Acute monocytic leukemia is a distinct subtype of acute myeloid leukemia (AML) with characteristic biology and clinical features. This study was designed to compare the immunophenotypical features and clinical manifestations of the patients with AML-M(5a) to that of patients with AML-M(5b), and to identify differences between M(5a) and M(5b) and to explore their relations. A total of 58 cases of de novo adult patients with AML M(5) were investigated. Immunofluorescence analysis by flow cytometry was performed to determine the immunophenotype of the leukemic cells in all cases. Meanwhile, clinical data of these cases were studied retrospectively. The results showed that the immunophenotypes of monocytic leukemic cells in patients with AML M(5) were heterogeneous, and CD68 and CD11b were expressed higher in patients with AML M(5a), compared with that in patients with AML M(5b) (P < 0.01). The significant differences in sex, extramedullary infiltration, WBC counts of peripheral blood, complete remission rate and disease-free survival (DFS > 300 days) between the patients with AML M(5a) and M(5b) did not exist (P > 0.05). It is concluded that the special individual immunophenotype features can be detected in patients with either of AML M(5a) or M(5b), and that expressions of CD68 and CD11b were much higher in M(5a). It seems that the complete remission rate and disease-free survival of patients with M(5a) and M(5b) are not different from that of currently available therapy.
Adolescent ; Adult ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; CD11b Antigen ; analysis ; Female ; Fluorescent Antibody Technique ; Humans ; Immunophenotyping ; Leukemia, Monocytic, Acute ; classification ; immunology ; Male ; Middle Aged ; Prognosis

BACKGROUND/AIMS: For unknown reasons, caspase-1 -/- mice, protected against cisplatin-induced acute renal failure (ARF), are deficient in interleukin (IL)-1alpha. We thus asked whether IL-1alpha deficiency underlies the mechanism of protection against cisplatin-induced ARF in these mice. METHODS: Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice to produce a cisplatin-induced model of ARF. IL-1alpha was measured in control vehicle- and cisplatin-treated wild-type animals. We also examined whether IL-1alpha -/- mice were similarly protected against cisplatin-induced ARF. Additionally, infiltration of CD11b- and CD49b-positive cells, as markers of macrophages, natural killer, and natural killer T cells (pan-NK cells), was investigated in wild-type and IL-1alpha -/- mice. RESULTS: Compared with vehicle-treated mice, renal IL-1alpha increased in cisplatin-treated wild-type mice beginning on day 1. IL-1alpha -/- mice were shown to be protected against cisplatin-induced ARF. No significant difference in the infiltration of neutrophils or CD11b- and CD49b-positive cells were observed between wild-type and IL-1alpha -/- mice. CONCLUSIONS: Mice deficient in IL-1alpha are protected against cisplatin-induced ARF. The lack of IL-1alpha may explain, at least in part, the protection against cisplatin-induced ARF observed in caspase-1 -/- mice. Investigation of the protective mechanism (s) in IL-1alpha -/- mice in cisplatin-induced ARF merits further study.
Acute Kidney Injury/chemically induced/*immunology/pathology/physiopathology/prevention & control ; Animals ; Antigens, CD11b/analysis ; Apoptosis ; Biological Markers/blood ; Blood Urea Nitrogen ; *Cisplatin ; Creatinine/blood ; Disease Models, Animal ; Fluorescent Antibody Technique ; Integrin alpha2/analysis ; Interleukin-1alpha/deficiency/genetics/*metabolism ; Kidney/*immunology/pathology/physiopathology ; Killer Cells, Natural/immunology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Natural Killer T-Cells/immunology ; Necrosis ; Neutrophil Infiltration ; Time Factors

The possibility that P2X7 receptor (P2X7R) expression in microglia would mediate neuronal damage via reactive oxygen species (ROS) production was examined in the APPswe/PS1dE9 mouse model of Alzheimer's disease (AD). P2X7R was predominantly expressed in CD11b-immunopositive microglia from 3 months of age before Abeta plaque formation. In addition, gp91phox, a catalytic subunit of NADPH oxidase, and ethidium fluorescence were detected in P2X7R-positive microglial cells of animals at 6 months of age, indicating that P2X7R-positive microglia could produce ROS. Postsynaptic density 95-positive dendrites showed significant damage in regions positive for P2X7R in the cerebral cortex of 6 month-old mice. Taken together, up-regulation of P2X7R activation and ROS production in microglia are parallel with Abeta increase and correlate with synaptotoxicity in AD.
Aging ; *Alzheimer Disease/genetics/metabolism/pathology ; Amyloid beta-Peptides ; Animals ; Antigens, CD11b/immunology ; Blotting, Western ; Cerebral Cortex/metabolism/*pathology ; Disease Models, Animal ; Gene Expression ; Mice ; Mice, Transgenic ; Microglia/*metabolism/pathology ; Neurons/metabolism/*pathology ; Plaque, Amyloid ; Reactive Oxygen Species/*metabolism ; Receptors, Immunologic/analysis ; Receptors, Purinergic P2X7/*genetics/metabolism

To study the effects and possible mechanism of Vitamin K(2) (VK(2)) in the treatment of MDS-JSN04 cells, the changes of morphologic features of MDS-JSN04 cells were investigated by cytomorphology, the apoptosis of MDS-JSN04 cells was observed by transmission electron microscope; cellular proliferation was determined by the MTT assay; cell apoptosis, cell cycle shift and expression of myeloid-specific differentiation antigen (CD11b, CD13) were analyzed by flow cytometry (FCM). The expression of apoptosis-related genes bcl-2, survivin and bax were detected by retrotranscriptase polymerase chain reaction (RT-PCR); the activity of caspase-3 was determined by chemiluminescence assay. The results showed that the typical apoptotic morphological features appeared in cells treated with VK(2) for 72 hours; VK(2) induced apoptosis of MDS-JSN04 cells and in a dose-and-time-dependent manner, G(0)/G(1) cell arrest and significantly down-regulated the expression of bcl-2 and survivin, but had no effect on the expression of bax; the activity of caspase-3 significantly increased. It is concluded that VK(2) induces apoptosis of MDS-JSN04 cells through activating caspase-3 pathways and the apoptosis-related genes bcl-2, survivin may play an important role in this process.
Apoptosis ; drug effects ; CD11b Antigen ; analysis ; CD13 Antigens ; analysis ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Inhibitor of Apoptosis Proteins ; Luminescent Measurements ; methods ; Microscopy, Electron, Transmission ; Microtubule-Associated Proteins ; genetics ; Myelodysplastic Syndromes ; genetics ; metabolism ; pathology ; Neoplasm Proteins ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Vitamin K 2 ; pharmacology ; bcl-2-Associated X Protein ; genetics

To explore the regulation mechanism of survivin gene, the NB4 and HL-60 cells were used in experiments, the cell culture in vitro and cell morphological observation were performed and survivin mRNA expression was detected by semi-quantitative RT-PCR. The results showed that the survivin expression in NB4 cell was positive. By treatment of 1 micromol/L ATRA, cell differentiation antigen CD11b was gradually increased ([chi = 47.002, P = 0.000) and CD33 was gradually decreased (chi = 1.614, P = 0.806) with time. Simultaneously, survivin mRNA expression was down-regulated and the cell cycle was arrested at G(0)-G(1) phase (chi = 58.566, P = 0.000). ATRA could down-regulate the survivin mRNA expression of HL-60 cell, but G-CSF, GM-CSF and PHA could up-regulate the survivin expression of HL-60 cell. The cytokine could regulate survivin expression in gene transcription level. The up-regulation of survivin expression was observed while HL-60 cell was stimulated by PHA. The survivin gene expression could be blocked by the survivin antisense oligonucleotide. The survivin mRNA expression of NB4 cell was inhibited by 100 nmol/L-1000 nmol/L survivin antisense oligonucleotide in a dose-dependent manner. The survivin mRNA expression in the NB4 cell was obviously inhibited in 600 nmol/L survivin AS-ODN groups (38%) while the AS-ODN dose increases, the inhibition rate does not descend, but was not inhibited in the control groups, liposomes groups and ODN groups. After NB4 cell was treated by survivin AS-ODN, the typical morphological changes for the apoptosis emerged in NB4 cell. These changes were not found in control groups. It is concluded that PHA, GM-CSF and G-CSF can up-regulate the survivin gene expression, but survivin AS-ODN and ATRA can down-regulate survivin gene expression. The cell cycle arrest at G(0)-G(1) phase while the survivin gene expression was down-regulated by ATRA. It suggested that the survivin gene expression is very related to cell cycle. The morphological changes of cell apoptosis can be observed when the survivin gene expression of NB4 cell was suppressed.
Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Apoptosis ; drug effects ; genetics ; CD11b Antigen ; analysis ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Down-Regulation ; drug effects ; genetics ; Flow Cytometry ; Fluorescent Antibody Technique ; Gene Expression Regulation, Neoplastic ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; HL-60 Cells ; Humans ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins ; genetics ; Neoplasm Proteins ; genetics ; Oligonucleotides, Antisense ; genetics ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sialic Acid Binding Ig-like Lectin 3 ; Tretinoin ; pharmacology ; Up-Regulation ; drug effects ; genetics