CD16+, CD3- cells from age-sex-matched controls or B-CLL patients with normal Ig were either nonregulatory or enhanced mitogen-induced B-cell Ig secretion. An alternative explanation for hypogammaglobulinemia in B-CLL patients is the immunomodulation of B- cell Ig production/secretion by CD16+, CD3- blood cells.
Rare occurrence of N-ras point mutations in Philadelphia chromosome positive chronic myeloid leukemia
Authors: Collins SJ , Howard M , Andrews DF , Agura E , Radich J 
Published: October 2019

Abstract
Point mutations of the N-ras oncogene are relatively common in acute myelogenous leukemia (AML) cells, occurring in some 25% to 50% of patient samples. We used a technique involving the direct nucleotide sequencing of in vitro amplified N-ras genomic fragments to determine the frequency of N-ras point mutations in chronic myeloid leukemia (CML) cells at various stages of the disease. This approach will detect N-ras point mutations in a mixed population of cells if the mutation is present in 25% or more of the cells. We could not demonstrate any point mutation at N-ras codons 12,13 or 59–63 in any of the 44 CML cases analyzed, which included 21 blast crisis samples. In contrast with AML N-ras point mutations are exceedingly rare in CML.