NF-kappaB transcription factors are key regulators of immune and stress responses, apoptosis, and differentiation. Human cytomegalovirus (HCMV) activates or represses NF-kappaB signaling at different times during infection. An initial increase in NF-kappaB activity occurs within a few hours of infection. The virus appears to adapt to this change since initial viral gene expression is promoted by the elevated NF-kappaB activity. Because NF-kappaB upregulates innate immune responses and inflammation, it has also been suggested that HCMV needs to downregulate NF-kappaB signaling. Recent studies have shown that HCMV has various mechanisms that inhibit NF-kappaB signaling. HCMV reduces cell surface expression of tumor necrosis factor receptor 1 (TNFR1) and blocks the DNA binding activity of NF-kappaB. Furthermore, some HCMV tegument proteins antagonize NF-kappaB activation by targeting the key components of NF-kappaB signaling at late stages of infection. In this review, we summarize the recent findings on the relationship between HCMV and NF-kappaB signaling, focusing, in particular, on the viral mechanisms by which the NF-kappaB signaling pathway is inhibited.
Apoptosis ; Cytomegalovirus ; Cytomegalovirus Infections* ; DNA ; Genes, Viral ; Humans ; Immunity, Innate ; Inflammation ; NF-kappa B* ; Receptors, Tumor Necrosis Factor ; Transcription Factors

Deoxyribonucleotides (dNTPs) are important for the efficient growth of DNA viruses. Therefore, many DNA viruses have strategies for the upregulation of cellular dNTP levels. Both α- and γ-herpesviruses encode functional homologs of cellular dNTP anabolic enzymes, including the class I ribonucleotide reductase (RNR) large (R1) and small (R2) subunits, whereas β-herpesviruses modulate host cells to induce genes that increase dNTP levels. Interestingly, β-herpesviruses still express the nonfunctional RNR R1 subunit. However, it is not clear why β-herpesviruses still carry inactive R1 homologs. Recently, the R1 homologs of herpesviruses have been shown to inhibit innate immune signaling pathways. In particular, both functional and nonfunctional R1 homologs target receptor-interacting protein kinase 1 (RIP1) and inhibit RIP1-mediated signaling pathways to promote viral replication. Here, we summarize recent findings on the activity of herpesviral R1 homologs and discuss their roles in the regulation of innate immune signaling pathways.
Deoxyribonucleotides ; DNA Viruses ; Herpesviridae ; Protein Kinases ; Ribonucleotide Reductases* ; Up-Regulation

Humans ; Malocclusion ; Mandibular Condyle ; Mouth ; Prognosis ; Retrospective Studies ; Temporomandibular Joint ; Temporomandibular Joint Disorders

PURPOSE: We evaluated whether Cyberknife radiosurgery is an effective and safe method of therapy for medically intractable trigeminal neuralgia (TN). MATERIALS AND METHODS: We retrospectively analyzed the outcome of 26 patients, who failed to surgery or were not suitable candidates for invasive intervention and were treated by Cyberknife radiosurgery between March 2004 and May 2005. Radiosurgery doses of 60~64 Gy were delivered to the 80% isodose line prescribed to an 6 mm length of the nerve, sparing the most proximal 3 mm away from the trigeminal nerve root entry zone (median dose: 64 Gy). RESULTS: Follow-up period was 3~15 months (median follow-up period: 9 months) Preliminary results from a cohort of 26 patients undergoing Cyberknife radiosurgery for TN showed that pain relief was achieved in 50% (13/26) of patients within the first 24 hrs after treatment. At last follow-up, 96.2% (25/26) of patients reported early pain relief within 7 days. Treatment failure developed in 2 of 26. Poor response occurred in one patient and relapse was observed in the other patient. 3 patients had hypoesthesia (11.5%), which was the only complication observed with any of our patients. CONCLUSION: With these results, authors assumed that Cyberknife radiosurgery for TN could be one of safe and effective therapeutic methods.
Cohort Studies ; Follow-Up Studies ; Humans ; Hypesthesia ; Radiosurgery* ; Recurrence ; Retrospective Studies ; Treatment Failure ; Trigeminal Nerve ; Trigeminal Neuralgia*

The treatment of moya moya disease, a chronic occlusive cerebrovascular disease of unknown etiology, isn't settled ut various operative methods to maximize cerebral revascularization have been reported. Two cases in children treated surgically are presented, one with cerebroarteriosynangiosis and the other with encephalo-duro-arterio-synangiosis(EDAS). The methods of cerebral revascularization are discussed in detail.
Cerebral Revascularization ; Child* ; Humans ; Moyamoya Disease*

BACKGROUND/AIMS: There are few data on the effects of low hemoglobin levels on the left ventricle (LV) in patients without heart disease. The objective of this study was to document changes in the echocardiographic variables of LV structure and function after the correction of anemia without significant cardiovascular disease. METHODS: In total, 34 iron-deficiency anemia patients (35 +/- 11 years old, 32 females) without traditional cardiovascular risk factors or cardiovascular disease and 34 age- and gender-matched controls were studied. Assessments included history, physical examination, and echocardiography. Of the 34 patients with anemia enrolled, 20 were followed and underwent echocardiography after correction of the anemia. RESULTS: There were significant differences between the anemia and control groups in LV diameter, left ventricular mass index (LVMI), left atrial volume index (LAVI), peak mitral early diastolic (E) velocity, peak mitral late diastolic (A) velocity, E/A ratio, the ratio of mitral to mitral annular early diastolic velocity (E/E'), stroke volume, and cardiac index. Twenty patients underwent follow-up echocardiography after treatment of anemia. The follow-up results showed significant decreases in the LV end-diastolic and end-systolic diameters and LVMI, compared with baseline levels. LAVI, E velocity, and E/E' also decreased, suggesting a decrease in LV filling pressure. CONCLUSIONS: Low hemoglobin level was associated with larger cardiac chambers, increased LV, mass and higher LV filling pressure even in the subjects without cardiovascular risk factors or overt cardiovascular disease. Appropriate correction of anemia decreased LV mass, LA volume, and E/E'.
Adult ; Anemia, Iron-Deficiency/blood/diagnosis/*drug therapy/physiopathology ; Biological Markers/metabolism ; Case-Control Studies ; Echocardiography, Doppler ; Female ; Heart Ventricles/*physiopathology/ultrasonography ; Hematinics/*therapeutic use ; Hemoglobins/metabolism ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recovery of Function ; Time Factors ; Treatment Outcome ; *Ventricular Function, Left ; *Ventricular Pressure ; *Ventricular Remodeling ; Young Adult

PURPOSE: Combined chemoradiotherapy is standard management for locally advanced non-small cell lung cancer (LA-NSCLC), but standard treatment for elderly patients with LA-NSCLC has not been confirmed yet. We evaluated the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for elderly patients with LA-NSCLC. MATERIALS AND METHODS: Among patients older than 65 years with LA-NSCLC, 36 patients, who underwent CCRT were retrospectively analyzed. Chemotherapy was administered 3-5 times with 4 weeks interval during radiotherapy. Thoracic radiotherapy was delivered to the primary mass and regional lymph nodes. Total dose of 54-59.4 Gy (median, 59.4 Gy) in daily 1.8 Gy fractions and 5 fractions per week. RESULTS: Regarding the response to treatment, complete response, partial response, and no response were shown in 16.7%, 66.7%, and 13.9%, respectively. The 1- and 2-year overall survival (OS) rates were 58.2% and 31.2%, respectively, and the median survival was 15 months. The 1- and 2-year progression-free survivals (PFS) were 41.2% and 19.5%, respectively, and the median PFS was 10 months. Regarding to the toxicity developed after CCRT, pneumonitis and esophagitis with grade 3 or higher were observed in 13.9% (5 patients) and 11.1% (4 patients), respectively. Treatment-related death was not observed. CONCLUSION: The treatment-related toxicity as esophagitis and pneumonitis were noticeably lower when was compared with the previously reported results, and the survival rate was higher than radiotherapy alone. The results indicate that CCRT is an effective in terms of survival and treatment related toxicity for elderly patients over 65 years old with LA-NSCLC.
Aged ; Carcinoma, Non-Small-Cell Lung ; Chemoradiotherapy ; Disease-Free Survival ; Esophagitis ; Humans ; Lymph Nodes ; Pneumonia ; Retrospective Studies ; Survival Rate

Viruses interact with the host ubiquitination system in a variety of ways. Viral proteins are often a substrate for ubiquitination, which leads to proteasomal degradation. Viruses also have functions to modify the cellular ubiquitination machinery. Recently, deubiquitinating protease (DUB) activity has been found in many viral proteins. In herpesviruses, the DUB domain is found within the large tegument protein, which is conserved in all members of the herpesvirus family. Although a limited number of viral and cellular targets have been identified to date, accumulating evidence shows that herpesviral DUBs may primarily target key cellular regulators of immune signaling pathways to promote viral replication. In this review, we summarize the recent findings on viral DUBs. In particular, we focus on the herpesviral DUBs and their targets, and discuss their potential roles in the regulation of immune signaling pathways.
Herpesviridae ; Humans ; Peptide Hydrolases* ; Ubiquitin ; Ubiquitination ; Viral Proteins

To identify regulatory molecules which play key roles in the development of obesity, we investigated the transcriptional profiles in 3T3-L1 cells at early stage of differentiation and analyzed the promoter sequences of differentially regulated genes. One hundred and sixty-one (161) genes were found to have significant changes in expression at the 2nd day following treatment with differentiation cocktail. Among them, 86 transcripts were up-regulated and 75 transcripts were down-regulated. The 161 transcripts were classified into 10 categories according to their functional roles; cytoskeleton, cell adhesion, immune, defense response, metabolism, protein modification, protein metabolism, regulation of transcription, signal transduction and transporter. To identify transcription factors likely involved in regulating these differentially expressed genes, we analyzed the promoter sequences of up- or -down regulated genes for the presence of transcription factor binding sites (TFBSs). Based on coincidence of regulatory sites, we have identified candidate transcription factors (TFs), which include those previously known to be involved in adipogenesis (CREB, OCT-1 and c-Myc). Among them, c-Myc was also identified by our microarray data. Our approach to take advantage of the resource of the human genome sequences and the results from our microarray experiments should be validated by further studies of promoter occupancy and TF perturbation.
3T3-L1 Cells* ; Adipogenesis* ; Binding Sites ; Cell Adhesion ; Cytoskeleton ; Gene Expression Profiling* ; Genome, Human ; Humans ; Metabolism ; Microarray Analysis ; Obesity ; Signal Transduction ; Transcription Factors ; Transcriptome*

Over the past years, university administrators have known how hard it is to transform into the modern university. Rigid in-bred research system, narrow interest, unworkable graduate programs are complicatedly woven into a network of academic fraction. Cronyism and protectionism flood various laboratories and research institutes affiliated with the university. Until recently, the department structure of medical school has steadfastly guarded its territory and refused to allow non-medical undergraduate students to apply for the graduate schools of medical science. The graduate schools in medical science are considered just extra appendages because most of graduate students should be engaged in hard work position such as junior faculty or residentship training course of university hospital. In the present environment of graduate program, medical schools are consequently not able to bring in full-time young researchers, but only recently has its door been open for others. It should be time to reorganize the medical school graduate course into large multidisciplinary research group by expanding graduate programs.
Academies and Institutes ; Administrative Personnel ; Humans ; Schools, Medical*