KIRs Expression and Cytotoxic Activities of Cord Blood Natural Killer Cells Against Acute Lymphoblastic Leukemia with MLL Gene Rearrangement.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2803-2803
Author(s):  
Hiroko Honna ◽  
Kumiko Goi ◽  
Kinuko Hirose ◽  
Itaru Kuroda ◽  
Takeshi Inukai ◽  
...  

Abstract MLL-rearranged ALL is associated with an extremely poor prognosis despite intensive chemotherapy and hematopoietic stem cell transplantation (SCT). We have reported that MLL-rearranged ALL is resistant to death-inducing ligands TRAIL and FasL expressed on cytotoxic T lymphocytes, and therefore T-cell mediating graft-versus-leukemia (GVL) effect is not expected post allogeneic SCT. We recently demonstrated that MLL-rearranged ALL cells were effectively killed by allogeneic NK cells from adult peripheral blood (PB) in a perforin-dependent manner when KIR (killer cell Ig-like receptor) ligand incompatibility exists between ALL cells and NK cells. This KIR ligand incompatibility has been reported to possibly reduce the relapse rate of acute myeloid leukemia post SCT. To pursue the clinical implication in KIR ligand incompatible cord blood transplantation (CBT) for the treatment of MLL-rearranged ALL, we examined the KIRs expression on allogeneic NK cells from umbilical cord blood (CB) by flow cytometry and their in vitro cytotoxic activities against MLL-rearranged ALL cell lines by a standard Cr-release assay at an effector-to-target ratio of 20 to 40. The results were compared between NK cells from adult PB and CB, and between KIR ligand compatible and incompatible NK cells. NK cells from CB were enriched by negative selection and classified into 2 groups based on HLA-C alleles; C1/C1 type (n=5) both alleles belonging to group I (Cw1, Cw3 et. al.) and C1/C2 type (n=4) each of alleles belonging to group I and group II (Cw2, Cw4, et. al.). NK cells from adult PB were similarly classified into C1/C1 type (n=4) and C1/C2 type (n=5). All of the MLL-rearranged ALL cell lines established in our laboratory (n=10) were C1/C1 type, and two cell lines with MLL-ENL (KOPN1, KOCL50) were used as targets. K562 lacking HLA class I expression was used as a positive control target. Although there was no significant difference in the HLA-C group II receptor (KIR2DL1, CD158a) expression between CB- and adult PB-NK cells (17.8±6.3% vs. 26.5±15.2%), the HLA-C group I receptor (KIR2DL2/L3, CD158b) expression on CB-NK cells was significantly lower than on adult PB-NK cells (24.3±10.2% vs. 47.4±19.2%, p=0.009). The CD158b expression showed no difference between C1/C1 and C1/C2 types of CB-NK cells, but it expressed higher on C1/C1 type of adult PB-NK cells than on C1/C2 type (58.9±17.4% vs. 35.9±14.0%. p=0.047), suggesting that the CD158b expression on NK cells increases as getting older particularly in C1/C1 type individuals. In the cytotoxic assay, CB-NK cells irrespective of C1/C1 and C1/C2 types exhibited a lower cytotoxicity against K562 compared with adult PB-NK cells (42.0±19.2% vs. 63.6±9.5%, p=0.009). Of importance, although both C1/C1 and C1/C2 CB-NK cells showed a similar cytotoxicity against K562, C1/C2 CB-NK cells exhibited a significantly higher cytotoxicity against C1/C1 MLL-rearranged ALL cell lines than did C1/C1 CB-NK cells when assessed by a relative cytotoxicity to K562 (KOPN1, 0.84±0.19 vs. 0.47±0.13, p=0.028; KOCL-50, 0.87±0.27 vs. 0.40±0.14, p=0.028), suggesting that a loss of inhibitory signal to CD158a on NK cells from leukemia cells can specifically enhance their alloreactivity. Taken together, MLL-rearranged ALL cells are sensitive to killing by KIR ligand incompatible allogeneic CB-NK cells, and therefore the maximal GVL effect against this leukemia could be expected if the specific CB whose NK cells can exert their alloreactivity is selected for CBT.

Author(s):  
Mahir Tıraş ◽  
Emrah Can ◽  
Şahin Hamilçıkan

Objective This study aimed to assess whether cord blood carboxyhemoglobin (COHb) levels in jaundiced term neonates with and without a positive direct Coombs test (DCT) and in healthy controls could be used as a predictor of severe hyperbilirubinemia. The percentage of cord blood COHb should be higher among neonates with Coombs-positive ABO hemolytic disease than among those with Coombs-negative ABO incompatibility and higher than that of ABO-compatible control neonates. Study Design This cross-sectional descriptive study of 198 term neonates comprised three subgroups: group I featured 68 DCT-positive ABO-incompatible neonates (ABO + DCT), group II featured 60 DCT-negative ABO-incompatible neonates with hyperbilirubinemia (ABO–DCT), and group III featured 70 healthy controls. COHb was determined by an OSM3 hemoximeter. Results Group I differed from groups II and III for cord blood bilirubin, cord blood hemoglobin, and cord blood hematocrit. Groups I and II had higher mean total serum bilirubin (TSB) levels than group III, while there was no difference in the mean TSB levels between groups I and II. There was no significant difference between the COHb group means for groups I, II, and III (p = 0.98). The area under the receiver operating characteristic curve calculated for group I/group III and group II/group III were found to be 0.62 and 0.54, respectively. Conclusion COHb levels did not prove to be superior to the DCT for predicting the risk of developing severe hyperbilirubinemia in term neonates. Key Points


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5681-5681
Author(s):  
Mei Xie ◽  
Weihong Chen ◽  
Qiaoxia Zhang ◽  
Xin Du

Abstract Objective: To study the feasibility of using cyclophosphamide alone without total body irradiation (TBI) as conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and establish a graft-versus-host disease (GVHD) mouse model. Methods: Single cell suspension of spleen and bone marrow were prepared from donor C57/BL/6 mice (B6 mice) . The recipient B6D2F1 mice (F1 mice) were signed into 4 groups with 12 mice per each group. Groups I~III mice were conditioned with peritoneal injection of cyclophosphamide (300 mg/m 2/d) on day -5, -4 and -3 of allo-HSCT, and group IV mice were used as control with saline injection. On day 0, group I mice were injected through tail vein with a mixture of 2×107 spleen cells, 5×106 bone marrow cells and 1×104 P815 cells; group II with 5×106 bone marrow cells and 1×104 P815 cells; group III with 1×104 P815 cells and group IV with RPMI1640 culture medium. The blood leukocyte counts were analyzed, GVHD score and the pathological leukemia infiltration of skin, liver and colon were evaluated and compared on day 30 after allo-HSCT. Results: (1) The GVHD scores of group I mice were 2 to 4 on day 14 post allo-HSCT, and mice started to die on day 15, eight (8) mice survived and the GVHD scores of them were 1 to 6 with a survival rate of 66.7% on day 30. Group II mice began to die on day 6 and only one survived on day 30 with a survival rate of 8.3%. All of group III mice died on day 18. Group IV mice survived (Figure 1). (2) The leukocyte counts in group I and group II were significantly increased on day 7 post allo-HSCT(p<0.05). There was also a significant difference in total leukocyte counts between groups I/II and group IV (p<0.05). The leukocyte counts in mice of groups I~III were significantly decreased, and there were a significant difference between group I and groups II/III/IV respectively (p<0.05) on day 14 post allo-HSCT. On day 21 after allo-HSCT, the leukocyte count of Group I and II mice were ≥1×109/L, which means that allo-HSCT were successful. The leukocyte counts in group I mice were again increased on day 28 post allo-HSCT. There was no significant difference between Group I and Group IV (p>0.05). (3) Pathological observation: The cell atrophy and necrosis in the hepatic portal area and slight infiltration of the leukemia cells in central vein were observed in group I recipient mice. The number of hepatocytes of the mice decreased, and the infiltration of the leukemia cells in the liver sinus were observed in group II. The liver was heavily infiltrated by leukemic cells in group III mice. The mouse livers were normal in group IV mice. Conclusion: It is feasible to establish GVHD model of the leukemia mice with cyclophosphamide conditioning regimen of allo-HSCT, and simple to operate. This is less harmful to people, animals and the environment. Discussion: The traditional animal model of GVHD is based on TBI conditioning regimen prior to allo-HSCT. However, the process can lead to systemic adverse reactions such as myelosuppression, radiation gastroenteritis, endocrine disorders and systemic function disorders, etc. in both the operators and animals. Therefore, the radiotherapy doses have to be low. At the same time, it is difficult to establish animal models of GVHD due to the uneven distribution of the doses. Cyclophosphamide was selected for the conditioning regimen of allo-HSCT in the study. Cyclophosphamide had the effect direct on killing tumor cells, induced recipients to tolerate the immune of donors, enabled to implant donor cells into recipients smoothly. The stable chimeras were obtained. There are a large number of T and B lymphocytes in donor's spleen cells. By injecting donor spleen cells and active immune cells derived from proliferation and differentiation of hematopoietic stem cells, the effects of graft-anti-leukemia are availably activated in recipients. Acknowledgments We thank Dr Zhifu Xiang very much for his great helpful revisions. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5178-5178
Author(s):  
Tokiko Nagamura-Inoue ◽  
Cui Yan ◽  
Hideki Kodo ◽  
Hideo Mugishima ◽  
Michiko Sugo ◽  
...  

Abstract Recently, cord blood transplantation (CBT) for adult is rapidly increasing in number, Especially for the patients over 50 years of age. By the end of 2003, 224 units were shipped for the patients Group I: <15 y.o. 39%, Group II: 15~50 y.o.40% and Group III :> 50 y.o.21%. We analyzed 152 patients with hematological malignancies including ALL, AML, CML, MDS, malignant lymphoma, myeloma and neuroblastoma reported from CBT center in the world by the end of 2003. Patients and Methods:Group I included 58 patients with 13 standard risk and 45 high risk patients and showed mean±SD of age; 5.3 ±4.1y.o.,BW; 20.5±13.4kg, CB volume at collection; 91.6±27.1ml, NC; 5.5±3.3x107/kg, CFC; 8.6±6.4x104/kg, CD34; 1.5±1.1x105/kg, Group II: 64 cases with 25 standard and 39 high risk patients and age; 30.6±10.3y.o., BW; 51.9±9.5kg, CB volume at collection;116.6±27.7ml, NC;2.6±0.7x107/kg, CFC;5.2±2.6x104/kg and CD34;0.8±0.5x105/kg, Group III: 30 cases with 9 standard and 21 high risk patients and age; 54.1±3.3y.o., BW;55.9±11.0kg, CB vol.at collection;118.8±24.7ml NC;2.4±0.4x107/kg, CFC;4.8±1.9x104/kg and CD34;0.8±0.4x105/kg. The patients who underwent CBT for graft failure (GF) of prior transplant were excluded. Conditioning regimen in Group I demonstrated 54 patients with full regimen and 4 with reduced intensity regimen (RIST); in Group II, 62 patients with full regimen and 2 RIST; and in Group III, 14 cases full regimen and 15 cases RIST. Results: Cumulative myeloid engraftment was seen 67.2% in Group I, 73.4% in Group II and 46.7% in Group III (*Group II vs. Group III: P<0.05). Overall survival /EFS on day 100 showed 73.4%/59.4% in Group I, 74.0%/58.6% in Group II and 43.3%/34.5% in Group III (*Group III vs. others: P<0.05). In Group III, the survival rate indicated 42.8% in full regimen group and 13.3% in RIST group at 1year after CBT. In Group I, four patients died of GF, 13 of relapse, 11 of Transplantation related disease (TRD); in Group II, 5 patients died of GF, 8 of TRD, 10 of relapse. In Group III, four patients died of TRD, 3 of GF and 3 of relapse in full regimen, while in RIST, six patients died of TRD, 1 of relapse and 1 of acute GVHD. Conclusion: The application of CBT has been expanded to the elderly patients (>50 y.o.), although the conditioning regimen and the special medical care for the complications in the early pahse after UCBT has remained to be discussed.


Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 399-410 ◽  
Author(s):  
Mariella Della Chiesa ◽  
Michela Falco ◽  
Marina Podestà ◽  
Franco Locatelli ◽  
Lorenzo Moretta ◽  
...  

Abstract Natural killer (NK) cells play a crucial role in early immunity after hematopoietic stem cell transplantation because they are the first lymphocyte subset recovering after the allograft. In this study, we analyzed the development of NK cells after intrabone umbilical cord blood (CB) transplantation in 18 adult patients with hematologic malignancies. Our data indicate that, also in this transplantation setting, NK cells are the first lymphoid population detectable in peripheral blood. However, different patterns of NK-cell development could be identified. Indeed, in a group of patients, a relevant fraction of NK cells expressed a mature phenotype characterized by the KIR+NKG2A− signature 3-6 months after transplantation. In other patients, most NK cells maintained an immature phenotype even after 12 months. A possible role for cytomegalovirus in the promotion of NK-cell development was suggested by the observation that a more rapid NK-cell maturation together with expansion of NKG2C+ NK cells was confined to patients experiencing cytomegalovirus reactivation. In a fraction of these patients, an aberrant and hyporesponsive CD56−CD16+p75/AIRM1− NK-cell subset (mostly KIR+NKG2A−) reminiscent of that described in patients with viremic HIV was detected. Our data support the concept that cytomegalovirus infection may drive NK-cell development after umbilical CB transplantation.


2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Um-e-Kalsoom ◽  
Sabiha Khan ◽  
Israr Ahmad

Abstract Background Hemodialysis may have serious psychological impact upon patients suffering from chronic kidney diseases. The aim of the present study is to investigate the impact of hemodialysis on the wellbeing of individuals with chronic kidney diseases (CKD). Result A sample consists of (N = 100) CKD patients referred from neurology ward of Leady Reading Hospital Peshawar. Data was collected from both male (50%) and female (50%) in 2017. Participants were divided into two groups on the basis of pre-set criteria. In group I, individuals with 4–5 stage of CKD referred first time for dialysis treatment were recruited. Group II comprised of CKD patients with 1–3 stage. Demographic data sheet, Pakistan Anxiety and Depression, WHO Quality of Life scale, and Perceived Social support scale (PSS) were used to test the hypotheses. Paired sample t test was use to see the difference between pre- and post-analysis of depression, anxiety, QOL, and PSS in group I (experimental group). Results suggests significant difference on depression (p > .001), anxiety (p > .001), and QOL (p > .001), while no significant difference was reported on perceived social support (p <.673). Findings also indicate no significant difference between group I and group II on QOL depression, anxiety, and PSS. Conclusion The findings concluded that patients under hemodialysis treatment suffered from depression, anxiety, and poor quality of life.


Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 874-880 ◽  
Author(s):  
AD D'Andrea ◽  
PJ Szklut ◽  
HF Lodish ◽  
EM Alderman

Abstract We have generated four high affinity monoclonal antibodies (MoAbs) to recombinant human erythropoietin (EPO). All four MoAbs immunoprecipitate radioiodinated native EPO, and the concentrations of MoAbs required for maximum binding range from 10 nmol/L to 100 nmol/L. Two MoAbs, designated Group I MoAbs, bind to an epitope within the N- terminal 20 amino acids of EPO and also immunoprecipitate sodium dodecyl sulfate (SDS)-denatured EPO. Two other MoAbs (Group II MoAbs) do not immunoprecipitate SDS-denatured EPO and do not bind to any of the eight endo C fragments of EPO. We first used murine erythroleukemia (MEL) cells to test the MoAbs for inhibition of EPO-receptor binding. MEL cells, although unresponsive to EPO, express 760 high affinity receptors for EPO per cell (Kd = 0.24 nmol/L). To assay our MoAbs, MEL cells were grown as monolayers on fibronectin-coated Petri dishes and incubated at 4 degrees C with radioiodinated EPO. Group I MoAbs do not inhibit binding of radioiodinated EPO to the MEL EPO-receptor, but Group II MoAbs do inhibit binding in a dose-dependent manner. We next examined the neutralization of EPO bioactivity by our MoAbs, using EPO- dependent cell line. Only Group II MoAbs inhibit a newly developed EPO- dependent cell growth, demonstrating that inhibition of EPO-receptor binding correlates with neutralization of EPO bioactivity.


2019 ◽  
Vol 9 (20) ◽  
pp. 4322 ◽  
Author(s):  
Lv ◽  
Liu ◽  
Zhu ◽  
Bai ◽  
Qi

The significant difference between recycled aggregate and natural aggregate is the content of the attached mortar layer. With the increase of the replacement rate of recycled aggregate, the shrinkage and creep of recycled aggregate concrete is significantly increased. In this paper, 180-day shrinkage and creep tests of recycled aggregate concrete with different water–cement ratios were designed in order to analyze the effect of the substitution rate and water–cement ratio on shrinkage and creep properties. The results show that the shrinkage strain of recycled aggregate concrete with a substitution rate of 50% and 100% at 180 days is 26% and 48% higher than that of ordinary concrete, respectively, and the growth of group II is 22% and 47%, respectively. When the load was 180 days old, the creep coefficient of recycled aggregate concrete with a substitution rate of 50% and 100% in group I increased by 19.6% and 39.6%, respectively compared with ordinary concrete, and group II increased by 23.6% and 44.3%, respectively. Based on the difference of adhering mortar content, the creeping increase coefficient and shrinkage increase coefficient of the attached mortar were proposed, and a shrinkage and creep model of recycled aggregate concrete was established. When compared with the experimental results, the model calculation results met the accuracy requirements.


2021 ◽  
Vol 45 (6) ◽  
pp. 389-394
Author(s):  
Supriya Kumari ◽  
Rachana Bahuguna ◽  
Nishita Garg ◽  
Ramakrishna Yeluri

Objective: To evaluate the efficacy of immersive VR (IVR) and non-immersive VR (NIVR) distraction on perceived pain during intraoral injections in children undergoing dental procedures. The objective was to introduce 3-dimensional nature of virtual reality during the provoking phase of dental treatment as a means of distraction in children. Study design: A total of 200 children were selected for the study, 100 for IVR group and 100 for NIVR group. After randomization, children were introduced to Oculus Go Standalone equipment; MCDAS (f), VAS, WBFRS and the treatment procedure using tell show do technique. Group I children were introduced to oculus go standalone headset with hand held controller to play temple run or roller coaster game while in group II, children watched cartoon movies of their choice. Pre-operative & post-operative MCDAS scores were obtained using MCDAS (f) questionnaire in local language. Post-operatively, VAS and WBFRS scores were also obtained. The data was analyzed using independent t-test and chi-square analysis. Results: Pre-operatively, the mean MCDAS scores were similar in both the groups viz. Group–I (29.20 ± 3.197) and Group–II (29.09 ± 3.803) and is statistically not significant. Post-operatively, the mean MCDAS scores were higher in non-immersive group (20.72 ± 2.822) as compared to immersive group (10.99 ± 2.227). VAS score was higher in non-immersive group (2.72 ± 0.99) as compared to immersive group (0.75 ± 0.88). WBFRS scores were higher in non-immersive group (2.78 ± 1.097) as compared to immersive group (0.82 ± 1.104). Conclusion: Three-dimensional virtual reality was found to be an effective means of distraction in children undergoing dental procedures and especially during the provoking phase. The significant difference obtained clearly indicates irrespective of immersiveness of virtual reality, anxiety had been decreased and on comparison the pain perception to intraoral injection is less in immersive virtual reality environment. Immersive VR distraction technique can serve as an adjunct to traditional behavior management strategies already available to the pediatric dentist.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
N Hazzaa ◽  
DM Hassan ◽  
Sh Mahmoud

Abstract Objective To investigate the effect of visual fatigue caused by smart phone on the balance function. Subjects and Methods Forty subjects divided into 2 groups were included in the present study . Group I, twenty normal healthy subjects with mean age of 28.8 years. Group II, twenty subjects with a clinical diagnosis of peripheral vestibular disorder with mean age of 38.85years. They were subjected to a computer vision syndrome questionnaire (CVS-Q) , occulomotor tests of videonystagmography (VNG) and sensory organization test (SOT) of computerized dynamic posturography (CDP) before and after visual fatigue induction. Results Significant differences existed between C5, 6 and composite scores in group I and in C4 and composite scores in group II after visual fatigue induction. However, there was no significant difference between occulomotor tests in both groups after visual fatigue induction. Conclusions The smart phone use can affect the balance function in healthy subjects and augment the deficit in those with balance problem. Reducing visual fatigue should be considered through various procedures as taking proper rest, adjusting the brightness of screen, avoid any wrong posture and using filters if possible.


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