bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Auto-Antibodies on Bone Marrow Cells in the Patients with Systemic Lupus Erythematosus.
Authors: Fu Rong , Deng Jizi , Yuan Shang , Gong Lu , Sun Jun , Shao Zonghong 
Published: October 2019

Abstract
Objective:To explore the pathogenesis of cytopenia in the patients with systemic lupus erythematosus (SLE), the auto-antibodies on bone marrow mononuclear cells (BMMBC) in the patients with SLE were determined.
Methods:Twenty one patients with SLE and ten healthy controls were enrolled in this study. BMMNC Coombs test was used to determine the aotoantibodies. The correlation between the types of auto-antibodies on BMMNC, the types of serum auto-antibodies and the counts of blood cells in the patients with SLE were also investigated.
Results:Positive results of BMMBC-Coombs test were seen in 12 patients with SLE (57.1%), among them, 10 with hemocytopenia (58.82%), and 2 without hemocytopenia (50%). The positive rate of BMMNC Coombs test was higher in the patients with SLE than that in healthy controls, and was higher in SLE patients with hemocytopenia than that in healthy controls. There were no significant difference of BMMNC-Coombs positive rate between the SLE patients without hemocytopenia and healthy controls, and there were also no significant differences between the SLE patients without hemocytopenia and SLE patients with hemocytopenia. In the 12 SLE patients with positive BMMBC-Coombs tests, IgM auto-antibody accounted for 75.0%, and C3 50.0%, IgG 8.33%, IgG+IgM 8.33%, C3+IgM 16.67%, IgG+IgM+C3 16.67%. In the SLE patients without hemocytopenia, IgG+IgM accounted for 8.33%, C3 8.33%, but IgA autoantibody were not seen in any case. There was a significant positive correlation between the auto-antibodies on BMMNC and peripheral anti-SSA, but there was no significant correlation between the results of BMMBC Coombs tests and peripheral blood cell counts.
Conclusion:There were auto-antibodies on BMMNC in the patients with SLE. The hemocytopenia in the patients with SLE maybe resulted from the destructions of bone marrow hematopoietic cells by the autoantibodies.
Analyses of Prognostic Factors for Survival in East African Patients with AIDS-Related Non-Hodgkin’s Lymphoma (AR-NHL) Treated with Dose Modified Oral Chemotherapy.
Authors: Subbiah Vivek , Mwanda O.W. , Orem Jackson , Fu P. , Banura C. , Kakembo J. , Ness A. , Johnson J. , Bako J. , Katongole-Mbidde E. , Remick Scot 
Published: October 2019

Abstract
Background: The results of our feasibility trial of dose-modified oral chemotherapy for AR-NHL in East Africa are encouraging to frame / sustain alternative non-myelotoxic and pragmatic therapeutic strategies suitable for evaluation in the resource-constrained setting. To define a group of patients who may have a better outcome univariate and multivariate analyses of prognostic factors were performed.
Methods: Forty nine patients with AR-NHL received dose-modified oral chemotherapy. The following baseline variables were included as potential predictors of survival: age (≤60 vs. >60 yrs.); sex; stage (≤2 vs. >2); ECOG performance status (0/1 vs. 2/3); LDH (≤270 vs. >270 U/L); extranodal sites of involvement (≤1 vs. >1 site); prior thrush; prior AIDS [wasting or opportunistic infection(s)]; A/B symptoms; m-CHOP salvage chemotherapy (n=10); antiretroviral (ARV) therapy (n=18); and baseline albumin. International Prognostic Index (IPI) excluding LDH since not available for all patients (N Engl J Med1993;329:987) and ACTG 142 prognostic variables (J Clin Oncol1998;16:3601) were also analyzed.
Results: By univariate analysis, only LDH (p=0.0013) was significantly related to overall survival (OS). Hypoalbuminemia and LDH affected event free survival (EFS). By multiple regression, LDH and IPI were significantly related to OS (p=0.012). Similarly, the hazard ratio of patients without and with ARV therapy was 17.45 (p=0.0007); and the hazard ratio of patients IPI 2 comparing to those with IPI 0 was 6.62 (p = 0.028). LDH, ARV status and IPI were significantly related to EFS. The complete response rate was 56% and objective response rate was 77%. Median OS and EFS were 12.3 and 7.9 months respectively.
Conclusions: For patients with AR-NHL in East Africa and treated with dose-modified oral chemotherapy IPI and not ACTG 142 prognostic covariates best predicts survival. Albumin (perhaps substituting for LDH since more readily tested in East Africa) and ARV status provide further independent prognostic information. These factors may further guide therapeutic options in future trials in resource poor settings.
Identification and Characterization of a Novel Lymphotoxin Alpha Mutant Recovered from an ENU Mutagenesis Screen.
Authors: Wang Hongsheng , Feng Jianxun , Qi Chenfeng , Morse Herbert 
Published: October 2019

Abstract
N-ethyl-N-nitrosourea (ENU)-induced mutagenesis in mice has been an important approach in identifying genes that are involved in immune regulation and diseases. We have characterized the features of a new mutant C57BL/6J strain, HLB382, derived from an ENU mutagenesis screen and identified initially as having hereditary leukocytosis. Grossly, the mutant mice had no peripheral or mesenteric lymph nodes or Peyer’s patches. Histological analysis showed that there were no marginal zone B cells or germinal centers. The development of T cells and myeloid cells was normal, as assessed by flow cytometry (FACS), the development of NK cells was impaired. Although this phenotype is strikingly similar to that of mice with genetically engineered knockouts of the Lta gene, we found that the numbers of peritoneal B1b cells was significantly increased, a feature not reported for the knockouts. Since FACS analyses did not detect LTA protein on splenic B cells, we sequenced cloned Lta genomic DNA from the mutant mice and identified a single base insertion that caused a frame shift and a premature stop codon, consistent with the lack of detectable LTa proteins in mutant mice. This new mutant strain on a clean C57BL/6 background provides a useful model to study the functions of LTa in the immune system development and in various disease conditions.
The Role of Calcium/Calmodulin-Dependent Protein Kinase Cascade on MIP-1α Gene Expression in ATL Cells.
Authors: Matsumoto Kensuke , Murao Koji , Imachi Hitomi , Nishiuchi Takamasa , Ohnishi Hiroaki , Ishida Toshihiko 
Published: October 2019

Abstract
Adult T-cell leukemia (ATL) is a mature CD4+ T-cell malignancy caused by infection with human T-lymphotrophic virus (HTLV-1) and is associated with a marked hypercalcemia on many patients. Recently, it is proposed that Macrophage inflammatory protein-1α (MIP-1α) is the clinical hallmark of hypercalcemia in ATL, but the regulation of MIP-1α secretion has not been clarified yet. In this study, we examined the effect of calcium on the MIP-1α secretion and cell proliferation of ATL cells, and also the role of the Ca2+/calmodulin (CaM)-dependent protein kinase (CaM-K) cascade in transcriptional activation of MIP-1α. The addition of calcium nitrate to the medium enhanced the secretion of MIP-1α by ATL cell lines (ATN, MT-2, OKM-2T) and the proliferation in a dose dependent manner. The maximum response of MIP-1α secretion was induced at 10.42mM calcium in OKM-2T cells. CaM-KK selective inhibitor STO-609 inhibited the calcium dependent secretion of MIP-1α and proliferation of ATL cell lines. We investigated the effects of CaM-KK/CaM-KIV signaling pathway on MIP-1α promoter activity in OKM-2T. The transfection of CaM-KIV stimulated the MIP-1α promoter activity and the upstream kinase, CaM-KK enhanced the stimulatory effect of CaM-KIV on its activity. Furthermore, mutation of the cAMP response element (CRE) within the MIP-1α promoter significantly reduced the effect of CaM-KIV and calcium, and it wasn’t less enhanced by the addition of calcium nitrate to the medium than the wild type.
Our studies have indicated that hypercalcemia enhances MIP-1α secretion and the cell growth in ATL cells, and these mechanisms require the CaM-KK/CaM-KIV cascade. These findings raise the possibility that the inhibitory of CaM-KK/CaM-KIV cascade may be of therapeutic value for ATL.
High Activity of Peripheral Blood γδ T Cells in Term and Preterm Neonates.
Authors: Haque Syeda F.Y. , Gibbons Deena L. , Hamilton Katherine , Carr Robert , Hayday Adrian C. 
Published: October 2019

Abstract
The peripheral blood white cell compartment is well characterised in adults but relatively little is known in neonates. T cell function has been reported to be very different between neonates and adults. This is significant because the newborn faces the most precipitous encounter with environmental challenges. To further understand the neonatal T cell compartment, we have focussed on γδ T cells which are known to make essential contributions to the immunoprotection of very young mice. We compared γδ cells and αβ T cells from human cord and neonatal blood from term and preterm babies, and compared them with adults. We investigated T cell cultures ex vivo and derived clones. Several findings were evident. First, we confirmed that fresh neonatal αβ cells and clones are profoundly deficient in IFNγ production. Second, we showed that this is not so pronounced for γδ cells and we note that IFNγ production was higher in preterm babies than in term neonates, perhaps reflective of stress in utero. Neonatal γδ clones also made adult quantities of GM-CSF and TRAIL. We note thirdly that neonatal γδ clones make IL-4 and IL-5 (Th2 cytokines) and the immunosuppressive cytokine IL-10, which is not produced at all by adult Vγ9+ clones. Fourth, these pleiotropic activities of human neonatal γδ clones appears to be determined by the type of T cell receptor expressed.
Vδ1-expressing clones have broad functional potentials whereas Vγ9-expressing clones polarise to either a Th1 or Th2 like profile. Fifth, particularly high Th1 cytokine production is observed in Vγ9-Vδ1 (DP) cells which are more common and therefore more easily cloned from neonatal versus adult blood. We conclude that the neonatal γδ cells are highly active and broader in their cytokine production than either their adult γδ cell or their neonatal αβ T cell counterparts. Thus, γδ cells should be better understood vis-à-vis perinatal vaccination regimens and the development of childhood allergies.
Functions of Glycosylation Cooled Rabbit Platelets In Vivo and In Vitro.
Authors: Chen Bao-An , Huang Cheng-Yin , Pei Xiao-Ping , Gao Chong , Ding Jia-Hua , Sun Yun-Yu , Wang Jun , Cheng Jiang , Shi Guang-Yao , Chen Ning-Na , Fei Fei 
Published: October 2019

Abstract
This study was aimed to investigate functions of glycosylation cooled rabbit platelets in vivo and in vitro and the method to store cold platelets with UDP-gal. We collected rabbit heart blood, prepared concentrated platelet suspensions in a normal way to which we added UDP-Gal, and then stored them for ten days in 4° refrigerator. Thereafter platelet counts, mean platelet volume, platelet distributing width, platelet aggregation function, the activity to urge coagulation including PF3aT and APCT and apoptosis were determine- d. Meanwhile, survival time in vivo was tested after cold-stored rabbit platelets labeled with Cr51 were transfused into rabbits. Rabbit ear bleeding time and percentage plate recovery(PPR) were determined 1 hour and 24 hour after they were transfused into rabbit thrombocytopenia model. Results show that there was not significant difference in PLT counts, MPV, PDW, PF3aT and APCT between UDP-Gal cold-stored platelet group and fresh platelet group(p>0.05). On the contrary, platelet counts decreased significantly, MPV, PDW jumped and PF3aT and APCT went down in cold control group compared to fresh platelet group(p<0.01). Apoptosis increase in UDP-Gal cold-stored platelet group compared with fresh platelet group(p<0.05), but was significantly lower than that in cold control group(p<0.01). Although PagT(inducing reagent: C-PG) decreased, it could still be above 50% of fresh platelets. Survival time in rabbit vivo was close between UDP-Gal cold-stored platelet group and fresh platelet group(p<0.05). Survival rate seventy-two hours after transfusion in fresh platelet group, UDP-Gal cold-stored platelet group and cold control group was 57.5%±7.2%,50.3%±6.3% and 0.1%±0.1% respectively. Rabbit ear bleeding time was significantly shortened after transfusion of galactosylation cooled rabbit platelet (p<0.01), In contrast, it had less change in cold control group(p>0.05). PPR was 66.1%±0.5%,47.8%±0.6%;60.9%±0.3%,41.6%±0.4%;47.7%±0.5%,9.4%±0.5% respectively in fresh platelet group, UDP-Gal cold-stored platelet group and cold control group. PPR after transfusion of galactosylation cooled rabbit platelet had no statistical difference compared with that of fresh platelet group(p>0.05), and they in both groups were much higher than that in cold control group(p<0.01).
Conclusion: Galactosylation can improve functions of cooled rabbit platelets in vivo and in vitro. and prolong the storage time of them.
Bruton’s Tyrosine Kinase Is Essential for Botrocetin/vWf-Induced Signaling and GPIb-Dependent Thrombus Formation In Vivo.
Authors: Liu Junling , Fitzgerald Malinda , Berndt Michael C. , Jackson Carl W. , Gartner T. Kent 
Published: October 2019

Abstract
Botrocetin (bt) facilitated binding of von Willebrand factor (vWf) to the platelet membrane glycoprotein (GP) Ib-IX-V complex on platelets in suspension initiates a signaling cascade that causes αIIbβ3 activation and platelet aggregation. Previous work has demonstrated that bt/vWf-mediated agglutination activates αIIbβ3 and elicits ATP secretion in a thromboxane A2 (TxA2)-dependent manner. The signaling that results in TxA2 production is initiated by Lyn, enhanced by Src and propagated through Syk, SLP-76, PI3K, PLCγ2 and PKC. Here, we demonstrate that the signaling elicited by GPIb-mediated agglutination that results in TxA2 production is dependent on Bruton’s tyrosine kinase (Btk). The results demonstrate that Btk is downstream of Lyn, Syk, SLP-76 and PI3K, upstream of ERK1/2, PLCγ2 and PKC, and greatly enhances Akt phosphorylation. The relationship(s), if any between ERK1/2, PLCγ2 and PKC were not elucidated. The requirement for Btk and TxA2 receptor function in GPIb-dependent arterial thrombosis was confirmed in vivo by characterizing blood flow in ferric chloride treated mouse carotid arteries. These results demonstrate that the Btk family kinase, Tec, cannot provide the function(s) missing because of the absence of normal Btk function, and that Btk is essential for both bt/vWf-mediated agglutination-induced TxA2 production and GPIb-dependent stable arterial thrombus formation in vivo. Finally, consistent with the TxA2 receptor requirement for stable arterial thrombus formation in vivo, aspirin (at the appropriate concentration) prevented GPIb-dependent stable thrombus formation in vivo on ferric chloride damaged arterial endothelium.
The Endocannabinoid 2-Arachidonoylglycerol Regulates Platelet Function.
Authors: Baldassarri Samantha , Bertoni Alessandra , Lova Paolo , Reineri Stefania , Sarasso Chiara , Zanfa Manuela , Sanna Elena , Maccarrone Mauro , Torti Mauro , Sinigaglia Fabiola 
Published: October 2019

Abstract
2-Arachidonoylglycerol (2-AG) is a naturally occurring monoglyceride that activates cannabinoid receptors and meets several key requisites of an endogenous cannabinoid substance. It is present in the brain and hematopoietic cells, including macrophages, lymphocytes and platelets. 2-AG is released from cells in a stimulus-dependent manner and is rapidly eliminated by uptake into cells and enzymatic hydrolysis in arachidonic acid and glycerol. 2-AG might exert a very fine control on platelet function either through mechanisms intertwining with the signal transduction pathways used by platelet agonists or through mechanisms modulating specific receptors. The aim of this study was to define the role of 2-AG in human platelets and characterize the mechanisms by which it performs its action. Platelets from healthy donors were isolated from plasma by differential centrifugations and gel-filtration on Sepharose 2B. The samples were incubated with 2-AG (10–100 μM) under constant stirring in the presence or absence of various inhibitors. Platelet aggregation was measured by Born technique. We have found that stimulation of human platelets with 2-AG induced irreversible aggregation, which was significantly enhanced by co-stimulation with ADP (1–10 μM). Furthermore, 2-AG-dependent platelet aggregation was completely inhibited by ADP scavengers, aspirin, and Rho kinase inhibitor, as well as by antagonists of the 2-AG receptor (CB2), of the ADP P2Y12 receptor, and of the thromboxane A2 receptor. We further investigated the role of endocannabinoids on calcium mobilization. Intracellular [Ca2+] was measured using FURA-2-loaded platelets prewarmed at 37°C under gentle stirring in a spectrofluorimeter. 2-AG induced rapid increase of cytosolic [Ca2+] in a dose-dependent manner. This effect was partially blocked by ADP scavengers and CB2 receptor antagonists. Furthermore, 2-AG-induced [Ca2+] mobilization was totally suppressed by aspirin or the thromboxane A2 receptor antagonist. These results suggest that 2-AG is able to trigger platelet activation, and that this action is partially mediated by CB2 receptor and ADP. Furthmore, 2-AG-dependent platelet activation is totally dependent on thromboxane A2 generation.
Platelet Proinflammatory and Hemostatic Function Is Differentially Regulated in Cystic Fibrosis.
Authors: Sturm Alexander , Hebestreit Helge , Grossmann Ralf 
Published: October 2019

Abstract
Introduction: Platelet function and mechanisms of platelet-leukocyte interactions have been investigated in several vascular und inflammatory disorders. In most studies, platelet activation and an increase of platelet-leukocyte-aggregates (PLA) could be observed. We investigated platelet function in clinically stable patients with cystic fibrosis (CF).
Methods: In addition to routine markers of inflammation (e. g. CRP, IgG, ESR) parameters of platelet function were measured in 54 clinically stable CF patients and 55 healthy controls (age range 3 to 41 years): The percentage of P-selectin (CD62P) and PAC-1 (activated integrin αIIbβ3) positive resting and activated platelets (in-vitro activation with the thrombin receptor activating peptide 6) and the number of PLA were determined by flow cytometry. The plasma markers of platelet activation soluble P-selectin (sCD62P) and soluble CD40 ligand (sCD40L) were measured by ELISA. Furthermore, 15 CF patients and 14 healthy controls were investigated to determine CD41a-expression (integrin αIIbβ3) on resting and activated platelets as well as leukocyte expression of P-selectin-glycoprotein ligand 1 (PSGL-1, receptor of CD62P) and integrin αMβ2.
Results: Chronic inflammation leads to a decrease of PAC-1-binding to resting and activated platelets. The effects were stronger in patients with higher markers of inflammation. CD41a expression was reduced on in-vitro-activated CF platelets. In contrast, proinflammatory platelet functions remained unchanged (CD62P-expression on resting and activated platelets) or increased (sCD62P, sCD40L, PLA). Leukocyte integrin αMβ2 expression was increased and PSGL-1 expression remained unchanged in CF.
Discussion: Platelet function in clinically stable patients with CF is differentially regulated: Chronic inflammation leads to an upregulation of platelet proinflammatory function. In the presence of several procoagulatory mechanisms in inflammation there is a compensatory loss of platelet hemostatic function, shown by the decreased activation and exocytosis of the platelet major integrin αIIbβ3.
Anti-Platelet Glycoprotein Antibodies in Thrombocytosis Are Frequently Detected and Are Associated with Platelet Activation and Thrombosis.
Authors: Bidot Carlos J. , Jy Wenche , Bidot Loreta , Horstman Lawrence L. , Fontana Vincezo , Gonzalez Marta , Dudkyewicz Pamela , Ahn Yeon S. 
Published: October 2019

Abstract
Introduction: Thrombosis is the major cause of morbidity and mortality in patients with thrombocytosis (TS) associated with myeloproliferative disorders (MPD), but predicting which patients are at risk has been challenging. We recently reported that antiphospholipid antibodies (APLA) and platelet activation are risk factors in TS [C Bidot et al; Hematology, 10:451, 2005]. To shed further light on the cause of platelet activation in TS, we here report on measuring anti-platelet antibodies in a group of these patients.
Material and Methods: Thirty-three TS patients, 15 with clinical thrombosis and 18 without, were evaluated using PAICA method of L. Macchi et al [Thromb Haemost76:1020,1996]. We assayed anti-platelet antibodies against 3 target antigens, GPIIb/IIIa (CD41b), GP Ib/IX (CD42b) and GP IV (Cd36) for IgG and IgM. We also measured platelet activation marker CD62P, and microparticles from platelets (PMP, defined by CD31+/CD42+) and endothelial cells (EMP, defined by CD31+/CD42−) by flow cytometry.
Results: At least one anti-platelet antibody was detected in 19/33 (57.5%) of TS patients. Considering first IgG in the19 who were anti-platelet antibodies positive, 14/19 (73.6%) were positive for CD36, 12/19 (63%) for CD41b and 8/19 (42.1%) for CD42b. For IgM in these 19 patients, incidences were 58.8% for CD41b, 38.8% for CD36 and 35% for CD42b. When we compared the anti-platelet antibody positive group with the negative group, we observed that activation marker CD62P was significantly higher in the former (p= 0.04), as were EMP levels (p= 0.02), but PMP levels were not different. Next, we compared results with incidence of thrombosis. None of the IgG results discriminated thrombosis from non-thrombosis. However, all three IgM results were significant in this regard: CD36 (p< 0.05), CD42b (p< 0.02), and most notably, CD41b (p< 0.0003).
Conclusions: These results show that anti-platelet antibodies of IgM class, especially anti-CD41b, are associated with platelet activation, endothelial activation, and clinical thrombosis in TS. These findings parallel our previous report on APLA in TS. We suggest that IgM-CD41b may activate platelets, predisposing to hypercoagulable state in this disorder.