Mohd Lila Mohd Azmi;Field, Hugh-John;Frazer Rixon;Lauchlan, John-Mc
Journal of Microbiology
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v.40
no.1
/
pp.11-19
/
2002
Mice immunized with equine herpesvirus type-1(EHV-1) L-particles skewed a significant increase (p<7.75) in serum antibody titers. Upon a booster dose four weeks lateral antibody titers increased significantly. Interestingly, immunization via intravenous or intramuscular route induced significantly higher (p<0.75) antibody titers. However, mice iummunized with UV-treated L-particles, visions or immunization via intranasal route induced lower antibody titers. Upon challenge inoculation with wildtype EHV-1, our data showed there was a poor correlation between antibody titers and protection against virus replication. Therefore, the role of cell-mediated immunity Inwards protection was investigated. As predicted, the strongest cell-mediated immunity, as measured by delayed-hypersensitivity test, was detected in mice immunized with live virus particles. The magnitude of cell-mediated immune response correlated with the efficacy of L-particles as immunizing agent. The highest efficacy, as indicated in mice immunized via intranasal routed was highly correlated with cell-mediated immunity. A similar phenomenon was also demonstrated in mice immunized intranasally with UV-treated L-particles. However, the degree of protection was reduced when mice immunized intravenously or intramuscularly with UV-treated L-particles. In conclusion, protection conferred in these animals was highly implicated by immune cells and the least by antibodies. The route of immunization and the nature of the antigen also contributed to the efficacy of L-particles as immunizing agent. In contrast to that of herpes simplex virus type 1, our data showed EHV-1 non-infectious L-particles are highly suitable for immunization of the host against EHV-1 disease.
BACKGROUND/OBJECTIVES: Folate plays a critical role in DNA synthesis and methylation. Intracellular folate homeostasis is maintained by the enzymes folylpolyglutamate synthase (FPGS) and γ-glutamyl hydrolase (GGH). FPGS adds glutamate residues to folate upon its entry into the cell through a process known as polyglutamylation to enhance folate retention in the cell and to maintain a steady supply of utilizable folate derivatives for folate-dependent enzyme reactions. Thereafter, GGH catalyzes the hydrolysis of polyglutamylated folate into monoglutamylated folate, which can subsequently be exported from the cell. The objective of this review is to summarize the scientific evidence available on the effects of intracellular folate homeostasis-associated enzymes on cancer chemotherapy. METHODS: This review discusses the effects of FPGS and GGH on chemosensitivity to cancer chemotherapeutic agents such as antifolates, such as methotrexate, and 5-fluorouracil. RESULTS AND DISCUSSION: Polyglutamylated (anti)folates are better substrates for intracellular folate-dependent enzymes and retained for longer within cells. In addition to polyglutamylation of (anti)folates, FPGS and GGH modulate intracellular folate concentrations, which are an important determinant of chemosensitivity of cancer cells toward chemotherapeutic agents. Therefore, FPGS and GGH affect chemosensitivity to antifolates and 5-fluorouracil by altering intracellular retention status of antifolates and folate cofactors such as 5,10-methylenetetrahydrofolate, subsequently influencing the cytotoxic effects of 5-fluorouracil, respectively. Generally, high FPGS and/or low GGH activity is associated with increased chemosensitivity of cancer cells to methotrexate and 5-fluorouracil, while low FPGS and/or high GGH activity seems to correspond to resistance to these drugs. Further preclinical and clinical studies elucidating the pharmocogenetic ramifications of these enzyme-induced changes are warranted to provide a framework for developing rational, effective, safe, and customized chemotherapeutic practices.
Yu, Changchun;Xiong, Yongjian;Chen, Dapeng;Li, Yanli;Xu, Bin;Lin, Yuan;Tang, Zeyao;Jiang, Chunling;Wang, Li
The Korean Journal of Physiology and Pharmacology
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v.21
no.1
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pp.1-9
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2017
Intestinal disorders often co-occur with inflammation and dysmotility. However, drugs which simultaneously improve intestinal inflammation and co-occurring dysmotility are rarely reported. Atractylodin, a widely used herbal medicine, is used to treat digestive disorders. The present study was designed to characterize the effects of atractylodin on amelioration of both jejunal inflammation and the co-occurring dysmotility in both constipation-prominent (CP) and diarrhea-prominent (DP) rats. The results indicated that atractylodin reduced proinflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 in the plasma and inhibited the expression of inflammatory mediators iNOS and NF-kappa B in jejunal segments in both CP and DP rats. The results indicated that atractylodin exerted stimulatory effects and inhibitory effects on the contractility of jejunal segments isolated from CP and DP rats respectively, showing a contractile-state-dependent regulation. Atractylodin-induced contractile-state-dependent regulation was also observed by using rat jejunal segments in low and high contractile states respectively (5 pairs of low/high contractile states). Atractylodin up-regulated the decreased phosphorylation of 20 kDa myosin light chain, protein contents of myosin light chain kinase (MLCK), and MLCK mRNA expression in jejunal segments of CP rats and down-regulated those increased parameters in DP rats. Taken together, atractylodin alleviated rat jejunal inflammation and exerted contractile-state-dependent regulation on the contractility of jejunal segments isolated from CP and DP rats respectively, suggesting the potential clinical implication for ameliorating intestinal inflammation and co-occurring dysmotility.
Objective : Microscopic indocyanine green (ICG) angiography is useful for identifying the completeness of aneurysm clipping and the preservation of parent arteries and small perforators. Neuroendoscopy is helpful for visualizing structures beyond the straight line of the microscopic view. We evaluated our prototype of endoscopic ICG fluorescence angiography in swine, which we developed in order to combine the merits of microscopic ICG angiography and endoscopy. Methods : Our endoscopic ICG system consists of a camera, a light source, a display and software. This system can simultaneously display real-time visible and near infrared fluorescence imaging on the same monitor. A commercially available endoscope was used, which was 4 mm in diameter and had an angle of $30^{\circ}$. A male crossbred swine was used. Results : Under general anesthesia, a small craniotomy was performed and the brain surface of the swine was exposed. ICG was injected via the ear vein with a bolus dose of 0.3 mg/kg. Visible and ICG fluorescence images of cortical vessels were simultaneously observed on the display monitor at high resolution. The real-time merging of the visible and fluorescent images corresponded well. Conclusion : Simultaneous visible color and ICG fluorescent imaging of the cortical vessels in the swine brain was satisfactory. Technical improvement and clinical implication are expected.
Journal of the Korea Academia-Industrial cooperation Society
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v.19
no.4
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pp.353-361
/
2018
This study aimed to examine the effects of rejection sensitivity on depression and anxiety, and the moderating effects of school violence victimization experiences on the relationships between rejection sensitivity and both anxiety and depression. Based on the results, we suggested a method of screening soldiers at high risk of depression and anxiety and interventions for their psychological adaptation. The data about anxiety, depression, rejection sensitivity, and school violence victimization experiences was collected from 126 airmen in S city, South Korea. To test the moderation effects, multiple regression analyses were conducted in which the rejection sensitivity, anxiety, school violence victimization experiences and their interaction terms were hierarchically entered. The moderation of school violence victimization experiences was found in the relationship between rejection sensitivity and school violence victimization experiences. The specific interaction patterns in each of these significant interaction effects were examined. Finally, the importance of school violence victimization experiences as a high-risk factor in army life and the clinical implication of these findings were discussed.
Ha, Ji-Young;Kim, Jong-In;Seo, Jung-Chul;Ko, Hyung-Kyun
Journal of Acupuncture Research
/
v.24
no.1
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pp.151-163
/
2007
Objectives : Juglandis Semen herbal acupuncture solution(JSS) has a broad array of clinical applications in oriental medicine, including treatment of chronic musculoskeletal diseases such as arthritis. This study was performed to investigate the global gene expression profiles using microarray assay in RAW 264.7 cell line treated with JSS and to advance our understanding of the pharmacologic effect of JSS. Methods : Change of the gene expression profile in RAW cell line following treatment with lipopolysaccharide(LPS) alone, or with LPS plus JSS was investigated with a cut-off level of 2 fold change in the expression. Especially, Change of the gene expression by treatment with LPS alone was compared with that by treatment with LPS plus JSS with a cut-off level of 1/2 fold change in the expression. Results: Of the 8170 genes profiled in this study, 51 were upragulated and 21 downregulated following LPS treatment, and 88 were upregulated and 69 downregulated following costimulation of JSS and LPS. Of the 51 genes upregulated following LPS treatment, 10 were downregulated following costimulation of JSS and LPS. Of the 21 genes downregulated following LPS treatment, 3 were upregulated following costimulation of JSS and LPS. Conclusion : JSS treatment induced upregulation of some genes including IL-10 and downregulation of that including MMP13 with its possible implication in an antiinflammatory action of JSS. However, further research on expression profile changes induced by JSS treatment is expected.
The loudness dependence of the auditory evoked potential (LDAEP) has been proposed as a valid biomarker of central serotoninergic activity in humans. The specificity and sensitivity of the LDAEP to changes in serotonergic neurotransmission have recently been explored in many studies about pharmacology and genetics. The majority of evidence for an association between the LDAEP and serotonin activity has come from animal studies. Genetic association studies with the LDAEP have provided conflicting reports with additional evidence outlining sensitivity to other neurotransmitter systems including the dopamine and glutamatergic systems. The LDAEP has been revealed to reflect the pathophysiology of various psychiatric illnesses. There is supporting evidence that major psychiatric disorders have differential LDAEP activities. Overall, the LDAEP shows strong evidence as a potential predictor of antidepressant treatment response. It need to be explored whether the LDAEP could be a biological marker of various psychiatric diseases and treatment prediction of antidepressants and serotonin related drugs.
The presence of HPV DNA and the expression of p53 protein and proliferating cell nuclear antigen(PCNA) in head and neck squamous cell carcinoma were determined to evaluate the relationship of these factors and their association with their pathologic stages and cervical lymph node metastasis. Among 65 patients the presence of HPV DNA was found in 12 cases(18.5%), p53 was found positive in 32 cases(49.2%) and expression of PCNA was observed in 24 cases(36.9%). The expression of PCNA was more frequent in the HPV positive cancers compared with the HPV negative ones(p =0.0018), and p53 revealed its higher rate of cooccurrence with the expression of PCNA(p =0.008), which might suggest that PCNA expression has a positive relationship with HPV and p53 mutation in head and neck cancer. There might be inverse relationship between HPV and p53 mutation(p =0.063), but 3 cases showed both HPV DNA positivity and p53 expression. HPV was detected at a higher rate in the early pathologic stages than in the advanced stages of cancer, and p53 expression was more frequently found in the advanced stages(p =0.044). These results suggests that HPV and p53 mutation might have different etiologic roles in the development of head and neck cancer, or cases with p53 mutation might have more aggressive behavior. PCNA expression showed no difference between early and late stages of cancer, and between cases with and without cervical lymph node metastasis.
Background: Because there is no clear consensus for the prognostic implication of KRAS mutations in patients with non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to draw a more accurate conclusion. Materials and Methods: A systematic computer search of articles from inception to May 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articles and extraction of data were independently performed by two authors. Results: Our analysis was based on the endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS) comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations. In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) and PFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC. According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS and PFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However, the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treated with chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643). Conclusions: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLC but not for those treated with chemotherapies integrating cetuximab.
Purpose: The purpose of this study was to determine the frequency of $CD4^+CD25^+FoxP3^+$ regulatory T cells (Treg) in the peripheral blood of patients with childhood chronic immune thrombocytopenic purpura (ITP) exhibiting thrombocytopenia and spontaneous remission. The findings of this study indicate the possibility of predicting spontaneous recovery and pathogenesis of childhood chronic ITP. Methods: Eleven children with chronic ITP (seven thrombocytopenic and four spontaneous remission cases; mean age, 8.8 years; range, 1.7-14.9 years) were enrolled in this study. Five healthy children and eight healthy adults were included as controls. The frequency of Treg was evaluated by flow cytometry in the peripheral blood. Results: In this study, four patients (36%) achieved spontaneous remission within 2.8 years (mean year; range, 1.0-4.4 years). The frequency of Treg was significantly lower in patients with persisting thrombocytopenia ($0.13%{\pm}0.09%$, P<0.05), than that in the patients with spontaneous remission ($0.30%{\pm}0.02%$), healthy adults controls ($0.55%{\pm}0.44%$), and healthy children controls ($0.46%{\pm}0.26%$). A significantly positive correlation was found between the frequency of Treg and the platelet count in children. Conclusion: These data suggest that a lower frequency of Treg contributes to the breakdown of self-tolerance, and may form the basis for future development of specific immunomodulatory therapies. Furthermore, Treg frequency has prognostic implication toward the natural course and long-term outcomes of childhood chronic ITP.
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