bluuebunny/crossref_metadata_2025_split huggingface dataset:
C3a and C5a Stimulate Chemotaxis of Human Mast Cells
Authors: Hartmann Karin , Henz Beate M. , Krüger-Krasagakes Sabine , Köhl Jörg , Burger Reinhard , Guhl Sven , Haase Ingo , Lippert Undine , Zuberbier Torsten 
Published: October 2019

AbstractThe factors that control migration of mast cells to sites of inflammation and tissue repair remain largely undefined. Whereas several recent studies have described chemotactic factors that induce migration of murine mast cells, only stem cell factor (SCF ) is known to induce migration of human mast cells. We report here that the anaphylatoxins C3a and C5a are chemotactic factors for the human mast cell line HMC-1, human cord blood-derived mast cells (CBMC) and cutaneous mast cells in vitro. The presence of an extracellular matrix protein, laminin, was required for chemotaxis in response to complement peptides. Migration of mast cells towards C3a and C5a was dose-dependent, peaking at 1 μg/mL (100 nmol/L), and was inhibited by specific antibodies. Pretreatment with pertussis toxin inhibited the anaphylatoxin-mediated migration of HMC-1 cells, indicating that Gi proteins are involved in complement-activated signal transduction pathways in human mast cells. Both C3a and C5a also induced a rapid and transient mobilization of intracellular free calcium ([Ca2+]i ) in HMC-1 cells. Besides SCF, other chemotactic factors tested, such as interleukin-3, nerve growth factor, transforming growth factor β, RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β, failed to stimulate migration of human mast cells. In summary, these findings indicate that C3a and C5a serve as chemotaxins for human mast cells. Anaphylatoxin-mediated recruitment of mast cells might play an important role in hypersensitivity and inflammatory processes.
The Potential of Iron Chelators of the Pyridoxal Isonicotinoyl Hydrazone Class as Effective Antiproliferative Agents II: The Mechanism of Action of Ligands Derived From Salicylaldehyde Benzoyl Hydrazone and 2-Hydroxy-1-Naphthylaldehyde Benzoyl Hydrazone
Authors: Richardson D.R. , Milnes K. 
Published: October 2019

AbstractWe have recently screened 36 analogues of the lipophilic iron (Fe) chelator, pyridoxal isonicotinoyl hydrazone (PIH), for their antiproliferative effect (Richardson et al, Blood 86:4295, 1995). Of these compounds, 1 chelator derived from salicylaldehyde benzoyl hydrazone (206) and 4 ligands derived from 2-hydroxy-1-naphthylaldehyde benzoyl hydrazone (308, 309, 311, and 315) showed pronounced antiproliferative activity, being far more effective than desferrioxamine (DFO). The present study was designed to investigate in detail the mechanism of action of these PIH analogues in a variety of neoplastic cell lines. This investigation showed that the analogues were far more active than DFO at inhibiting cellular proliferation and 3H-thymidine, 3H-leucine, and 3H-uridine incorporation. Additional experiments showed that, in contrast to DFO, the 5 analogues were potent at preventing 59Fe uptake from transferrin (Tf ) and increasing 59Fe release from cells at concentrations as low as 10 μmol/L. Examination of the distribution of 59Fe in neoplastic cells using native polyacrylamide gel electrophoresis (PAGE)/59Fe-autoradiography showed that most of the 59Fe taken up from Tf was incorporated into ferritin, although 3 other previously unrecognized components (bands A, B, and C) were also identified. Band C comigrated with 59Fe-citrate and was chelated on incubation of neuroblastoma cells with DFO, PIH, or the PIH analogues, with this compartment being the main intracellular target of these ligands. Further work showed that the effects of the chelators at inducing characteristics consistent with apoptosis or necrosis were cell line-specific, and while DFO increased the percentage of cells in the Go/G1 phases in all cell types, the effect of analogue 311 on the cell cycle was variable depending on the cell line. This study provides further evidence for the potential use of these Fe chelators as anticancer agents.
CD6-Depleted Allogeneic Bone Marrow Transplantation for Acute Leukemia in First Complete Remission
Authors: Soiffer Robert J. , Fairclough Diane , Robertson Michael , Alyea Edwin , Anderson Kenneth , Freedman Arnold , Bartlett-Pandite Lini , Fisher David , Schlossman Robert L. , Stone Richard , Murray Christine , Freeman Andrea , Marcus Karen , Mauch Peter , Nadler Lee , Ritz Jerome 
Published: October 2019

AbstractThe appropriate timing of bone marrow transplantation (BMT) for adults with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) is controversial. Although allogeneic transplantation results in a lower risk of disease recurrence than intensive chemotherapy alone, overall outcome following BMT may not be improved due to the higher incidence of therapy-related fatal complications, frequently as a result of the development of graft-versus-host disease (GVHD). Selective T-cell depletion of donor marrow can reduce the incidence of GVHD and thereby limit transplant-related toxicity. Herein we report the risk of GVHD, incidence of transplant related mortality (TRM), likelihood of disease relapse, and overall survival in adult patients undergoing BMT with CD6 depleted allogeneic marrow for acute leukemia in first remission. Forty-one consecutive allogeneic transplants were performed on patients with acute leukemia and high-risk features (28 AML, 13 ALL) using T12 monoclonal antibody and complement to remove CD6+ T cells from donor marrow. No pre- or posttransplant immune suppressive medications for GVHD prophylaxis were administered. The actuarial estimated risk of grade 2 to 4 acute GVHD was 15% in patients receiving HLA identical grafts. Chronic GVHD developed in five patients. The estimated risk of TRM for patients in first complete remission was 5% at Day +100 and 16% at 2 years. Fatalities attributable to infection with cytomegalovirus or Epstein-Barr virus occurred in only three patients. Estimated probabilities of relapse, overall survival, and event-free survival at 4 years were 25%, 71%, and 63%, respectively. No significant differences in GVHD, TRM, relapse rate, or survival was observed for patients with AML compared with those with ALL. Allogeneic transplantation with CD6 depleted bone marrow is effective in consolidating remissions of high-risk patients with acute leukemia in first remission without excessive toxicity.
Potent Antithrombin Activity and Delayed Clearance From the Circulation Characterize Recombinant Hirudin Genetically Fused to Albumin
Authors: Syed Summer , Schuyler Philip D. , Kulczycky Myron , Sheffield William P. 
Published: October 2019

AbstractIn this study we sought to extend the plasma half-life while maintaining the potent antithrombin activity of hirudin. We hypothesized that gene fusion of hirudin to albumin would result in the expression of a slowly cleared hirudin molecule. A hirudin variant 3 (HV3) cDNA was obtained by gene synthesis, while a 1,996-bp full-length rabbit serum albumin (RSA) cDNA was selected from a rabbit liver cDNA library. Expression of the former in COS-1 cells conferred antithrombin activity on media conditioned by the cells, while expression of the latter resulted in the secretion of a 67-kD protein that reacted with mono-specific anti-RSA antibodies. Having shown independent expression of the two proteins, we next expressed two fusion proteins: HV3 linked via its C-terminus to albumin (HLA), and HV3 linked via its N-terminus to albumin (ALH). The former, but not the latter, inhibited both the amidolytic and fibrinogenolytic activities of thrombin. HLA also retained the dye-binding characteristics of RSA, as judged by Affi-Gel Blue chromatography. Highly similar concentrations of either commercial HV1 (40 nmol/L) or HLA (30 nmol/L) were required to halve the initial rate of thrombin reaction with chromogenic substrate S2238, suggesting the retention of high-affinity inhibition of thrombin by the fusion protein. An His-tagged form of HLA was purified by Ni2+-chelate affinity and heparin-Sepharose chromatography. The purified, radioiodinated protein was injected into rabbits, and demonstrated a catabolic half-life of 4.60 ± 0.16 days. This represents an extension of hirudin half-life in vivo of greater than two orders of magnitude; gel analysis of HLA(H)6 recovered from rabbits showed that it circulated in intact form. Our results provide a rationale for future testing of the biological effects of HLA, and support our initial hypothesis.
Mechanism of Tissue Factor Activation on HL-60 Cells
Authors: Bach Ronald R. , Moldow Charles F. 
Published: October 2019

AbstractTissue factor (TF ) procoagulant activity (PCA) on the surface of intact HL-60 cells is encrypted. This latent TF PCA was activated by exposing the cells to ionomycin, a calcium ionophore. Within seconds an increase in TF PCA of greater than 100-fold was observed. The ionomycin effect was blocked by pretreating the cells with calmidazolium, a calmodulin inhibitor. Changes in TF structure and function, coincident with the ionophore-induced increase in TF PCA, were identified. TF-factor VIIa complexes formed on both untreated and ionophore-treated cells, but pseudosubstrate inhibitors only bound to TF-factor VIIa on the ionophore-treated cells. TF PCA was inhibited by reacting cells with sulfosuccinimidyl-6-(biotinamido)hexanoate, and the rate of this reaction increased twofold after cells were exposed to ionomycin. When proteins on the surface of untreated cells, expressing minimal TF PCA, were cross-linked with 3-3′-dithiobis(sulfosuccinimidylpropionate), cross-linked TF dimers were produced. TF cross-linking was prevented by first treating the cells with ionomycin. These results suggest a mechanism for the ionomycin-induced increase in TF PCA. TF activation appears to be a calmodulin-dependent process, which exposes an essential macromolecular substrate binding site on TF, possibly as the result of a change in TF quaternary structure.
Ongoing Ig Gene Hypermutation in Salivary Gland Mucosa-Associated Lymphoid Tissue-Type Lymphomas
Authors: Bahler David W. , Miklos John A. , Swerdlow Steven H. 
Published: October 2019

AbstractSalivary gland mucosa-associated lymphoid tissue (MALT) type lymphomas are typically indolent B-cell neoplasms that are often associated with Sjogren's syndrome. To better define the cell of origin and evaluate whether antigen receptor stimulation may be playing a role in tumor growth, the Ig heavy and light chain variable genes (VH and VL) expressed by five salivary gland MALT lymphomas were cloned and sequenced. Comparison to known germline sequences indicated that three of the lymphoma VH genes were derived from 51p1, a member of the VH1 family, while the other two used different VH gene segments from the VH3 family, 22-2B and HG19. All five of the VL genes belonged to the VkIII family, with three derived from Humkv325 and the other two from the Vg and Humkv328 genes. Numerous point mutations relative to the proposed germline genes were present in all of the lymphoma VH and VL genes. In addition, the VH and VL genes from each lymphoma showed intraclonal sequence heterogeneity indicative of ongoing somatic hypermutation. Because the process of Ig gene hypermutation is thought to occur at the germinal center stage of B-cell development, these findings suggest the MALT lymphoma cell of origin may be a germinal center B cell. Selection against mutations that result in replacement of amino acids suggested that Ig stimulation may be important for lymphoma growth. The possibility that antigen receptor stimulation may be involved in the growth of salivary gland MALT lymphomas is further suggested by the noted restricted use of VH and VL gene segments.
CD24, a Mucin-Type Glycoprotein, Is a Ligand for P-Selectin on Human Tumor Cells
Authors: Aigner Silke , Sthoeger Zev M. , Fogel Mina , Weber Erich , Zarn Jürg , Ruppert Michael , Zeller Yvonka , Vestweber Dietmar , Stahel Rolf , Sammar Marei , Altevogt Peter 
Published: October 2019

AbstractP-selectin (CD62P) is a Ca2+-dependent endogenous lectin that can be expressed by vascular endothelium and platelets. The major ligand for P-selectin on leukocytes is P-selectin glycoprotein ligand-1 (PSGL-1). P-selectin can also bind to carcinoma cells, but the nature of the ligand(s) on these cells is unknown. Here we investigated the P-selectin binding to a breast and a small cell lung carcinoma cell line that are negative for PSGL-1. We report that CD24, a mucin-type glycosylphosphatidylinositol-linked cell surface molecule on human neutrophils, pre B lymphocytes, and many tumors can promote binding to P-selectin. Latex beads coated with purified CD24 from the two carcinoma cell lines but also neutrophils could bind specifically to P-selectin-IgG. The binding was dependent on divalent cations and was abolished by treatment with O-sialoglycoprotein endopeptidase but not endoglycosidase F or sialidase. The beads were stained with a monoclonal antibody (MoAb) to CD57 (HNK-1 carbohydrate epitope) but did not react with MoAbs against the sialylLex/a epitope. The carcinoma cells and CD24-beads derived from these cells could bind to activated platelets or P-selectin transfected Chinese hamster ovary cells (P-CHO) in a P-selectin–dependent manner and this binding was blocked by soluble CD24. Transfection of human adenocarcinoma cells with CD24 enhanced the P-selectin–dependent binding to activated platelets. Treatment of the carcinoma cells or the CD24 transfectant with phosphatidylinositol-specific phospholipase C reduced CD24 expression and P-selectin–IgG binding concomitantly. These results establish a role of CD24 as a novel ligand for P-selectin on tumor cells. The CD24/P-selectin binding pathway could be important in the dissimination of tumor cells by facilitating the interaction with platelets or endothelial cells.
The Life Span of the Elliptocyte
Authors: MOTULSKY ARNO G. , SINGER KARL , CROSBY WILLIAM H. , SMITH VERNON 
Published: October 2019

Abstract
1. Red cells from three patients of different families with heteditary elliptocytosis were transfused and their survival followed by the Ashby technic of differential agglutination.
2. Life span of elliptocytes was normal in two cases.
3. A life span of forty-five days was obtained with the elliptocytes of a third patient who presented other evidence of hemolysis in the absence of anemia.
4. In two recipients with sickle cell anemia the survival of the transfused elliptocytes was also followed by counting the number of elliptocytes in sickle cell preparations. Rough agreement between the results of the Ashby and visual technics was obtained. There was no evidence of transformation from the elliptocytic into normal shape.
5. Elliptocytes from patients with hemolytic elliptocytosis were morphologically indistinguishable from elliptocytes with normal life span.
6. No hemoglobin abnormalities have yet been demonstrated in hereditary elliptocytosis. The basic defect responsible for hemolytic elliptocytosis remains unknown.
7. Symptomatic ovalocytosis occurs in many types of anemia, and must be differentiated from hereditary elliptocytosis.
8. The place of hereditary elliptocytosis in the classification of familial hemolytic diseases is discussed (table 4) and similarities to the other hereditary hemotic anemias are pointed out. It is shown that the red cell life span (and genetic) pattern of hereditary elliptocytosis resembles closely that found in thalassemia. As in thalassemia major, microspherocytosis and increased osmotic fragility due to red tell fragmentation may occur in cases of hemolytic elliptocytosis. Increased life span of these "fragmentation-spherocytes" after splenectomy may partially explain the success of the operation in hemolytic elliptocytosis.
9. No treatment is required for hereditary nonhemolytic elliptocytosis. Splenectomy is advised for "decompensated" hemolytic elliptocytosis.
Variation of the Hemoglobin Level with Age and Sex
Authors: HAWKINS W. W. , SPECK EIRLYS , LEONARD VERNA G. 
Published: October 2019

Abstract
During the winter and spring of 1952-53 a survey of hemoglobin values was made in Halifax among 1308 male subjects 6 to 98 years of age, and 1424 female subjects 6 to 94 years of age.
Among children 6 to 14 years old the values increased from about 13 to about 14 Gm. per 100 ml. of blood, and there were essentially no differences between the sexes. The average value for both the boys and the girls was 13.5 Gm.
In girls between 14 and 20 years of age the hemoglobin values decreased slightly, reaching about 13 Gm. per 100 ml. In boys of corresponding ages there was an increase to about 15 Gm. In both sexes these values were attained at about 20 years of age, and remained characteristic of the third decade of life. They were essentially the lowest and the highest shown respectively by the female and the male subjects of any age group.
Hemoglobin values in men between 20 and 60 years of age were typically 14.5 to 15 Gm. per 100 ml., the higher values tending to occur among the younger men. After the fifth decade there were progressive and marked decreases to an average of 12.4 in men between 80 and 90 years of age.
In women from 20 years of age onward the average hemoglobin values remained near 13 Gm. per 100 ml.
Some Immunohematologic Results of Large Transfusions of Group O Blood in Recipients of Other Blood Groups
Authors: CROSBY WILLIAM H. , AKEROYD JOSEPH H. 
Published: October 2019

Abstract
1. Following large transfusions of low titer group O blood into patients of group A, B, and AB it was not possible to demonstrate foreign isohemolysins or incomplete antibodies in the serum of recipients. Cold isoagglutinins were frequently demonstrated immediately after the transfusion, but they usually disappeared rapidly. Its several patients the titer of foreign anti-A isoagglutinin was quite high and the antibody persisted in the circulation for several days. It was suggested that the persistence of these agglutinins may have been possible because there was a relatively small amount of A substance in the body of the recipient. Where the transfused isoagglutinins persisted the patients were found to be nonsecretors or weak secretors of A substance in the saliva.
2. In most of these patients there was evidence of a selective destruction of recipient red cells after the transfusion of O blood. This was probably due to the activity of transfused isoantibodies in the plasma of the O blood. This hemolytic activity was observed where it was not possible to demonstrate the presence of foreign isoantibodies. It is suggested that there may exist forms of antibody that cannot be demonstrated by laboratory methods. These antibodies manifest themselves only by causing destruction of red cells in vivo.
3. Clinically the hemolytic disease on the basis of such transfused isoantibodies while causing destruction of native red cells did not threaten the lives or impede the recovery of these patients. No reactions were encountered and none were heard of in Korea that might have been ascribed to a dangerous universal donor. The partition of group O blood into high titer and low titer on the basis of dilution of 1:200 to 1:256 has proved in practice to be safe.
4. The persistence of foreign antibodies after a large transfusion of group O blood may make it impossible to cross match the patient’s blood with blood of his hereditary group. Severe transfusion reactions have occurred when group specific blood has been given following large transfusions of group O blood. It has been recommended that after a large transfusion of group O blood has been given, group specific blood should not be used for at least two weeks.
Changes in the Phagocytic Activity of Polymorphonuclear Leukocytes following Total Body X-Irradiation in the Rat
Authors: WILKINSON M. 
Published: October 2019

Abstract
The phagocytic activity of polymorphonuclear leukocytes from irradiated rats was studied over a period of thirteen days following 550 r total body x-irradiation.
Leukocytes from irradiated rats showed slightly increased phagocytosis of plague bacilli during the first six days after irradiation, but on statistical analysis this increase proved to be insignificant.
From the seventh to the thirteenth day after irradiation, these cells showed a markedly reduced capacity to phagocytose plague bacilli.
Phagocytic studies on suspensions of normal cells in plasma from irradiated animals and on cells from irradiated animals in normal plasma showed that the deficient phagocytosis during the second week following irradiation was due mainly to a defect in the polymorphonuclear leukocytes themselves, though the fact that the addition of normal plasma to cells from irradiated animals did increase their phagocytic capacity by a small but definite degree suggests that there is also a defect in the plasma of irradiated animals.
Mitogenic Responses Mediated Through the Proteinase-Activated Receptor-2 Are Induced by Expressed Forms of Mast Cell α- or β-Tryptases
Authors: Mirza Humayun , Schmidt Valentina A. , Derian Claudia K. , Jesty Jolyon , Bahou Wadie F. 
Published: October 2019

AbstractThe proteinase-activated receptor-2 (PAR-2) is the second member of a putative larger class of proteolytically activated receptors that mediate cell activation events by receptor cleavage or synthetic peptidomimetics corresponding to the newly generated N-terminus. To further study the previously identified mitogenic effects of PAR-2, we used the interleukin-3 (IL-3)–dependent murine lymphoid cell line, BaF3, for generation of stable cell lines expressing PAR-2 (BaF3/PAR-2) or the noncleavable PAR-2 mutant PAR-2Arg36 → Ala36. Only BaF3 cells expressing either wild-type or mutated receptor exhibited mitogenic responses when grown in IL-3–deficient media supplemented with PAR-2 activating peptide (SLIGRL, PAR39-44). This effect was dose dependent with an EC50 of ∼80 μmol/L, sustained at 24, 48, and 72 hours, and was also demonstrable using thrombin receptor peptide TR42-47. Because tryptase shares ∼70% homology with trypsin (previously shown to activate PAR-2), we studied recombinantly expressed forms of α- and β-tryptases as candidate protease agonists for PAR-2. Hydrolytic activity of the chromogenic substrate tosyl-glycyl-prolyl-argly-4-nitroanilide acetate was present as a sharp peak at Mr ∼130, confirming the presence of secretable and functionally active homotetrameric α- and β-tryptases in transfected COS-1 cells. Dose-dependent proliferative responses were evident using either secreted form of tryptase with maximal responses seen at ∼3 pmol/L (0.1 U/L). Receptor proteolysis was necessary and sufficient for mitogenesis because active site-blocked tryptase failed to induce this response, and proliferative responses were abrogated in BaF3 cells expressing PAR-2Arg36 → Ala36. These results specifically identify both forms of mast cell tryptases as serine protease agonists for PAR-2 and have implications for elucidating molecular mechanisms regulating cellular activation events mediated by proteases generated during inflammatory, fibrinolytic, or hemostatic-regulated pathways.