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1.
Elizabeth L. Courville Megan Griffith Celalettin Ustun Sophia Yohe Erica Warlick 《BMC clinical pathology》2017,17(1):28
Background
The only potentially curative therapy for myelodysplastic syndrome is allogeneic hematopoietic cell transplant; unfortunately, there is a high relapse rate. The objective of this study was to perform a detailed clinicopathologic study of patients with relapsed myeloid neoplasm following allogeneic hematopoietic cell transplant for myelodysplastic syndrome.Methods
Pre-transplant, post-transplant, and relapse bone marrow and peripheral blood morphologic features (including dysplasia) were retrospectively evaluated by study authors. Clinical features and results of cytogenetic analysis and engraftment/chimerism studies were obtained from the medical record.Results
Our study describes 21 patients with a median time to relapse of 6 months (range 2–82). Ten of the patients relapsed with higher grade disease, including six with overt acute myeloid leukemia. Pre-transplant megakaryocyte dysplasia was associated with dysplastic megakaryocytes in the relapse specimen; however, neither erythroid dysplasia nor granulocytic dysplasia were associated with their counterpart in the relapse specimen. Relapse specimens had a lower marrow cellularity and higher blast percentage than pre-transplant disease. Cytogenetic comparisons before and after transplant showed variety, including clonal evolution (22%), the same abnormal clone (33%), or a different abnormal clone (22%).Conclusions
Our detailed review of post-transplant marrow biopsies prior to relapse highlights the difficulty in diagnosing relapse and particularly impending relapse.2.
Mehdi Najar Hussein Fayyad-Kazan Wissam H. Faour Bassam Badran Fabrice Journe Laurence Lagneaux 《Inflammation research》2017,66(2):129-139
Objective
The role of direct cell–cell interactions mediating selective bone metastasis by breast cancer cells (BCCs) niche is still mostly unknown.Materials and methods
Conditioned medium and direct cell–cell contacts experiments were used to investigate the effect of bone marrow-derived mesenchymal stromal cells (MSCs), osteoprogenitor-like cells (MG-63) and osteosarcoma cells (SaOS-2) on luminal-like (MCF-7) and basal-like (MDA-MB-231) BCCs flow cytometry was used to assess the purity of isolated BCCs and osteoblasts. Expression of osteoblastic markers was investigated by semi-quantitative RT-PCR. RANKL and OPG levels were measured by ELISA.Results
Conditioned medium from MSCs and osteoblasts induced the expression of osteoblastic markers in BCCs. While co-culture assays with SaOS-2 increased the expression of osteoblastic markers in MCF-7 cells, SaOS-2 cell conditioned medium increased the expression of RANKL, PTHrP, VEGF and NOGGIN in MCF-7 cells. Co-cultures with either MG-63 cells or MSCs induced OPG and MMP-2 in both tumor cell lines. Interestingly, conditioned medium from co-cultures of MSCs and MDA-MB-231 cells significantly decreased the proliferation of activated T lymphocytes which was reversed by addition of anti-OPG antibodies to the co-cultures.Conclusion
Our data suggest that MSCs strongly contribute to the adaptation and invasiveness of breast cancer cells in skeletal tissues.3.
Hong Wang Mingqiang Hua Shukang Wang Jie Yu Chen Chen Xueyun Zhao Chen Zhang Chaoqin Zhong Ruiqing Wang Na He Ming Hou Daoxin Ma 《Inflammation research》2017,66(3):249-258
Background
Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML.Methods and results
We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1β (rs16944), IL-18 (rs1946518) and NF-κB ?94 ins/del ATTG in de novo AML patients to find out whether they play roles in the susceptibility and severity of AML. In our study, 383 AML cases and 300 randomly selected healthy individuals were examined for the polymorphisms and expression of NLRP3 genes. IL-1β (rs16944) polymorphism in different risk AML subgroups was found statistically different, with more GA genotype in favorable-risk cytogenetics group. We also demonstrated that the bone marrow blasts of patients carrying IL-18 (rs1946518) GG or GT genotype were higher than patients of TT genotype. IL-18 plasma level of patients with IL-18 (rs1946518) GT or TT genotype was higher than GG genotype. Moreover, the GT genotype of IL-18 (rs1946518) led to statistically poorer AML-specific survival.Conclusion
IL-1β (rs16944) and IL-18 (rs1946518) may be served as potential predictors for AML.4.
5.
Ragheda Yaseen Stefanie Blodkamp Petra Lüthje Friederike Reuner Lena Völlger Hassan Y. Naim Maren von Köckritz-Blickwede 《Journal of negative results in biomedicine》2017,16(1):2
Background
The human leukemia cell line HL-60 is considered an alternative cell culture model to study neutrophil differentiation and migration. The aim of this study was to characterize the suitability of HL-60 cells differentiated to neutrophil-like cells (nHL-60) as substitute for blood-derived human neutrophils to investigate the interaction of neutrophils with Staphylococcus aureus.Methods
For this purpose, antimicrobial activity, bacterial uptake, production of reactive oxygen species and the release of neutrophil extracellular traps (NETs) by nHL-60 cells were analyzed and compared to primary blood-derived neutrophils using Staphylococcus aureus as important human and animal pathogen.Results
Overall, the antimicrobial activities of nHL-60 cells were distinctly lower compared to blood-derived neutrophils. Furthermore, production of reactive oxygen species as well as NET formation was clearly impaired in nHL-60 cells.Conclusion
This study indicates that HL-60 cells are of limited usage as an alternative model to study antimicrobial functions of neutrophils against Staphylococcus aureus.6.
Leonardo Pedrazza Talita Carneiro Brandão Pereira Ana Lucia Abujamra Fernanda Bordignon Nunes Maurício Reis Bogo Jarbas Rodrigues de Oliveira 《Inflammation research》2017,66(7):547-551
Objective and design
Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues.Materials and methods
Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 106 cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR.Results
We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group.Conclusions
In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.7.
Background
CCR5-delta32 heterozygous individuals are susceptible to HIV-1. However, it is not clear if there is a relevant protective effect against transmission and a beneficial effect in terms of HIV progression which cannot be attributed to CCR5 surface density alone. Therefore we investigated HIV-1 dependency factors (HDF) which might be differently regulated in CCR5 wild type (WT) and CCR5-delta32 heterozygous individuals.Methods
We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers, 12 individuals with CCR5 WT and 7 with heterozygous CCR5-delta32 deletion. Samples were analyzed using a global gene expression oligonucleotide microarray (HG-U133plus 2.0, Affymetrix Inc.).Results
A total of 205 genes were found with altered expression (3fold difference, present call rate of 75%, p?<?0.05) and 7 of these had a connection to HIV-1 pathogenesis. In 4 genes: TOP1, CXCR2, SREBF2, and TAP we found a different regulation which was consistent with a supposed beneficial effect for CCR5-delta32 heterozygotes.Conclusion
The CCR5-delta32 deletion is associated with other HDFs in HIV-1 pathogenesis as a possible explanation for beneficial effects regarding the deletion leading to a variant expression profile in heterozygous carriers of this mutation.8.
Maísa Mota Antunes Alan Moreira Araújo Ariane Barros Diniz Rafaela Vaz Sousa Pereira Débora Moreira Alvarenga Bruna Araújo David Renata Monti Rocha Maria Alice Freitas Lopes Sarah Cozzer Marchesi Brenda Naemi Nakagaki Érika Carvalho Pedro Elias Marques Bernhard Ryffel Valérie Quesniaux Rodrigo Guabiraba Brito José Carlos Alves Filho Denise Carmona Cara Rafael Machado Rezende Gustavo Batista Menezes 《Inflammation research》2018,67(1):77-88
Objective and design
The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI).Material and treatments
DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL).Methods
Blood and liver were collected for biochemical, immunologic and genetic analyses. Mice were imaged by confocal intravital microscopy and liver non-parenchymal cells and hepatocytes were isolated for flow cytometry, genetic and immunofluorescence studies.Results
Acetaminophen overdose caused a massive necrosis and accumulation of immune cells within the liver, concomitantly with IL-33 and chemokine release. Liver non-parenchymal cells were the major sensors for IL-33, and amongst them, neutrophils were the major players in amplification of the inflammatory response triggered by IL-33/ST2 signalling pathway.Conclusion
Blockage of IL-33/ST2 axis reduces APAP-mediated organ injury by dampening liver chemokine release and activation of resident and infiltrating liver non-parenchymal cells.9.
Wei Shen Hui Luo Liangliang Xu Zhifang Wu Hongtai Chen Yamei Liu Lijuan Yu Liuchao Hu Bin Wang Yiwen Luo 《Chinese medicine》2018,13(1):45
Background
Bushen Huoxue decoction (BHD) has a significant effect on fracture rehabilitation, yet its underlying mechanism is still unknown. The purpose of this study was to explore whether BHD promotes bone marrow mesenchymal stem cell (BMSC) migration through the Wnt5a signalling pathway.Methods
BHD was extracted by petroleum, and its composition was analysed. Cell viability in the presence of various concentrations of BHD for 24, 48 and 72 h was measured using a Cell Counting Kit-8 assay. Transwell assays and wound healing assays were used to observe the migration ability of BMSCs. Lentiviral vectors were used to knock down Wnt5a. Polymerase chain reaction and Western blot analyses were used to further compare Wnt5a signalling components at the mRNA and protein levels between groups.Results
BHD treatment groups showed increased migration ability and Wnt5a expression. Knocking down Wnt5a using a lentivirus significantly inhibited the effects of BHD, which implies that BHD promotes BMSC migration ability through activation of Wnt5a.Conclusions
BHD can enhance BMSC migration, possibly by activating Wnt5a signalling.10.
Philippe Clavert R.-M. Javier J. L. Charrissoux L. Obert L. Pidhorz F. Sirveaux P. Mansat T. Fabre 《Surgical and radiologic anatomy : SRA》2016,38(4):389-393
Introduction
The aim of this study was to investigate three methods of prediction of the bone quality of the distal humerus: dual-energy X-ray absorptiometry (DEXA), Ct-Scan and plain radiographs.Materials and methods
The bone mineral density (BMD) of 21 cadaveric distal humerus was determined using DEXA at two levels. Then a CT-scan and anteroposterior radiographs were taken. The cancellous density was estimated with the CT-scan. The cortico-medullar index (CMI) was calculated as cortical thickness divided by total bone thickness on AP views.Results
A significant positive correlation was found between the BMD of the epiphysis and the CMI of r = 0.61. The mean BMD of the distal humerus was 0.559 g/cm2. Male specimens showed a significantly higher BMD than females. The mean CMI of diaphysis was 1.431 and the mean BMD of the metaphysis region was 0.444 g/cm2.Discussion
More than a direct evaluation of the bone density with a CT-scan, the CMI of the distal humerus diaphysis is a predictor of the bone quality of the distal humerus. This should be of great help for the surgeon’s decision making in case of fracture of the distal humerus, as open Reduction and Internal Fixation (ORIF) of fractures of the distal humerus can lead to failure due to poor bone quality.Level of evidence
Basic Science Study, Anatomic Cadaver Study.11.
Maryam?Maghbool Mani?Ramzi Inga?Nagel Pablo?Bejarano Reiner?Siebert Abolfazl?Saeedzadeh Yahya?Daneshbod
Background
Primary adenocarcinoma of thymus is extremely rare.Case presentation
This is a case of primary adenocarcinoma with intestinal differentiation and focal mucin production in the thymus. Thymic cyst was associated with this tumor. Intestinal differentiation was confirmed by immunohistochemical stain with positivity for CDX-2, CK20, villin, MOC31 and focal positivity of CK7. Array comperative genomic hybridization (CGH) analysis showed a complex pattern of chromosomal imbalances including homozygous deletion at the HLA locus in chromosomal region 6p21.32.Conclusion
This rare tumor shows a similar genetic aberration with other studied thymic epithelial tumors.12.
Shintaro Ono Tsubasa Okano Akihiro Hoshino Masakatsu Yanagimachi Kazuko Hamamoto Yozo Nakazawa Toshihiko Imamura Masaei Onuma Hidetaka Niizuma Yoji Sasahara Hiroshi Tsujimoto Taizo Wada Reiko Kunisaki Masatoshi Takagi Kohsuke Imai Tomohiro Morio Hirokazu Kanegane 《Journal of clinical immunology》2017,37(1):85-91
Background
X-linked inhibitor of apoptosis protein (XIAP) deficiency is a rare immunodeficiency that is characterized by recurrent hemophagocytic lymphohistiocytosis (HLH) and splenomegaly and sometimes associated with refractory inflammatory bowel disease (IBD). Although hematopoietic stem cell transplantation (HSCT) is the only curative therapy, the outcomes of HSCT for XIAP deficiency remain unsatisfactory compared with those for SLAM-associated protein deficiency and familial HLH.Aim
To investigate the outcomes and adverse events of HSCT for patients with XIAP deficiency, a national survey was conducted.Methods
A spreadsheet questionnaire was sent to physicians who had provided HSCT treatment for patients with XIAP deficiency in Japan.Results
Up to the end of September 2016, 10 patients with XIAP deficiency had undergone HSCT in Japan, 9 of whom (90%) had survived. All surviving patients had received a fludarabine-based reduced intensity conditioning (RIC) regimen. Although 5 patients developed post-HSCT HLH, 4 of them survived after etoposide administration. In addition, the IBD associated with XIAP deficiency improved remarkably after HSCT in all affected cases.Conclusion
The RIC regimen and HLH control might be important factors for successful HSCT outcomes, with improved IBD, in patients with XIAP deficiency.13.
14.
Yuliya V. Perfilyeva Nurshat Abdolla Yekaterina O. Ostapchuk Raikhan Tleulieva Vladimir C. Krasnoshtanov Nikolai N. Belyaev 《Inflammation research》2017,66(8):711-724
Objective
Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases.Subjects
67 CD-1 mice and in vitro MDSC cultures.Treatment
Adjuvant arthritis was induced by a subdermal injection of complete Freund’s adjuvant. LN was induced by illumination of 750 lx at night.Methods
Flow cytometry for evaluation of cell phenotypes and MTT standard test for cell proliferation were used.Results
Increased levels of splenic CD11b+Ly6Ghigh and CD11b+CD49d+ myeloid cells possessing suppressive potential in mice with adjuvant arthritis are shown. LN amplifies the process of CD11b+Ly6Ghigh expansion in mice with adjuvant arthritis. Expression of CD62L and CD195 is elevated on the myeloid cells during exposure to LN.Conclusions
Our study raises the possibility that CD11b+Ly6Ghigh and CD11b+CD49d+ MDSCs play an important role in the induction of immunosuppressive environment typical for chronic inflammation. Also, LN can affect immune responses during chronic inflammation through recruitment of MDSCs from the bone marrow.15.
Nicolas Degand Justine Dautremer Benoît Pilmis Agnès Ferroni Fanny Lanternier Julie Bruneau Olivier Hermine Stéphane Blanche Xavier Nassif Olivier Lortholary Marc Lecuit 《Journal of clinical immunology》2017,37(7):727-731
?
Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.Purpose
We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.Methods
16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.Results
Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.Conclusion
In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.16.
S. Le Pape L. Du Pouget T. Cloche M. Campana I. Obeid L. Boissiere J.-M. Vital 《Surgical and radiologic anatomy : SRA》2016,38(10):1191-1194
Purpose
For the past few years, anterior exposure for surgery of the lumbar spine has gained popularity for the treatment of disk disease or spondylosis. Cancellous bone remains the gold standard for fusion. Iliac crest bone harvesting is safe but there are donor site complications. Bone substitutes exist, like recombinant human bone morphogenic protein-2 rhBMP-2. This alternative offers a high rate of fusion but with local and general complications. The aim of our study is to show the feasibility of an endopelvic approach for iliac bone crest harvesting to avoid donor site complication.Method
Twenty anterior retroperitoneal lumbar spine approaches have been realized in the anatomy department of the University of Bordeaux. The volumes of cancellous bone have been measured and procedure complications have been reported.Results
The mean volume of cancellous bone was 5.9 cc, the maximum volume was 8.2 cc and the minimum volume was 4.5 cc. No complications have been reported during the approach or the bone harvesting.Conclusions
Anterior retroperitoneal approach for iliac bone crest harvesting is a safe way to obtain sufficient volume of cancellous bone for a single lumbar spinal fusion. This exposure avoids the risks of an iliac crest donor site complications or rhBMP-2 complications.17.
Background
Primary hyperoxaluria is a rare disease with an estimated prevalence of 1 to 3 cases per million. It is due to a hepatic enzyme deficiency responsible for an endogenous overproduction of oxalate. Oxalate crystals commonly deposit in the kidney and more rarely in bone marrow.The literature has reported, to the best of our knowledge, only two cases of hyperoxaluria diagnosed by bone marrow biopsy and our case is the only one that does not show radiological bone lesions.Case presentation
A young 22 year old chronic hemodialysis patient with nephrocalcinosis. The patient had a personal and family history of recurrent kidney stones. He presented bone pain with worsening of his general state. On physical examination, no organomegaly was detected. Biological check-up showed only a normochromic and normocytic regenerative anemia resistant to treatment and a bone marrow biopsy was performed. It showed deposits of crystals of oxalate in the bone marrow surrounded by inflammatory reaction against foreign bodies. Given our context, no liver biopsy or genetic studies, which are gold standard of diagnosis testing, were done. The diagnosis of primary hyperoxaluria was made based on morphological characteristics of crystals, his medical and family history, and the absence of any secondary cause of the condition. Since curative treatment is not available in our country, the patient only receives a palliative treatment.Conclusion
Primary hyperoxaluria is rarely evoked by the histological study of a bone marrow biopsy. The lack of the possibility of the only effective treatment in our context and the diagnosis, usually late, of this pathology are at the origin of the fatal evolution of the disease in almost all the cases.18.
Rachel Hamias Assaf Rudich George Greenberg Gabriel Szendro Talya Wolak 《Inflammation research》2018,67(3):265-275
Objective and design
Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin in comparison to angiotensin 1–7.Material and subjects
Human coronary endothelial cells (hcEC) treated with conditioned media from human U937 macrophages.Treatment
Macrophages were (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN-FL, OPN-N, respectively), angiotensin II, angiotensin 1–7 or TNF-α. OPN-C modulatory capacity was compared to that of Ang1–7 in inhibiting subsequent Ag II, OPN-FL or OPN-N-induced macrophage-mediated endothelial inflammation.Methods
Protein expression of NFκB, IκB, vCAM-1 and iCAM-1 was assessed using western blot. Promotor activation by NFκB was also assessed by dual-luciferase reporter assay.Results
Conditioned media of macrophages treated with OPN-C induced hcECs’ NfκB activation to a lower degree than OPN-FL or OPN-N. Priming of macrophages with angiotensin 1–7 attenuated the endothelial pro-inflammatory effect induced by subsequent exposure of the macrophages to angiotensin II, OPN-FL or OPN-N. This was evidenced by both NfκB activation and vCAM and iCAM expression. In contrast, priming macrophages with OPN-C did not significantly attenuate the subsequent response to the pro-inflammatory cytokines.Conclusions
OPN-C induces lower macrophage-induced endothelial inflammation compared to OPN-FL or OPN-N, but unlike angiotensin 1–7, fails to prevent endothelial inflammation induced by subsequent pro-inflammatory macrophage stimulation.19.
Kneginja Richter Lukas Peter Stefanie Kellner Thomas Hillemacher 《Somnologie - Schlafforschung und Schlafmedizin》2018,22(3):194-198
Background
Millions of people share a bed with their partner. Sleep und relationship could possibly influence each other.Objectives
To identify and discuss connections between relationship and sleep quality.Methods
Review of the literature in electronic databases.Results
Conflict and violence in relationships lead to decreases in both partners’ sleep quality. Constructive approaches to resolving conflicts is necessary for good sleep, and vice versa. Women prefer partners with sleep-wake rhythms matching their own and report higher relationship satisfactions when the couple’s chronotypes are compatible.Conclusions
Sleep and circadian rhythms play important roles in relationships. When treating insomnia, the relationship and the partner’s sleep should be taken into account.20.
Angela Park Juliana Barrera-Ramirez Indee Ranasinghe Sophie Pilon Richmond Sy Dean Fergusson David S. Allan 《Stem cell reviews》2016,12(3):327-339