共查询到20条相似文献,搜索用时 15 毫秒
1.
Ciesielski MJ Kozbor D Castanaro CA Barone TA Fenstermaker RA 《Cancer immunology, immunotherapy : CII》2008,57(12):1827-1835
Survivin is a tumor-associated antigen (TAA) that has significant potential for use as a cancer vaccine target. To identify
survivin epitopes that might serve as targets for CTL-mediated, anti-tumor responses, we evaluated a series of survivin peptides
with predicted binding to mouse H2-Kb and human HLA-A*0201 antigens in peptide-loaded dendritic cell (DC) vaccines. H2-Kb-positive, C57BL/6 mice were vaccinated using syngeneic, peptide-loaded DC2.4 cells. Splenocytes from vaccinated mice were
screened by flow cytometry for binding of dimeric H2-Kb:Ig to peptide-specific CD8+ T cells. Two survivin peptides (SVN57–64 and SVN82–89) generated specific CD8+ T cells. We chose to focus on the SVN57–64 peptide because that region of the molecule is 100% homologous to human survivin. A larger peptide (SVN53–67), containing multiple class I epitopes, and a potential class II ligand, was able to elicit both CD8+ CTL and CD4+ T cell
help. We tested the SVN53–67 15-mer peptide in a therapeutic model using a peptide-loaded DC vaccine in C57BL/6 mice with survivin-expressing GL261 cerebral
gliomas. This vaccine produced significant CTL responses and helper T cell-associated cytokine production, resulting in a
significant prolongation of survival. The SVN53–67 vaccine was significantly more effective than the SVN57–64 core epitope as a cancer vaccine, emphasizing the potential benefit of incorporating multiple class I epitopes and associated
cytokine support within a single peptide. 相似文献
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3.
Hao-Wen Kao Yi-Yu Lin Chao-Cheng Chen Kwan-Hwa Chi Der-Chi Tien Chien-Chung Hsia Ming-Hsien Lin Hsin-Ell Wang 《Bioorganic & medicinal chemistry letters》2013,23(11):3180-3185
This study evaluated the tumor targeting and therapeutic efficacy of a novel theranostic agent 131I-labeled immuno-gold-nanoparticle (131I-C225-AuNPs-PEG) for high epidermal growth factor receptor (EGFR)-expressed A549 human lung cancer. Confocal microscopy demonstrated the specific uptake of C225-AuNPs-PEG in A549 cells. 131I-C225-AuNPs-PEG induced a significant reduction in cell viability, which was not observed when incubated with AuNPs-PEG and C225-AuNPs-PEG. MicroSPECT/CT imaging of tumor-bearing mice after intravenous injection of 123I-C225-AuNPs-PEG revealed significant radioactivity retention in tumor suggested that 131I-labeled C225-conjugated radioimmuno-gold-nanoparticles may provide a new approach of targeted imaging and therapy towards high EGFR-expressed cancers. 相似文献
4.
Experimental evidence indicates that human brain cancer cells proliferate or migrate, yet do not display both phenotypes at the same time. Here, we present a novel computational model simulating this cellular decision-process leading up to either phenotype based on a molecular interaction network of genes and proteins. The model's regulatory network consists of the epidermal growth factor receptor (EGFR), its ligand transforming growth factor-alpha (TGF alpha), the downstream enzyme phospholipaseC-gamma (PLC gamma) and a mitosis-associated response pathway. This network is activated by autocrine TGF alpha secretion, and the EGFR-dependent downstream signaling this step triggers, as well as modulated by an extrinsic nutritive glucose gradient. Employing a framework of mass action kinetics within a multiscale agent-based environment, we analyse both the emergent multicellular behavior of tumor growth and the single-cell molecular profiles that change over time and space. Our results show that one can indeed simulate the dichotomy between cell migration and proliferation based solely on an EGFR decision network. It turns out that these behavioral decisions on the single cell level impact the spatial dynamics of the entire cancerous system. Furthermore, the simulation results yield intriguing experimentally testable hypotheses also on the sub-cellular level such as spatial cytosolic polarization of PLC gamma towards an extrinsic chemotactic gradient. Implications of these results for future works, both on the modeling and experimental side are discussed. 相似文献
5.
In postnatal developing optic nerves, astrocytes organize their processes in a cribriform network to group axons into bundles. In neonatal rat optic nerves in vivo, the active form of EGFR tyrosine kinase is abundantly present when the organization of astrocytes and axons is most actively occurring. Blocking activity of EGFR tyrosine kinase during the development of rat optic nerves in vivo inhibits astrocytes from extending fine processes to surround axons. In vitro, postnatal optic nerve astrocytes, stimulated by EGF, organize into cribriform structures which look remarkably like the in vivo structure of astrocytes in the optic nerve. In addition, when astrocytes are co-cultured with neonatal rat retinal explants in the presence of EGF, astrocytes that are adjacent to the retinal explants, re-organize to an astrocyte-free zone into which neurites grow out from the retinal tissue. We hypothesize that in the developing optic nerve, EGFR activity directs the formation of a histo-architectural structure of astrocytes which surrounds axons and provides a permissive environment for axon development. 相似文献
6.
Prof. Ubaldo Armato M.D. Flora Romano Paola G. Andreis Lucia Paccagnella Cinzia Marchesini 《Cell and tissue research》1986,245(3):471-480
Summary In untreated primary cultures of neonatal rat liver kept in high-calcium (1.8 mmol/l), foetal bovine serum (10%v/v)-containing minimal essential medium (FBSMEM), the absolute numbers of hepatocytes did not change between day 4 and day 9 because ongoing cell loss was counterbalanced by proliferation of a discrete sub-population of the cells. By contrast, the number of stromal cells increased linearly with time. Growth of hepatocytes and stromal cells was differently affected by the daily addition, between day 4 and day 8 of culture, of fresh medium to which peptide mitogen(s) in concentrations ranging from 10-14 to 10-8 mol/l had been added. Epidermal growth factor/urogastrone (EGF/URO) with or without equimolar mixtures of glucagon and insulin, induced first hyperplasia of hepatocytes and stromal cells and then apopotosis (degeneration and death) of the progeny of the stimulated cells. By contrast, equimolar mixtures of glucagon and insulin caused a progressive increase in the number of hepatocytes and stromal cells unbalanced by any increase in cell death. At subphysiological concentrations glucagon, in synergism with EGF/URO and/or some other unknown heat-stable component of serum, acted as a trophic factor for hepatocytes. By contrast, insulin alone did not enhance growth of hepatocytes, but rather blocked the mitogenic effects of EGF/URO. The three hormones exerted neither mitogenic nor apoptotic effects when administered in a low calcium (0.01 mmol/l) FBS-MEM medium.These results reveal that EGF/URO may control the size of cell populations in neonatal liver by calcium-dependent mechanisms that make it unlikely to be a promoter of hepatocyte tumours. They also show that glucagon acts as a positive trophic regulator for hepatocytes. 相似文献
7.
Philippe Dje N'Guessan Helge Haarmann Tamara Steiner Kerstin Heyl Frauke Schreiber Annina Heinrich Hortense Slevogt 《Biochemical and biophysical research communications》2014
Background
Chronic lower airway inflammation is considered to be a major cause of pathogenesis and disease progression in chronic obstructive pulmonary disease (COPD). Moraxella catarrhalis is a COPD-associated pathogen causing exacerbations and bacterial colonization in the lower airways of patients, which may contribute to chronic inflammation. Increasing evidence suggests that the epidermal growth factor receptor (EGFR) modulates inflammatory processes in the human airways. The goal of this study was to investigate the role of EGFR in the M. catarrhalis-induced pro-inflammatory immune response in airway epithelial cells.Methods
The effects of inhibition and gene silencing of EGFR on M. catarrhalis-dependent pro-inflammatory cytokine expression in human primary bronchial epithelial cells (NHBEs), as well as the pulmonary epithelial cell lines BEAS-2B and A549 were analyzed. We also assessed the involvement of EGFR-dependent ERK and NF-κB signaling pathways.Results
The M. catarrhalis-induced pro-inflammatory immune response depends, at least in part, on the phosphorylation and activation of the EGF receptor. Interaction of M. catarrhalis with EGFR increases the secretion of pro-inflammatory cytokines, which is mediated via ERK and NF-κB activation.Conclusion
The interaction between M. catarrhalis and EGFR increases airway inflammation caused by this pathogen. Our data suggest that the inhibition of EGFR signaling in COPD could be an interesting target for reducing M. catarrhalis-induced airway inflammation. 相似文献8.
Shao W Zhao S Liu Z Zhang J Ma S Sato JD Zhang P Tong M Han J Wang Y Bai D Wang F Sun L 《Biochemical and biophysical research communications》2006,349(2):816-824
Anti-EGFR monoclonal antibodies LA22 and Erbitux bind to different epitopes of EGFR. The chemimmunoconjugates of MMC with LA22 or Erbitux were prepared, and in vitro cytotoxicity assays with A549 cells showed that LA22-MMC was much more potent than Erbitux or Erbitux-MMC. Viabilities of A549 cells treated with LA22-MMC, Erbitux or Erbitux-MMC were 35%, 94%, and 81%, respectively. Immunoscintigraphy of xenografts of human A431 and A549 cells in nude mice both showed that (125)I-labeled-LA22-MMC enriched in tumor sites prominently. Most importantly, in vivo assays showed LA22-MMC was significantly more effective than free drug MMC in the treatment of subcutaneous xenografts of human A431 cells in nude mice (83% inhibition for LA22-MMC and 30% for MMC). We concluded that LA22-MMC could be a very potent drug for treatment of solid tumors. 相似文献
9.
Michael S. Munns Karen Moore Lyne Jossé Paul N. Fitchett John A. Bryant 《Experimental Biology Online》1998,3(7):1-5
A 13-residue oligopeptide corresponding to a conserved region of the MCM family of proteins was synthesised as a multiple antigen peptide in which eight copies of the peptide were conjugated to an oligo-lysine core. The multiple antigen peptide was used for raising antibodies. Western blots of the polypeptides present in the DNA polymerase–primase complex from pea (Pisum sativum L.) were challenged with the antibodies which, even at a dilution of 1:5000, clearly revealed a polypeptide of approximately 62 kDa. 相似文献
10.
Hemorrhagic cystitis is one of the devastating complications seen after receiving cyclophosphamide chemotherapy. Oleuropein is the most important phenolic compound of olive leaves that mediates most of its beneficial pharmacological properties. Herein, we investigated the possible uroprotective effect of oleuropein against cyclophosphamide induced hemorrhagic cystitis in a rat model. For this purpose, we measured bladder nitric oxide, reduced glutathione, catalase, tumor necrosis factor-alpha and vascular endothelial growth factor levels in addition to the bladder gene expression of intercellular adhesion molecule-1 after induction of hemorrhagic cystitis in the presence or absence of oleuropein. Histopathological examination of bladder tissues was also performed. After cyclophosphamide injection, we demonstrated a significant decrease in bladder reduced glutathione (39%) and catalase (55.4%) levels and a significant increase of nitric oxide (5.6 folds), tumor necrosis factor-alpha (3.3 folds), vascular endothelial growth factor (2 folds) and intercellular adhesion molecule-1 (8 folds) bladder contents when compared to those in normal control rats. Administration of oleuropein induced a marked elevation in bladder reduced glutathione (37.8%), catalase (100.4%) with a prominent reduction of bladder nitric oxide (40%), tumor necrosis factor-alpha (35.9%) and vascular endothelial growth factor (56.2%) levels along with downregulation of intercellular adhesion molecule-1 bladder expression (73.1%) in comparison to cyclophosphamide treated rats levels. Our data demonstrated that oleuropein counteracts the harmful effects of cyclophosphamide on the bladder through its antioxidant and anti-inflammatory activities. Oleuropein exerts a definite uroprotective effect against cyclophosphamide induced hemorrhagic cystitis in rats. 相似文献
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13.
《Cytokine》2016
Cisplatin is the first platinum-containing anti-cancer drugs. Cisplatin notable side effect of nephrotoxicity limits its use in clinic. Meanwhile, arjunolic acid possesses anti-inflammatory properties and plays protective roles against chemically induced organ pathophysiology. This study was conducted to find out whether arjunolic acid could attenuate kidney damage in rats, and to elucidate its possible mechanism of action. Fifty rats were treated with cisplatin (10 mg/kg) in the presence/absence of 100 or 250 mg/kg arjunolic acid. Arjunolic acid is given 1 h after cisplatin. Morphological changes were assessed in kidney sections stained with Hematoxylin/Eosin and Masson Trichrome. Kidney samples were used for measurements of transforming growth factor (TGF)-β1 and its type 1 receptor (TGF-βR1), tumor necrosis factor (TNF)-α and interleukin (IL)-1β by ELISA. Gene expression NFκB was determined by real time-PCR. Kidney tissue apoptosis was assessed by measuring the activities of caspase-3/8/9. The renal protective effect of arjunolic acid was confirmed by approximately normal appearance of renal tissue and the relatively unaffected serum creatinine and urea levels. Furthermore, arjunolic acid showed dose dependent reduction in cisplatin-induced elevation in renal levels of TGF-βR1, TGF-β1, TNF-α, IL-1β and caspases. These findings demonstrated that arjunolic acid attenuates cisplatin nephrotoxicity either indirectly by enhancing body antioxidant activity or directly through several mechanisms, including inhibition of pro-inflammatory cytokines, blocking activation of TGF-β1, and anti-apoptotic effects. 相似文献
14.
Huiying Zhang Minli Lv Zhongfu Zhao Jiantao Jia Lili Zhang Peng Xiao Limin Wang Chen Li Jingquan Ji Xiaoxia Tian Xujiong Li Yimin Fan Lina Lai Yan Liu Baohong Li Cuiying Zhang Mingshe Liu Jianhong Guo Dewu Han Cheng Ji 《Gene》2014
Objective
This study is to investigate the role of glucose-regulated protein 78 (GRP78) in the pulmonary microvascular remodeling during hepatopulmonary syndrome (HPS) development.Methods
The rat models with liver cirrhosis and HPS were induced by multiple pathogenic factors for 4 to 8 wk. The concentrations of alanine transferase (ALT) and endotoxin in plasma were detected in the models, followed by the detection of GRP78 expression. RT-PCR, quantitative real-time PCR and Western blotting were employed to assess the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), respectively. Immunohistochemistry staining was used to examine the expression of a specific vascular marker, factor VIII-related antigen (FVIII-RAg), and several cell proliferation- and apoptosis-related proteins, including CHOP/GADD153, caspase-12, Bcl-2 and nuclear factor (NF)-κB.Results
The levels of endotoxin and ALT in plasma were gradually increased as the disease progressed, so did GRP78, which were in a positive correlation. The expression levels of VEGF (both mRNA and protein) and FVIII-RAg were significantly elevated in the HPS models, indicating active angiogenesis, which was also positively correlated with GRP78 expression. Furthermore, the expression levels of the pro-apoptotic proteins of CHOP/GADD153 and caspase-12 were dramatically decreased, while the anti-apoptotic proteins of Bcl-2 and NF-κB were significantly elevated, in the HPS models. There were also close correlation between these proteins and GRP78.Conclusions
Over-expression of GRP78 in lungs may be the critical pathogenic factor for HPS. Through promoting cell proliferation and survival and inhibiting apoptosis, GRP78 may promote the pulmonary microvascular remodeling in HPS pathogenesis. Our results provide a potential therapeutic target for clinical prevention and treatment for HPS and related complications. 相似文献15.
Diana A. Aderetti Vashendriya V.V. Hira Remco J. Molenaar Cornelis J.F. van Noorden 《生物化学与生物物理学报:癌评论》2018,1869(2):346-354
Glioblastoma is the most lethal primary brain tumor and poor survival of glioblastoma patients is attributed to the presence of glioma stem cells (GSCs). These therapy-resistant, quiescent and pluripotent cells reside in GSC niches, which are specific microenvironments that protect GSCs against radiotherapy and chemotherapy. We previously showed the existence of hypoxic peri-arteriolar GSC niches in glioblastoma tumor samples. However, other studies have described peri-vascular niches, peri-hypoxic niches, peri-immune niches and extracellular matrix niches of GSCs. The aim of this review was to critically evaluate the literature on these five different types of GSC niches. In the present review, we describe that the five niche types are not distinct from one another, but should be considered to be parts of one integral GSC niche model, the hypoxic peri-arteriolar GSC niche. Moreover, hypoxic peri-arteriolar GSC niches are structural and functional look-alikes of hematopoietic stem cell (HSC) niches in the bone marrow. GSCs are maintained in peri-arteriolar niches by the same receptor-ligand interactions as HSCs in bone marrow. Our concept should be rigidly tested in the near future and applied to develop therapies to expel and keep GSCs out of their protective niches to render them more vulnerable to standard therapies. 相似文献
16.
《Microbes and infection / Institut Pasteur》2013,15(13):895-902
Oral mucosal immunization is a feasible and economic vaccination strategy. In order to achieve a successful oral mucosal vaccination, antigen delivery to gut immune inductive site and avoidance of oral tolerance induction should be secured. One promising approach is exploring the specific molecules expressed on the apical surfaces of M cells that have potential for antigen uptake and immune stimulation. We previously identified complement 5a receptor (C5aR) expression on human M-like cells and mouse M cells and confirmed its non-redundant role as a target receptor for antigen delivery to M cells using a model antigen. Here, we applied the OmpH ligand, which is capable of targeting the ligand-conjugated antigen to M cells to induce specific mucosal and systemic immunities against the EDIII of dengue virus (DENV). Oral immunization with the EDIII–OmpH efficiently targeted the EDIII to M cells and induced EDIII-specific immune responses comparable to those induced by co-administration of EDIII with cholera toxin (CT). Also, the enhanced responses by OmpH were characterized as Th2-skewed responses. Moreover, oral immunization using EDIII–OmpH did not induce systemic tolerance against EDIII. Collectively, we suggest that OmpH-mediated targeting of antigens to M cells could be used for an efficient oral vaccination against DENV infection. 相似文献
17.
Nai Wen Chang Ming-Hsui TsaiChingju Lin Hui Ting HsuPei-Yi Chu Chung-Min YehChang-Fang Chiu Kun-Tu Yeh 《生物化学与生物物理学报:疾病的分子基础》2011,1812(4):558-564
The excessive use of areca nut and/or tobacco may induce the production of free radicals and reactive oxygen species, which affect the lipid contents of the cell membrane and are possibly involved in tumorigenic processes in the oral cavity. The aim of this study was to investigate the therapeutic efficacy of fenofibrate (0.1% or 0.3%, w/w), a ligand of the peroxisome proliferator-activated receptor alpha (PPARα), in a 4-nitroquinoline 1-oxide (4-NQO)/arecoline-induced oral cancer mouse model. The carcinogen, 4-NQO/arecoline, was administrated to C57BL/6JNarl mice for 8 weeks followed by fenofibrate treatment for 12 or 20 weeks. After 28 weeks, changes in serum lipids, the multiplicity of tumor lesions, and tumor sizes were determined together with changes in the immunohistochemical expressions of PPARα, acetyl-coenzyme A carboxylase (ACC), the epidermal growth factor receptor (EGFR), and cyclooxygenase-2 (COX2). The results showed that when compared to the 4-NQO/arecoline only group, 0.3% fenofibrate treatment increased serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. 0.3% fenofibrate treatment suppressed the incidence rate of tongue lesions, reduced the multiplicity of squamous cell carcinoma (SCC), decreased the tumor size, and increased the immunoreactivity of EGFR and COX2 in oral dysplasia but decreased EGFR and COX2 expressions in SCC. These findings indicated that fenofibrate reduced the tumor incidence rate and suppressed the tumor progression into SCC and that these molecular events might be linked to the EGFR and COX2 regulatory pathways. We suggest that fenofibrate provides a new strategy for preventing oral tumor progression. 相似文献
18.
Xianfeng Xia Philip Wai Yan Chiu Ping Kuen Lam Wai Ching Chin Enders Kwok Wai Ng James Yun Wong Lau 《生物化学与生物物理学报:疾病的分子基础》2018,1864(1):178-188
Studies have indicated that the definitive engraftment and transdifferentiation potential of stem cells do not seem crucial for its property of tissue repair. Our previous study showed that transplantation of adipose-derived mesenchymal stem cells (ADMSCs) enhanced the healing of sutured gastric perforation. This study aimed to investigate the paracrine role of ADMSCs in the experimental gastric mucosal injury. Normoxia-conditioned medium (Nor CM) and hypoxia (HPO) CM were obtained after culturing ADMSCs in 20% O2 and 5% O2 for 48 h. Cell migration, proliferation, viability, and angiogenesis in vitro were significantly enhanced upon incubation with CM, especially the HPO CM. Experiments in vivo using a rodent model of gastric ulcer demonstrated that HPO CM treatment significantly accelerated wound healing by suppressing inflammation and promoting neovascularization and re-epithelization. Meanwhile, the infusion of HPO CM activated the COX2-PGE2 axis both in vitro and in vivo. And the upregulation of COX2 was further dependent on the activation of ErK1/2-MAPK pathway. In addition, vascular endothelial growth factor, tissue inhibitors of metalloproteinases-1, and chemokine (C-C motif) ligand 20 (CCL-20) were analyzed as being highly abundant factors secreted by ADMSCs under hypoxic condition. Notably, the blockade of CCL-20 abrogated the HPO CM-induced COX2 signaling in the primary gastric mucosal epithelial cells, while incubation with recombinant CCL-20 increased the expression of COX2. In conclusion, the secretome from hypoxia-conditioned ADMSCs facilitates the repair of gastric mucosal injury through the enhancement of angiogenesis and re-epithelization, as well as the activation of COX2-PGE2 axis with a paracrine activity involving CCL-20 factor. 相似文献
19.
Ohte S Shin M Sasanuma H Yoneyama K Akita M Ikebuchi K Jimi E Maruki Y Matsuoka M Namba A Tomoda H Okazaki Y Ohtake A Oda H Owan I Yoda T Furuya H Kamizono J Kitoh H Nakashima Y Susami T Haga N Komori T Katagiri T 《Biochemical and biophysical research communications》2011,(1):213-218
Naphthoquinone derivatives have been reported to possess various pharmacological activities, such as antiplatelet, anticancer, antifungal, and antiviral properties. In this study, we investigated the effects of a newly-synthesized naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2-decylamino-DMNQ), on VSMC proliferation and examined the molecular basis of the underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2-decylamino-DMNQ did not affect PDGF-Rβ or Akt, it did inhibit the phosphorylation of Erk1/2 and PLCγ1 induced by PDGF. Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G0/G1 phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that both U0126, an Erk1/2 inhibitor, and U73122, a PLCγ inhibitor, increased the proportion of cells in the G0/G1 phase of the cell cycle. Thus, these results suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC proliferation and the mechanism of this action is through cell cycle arrest at the G0/G1 phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation. 相似文献
20.
Molecular and structural analysis of C4-specific PEPC isoform from Pennisetum glaucum plays a role in stress adaptation 总被引:1,自引:0,他引:1
As an activator of adenylate cyclase, the neuropeptide Pituitary Adenylate Cyclase Activating Peptide (PACAP) impacts levels of cyclic AMP, a key second messenger available in brain cells. PACAP is involved in certain adult behaviors. To elucidate PACAP interactions, a compendium of microarrays representing mRNA expression in the adult mouse whole brain was pooled from the Phenogen database for analysis. A regulatory network was computed based on mutual information between gene pairs using gene expression data across the compendium. Clusters among genes directly linked to PACAP, and probable interactions between corresponding proteins were computed. Database “experts” affirmed some of the inferred relationships. The findings suggest ADCY7 is probably the adenylate cyclase isoform most relevant to PACAP's action. They also support intervening roles for kinases including GSK3B, PI 3-kinase, SGK3 and AMPK. Other high-confidence interactions are hypothesized for future testing. This new information has implications for certain behavioral and other disorders. 相似文献