The possible beneficial effects of chronic low-dose irradiation (LDR) and its mechanism of action in a variety of pathophysiological processes such as cancer are a subject of intense investigation. While animal studies involving long-term exposure to LDR have yielded encouraging results, the influence of LDR at the cellular level has been less well defined. We reasoned that since natural killer (NK) cells constitute an early responder to exogenous stress, NK cells may reveal sentinel alterations in function upon exposure to LDR. When purified NK cells received LDR at 4.2 mGy/h for a total of 0.2 Gy in vitro, no significant difference in cell viability was observed. Likewise, no functional changes were detected in LDR-exposed NK cells, demonstrating that LDR alone was insufficient to generate changes at the cellular level. Nonetheless, significant augmentation of cytotoxic, but not proliferative, function was detected when NK cells were stimulated with low-dose IL-2 prior to irradiation. This enhancement of NK cytotoxicity was not due to alterations in NK-activating receptors, NK1.1, NKG2D, CD69 and 2B4, or changes in the rate of early or late apoptosis. Therefore, LDR, in the presence of suboptimal cytokine levels, can facilitate anti-tumor cytotoxicity of NK cells without influencing cellular proliferation or apoptosis. Whether these results translate to in vivo consequences remains to be seen; however, our data provide initial evidence that exposure to LDR can lead to subtle immune-enhancing effects on NK cells and may explain, in part, the functional basis underlying, diverse beneficial effects seen in the animals chronically exposed to LDR.
Low-dose radiation; natural killer cells; natural cytotoxicity; innate immunity
The purpose of this study was to investigate effect of nutrition education at worksite program in male workers. The subjects were 75 male workers who had received nutrition education by a clinical dietitian for 4 months. The anthropometric data, blood pressure and biochemical blood indices were measured before and after nutrition education. Dietary habits and lifestyle were investigated by self-administered questionnaires. Nutrients intake was determined by 24-hour dietary recall method. The results showed significant decreases in body mass index (p < 0.05), fasting blood sugar (p < 0.01), total cholesterol (p < 0.05), and LDL-cholesterol (p < 0.05) after nutrition education. The correlation analyses among anthropometric and clinical parameters after nutrition education indicated that there was a significantly positive correlations between blood pressure and weight, r-GTP. A significantly positive correlations was observed between fasting blood sugar and triglycerides. A significantly positive correlations was observed between triglycerides and body mass index, r-GTP, SGPT. A significantly positive correlations was observed between SGPT and weight, body mass index. A significantly negative correlations was observed between HDL-cholesterol and weight. It could be concluded that nutrition education might be effective tool to improve anthropometric measures and clinical parameters in male workers. Continuing and systematic nutritional management programs should be developed and implemented for male workers at the worksites to maintain optimal health status.
Body mass index; Blood lipids; Blood pressure; Blood glucose; Liver function tests; Nutrition eduction
Fusarium graminearum virus 1 strain-DK21 (FgV1-DK21) is a mycovirus that confers hypovirulence to F. graminearum, which is the primary phytopathogenic fungus that causes Fusarium head blight (FHB) disease in many cereals. Understanding the interaction between mycoviruses and plant pathogenic fungi is necessary for preventing damage caused by F. graminearum. Therefore, we investigated important cellular regulatory processes in a host containing FgV1-DK21 as compared to an uninfected parent using a transcriptional approach.
Using a 3′-tiling microarray covering all known F. graminearum genes, we carried out genome-wide expression analyses of F. graminearum at two different time points. At the early point of growth of an infected strain as compared to an uninfected strain, genes associated with protein synthesis, including ribosome assembly, nucleolus, and ribosomal RNA processing, were significantly up-regulated. In addition, genes required for transcription and signal transduction, including fungal-specific transcription factors and cAMP signaling, respectively, were actively up-regulated. In contrast, genes involved in various metabolic pathways, particularly in producing carboxylic acids, aromatic amino acids, nitrogen compounds, and polyamines, showed dramatic down-regulation at the early time point. Moreover, genes associated with transport systems localizing to transmembranes were down-regulated at both time points.
This is the first report of global change in the prominent cellular pathways in the Fusarium host containing FgV1-DK21. The significant increase in transcripts for transcription and translation machinery in fungal host cells seems to be related to virus replication. In addition, significant down-regulation of genes required for metabolism and transporting systems in a fungal host containing the virus appears to be related to the host defense mechanism and fungal virulence. Taken together, our data aid in the understanding of how FgV1-DK21 regulates the transcriptional reprogramming of F. graminearum.
We report magnetic resonance image (MRI) and magnetic resonance spectroscopy (MRS) findings in a patient of cerebral fat embolism (CFE) occurred in a 26-year-old woman after an autologous fat injection into the face. After initial neurologic symptom onset, MRI and MRS data were obtained two times to investigate repeated CFE. We obtained the MRS data in the two different time intervals and two different echo times to compare the lesions with normal brain parenchyma. The results of MRS data showed that a decrease in N-acetyl-aspartate, an increase in lactate and a very high early peak of free lipids between 0.9 and 1.4 ppm were obtained at the acute infarcted lesion as compared with normal brain parenchyma. In addition, these findings were more clearly detected on short echo time spectrum rather than long spectrum. A close relationship between the clinical manifestations and MRI and MRS findings of the brain can helpful to distinguish CFE with other conditions and to evaluate the cause materials of infarctions rather than conventional MRI or diffusion-weighted imaging.
Cerebral fat embolism; Single-voxel MR spectroscopy; Point-resolved spectroscopy (PRESS); Autologous fat injection
We conducted a pilot study to evaluate the effects of pelvic radiotherapy on biologic markers of oxidative stress and plasma endotoxin levels, and to assess the relationship between the changes of such factors and radiotherapy-related complications.
Twelve gynecologic cancer patients who were treated via pelvic radiotherapy with or without concurrent chemotherapy were enrolled in this study. Biologic markers of oxidative stress, such as glutathione (GSH) and oxidized glutathione (GSSG), as well as endotoxin levels, were measured weekly during treatment. Subjective symptoms were assessed using the Korean version of the EORTC QLQ-C30 at the baseline and on the 5th week of radiotherapy.
No changes were noted in the level of GSH in whole blood, but the GSH/GSSG ratio was reduced dramatically after the initiation of radiotherapy. The mean plasma endotoxin for all patients tended to increase and persisted during radiotherapy, and the number of patients who evidenced clinically significant endotoxin levels (defined as >0.005 EU/mL) also increased. Nausea/vomiting and diarrhea were significantly changed (p=0.019 and p<0.001, respectively). A significant relationship was noted to exist between the changes in the endotoxin level and nausea/vomiting (p=0.001). However, such symptoms did not correlate with the changes of oxidative stress markers.
Pelvic radiotherapy oxidized the GSH redox system and increased plasma endotoxin. Further investigations containing interventional and longitudinal studies will be required to assess the effects of the changes in oxidative stress markers and endotoxin on radiotherapy-related adverse events.
Adverse effects; Endotoxins; Oxidative stress; Radiotherapy
Rhinocerebral mucormycosis is an acute fulminant opportunistic fungal infection usually seen in diabetic or immunocompromised patients. The fungi that cause mucormycosis inoculate the nasal mucosa and may spread to the paranasal sinuses, orbit, and brain. Our patient initially presented with mild ethmoid sinusitis. At that time, brain MRI and contrast-enhanced MR angiography were grossly normal. However, aggravation of sinusitis with extension to the right orbit and anterior cranial fossa rapidly developed within two months. Moreover, an occlusion of the right internal carotid artery was combined. We report a case of a pathologically-proven rhino-orbital-cerebral mucormycosis with serial follow-up imaging for over one year.
Mucormycosis; Carotid artery, Internal; Fungal sinusitis
Ultraviolet (UV) radiation is the primary environmental risk factor in the development of nonmelanoma skin cancer, and UVB in particular promotes tumor growth through various signaling pathways. Kaempferol, a flavonoid with anti-inflammatory and anti-oxidative properties, has been studied as a chemopreventive agent; however, little is known regarding its effects on UVB-induced photo-carcinogenesis. Here, we examined the effect of kaempferol on UVB-induced skin inflammation. We found that kaempferol suppressed UVB-induced cyclooxygenase-2 (COX-2) protein expression in mouse skin epidermal JB6 P+ cells and attenuated the UVB-induced transcriptional activities of cox-2 and activator protein-1 (AP-1). Kaempferol attenuated the UVB-induced phosphorylation of several mitogen-activated protein kinases (MAPKs), including ERKs, p38, and JNKs, but had no effect on the phosphorylation of the upstream MAPK regulator Src. However, in vitro and ex vivo kinase assays demonstrated that kaempferol suppressed Src kinase activity. Furthermore, in vivo data from mouse skin support the idea that kaempferol suppresses UVB-induced COX-2 expression by blocking Src kinase activity. A pull-down assay revealed that kaempferol competes with ATP for direct binding to Src. Docking data suggest that kaempferol docks easily into the ATP-binding site of Src, which is located between the N and C lobes of the kinase domain. Taken together, these results suggest that kaempferol is a potent chemopreventive agent against skin cancer through its inhibitory interaction with Src.
flavonoid; photo-carcinogenesis; skin cancer
Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)-p21Cip/WAF1 activation, and suppressed by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and p21Cip/WAF1 short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway.
cyclin-dependent kinase inhibitor p21; fibroblast growth factor 2; mitogen-activated protein kinases; N,N-dimethylarginine; peptide elongation factor 2; protein-arginine N-methyltransfe
There is increasing concern regarding the use of fungicides to control plant diseases, whereby interest has increased in the biological control of phytopathogenic fungi by the application of hypovirulent mycoviruses as a possible alternative to fungicides. Transmission of hypovirulence-associated double-stranded RNA (dsRNA) viruses between mycelia, however, is prevented by the vegetative incompatibility barrier that often exists between different species or strains of filamentous fungi. We determined whether protoplast fusion could be used to transmit FgV1-DK21 virus, which is associated with hypovirulence on F. boothii (formerly F. graminearum strain DK21), to F. graminearum, F. asiaticum, F. oxysporum f. sp. lycopersici, and Cryphonectria parasitica. Relative to virus-free strains, the FgV1-DK21 recipient strains had reduced growth rates, altered pigmentation, and reduced virulence. These results indicate that protoplast fusion can be used to introduce FgV1-DK21 dsRNA into other Fusarium species and into C. parasitica and that FgV1-DK21 can be used as a hypovirulence factor and thus as a biological control agent.
Arsenite is a well-known human carcinogen that especially targets skin. The tumor progression locus 2 (Tpl2) gene encodes a serine/threonine protein kinase that is overexpressed in various cancer cells. However, the relevance of Tpl2 in arsenite-induced carcinogenesis and the underlying mechanisms remain to be explored. We demonstrate that arsenite increased Tpl2 kinase activity and its phosphorylation in mouse epidermal JB6 P+ cells in a dose- and time-dependent manner. Exposure to arsenite resulted in a marked induction of cyclooxygenase (COX)-2 and prostaglandin (PG)E2, important mediators of inflammation and tumor promotion. Treatment with a Tpl2 kinase inhibitor (TKI) or Tpl2 short hairpin RNA (shRNA) suppressed COX-2 expression and PGE2 production induced by arsenite treatment, suggesting that Tpl2 is critical in arsenite-induced carcinogenesis. We also found that arsenite-induced phosphorylation of extracellular signal-regulated kinases (ERKs) or c-Jun NH2-terminal kinases (JNKs) was markedly suppressed by TKI or Tpl2 shRNA. Inhibition of arsenite-induced ERKs or JNKs signaling using a pharmacological inhibitor of ERKs or JNKs substantially blocked COX-2 expression. Furthermore, inhibition of Tpl2 reduced the arsenite-induced promoter activity of nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1), indicating that NF-κB and AP-1 are downstream transducers of arsenite-triggered Tpl2. Our results demonstrated that Tpl2 plays a key role in arsenite-induced COX-2 expression and PGE2 production and further elucidated the role of Tpl2 in arsenite signals that activate ERKs/JNKs and NF-κB/AP-1 in JB6 P+ cells.
tumor progression locus 2 (Tpl2); arsenite; cyclooxygenase (COX)-2; prostaglandin (PG)E2
The aim of this study was to compare the surgical outcomes of laparoscopic surgery and conventional laparotomy for endometrial cancer.
A total of 104 consecutive patients were non-randomly assigned to either laparoscopic surgery or laparotomy. All patients underwent comprehensive surgical staging procedures including total hysterectomy, bilateral salpingo-oophorectomy, and pelvic/para-aortic lymphadenectomy. The safety, morbidity, and survival rates of the two groups were compared, and the data was retrospectively analyzed.
Thirty-four patients received laparoscopic surgery and 70 underwent laparotomy. Operation time for the laparoscopic procedure was 227.0±28.8 minutes, which showed significant difference from the 208.1±46.4 minutes (p=0.032) of the laparotomy group. The estimated blood loss of patients undergoing laparoscopic surgery was 230.3±92.4 mL. This was significantly less than that of the laparotomy group (301.9±156.3 mL, p=0.015). The laparoscopic group had an average of 20.8 pelvic and 9.1 para-aortic nodes retrieved, as compared to 17.2 pelvic and 8.5 para-aortic nodes retrieved in the laparotomy group. There was no significant difference (p=0.062, p=0.554). The mean hospitalization duration was significantly greater in the laparotomy group than the laparoscopic group (23.3 and 16.4 days, p<0.001). The incidence of postoperative complications was 15.7% and 11.8% in the laparotomy and laparoscopic groups respectively. No statistically significant difference was found between the two groups in the survival rate.
Laparoscopic surgical staging operation is a safe and effective therapeutic procedure for management of endometrial cancer with an acceptable morbidity compared to the laparotomic approach, and is characterized by far less blood loss and shorter postoperative hospitalization.
Endometrial cancer; Laparoscopic surgical staging; Laparotomy
Recent data suggest that pretreatment HPV (Human papillomavirus) viral load is useful to predict the severity of intraepithelial lesions of the uterine cervix and formulate a treatment plan. However, the relationship between initial HPV viral load and prognosis of cervical cancer patients has not yet been clearly defined. The objective of this study was to determine whether HPV viral load has prognostic significance in patients with early stage cervical carcinoma treated by surgery.
A retrospective review of all patients with early stage cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy at our institution from August 2003 to December 2007 was conducted. Patients were included only if they had pretreatment Hybrid Capture II test for HPV DNA detection.
We identified 34 patients who met the inclusion criteria. Two groups were identified: patients who had low HPV viral load (≤100 RLU) versus those who had high viral load (>100 RLU). There were no differences in age, FIGO stage, histology, pathologic risk factors - tumor size, deep stromal invasion, lymph-vascular space invasion, parametrial extensions, vaginal margin involvement, and lymph node metastasis - and adjuvant CCRT. There was no significant difference of disease-free survival regard to pretreatment HPV viral load (p=0.7756).
In our study, survival was not significantly different between early stage cervical cancer patients who had low and high pretreatment HPV viral load. It seems that pretreatment HPV viral load may not be of help to predict disease prognosis.
HPV load; Cervical cancer; Prognosis
Natural killer (NK) cells are critical in the immune response to tumor cells, virally infected cells, and bone marrow allografts. 2B4 (CD244) is expressed on all NK cells and the ligand for 2B4, CD48, is expressed on hematopoietic cells. Cross-linking 2B4 on NK cells with anti-2B4 monoclonal antibody leads to NK cell activation in vitro. Therefore, 2B4 is considered to be an activating receptor. Surprisingly, we have found, using antibody-blocking and 2B4-deficient NK cells, that NK lysis of CD48+ tumor and allogeneic targets is inhibited by 2B4 ligation. Interferon γ production by NK cells is also inhibited. Using a peritoneal tumor clearance assay, it was found that 2B4−/− mice have increased clearance of CD48+ tumor cells in vivo. Retroviral transduction of 2B4 was sufficient to restore inhibition in 2B4−/− primary NK cells. It was found that although mature NK cells express SH2D1A, in vitro–derived NK cells do not. However, both populations are inhibited by 2B4 ligation. This indicates that 2B4 inhibitory signaling occurs regardless of the presence of SH2D1A. These findings reveal a novel role for 2B4 as a non–major histocompatibility complex binding negative regulator of NK cells.
CD48; CD150; tumor; IFN-γ; innate immunity