ABL gene fuses BCR during t(20;22) results in Philadelphia-negative, but BCR/ABL-positive chronic myeloid leukemia.
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Chromosomes, Human, Pair 20↗
Biomedical subjects
A Nakajima
Publications and source records attributed to A Nakajima.
Imatinib mesylate-induced hepato-toxicity in chronic myeloid leukemia demonstrated focal necrosis resembling acute viral hepatitis.
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Benzamides↗
Removal of bromate ion from water using TiO2 and alumina-loaded TiO2 photocatalysts.
The effects of pH and the surface charge of photocatalyst on photocatalytic reduction of bromate ions in water were examined by using TiO2 and alumina-loaded TiO2 photocatalysts. The amount of adsorbed bromate ion on TiO2 and the reduction rate of bromate ion by the TiO2 photocatalyst increased with lowering pH. It was suggested that the bromate ion adsorbed predominantly on the positively charged surface sites of TiO2 at lower pH, which thus promotes the rate of reduction. The iso-electric point of the TiO2 photocatalyst was shifted to the higher pH region by loading alumina on the TiO2 surface, which resulted in the increase of the adsorbed amount of bromate on the photocatalyst and the reduction rate of bromate ion by the photocatalyst at neutral pH. It was concluded from these results that the photocatalytic reduction of bromate ion can be promoted by pH control of water or by controlling the surface charge of the photocatalyst by loading alumina without pH control of water.
Adsorption↗
Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats.
Chlorpyrifos (CPF) is a widely used insecticides which has been shown to alter brain cell development. The current project was conducted to determine whether there are persistent behavioral effects of early [1 mg/kg/day postnatal days (PNDs) 1-4] or late (5 mg/kg/day PNDs 11-14) postnatal CPF exposure in rats. We tested spontaneous alternation in a T-maze, locomotor activity in the Figure-8 apparatus and learning in the 16-arm radial maze, throughout adolescence and into adulthood. Exposure during either neonatal period elicited significant long-term effects on cognitive behavior. In the radial-arm maze, as has been seen previously, control male performed more accurately than control females. Early postnatal CPF exposure reversed this effect. With exposure on PNDs 1-4, females in the CPF group showed a reduction in working and reference memory errors in the radial maze, reducing their error rate to that seen in control males; in contrast, CPF-exposed males exhibited an increase in errors during the initial stages of training. When animals were exposed on PNDs 11-14 and then tested in adolescence and adulthood, males showed a significant slowing of response latency in the T-maze and the rate of habituation in the Figure-8 apparatus was slowed in both sexes. When females were challenged acutely with the muscarinic antagonist, scopolamine, they did not show reference memory impairment, whereas controls did; these results suggest that adaptations occur after CPF exposure that lead to loss of muscarinic cholinergic control of reference memory. No such changes were seen with a nicotinic cholinergic antagonist (mecamylamine). These results indicate that early neonatal exposure to CPF induces long-term changes in cognitive performance that, in keeping with the neurochemical changes seen previously, are distinctly gender-selective. Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus uncovering the adaptive mechanisms that maintain basal performance.
Animals↗
Adoptive immunotherapy of experimental autoimmune encephalomyelitis via T cell delivery of the IL-12 p40 subunit.
CD4+ T cells are believed to play a central role in the initiation and perpetuation of autoimmune diseases such as multiple sclerosis. In the murine model for multiple sclerosis, experimental autoimmune encephalomyelitis, pathogenic T cells exhibit a Th1-like phenotype characterized by heightened expression of proinflammatory cytokines. Systemic administration of "regulatory" cytokines, which serve to counter Th1 effects, has been shown to ameliorate autoimmune responses. However, the inherent problems of nonspecific toxicity limit the usefulness of systemic cytokine delivery as a potential therapy. Therefore, we used the site-specific trafficking properties of autoantigen-reactive CD4+ T cells to develop an adoptive immunotherapy protocol that provided local delivery of a Th1 cytokine antagonist, the p40 subunit of IL-12. In vitro analysis demonstrated that IL-12 p40 suppressed IFN-gamma production in developing and effector Th1 populations, indicating its potential to modulate Th1-promoted inflammation. We have previously demonstrated that transduction of myelin basic protein-specific CD4+ T cells with pGC retroviral vectors can result in efficient and stable transgene expression. Therefore, we adoptively transferred myelin basic protein-specific CD4+ T cells transduced to express IL-12 p40 into mice immunized to develop experimental autoimmune encephalomyelitis and demonstrated a significant reduction in clinical disease. In vivo tracking of bioluminescent lymphocytes, transduced to express luciferase, using low-light imaging cameras demonstrated that transduced CD4+ T cells trafficked to the central nervous system, where histological analysis confirmed long-term transgene expression. These studies have demonstrated that retrovirally transduced autoantigen-specific CD4+ T cells inhibited inflammation and promoted immunotherapy of autoimmune disorders.
3T3 Cells↗
Screening for genes involved in tissue invasion based on placenta formation and cancer cell lines with low and high metastatic potential.
During the formation of placenta, trophoblast cells vigorously invade maternal uterine tissues, sharing many features with the invasion of cancers. We applied RNA differential display to placenta tissues from 8.5 to 17.5 days post-coitus (dpc) ICR mice, and isolated 188 cDNA fragments expressed differentially. Among the 25 known cDNA fragments thus far analyzed, six cDNAs have been reported to be relevant to tumor invasion and/or metastasis. Furthermore, 11 of 20 unknown cDNAs isolated showed differential expression between the pairs of cancer cell lines with low and high metastatic potential, indicating potential usefulness of the present two-step approach.
Animals↗
Phencyclidine-induced discriminative stimulus is mediated via phencyclidine binding sites on the N-methyl-D-aspartate receptor-ion channel complex, not via sigma(1) receptors.
The effects of several N-methyl-D-aspartate (NMDA) receptor- and sigma receptor-related compounds on the discriminative stimulus effects of phencyclidine (PCP) were examined in rats trained to discriminate PCP (1.5 mg/kg, i.p.) from saline under a two-lever fixed ratio 20 schedule of food reinforcement. PCP produced a dose-dependent increase in PCP-appropriate responding. A non-competitive NMDA receptor antagonist, dizocilpine (0.2 mg/kg, i.p.) and a putative sigma(1) receptor agonist, (+)-SKF-10047 (10 mg/kg, i.p.) fully substituted for PCP in every rat tested. Neither a competitive NMDA receptor antagonist, CGS-19755 (0.1-3 mg/kg, i.p.), sigma(1) receptor agonist, (+)-pentazocine (10-30 mg/kg, i.p.) nor dextromethorphan (10-20 mg/kg, i.p.) produced PCP-like discriminative stimulus effects. The discriminative stimulus effects of PCP (1.5 mg/kg, i.p.), dizocilpine (0.2 mg/kg, i.p.) and (+)-SKF-10047 (10 mg/kg, i.p.) were significantly attenuated by CGS-19755 (1 mg/kg, i.p.), but not by sigma(1) receptor antagonist BMY-14802 (10 mg/kg, i.p.) and NE-100 (5 mg/kg, i.p.). These results suggest that the discriminative stimulus effects of PCP are predominantly mediated via PCP binding sites on the NMDA receptor-ion channel complex, not via sigma(1) receptors. In addition, the PCP-like discriminative stimulus effects of (+)-SKF-10047 were demonstrated to be mediated via PCP binding sites.
Animals↗
Amelioration of experimental autoimmune encephalomyelitis with anti-OX40 ligand monoclonal antibody: a critical role for OX40 ligand in migration, but not development, of pathogenic T cells.
OX40 (CD134) and its ligand (OX40L) have been implicated in T cell activation and migration. In this study, we examined the contribution of these molecules to the pathogenesis of experimental autoimmune encephalomyelitis (EAE) by administering a neutralizing mAb against murine OX40L (RM134L) to proteolipid protein (139-151) peptide-induced EAE in SJL mice. Administration of RM134L effectively ameliorated the disease in both actively induced and adoptively transferred EAE models. Histological examination showed that the RM134L treatment greatly reduced mononuclear cell infiltration into the spinal cord. The RM134L treatment did not inhibit the development of pathogenic T cells, given that proliferative response and IFN-gamma production by draining lymph node cells were not reduced or rather enhanced upon restimulation with proteolipid protein (139-151) in vitro, and these cells effectively transferred EAE to naive SJL mice. Flow cytometric analyses showed that the RM134L treatment inhibited the accumulation of OX40-expressing CD4(+) T cells and the migration of adoptively transferred CD4(+) T cells in the spinal cord. Immunohistochemical staining showed that OX40L was most prominently expressed on endothelial cells in the inflamed spinal cord. These results suggest that the OX40/OX40L interaction plays a critical role for the migration of pathogenic T cells into the CNS in the pathogenesis of EAE.
Adoptive Transfer↗
Suppression of tumor necrosis factor-alpha production and neutrophil infiltration during ischemia-reperfusion injury of the liver after heat shock preconditioning.
BACKGROUND/AIMS: Heat shock preconditioning provides the liver with ischemic tolerance. In this study we examined the effects of heat shock preconditioning on hepatic nonparenchymal cells in light of tumor necrosis factor-alpha (TNF-alpha) production and neutrophil infiltration. METHODS: Rats were exposed to heat shock pretreatment at 42 degrees C in the heat shock group (group HS) and at 37 degrees C in the control group (group C). After a 48-h recovery, the left hepatic lobes were given a 90-min ischemia and reperfused. Plasma concentrations of TNF-alpha, cytokine-induced neutrophil chemoattractant (CINC) and alanine aminotransferase (ALT) were measured. Liver tissues were checked for the presence of TNF-alpha mRNA. Histological staining for CINC and polymorphonuclear leukocyte (PMN) was also evaluated. RESULTS: In group HS, plasma TNF-alpha levels were significantly more suppressed than in group C (P<0.0001). Expressions of TNF-alpha mRNA in the liver was suppressed in group HS. Production of CINC 2 h after reperfusion was reduced in group HS (P<0.05). PMN infiltration was significantly reduced in group HS (P<0.01). In group HS, liver histology revealed less cellular damage and the plasma level of ALT was significantly reduced (P<0.0001). CONCLUSIONS: Heat shock preconditioning suppressed the production of TNF-alpha and CINC in the liver during reperfusion and consequently reduced neutrophil infiltration.
Alanine Transaminase↗
In situ pedicle resection in left trisegmentectomy of the liver combined with reconstruction of the right hepatic vein to an inferior vena caval segment transpositioned from the infrahepatic portion.
A combination of an in situ pedicle resection of the liver and a hepatic vein reconstruction using a cranially transpositioned segment of the IVC after implantation of an ePTFE graft at the missing IVC was useful in treating a patient who suffered from a huge liver tumor involving all of the hepatic venous confluence and the IVC. Although early tumor recurrence remains an unresolved problem for such patients, a surgical approach is feasible. This technique can be justified as a therapeutic modality, not only because it improves quality of life, but also because it provides patients with an opportunity for additional treatment.
Anastomosis, Surgical↗
PPARgamma and inflammatory bowel disease: a new therapeutic target for ulcerative colitis and Crohn's disease.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that is known to play a central role in adipocyte differentiation and insulin sensitivity. Through work in several animal models of intestinal inflammation, it is now recognized that PPARgamma also inhibits tissue injury associated with immune activation. These studies point to PPARgamma as a novel anti-inflammatory mediator with broad therapeutic potential.
Animals↗
Spatial and temporal gene expression for fibroblast growth factor type I receptor (FGFR1) during fracture healing in the rat.
Recent experiments have shown that exogenous basic fibroblast growth factor (bFGF) enlarges fracture callus and accelerates the healing of osteotomized long bones. The actions of bFGF are mediated by four different transmembrane receptors (FGFR1-4). Among them, FGFR1 has a high affinity for bFGF, and gain-of-function mutations of the FGFR1 gene cause craniosynostosis in humans. Gene expression for FGFR1 has been analyzed in embryogenesis; however, in skeletal repair, detailed expression of FGFR1 has not been fully established. In the present study, a rat model of closed femoral fracture healing was used to quantify mRNA encoding the FGFR1 and to characterize cells expressing FGFR1 by in situ hybridization. Gene expression for FGFR1 was rapidly upregulated after fracture; its mRNA level on day 1 was 3.4-fold higher than that of unfractured femora. At this stage, a moderate signal for FGFR1 was detected in periosteal osteoprogenitor cells, inflammatory cells near fracture sites, and cells among muscle layers. FGFR1 mRNA reached peak expression when callus remodeling actively progressed (6.8-fold on day 14), and remained elevated even in the later stages of healing (6.3-fold on day 28). During the intermediate stage of fracture healing, a strong signal for FGFR1 was diffusely distributed in mature osteoblasts in the hard callus, and mature osteoclasts also expressed a weak signal for FGFR1. These results suggest that FGF/FGFR1 signaling has multifunctional roles during fracture healing and may regulate both osteoblasts and osteoclasts, contributing to bone formation and callus remodeling.
Animals↗
ABL-specific tyrosine kinase inhibitor, STI571 in vitro, affects Ph-positive acute lymphoblastic leukemia and chronic myelogenous leukemia in blastic crisis.
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Antineoplastic Agents↗
Collapse of extracellular glutamate regulation during epileptogenesis: down-regulation and functional failure of glutamate transporter function in rats with chronic seizures induced by kainic acid.
We used northern and western blotting to measure the quantity of glutamate and GABA transporters mRNA and their proteins within the hippocampal tissue of rats with epileptogenesis. Chronic seizures were induced by amygdalar injection of kainic acid 60 days before death. We found that expression of the mRNA and protein of the glial glutamate transporters GLAST and GLT-1 were down-regulated in the kainic acid-administered group. In contrast, EAAC-1 and GAT-3 mRNA and their proteins were increased, while GAT-1 mRNA and protein were not changed. We performed in vivo microdialysis in the freely moving state. During the interictal state, the extracellular glutamate concentration was increased, whereas the GABA level was decreased in the kainic acid group. Following potassium-induced depolarization, glutamate overflow was higher and the recovery time to the basal release was prolonged in the kainic acid group relative to controls. Our data suggest that epileptogenesis in rats with kainic acid-induced chronic seizures is associated with the collapse of extracellular glutamate regulation caused by both molecular down-regulation and functional failure of glutamate transport.
ATP-Binding Cassette Transporters↗
Endogenous PPAR gamma mediates anti-inflammatory activity in murine ischemia-reperfusion injury.
BACKGROUND & AIMS: Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor whose activation has been linked to several physiologic pathways including those related to the regulation of intestinal inflammation. We sought to determine whether PPAR gamma could function as an endogenous anti-inflammatory pathway in a murine model of intestinal ischemia-reperfusion (I/R) injury. METHODS: PPAR gamma-deficient and wild-type mice were examined for their response to I/R procedure. Treatment with a PPAR gamma-specific ligand was also performed. RESULTS: In a murine model of intestinal I/R injury, we observed more severe injury in PPAR gamma-deficient mice and protection against local and remote tissue injury in mice treated with a PPAR gamma-activating ligand, BRL-49653. Activation of PPAR gamma resulted in down-regulation of intercellular adhesion molecule 1 expression by intestinal endothelium and tissue tumor necrosis factor alpha messenger RNA levels most likely by inhibition of the NF-kappa B pathway. CONCLUSIONS: These data strongly suggest that an endogenous PPAR gamma pathway exists in tissues that may be amenable to therapeutic manipulation in I/R-related injuries.
Animals↗
Uveitopathogenic sites in recoverin.
PURPOSE: This study was carried out in order to determine the most potent and novel uveitopathogenic sites of recoverin using synthetic peptides. METHODS: Several synthetic peptides containing the recoverin sequence plus adjuvants were injected into Lewis rats, and the uveitopathogenic sequence was defined, clinically, histologically, and immunologically. RESULTS: Peptides containing of amino acids 57-85 and 136-167 induced severe EAU, and the lowest doses to induce EAU were 20 microg and 10 microg, respectively. Lymphocyte proliferative reactions were also positive for peptides 57-85 and 136-167. The core sequences within the uveitopathogenic site were 65-79 and 153-164. Peptides of amino acids 65-79 within 57-85 and 149-167 within 136-167 were the smallest in the recoverin sequence, respectively, that could induce severe EAU. CONCLUSION: We found recoverin has some novel potent uveitopathogenic sites, 149-167. These findings of the uveitopathogenic sites in recoverin may lead to improved understanding of the pathogenesis of uveitis and the means to design specific treatment.
Animals↗
Production of secretory leukocyte protease inhibitor by human amniotic membranes and regulation of its concentration in amniotic fluid.
Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. SLPI is a protein found in various human fluids, including parotid secretions, cervical mucus, seminal plasma and ascites. Western blot analysis revealed that SLPI protein is detected as a 12 kDa band in both the amniotic fluid and the amniotic membrane. The amniotic fluid concentrations of SLPI were assayed by enzyme-linked immunosorbent assay. SLPI concentrations in the amniotic fluid of women in the third trimester were higher than those in the second trimester. Immunohistochemistry using an anti-SLPI polyclonal antibody revealed positive staining in epithelial cells in amniotic membranes. Reverse transcription-polymerase chain reaction demonstrated that SLPI transcripts could be detected in the amniotic membranes. To determine the mechanism of SLPI production by amniotic cells, purified amniotic cells were stimulated with various cytokines. Amniotic cells produced SLPI in a dose-dependent manner when stimulated with interleukin (IL)-1alpha, IL-1beta, and tumour necrosis factor-alpha. The present findings show that SLPI is produced by the amniotic membranes in response to cytokine concentrations. The SLPI in the amniotic fluid may contribute to immunodefence mechanisms during pregnancy.
Amniotic Fluid↗
Inhibition of lung natural killer cell activity by smoking: the role of alveolar macrophages.
BACKGROUND: It is known that natural killer (NK) cell activity in the lung of smokers (SM) is lower than in non-smokers (NS). However, little is known about the underlying mechanisms. OBJECTIVE: The purpose of this work was to investigate the mechanisms of the inhibition of NK cell activity by alveolar macrophages (AM) in SM. METHODS: Lung effector cells and AM were obtained using bronchoalveolar lavage. The NK cell activity was assayed by 51Cr release method after incubation of 4 and 24 h, using K562 as target cell. AM were added at a concentration of 25% to effector cells. RESULTS: Following 24-hour culture, NK cell activity significantly increased in the NS but not in the SM. Lung NK cell activity was significantly augmented by interleukin-2 in the NS but not in the SM. Addition of AM to the NK cell preparation from SM exerted a significantly greater suppressive effect on autologous blood NK cell activity than in the NS. Indomethacin, catalase or thiourea did not prevent AM-mediated suppression of NK cell activity, in contrast to superoxide dismutase. CONCLUSIONS: These results suggest that the suppression of NK cell activity by AM in SM may be caused by O2- release rather than by prostaglandins, H2O2 or OH release from AM.
Adult↗