Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure. Based on the underlying cellular and molecular mechanisms of a liver fibrosis, there has been proposed several kinds of approaches for the treatment of liver fibrosis. Recently, liver gene therapy has been developed as an alternative way to liver transplantation, which is the only effective therapy for chronic liver diseases. The activation of hepatic stellate cells, a subsequent release of inflammatory cytokines and an accumulation of extracellular matrix during the liver fibrogenesis are the major obstacles to the treatment of liver fibrosis. Several targeted strategies have been developed, such as antisense oligodeoxynucleotides, RNA interference and decoy oligodeoxynucleotides to overcome this barriers. With this report an overview will be provided of targeted strategies for the treatment of liver cirrhosis, and particularly, of the targeted gene therapy using short RNA and DNA segments.
Liver cirrhosis; Gene therapy; Oligodeoxynucleotides; Antisense; Small interfering RNA; Micro RNA; Decoy
Liver injuries are repaired by fibrosis and regeneration. The cause of fibrosis and diminished regeneration, especially in liver cirrhosis, is still unknown. Epithelial-mesenchymal transition (EMT) has been found to be associated with liver fibrosis. The possibility that EMT could contribute to hepatic fibrogenesis reinforced the concept that activated hepatic stellate cells are not the only key players in the hepatic fibrogenic process and that other cell types, either hepatic or bone marrow-derived cells could contribute to this process. Following an initial enthusiasm for the discovery of this novel pathway in fibrogenesis, more recent research has started to cast serious doubts upon the real relevance of this phenomenon in human fibrogenetic disorders. The debate on the authenticity of EMT or on its contribution to the fibrogenic process has become very animated. The overall result is a general confusion on the meaning and on the definition of several key aspects. The aim of this article is to describe how EMT participates to hepatic fibrosis and discuss the evidence of supporting this possibility in order to reach reasonable and useful conclusions.
Epithelial-mesenchymal transition; Liver; Fibrosis; Transforming growth factor-beta1; Biological markers
We describe a surgical tool that uses the distractor pin as a reference for determining proper screw length in ACDF. It is critical that screw purchase depth be as deep as possible without violating or penetrating the posterior cortical wall, which ensures strong pull out strength.
We enrolled 81 adult patients who underwent ACDF using an anterior cervical plate from 2010 to 2012. Patients were categorized into Groups A (42 patients: retractor pin used as a reference for screw length) and B (39 patients: control group). Intraoperative lateral x-rays were taken after screwing the retractor pin to confirm the approaching vertebral level. The ratio of retractor pin length to body anteroposterior (A-P) diameter was measured as a reference. Proper screw length was determined by comparison to the reference.
The average distance from screw tip to posterior wall was 3.0±1.4mm in Group A and 4.1±2.3mm in Group B. The ratio of screw length to body sagittal diameter was 86.2±5.7% in Group A and 80.8±9.0% in Group B. Screw length to body sagittal diameter ratios higher than 4/5 occurred in 33 patients (90%) in Group A and 23 patients (59%) in Group B. No cases violated the posterior cortical wall.
We introduce a useful surgical method for determining proper screw length in ACDF using the ratio of retractor pin length to body A-P diameter as a reference. This method allows for deeper screw purchase depth without violation of the posterior cortical wall.
Anterior cervical discectomy and fusion (ACDF); Screw pullout strength; Screw length
To study practical guidelines and strategies in the treatment of cervical osteomyelitis.
We retrospectively reviewed 14 patients who underwent surgical treatment for cervical osteomyelitis from May 2000 to July 2008. We investigated their clinical course, antibiotic regimen, surgical methods, and laboratory and radiologic findings including X-ray, CT and MRI.
5 patients had primary spondylodiscitis, 5 patients had post operative spondylodiscitis and 4 patients had tuberculosis in cervical spine. The causative microorganisms were MRSA (5), P. aeruginosa (1), Methicillin resistant coagulase negative streptococcus (1), P. aeruginosa changed to MRSA (1), and 2 patients showed no growth on culture studies. Patients were treated 13.8 weeks (range, 5.4-25.8) with IV antibiotics and then treated for 58.2 days (range, 13-106) with oral antibiotics. Antituberculotic medications were used for a mean of 383.8 days. Patients were treated with anterior debridement and fusion (5), irrigation and debridement (5), simultaneous cervical anterior interbody and transthoracic thoracic interbody fusion (1). 3 patients underwent the planned 2-staged operation, which included an anterior debridement with or without fusion for the 1st operation and posterior instrumentation for 2nd operation. 10 patients (71.4%) had neurologic deficits at the time of diagnosis and 7 patients (70%) among them improved post-operatively.
Anterior cervical spine surgery is the preferable treatment option in patients with neurological deterioration, extensive bony destruction with expected kyphotic deformity, and uncontrolled infection being managed only with antibiotics. Antibiotics are also important for thorough treatment.
Cervical spine; Spinal infection; Osteomyelitis; Spondylodiscitis
The appearance of proliferating bile ductular structures, which is called the “atypical ductular reaction” is frequently observed in various chronic liver diseases associated. However, the origin of these increased bile ductules has been a matter of controversy. In this study, we investigated the origin of ductular cells as an aspect of relation between epithelial to mesenchymal transition (EMT) and epithelial members of liver parenchyme, such as hepatocyte and cholangiocyte by immunohistochemical staining of human liver. Thirteen specimens of surgically resected liver with biliary cirrhosis were selected. Three sets of double immunohistochemical stains were done; Hep-Par 1 - cytokeratin 19 (CK19), Hep-Par 1 - α-sm ooth mus cle actin (α-SMA) and CK19 - α-SMA. As a result, we investigated the dual expression of the markers of hepatocyte and cholangiocyte in the same cell; in ductular cell and surrounding hepatocyte. However, there seems to be no dual expression of markers for EMT with epithelial markers. This study suggests a possibility of phenotypic change of mature hepatocyte into cholangiocyte. Future studies will be necessary to determine the role that proliferating cholangiocytes play in the pathogenesis of biliary fibrosis and how cholangiocytes interact with other cell types of the liver such as hepatic stellate cells or Kupffer cells.
Liver; hepatocyte; bile duct cell; ductular reaction; transdifferentiation; immunohistochemistry
The tumor microenvironment has many roles involving tumor progression, invasion and metastasis. The tumor cells at the tumor border loose epithelial properties and acquire mesenchymal features. This, epithelial-to-mesenchymal transition (EMT) has been suggested to be an important process for tissue and lymphovascular invasion. Pulmonary tissue samples from 15 patients with primary adenocarcinoma were evaluated with using immunofluorescence multi-staining the EMT-associated markers including E-cadherin and alpha-smooth muscle actin (α-SMA), and transcription factors including E-SNAIL and SLUG, and ZEB1. The data were analyzed in specific area, such as tumor center and tumor border. In this study we show that the invasive adenocarcinoma differentially expressed SNAIL and SLUG, and Zeb1 and it was associated with the loss of epithelial marker (E-cadherin) and gaining of mesenchymal marker (α-SMA) at the invasive border of lung carcinoma. The positive rates of SNAIL and ZEB1 were 26.7% and 0% in the tumor center and 40% and 20% in tumor margin, respectively. In addition, the expression of both SNAIL and ZEB1 at the border of tumor was observed in two cases (2/10). These two cases were associated with lymph node metastasis and advanced stage. The process of EMT has been suggested to be of prime importance for tissue and lymphovascular invasion. The process of EMT may be activated in the tumor border of lung adenocarcinoma. Related transcription factors, such as SNAIL and SLUG, and ZEB1, might be induced by paracrine effects of surrounded inflammatory cells and fibroblasts.
Epithelial mesenchymal transition; lung adenocarcinoma; SNAIL; SLUG; ZEB1
Minimally invasive surgery with a transforaminal lumbar interbody fusion (MIS TLIF) is an important minimally invasive fusion technique for the lumbar spine. Lumbar spine reoperation is challenging and is thought to have greater complication risks. The purpose of this study was to compare MIS TLIF with unilateral screw fixation perioperative results between primary and revision surgeries. This was a prospective study that included 46 patients who underwent MIS TLIF with unilateral pedicle screw. The patients were divided into two groups, primary and revision MIS TLIF, to compare perioperative results and complications. The two groups were similar in age, sex, and level of operation, and were not significantly different in the length of follow-up or clinical results. Although dural tears were more common with the revision group (primary 1; revision 4), operation time, blood loss, total perioperative complication, and fusion rates were not significantly different between the two groups. Both groups showed substantial improvements in VAS and ODI scores one year after surgical treatment. Revision MIS TLIF performed by an experienced surgeon does not necessarily increase the risk of perioperative complication compared with primary surgery. MIS TLIF with unilateral pedicle screw fixation is a valuable option for revision lumbar surgery.
It is well known that arthrodesis is associated with adjacent segment degeneration (ASD). However, previous studies were performed with simple radiography or CT. MRI is most sensitive in assessing the degenerative change of a disc, and this is the first study about ASD by radiography, CT and MRI. We sought to factors related to ASD at cervical spine by an MRI and CT, after anterior cervical spine surgery.
Materials and methods
This is a retrospective cross-sectional study of cervical disc herniation. Patients of cervical disc herniation with only radiculopathy were treated with either arthroplasty (22 patients) or ACDF with cage alone (21 patients). These patients were required to undergo MRI, CT and radiography preoperatively, as well as radiography follow-up for 3 months and 1 year, and we conducted a cross-sectional study by MRI, CT and radiography including clinical evaluations 5 years after. Clinical outcomes were assessed using VAS and NDI. The fusion rate and ASD rate, and radiologic parameters (cervical lordosis, operated segmental height, C2-7 ROM, operated segmental ROM, upper segmental ROM and lower segmental ROM) were measured.
The study groups were demographically similar, and substantial improvements in VAS (for arm) and NDI (for neck) scores were noted, and there were no significant differences between groups. Fusion rates were 95.2 % in the fusion group and 4.5 % in the arthroplasty group. ASD rates of the fusion and arthroplasty groups were 42.9 and 50 %, respectively. Among the radiologic parameters, operated segmental height and operated segmental ROM significantly decreased, while the upper segmental ROM significantly increased in the fusion group. In a comparative study between patients with ASD and without ASD, the clinical results were found to be similar, although preexisting ASD and other segment degeneration were significantly higher in the ASD group. C2-7 ROM was significantly decreased in ASD group, and other radiologic parameters have no significant differences between groups.
The ASD rate of 46.5 % after ACDF or arthroplasty, and arthroplasty did not significantly lower the rate of ASD. ASD occurred in patients who had preexisting ASD and in patients who also had other segment degeneration. ASD may be associated with a natural history of cervical spondylosis rather than arthrodesis.
Adjacent segment degeneration; ACDF; Arthroplasty; Spondylosis
Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01) and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The β-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus.
The ergonomic problems for surgeons during spine surgery are an awkward body posture, repetitive movements, increased muscle activity, an overflexed spine, and a protracted time in a standing posture. The authors analyzed whole spine angles during discectomy. The objective of this study is to assess differences in surgeon whole spines angles according to operating table height and the methods used to visualize surgical field.
Materials and methods
A cohort of 12 experienced spine surgeons was enrolled. Twelve experienced spine surgeons performed discectomy using a spine surgery simulator. Three different methods were used to visualize the surgical field (naked eye, loupe, and out of loupe) and three different operating table heights. Whole spine angles were compared for three different views during discectomy simulation; midline, ipsilateral, and contralateral. A 16-camera optoelectronic motion analysis system was used, and 16 markers were placed from head to pelvis. Lumbar lordosis, thoracic kyphosis, cervical lordosis, and occipital angle were compared at the different operating table heights, while using the three visualization methods, with natural standing position.
Whole spine angles were significantly different for visualization methods. Lumbar lordosis, cervical lordosis, and occipital angle were closer to natural standing values when discectomy was performed with a loupe, but most measures differed from natural standing values when performed out of loupe. Thoracic kyphosis was also similar to the natural standing position during discectomy using a loupe, but differed from the natural standing position when performed with naked eye. Whole spine angles were also found to differ from the natural standing position according to operating table height, and became closer to natural standing position values as operating table height increased, when simulation was conducted with loupe.
This study suggests that loupe use and a table height midpoint between the umbilicus and sternum are optimal for reducing surgeon musculoskeletal fatigue.
Spine; Surgeon; Kinematics; Discectomy
Honeybee (Apis mellifera L.) venom (BV) has been traditionally used for the treatment of pain and inflammatory diseases such as itchy skin problems. However, the precise mechanism of BV in ameliorating the scratching behavior is not fully understood. Objective: In order to evaluate the effect of BV on atopic dermatitis-related symptoms in mice, we used a mouse skin scratching model induced by compound 48/80. The anti-itch effect of BV was investigated in a compound 48/80-induced mouse scratching behavior model. BALB/c mice were injected intraperitoneally with vehicle (saline 0.9%) or BV (0.01 and 0.1 mg/kg). One hour after treatment, the animals received a subcutaneous injection of compound 48/80. Intraperitoneal administration of BV (0.01 and 0.1 mg/kg) attenuated compound 48/80-induced scratching behaviors. The anti-scratching behavior effect of BV was in proportional to its vascular permeability effects. Treatment with BV also inhibited the degranulation of mast cells and the production of pro-inflammatory cytokines in compound 48/80-treated skin tissues. According to these results, BV may improve atopic dermatitis-related symptoms by inhibiting the mast cell degranulation and pro-inflammatory cytokine expression.
Bee venom; scratching behavior; mast cell degranulation; compound 48/80; inflammation
All structures of the spine, including the spinal canal, change continuously with age. The purpose of this study was to determine how the spinal canal of the lumbar spine changes with age. The L4/5 is the most common site of spinal stenosis and has the largest flexion-extension motion, whereas the T5/6 has the least motion. Therefore, we measured the spinal canal diameter and vertebral body height at T5, T6, L4, and L5 with age.
Materials and Methods
This was a retrospective study of aged 40 to 77 years. We reviewed whole spine sagittal MRIs of 370 patients with lumbar spinal stenosis (LSS) (Group 2) and 166 herniated cervical disc (HCD) (Group 1). Each group was divided into four age groups, and demographic parameters (age, gender, height, weight, BMI), the mid-spinal canal diameter, and mid-vertebrae height at T5, T6, L4, L5 were compared. Within- and between-group comparisons were made to evaluate changes by age and correlations were carried out to evaluate the relationships between all parameters.
Height, weight, and all radiologic parameters were significantly lower in Group 2 than Group 1. Group 1 did not show any differences, when based on age, but in Group 2, height, weight, and T6, L4, and L5 height were significantly decreased in patients in their 70's than patients in their 40's, except for spinal canal diameter. Age was associated with all parameters except spinal canal diameter.
Vertebral height decreased with age, but spinal canal diameter did not change in patients with either LSS or HCD. Mid-spinal canal diameter was not affected by aging.
Lumbar spinal stenosis; herniated cervical disc; spinal canal diameter
Cerebral hyperperfusion syndrome (CHS) is a serious complication after carotid endarterectomy (CEA). However, the prevalence of CHS has decreased as techniques have improved. This study evaluates the role of strict blood pressure (BP) control for the prevention of CHS.
All 18 patients who received CEA from February 2009 through November 2012 were retrospectively reviewed. All patients were routinely managed in an intensive care unit by a same protocol. The cerebral perfusion state was evaluated on the basis of the regional cerebral blood flow (rCBF) study by perfusion computed tomography (pCT) and mean velocity by transcranial doppler (TCD). BP was strictly controlled (<140/90 mm Hg) for 7 days. When either post-CEA hyperperfusion (>100% increase in the rCBF by pCT or in the mean velocity by TCD compared with preoperative values) or CHS was detected, BP was maintained below 120/80 mm Hg.
TCD and pCT data on the patients were analyzed. Ipsilateral rCBF was significantly increased after CEA in the pCT (p=0.049). Post-CEA hyperperfusion was observed in 3 patients (18.7%) in the pCT and 2 patients (12.5%) in the TCD study. No patients developed clinical CHS for one month after CEA. Furthermore, no patients developed additional neurological deficits related to postoperative cerebrovascular complications.
Intensive care with strict BP control (<140/90 mm Hg) achieved a low prevalence of post-CEA hyperperfusion and prevented CHS. This study suggests that intensive care with strict BP control can prevent the prevalence of post-CEA CHS.
Carotid endarterectomy; Hyperperfusion; Cerebral blood flow; Blood pressure; Cerebral hyperperfusion syndrome
Influenza epidemics arise through the accumulation of viral genetic changes. The emergence of new virus strains coincides with a higher level of influenza-like illness (ILI), which is seen as a peak of a normal season. Monitoring the spread of an epidemic influenza in populations is a difficult and important task. Twitter is a free social networking service whose messages can improve the accuracy of forecasting models by providing early warnings of influenza outbreaks. In this study, we have examined the use of information embedded in the Hangeul Twitter stream to detect rapidly evolving public awareness or concern with respect to influenza transmission and developed regression models that can track levels of actual disease activity and predict influenza epidemics in the real world. Our prediction model using a delay mode provides not only a real-time assessment of the current influenza epidemic activity but also a significant improvement in prediction performance at the initial phase of ILI peak when prediction is of most importance.
"Tumor-to-tumor" metastasis is a rare event; meningioma has been reported as the most common primary intracranial tumor to harbor cancer metastases. Several hypotheses have been previously proposed to explain this occurrence, but the exact mechanism by which these metastases develop into meningiomas is not yet understood. Magnetic resonance imaging and spectroscopy have been valuable diagnostic tools, but preoperative diagnosis of metastasis to meningioma remains highly difficult. We present a case report of a metastasis of non-small cell lung cancer into an intracranial meningioma.
Metastasis; Meningioma; Lung cancer; Non-small cell; Tumor-to-tumor; Harbor cancer
A spinal epidural hemangioma is rare. In this case, a 51 year-old female patient had low back pain and right thigh numbness. She was initially misdiagnosed as having a ruptured disc with possible sequestration of granulation tissue formation due to the limited number of spinal epidural hemangiomas and little-known radiological findings. Because there are no effective diagnostic tools to verify the hemangioma, more effort should be put into preoperative imaging tests to avoid misdiagnosis and poor decisions).
Spinal hemangioma; Indocyanine green videoangiography; Spinal cavernous; Hemangioma; Spinal epidural hemangioma
Apamin, a peptide component of bee venom (BV), has anti-inflammatory properties. However, the molecular mechanisms by which apamin prevents atherosclerosis are not fully understood. We examined the effect of apamin on atherosclerotic mice. Atherosclerotic mice received intraperitoneal (ip) injections of lipopolysaccharide (LPS, 2 mg/kg) to induce atherosclerotic change and were fed an atherogenic diet for 12 weeks. Apamin (0.05 mg/kg) was administered by ip injection. LPS-induced THP-1-derived macrophage inflammation treated with apamin reduced expression of tumor necrosis factor (TNF)-α, vascular cell adhesion molecule (VCAM)-1, and intracellular cell adhesion molecule (ICAM)-1, as well as the nuclear factor kappa B (NF-κB) signaling pathway. Apamin decreased the formation of atherosclerotic lesions as assessed by hematoxylin and elastic staining. Treatment with apamin reduced lipids, Ca2+ levels, and TNF-α in the serum from atherosclerotic mice. Further, apamin significantly attenuated expression of VCAM-1, ICAM-1, TGF-β1, and fibronectin in the descending aorta from atherosclerotic mice. These results indicate that apamin plays an important role in monocyte/macrophage inflammatory processing and may be of potential value for preventing atherosclerosis.
Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the intrahepatic bile duct epithelium, has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Thus, there is an urgent need to develop new effective therapeutic strategies for this disease. We previously found that L1 cell adhesion molecule (L1CAM) plays an important role in tumor progression of ICC, and we generated a murine mAb, A10-A3 (IgG1), that binds to the Ig1 domain of L1CAM. In the present study, we further characterized A10-A3, constructed a chimeric A10-A3 antibody (cA10-A3) containing the constant regions of human IgG1, and evaluated the therapeutic potential in a human ICC xenograft nude mice model. The affinities (KD) of A10-A3 and cA10-A3 for soluble L1CAM were 1.8 nM and 1.9 nM, respectively, as determined by competition ELISA. A10-A3 inhibited L1CAM homophilic binding and was slowly internalized into the tumor cells, but it did not significantly inhibit proliferation of ICC cells in vitro. cA10-A3 mediated antibody-dependent cell-mediated cytotoxicity in vitro and displayed anti-tumor activity in the ICC animal model. These results suggest that the humanized A10-A3 antibody may have potential as an anticancer agent for the treatment of ICC.
immunization, passive; intrahepatic cholangiocarcinoma; neural cell adhesion molecule L1
Retrospective analysis to compare the effect and complication of epidural patient-controlled analgesia (epidural PCA) with intravenous patient-controlled analgesia (IV PCA) for the treatment of the post-operative pain after posterior lumbar instrumented fusion.
Sixty patients who underwent posterior lumbar instrumented fusion for degenerative lumbar disease at our institution from September 2007 to January 2008 were enrolled in this study. Out of sixty patients, thirty patients received IV PCA group and thirty patients received epidural PCA group. The pain scale was measured by the visual analogue scale (VAS) score.
There were no significant difference between IV PCA group and epidural PCA group on the PCA related complications (p=0.7168). Ten patients in IV PCA group and six patients in epidural PCA group showed PCA related complications. Also, there were no significant differences in reduction of VAS score between two groups on postoperative 2 hours (p=0.9618) and 6 hours (p=0.0744). However, postoperative 12 hours, 24 hours and 48 hours showed the significant differences as mean of reduction of VAS score (p=0.0069, 0.0165, 0.0058 respectively).
The epidural PCA is more effective method to control the post-operative pain than IV PCA after 12 hours of spinal fusion operation. However, during the first twelve hours after operation, there were no differences between IV PCA and epidural PCA.
Patient-controlled analgesia; Postoperative pain; Spinal fusion
Influenza epidemics arise through the accumulation of viral genetic changes, culminating in a novel antigenic type that is able to escape host immunity. Following an outbreak of the A/Fujian/411/2002-like strains in Asia, including China, Japan, and South Korea, in 2002, Australia and New Zealand experienced substantial outbreaks of the same strains in 2003, and subsequently worldwide outbreaks occurred in the 2003-2004 season. The emergence of A/Fujian/411/2002-like strains coincided with a higher level of influenza-like illness in South Korea than what is seen at the peak of a normal season, and there was at least a year's difference between South Korea and the United States. Genetic evolution of human influenza A/H3N2 viruses was monitored by sequence analysis of hemagglutinin (HA) genes collected in Asia, including 269 (164 new) HA genes isolated in South Korea from 1999 to 2007. The Fujian-like influenza strains were disseminated with rapid sequence variation across the antigenic sites of the HA1 domain, which sharply distinguished between the A/Moscow/10/1999-like and A/Fujian/411/2002-like strains. This fast variation, equivalent to approximately 10 amino acid changes within a year, occurred in Asia and would be the main cause of the disappearance of the reassortants, although the reassortant and nonreassortant Fujian-like strains circulated simultaneously in Asia.
Influenza epidemics arise through the acquisition of viral genetic changes to overcome immunity from previous infections. An increasing number of complete genomes of influenza viruses have been sequenced in Asia in recent years. Knowledge about the genomes of the seasonal influenza viruses from different countries in Asia is valuable for monitoring and understanding of the emergence, migration and evolution of strains. In order to make full use of the wealth of information from such data, we have developed an integrated user friendly relational database, Influenza Sequence and Epitope Database (ISED), that catalogs the influenza sequence and epitope information obtained in Asia. ISED currently hosts a total of 13 020 influenza A and 2984 influenza B virus sequence data collected in 17 countries including 9 Asian countries, and a total of approximately 545 amantadine-resistant influenza virus sequences collected in Korea. ISED provides users with prebuilt application tools to analyze sequence alignment and different patterns and allows users to visualize epitope-matching structures, which is freely accessible at http://influenza.korea.ac.kr and http://influenza.cdc.go.kr.
Biomarkers enable early diagnosis, guide molecularly targeted therapy and monitor the activity and therapeutic responses across a variety of diseases. Despite intensified interest and research, however, the overall rate of development of novel biomarkers has been falling. Moreover, no solution is yet available that efficiently retrieves and processes biomarker information pertaining to infectious diseases. Infectious Disease Biomarker Database (IDBD) is one of the first efforts to build an easily accessible and comprehensive literature-derived database covering known infectious disease biomarkers. IDBD is a community annotation database, utilizing collaborative Web 2.0 features, providing a convenient user interface to input and revise data online. It allows users to link infectious diseases or pathogens to protein, gene or carbohydrate biomarkers through the use of search tools. It supports various types of data searches and application tools to analyze sequence and structure features of potential and validated biomarkers. Currently, IDBD integrates 611 biomarkers for 66 infectious diseases and 70 pathogens. It is publicly accessible at http://biomarker.cdc.go.kr and http://biomarker.korea.ac.kr.
Emergence and spread of low-level mupirocin resistance in staphylococci have been increasingly reported in recent years. The aim of this study was to characterize missense mutations within the chromosomal isoleucyl-tRNA synthetase gene (ileS) among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) with low-level mupirocin resistance. A total of 20 isolates of MRSA with low-level mupirocin resistance (minimal inhibitory concentration, 16-64 µg/mL) were collected from 79 patients in intensive care units for six months. The isolates were analyzed for isoleucyl-tRNA synthetase (IleS) mutations that might affect the binding of mupirocin to the three-dimensional structure of the S. aureus IleS enzyme. All isolates with low-level mupirocin resistance contained the known V588F mutation affecting the Rossman fold, and some of them additionally had previously unidentified mutations such as P187F, K226T, F227L, Q612H, or V767D. Interestingly, Q612H was a novel mutation that was involved in stabilizing the conformation of the catalytic loop containing the KMSKS motif. In conclusion, this study confirms that molecular heterogeneity in ileS gene is common among clinical MRSA isolates with low-level mupirocin resistance, and further study on clinical mutants is needed to understand the structural basis of low-level mupirocin resistance.
Staphylococcus aureus; Mupirocin; Drug Resistance; Isoleucine-tRNA Ligase; Mutation, Missense