To develop a gentamicin-loaded wound dressing, cross-linked hydrogel films were prepared with polyvinyl alcohol (PVA) and dextran using the freezing–thawing method. Their gel properties such as gel fraction, swelling, water vapor transmission test, morphology, tensile strength, and thermal property were investigated. In vitro protein adsorption test, in vivo wound healing test, and histopathology were performed. Dextran decreased the gel fraction, maximum strength, and thermal stability of hydrogels. However, it increased the swelling ability, water vapor transmission rate, elasticity, porosity, and protein adsorption. The drug gave a little positive effect on the gel properties of hydrogels. The gentamicin-loaded wound dressing composed of 2.5% PVA, 1.13% dextran, and 0.1% drug was more swellable, flexible, and elastic than that with only PVA because of its cross-linking interaction with PVA. In particular, it could provide an adequate level of moisture and build up the exudates on the wound area. From the in vivo wound healing and histological results, this gentamicin-loaded wound dressing enhanced the healing effect more compared to conventional product because of the potential healing effect of gentamicin. Thus, this gentamicin-loaded wound dressing would be used as a potential wound dressing with excellent forming and improved healing effect in wound care.
dextran; gentamicin; histological examination; wound dressing; wound healing effect
Stricture frequently occurs after endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma with near- or whole-circumferential mucosal defects, and post-ESD stricture is difficult to treat and usually requires multiple sessions of endoscopic balloon dilatation. Intralesional steroid injection has previously been used to prevent stricture; however, there have been few experiences with this method after near- or whole-circumferential ESD. We present a case of a single session of intralesional steroid injection performed immediately after near-circumferential ESD to prevent post-ESD stricture. After a follow-up period of 6 months, the patient showed good outcome without dysphagia.
Injections, intralesional; Esophageal stenosis; Endoscopic submucosal dissection; Esophageal neoplasms
Accumulating line of evidence support that adult tissues contain a rare population of pluripotent stem cells (PSCs), which differentiate into all types of cells in our body. Bonghan microcell (primo microcells (PMCs)) discovered in 1960s was reported to have a pluripotency like a stem cell in vivo as well as in vitro condition. Here, we describe the detailed morphology and molecular features of PMCs. PMCs reside in Bonghan duct (primo vessel (PV)) reported as a corresponding structure of acupuncture points and meridian system. We found that PMCs were frequently observed in the liver surface of the rat between 300 g and 400 g from April to June, suggesting that the their detection frequency depends on the weight, the season, and the organ of rat. As reported, PMCs freshly isolated from PVs were spherical ~1-2 μm microsized cells. In contrast, a unique bithread or budding-shaped PMCs emerged during tissue culture around 8 days. RT-PCR analysis demonstrated that PVs-derived cells express the Oct4, the most important PSCs gene, in addition to several PSCs markers (Sox2, Stella, Rex1, and Klf4). Thus, we for the first time provide the evidence about Oct4-expressing stem-like characteristics for cells resident in PVs, a possible novel stem cell enriched niche.
Tissue inflammation and remodeling have been extensively studied in various tumors in relation with their invasiveness and metastasis.
The purpose of this study was to investigate the change in tissue inflammation and remodeling markers in cutaneous squamous cell carcinoma (SCC).
Expression levels of cyclooxygenase-2 (COX-2) as an inflammatory marker and matrix metalloproteinases-2 and -9 (MMPs 2/9) as remodeling markers were studied in mouse and human SCCs. Western blot analysis and RT-PCR for COX-2 and MMPs 2/9 were performed with skin samples from SCC patients and chronic ultraviolet B (UVB)-induced SCC from hairless mice.
mRNA and protein levels of COX-2 and MMPs 2/9 were up-regulated with the higher sensitivity for MMP-9 in mouse SCCs, which were induced by chronic UVB irradiation. Consistently, COX-2 and MMPs 2/9 were up-regulated with the higher sensitivity for MMP-9 in human SCCs.
COX-2 and MMPs 2/9 are up-regulated in well-differentiated cutanous SCC. Our findings indicate that inflammatory and tissue remodeling processes are actively induced during carcinogenesis of cutaneous SCC.
Cyclooxygenase 2; MMP-2; MMP-9; SCC
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major adult liver cancers. The existence of combined hepatocellular-cholangiocarcinoma (CHC), a histopathological intermediate form between HCC and CC, suggests phenotypic overlap between these tumors. Here, we applied an integrative oncogenomic approach to address the clinical and functional implications of the overlapped phenotype between these tumors. By performing gene expression profiling of human HCC, CHC, and CC, we identified a novel HCC subtype, namely, CC-like HCC (CLHCC), which expressed CC-like traits (CC signature). As like CC and CHC, CLHCC showed aggressive phenotype with shorter recurrence-free and overall survival. In addition, we found that CLHCC coexpressed embryonic stem cell-like expression traits (ES signature) suggesting its derivation from bipotent hepatic progenitor cells. By comparing the expression of CC signature with previous ES-like, hepatoblast-like, or proliferation-related traits, we observed that that the prognostic value of the CC signatures is independent of the expression of those signatures. In conclusion, we suggest that the acquisition of CC like-expression traits play a critical role in the heterogeneous progression of HCC.
microarray; stem cell; prognosis; cholangiocarcinoma-like HCC
A 66-year-old female presented with a 1-month history of dyspepsia. An initial upper gastrointestinal endoscopy with biopsy revealed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. A rapid urease test was positive for Helicobacter pylori. Endoscopic ultrasound (EUS) and computed tomography (CT) revealed a 30×15-mm lymph node (LN) in the subcarinal area. Histopathologic and phenotypic analyses of the biopsy specimens obtained by EUS-guided fine-needle aspiration revealed a MALT lymphoma, and the patient was diagnosed with a stage 4E gastric MALT lymphoma. One year after H. pylori eradication, the lesion had disappeared, as demonstrated by endoscopy with biopsy, CT, fusion whole-body positron emission tomography, and EUS. Here, we describe a patient with gastric MALT lymphoma that metastasized to the mediastinal LN and regressed following H. pylori eradication.
Marginal zone B-cell lymphoma; Stomach
Facial nerve palsy due to temporal bone metastasis of hepatocellular carcinoma (HCC) has rarely been reported. We experienced a rare case of temporal bone metastasis of HCC that initially presented as facial nerve palsy and was diagnosed by surgical biopsy. This patient also discovered for the first time that he had chronic hepatitis B and C infections due to this facial nerve palsy. Radiation therapy greatly relieved the facial pain and facial nerve palsy. This report suggests that hepatologists should consider metastatic HCC as a rare but possible cause of new-onset cranial neuropathy in patients with chronic viral hepatitis.
Metastasis; Hepatocellular carcinoma; Temporal bone; Cranial nerve palsy
Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients.
Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, including serum tumor markers.
A total of 354 patients were included. Seventy-six patients (21%) had extrahepatic metastases during the observation period (median, 25.3 months; range, 0.6-51.3 months). Cox regression multivariate analysis showed that serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) production levels, the intrahepatic tumor stage, platelet count, and portal vein thrombosis were independent risk factors for extrahepatic metastases. Patients with a PIVKA-II production ≥ 300 mAU/mL had a 2.7-fold (95% confidence interval; 1.5-4.8; P < 0.001) and 3.7-fold (95% confidence interval; 2.0-6.6; P < 0.001) increased risk for extrahepatic metastases after adjustment for stage, platelet count, alpha-fetoprotein ≥ 400 ng/mL, and portal vein thrombosis according to the AJCC and BCLC staging systems, respectively.
PIVKA-II production levels might be a good candidate predictive marker for extrahepatic HCC metastases, especially in patients with smaller and/or fewer tumors in the liver with in stages regardless of serum alpha-fetoprotein.
Protein induced by vitamin K absence or antagonist-II; hepatocellular carcinoma; metastases; predictive marker
As the Resource Description Framework (RDF) data model is widely used for modeling and sharing a lot of online bioinformatics resources such as Uniprot (dev.isb-sib.ch/projects/uniprot-rdf) or Bio2RDF (bio2rdf.org), SPARQL - a W3C recommendation query for RDF databases - has become an important query language for querying the bioinformatics knowledge bases. Moreover, due to the diversity of users’ requests for extracting information from the RDF data as well as the lack of users’ knowledge about the exact value of each fact in the RDF databases, it is desirable to use the SPARQL query with regular expression patterns for querying the RDF data. To the best of our knowledge, there is currently no work that efficiently supports regular expression processing in SPARQL over RDF databases. Most of the existing techniques for processing regular expressions are designed for querying a text corpus, or only for supporting the matching over the paths in an RDF graph.
In this paper, we propose a novel framework for supporting regular expression processing in SPARQL query. Our contributions can be summarized as follows. 1) We propose an efficient framework for processing SPARQL queries with regular expression patterns in RDF databases. 2) We propose a cost model in order to adapt the proposed framework in the existing query optimizers. 3) We build a prototype for the proposed framework in C++ and conduct extensive experiments demonstrating the efficiency and effectiveness of our technique.
Experiments with a full-blown RDF engine show that our framework outperforms the existing ones by up to two orders of magnitude in processing SPARQL queries with regular expression patterns.
Benign bronchoesophageal fistula (BEF) is a rare condition that is usually treated surgically; however, less invasive endoscopy procedures have been attempted to overcome the disadvantages of surgery. The aim of this study was thus to determine the results of endoscopic management as a primary treatment in patients with BEF.
We retrospectively analyzed data from 368 patients with BEF who were treated at a tertiary care, academic medical center between January 2000 and August 2009.
Benign causes were found for only 18 of the 368 patients. Of these, seven were treated endoscopically and the others by surgery or other methods. The first endoscopy procedures failed in all seven patients, with second trials of endoscopy performed in four patients at a median of 8 days (range, 3 to 11 days) after the first procedure. The second endoscopic procedure was successful in two out of four patients; one patient showed no recurrence of the fistula, whereas the second patient experienced a recurrence after 24 months. All patients underwent successful surgical procedures after the failure of endoscopic treatment, with no further recurrences.
Although we observed a low rate of success for primary endoscopic treatment of benign BEF, the invasive nature of surgery suggests the need for a prospective study with a large number of patients to evaluate the efficacy of less invasive procedures such as endoscopic treatment.
Esophageal fistula; Endoscopy; Fibrin glue
P2/MS is known as a simple, accurate, and noninvasive marker for determination of the degree of hepatic fibrosis in patients with viral hepatitis. We aimed to validate P2/MS in patients with HCC.
Consecutive HCC patients
who underwent surgical resection between June 2007 and March 2009 at Seoul National University Hospital were enrolled. Fibrosis stage was reviewed and assessed according to METAVIR scoring. P2/MS values [platelet count (109/L)]2/[monocyte fraction (%)×segmented neutrophil fraction (%)] and other noninvasive fibrosis scoring systems were calculated.
of 171 patients were included; seven patients with METAVIR F1, 31 with F2, 41 with F3, and 92 with F4. The area under the receiver-operating characteristic curve of P2/MS was 0.804 [95% confidence interval (CI), 0.681~0.927] for detection of significant fibrosis (F2-F4) and 0.769 (95% CI, 0.698~0.839) for detection of histological cirrhosis (F4). At a value < 62, P2/MS detected significant fibrosis with a specificity of 85.7% (95% CI, 42.0~99.2) and a positive likelihood ratio of 4.268 (95% CI, 0.692~26.309); and at a value > 115, P2/MS ruled out significant fibrosis with a sensitivity of 90.2% (95% CI, 84.4~94.1) and a negative likelihood ratio of 0.34 (95% CI, 0.106~0.095). P2/MS had a superior efficacy for detection of hepatic fibrosis in patients with HCC compared to the other noninvasive panels.
P2/MS can accurately detect fibrosis in patients with HCC. Thus, P2/MS might be utilized as a noninvasive index reflecting the degree of hepatic fibrosis in HCC patients.
P2/MS; Fibrosis; Hepatocellular carcinoma
Here, we report a new method of concentration-enhanced binding kinetics for a rapid immunoassay screening test on a gold surface in a poly(dimethylsiloxane) (PDMS) microfluidic chip format. The use of alkylthiolate self-assembled monolayers on gold surfaces of a PDMS-glass microchip resulted in accelerated binding kinetics of Human chorionic gonadotropin (hCG) at an electrokinetic trapping zone. We used a PBS solution (buffer concentration ~ 150 mM), not a dibasic buffer system (~10 mM), for the dynamic preconcentrating operation and the preconcentration of cy3 labeled streptavidin onto biotinylated Au surface revealed that the binding kinetics of the protein were linearly proportional to the concentration profile of the preconcentration plug. We showed rapid detection of hCG in the clinical range with a shorten assay time of 10 min. Also, we demonstrated that the amount of sample needed were detection was decreased from ~4 mL to ~25 μL in the standard serum tests. The enhanced binding kinetics between hcG Ag-Ab via preconcentration showed good feasibility for use in a rapid immunoassay screening test.
microfluidic; nanofluidic; hCG; preconcentrator; rapid immunoassays; NafionR membrane
In this study, flat piezoelectric microcantilevers were fabricated under low-stress Pb(Zr0.52Ti0.48)O3 (PZT) film conditions. They were analyzed using the Raman spectrum and wafer curvature methods. Based on the residual stress analysis, we found that a thickness of 1 μm was critical, since stress relaxation starts to occur at greater thicknesses, due to surface roughening. The (111) preferred orientation started to decrease when the film thickness was greater than 1 μm. The d33 value was closely related to the stress relaxation associated with the preferred orientation changes. We examined the harmonic response at different PZT cantilever lengths and obtained a 9.4-μm tip displacement at 3 Vp-p at 1 kHz. These analyses can provide a platform for the reliable operation of piezoelectric microdevices, potentially nanodevice when one needs to have simultaneous control of the residual stress and the piezoelectric properties.
Nanomechanics; Residual stress; Piezoelectric; Cantilever; Biosensor
In this paper, we reported a simple, disposable PDMS micro/nanofluidic preconcentration chip for In-vitro concentration-enhanced cell kinase assays. Utilizing the preconcentration (electrokinetic trapping) directly from cell lysate (1 mM ATP) samples, we could achieve at least 25-fold increase in reaction velocity and 65-fold enhancement in sensitivity. In addition, we shorten the assay time down to less than 10 mins, with the sample volume requirements of down to ~5 cells. This device could be a generic and powerful tool for diagnostics and systems biology studies at the single-cell level, if properly optimized and integrated with the cell culture microdevices.
The CYP2C19 polymorphism plays an important role in the metabolism of various proton-pump inhibitors. Several trials have produced conflicting data on eradication rates of Helicobacter pylori (H. pylori) among CYP2C19 genotypes. We investigated whether the CYP2C19 genotype affects the eradication rate of H. pylori by direct comparing the effects of lansoprazole- and rabeprazole-based triple therapies.
A total of 492 patients infected with H. pylori was randomly treated with either 30 mg of lansoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin and 1,000 mg of amoxicillin twice daily for 1 week. CYP2C19 genotype status was determined by a PCR-restriction-fragment-length polymorphism method. After 7 to 8 weeks, H. pylori status was evaluated by a C13-urea breath test.
Four hundred and sixty-three patients were analyzed, and the eradication rate was 75.2% in a per-protocol analysis. Eradication rates for the lansoprazole regimen (n=234) were 73.8%, 80.7%, and 85.4% in the homozygous extensive (HomEM), heterozygous extensive (HetEM), and poor metabolizers (PM) groups, respectively (p=0.303). In the case of the rabeprazole regimen (n=229), the eradication rates were 68.6%, 73.0%, and 71.9% in the HomEM, HetEM, and PM groups, respectively (p=0.795).
The efficacies of triple therapies that include lansoprazole or rabeprazole are not affected by CYP2C19 genetic polymorphisms.
Helicobacter pylori; CYP2C19; Proton pump inhibitor; Lansoprazole; Rabeprazole
Hilar cholangiocarcinomas are often treated with liver resections. Hepatic dysfunction and infection are common postoperative complications. Although secondary bacterial peritonitis due to abdominal abscess or perforation is common, we report herein the first case of spontaneous bacterial peritonitis after hepatic resection. A 61-year-old male patient without underlying liver disease was diagnosed as having a Klatskin tumor, and a right trisectionectomy with caudate lobectomy was performed. From postoperative days 18-28, the patient gained 4.1 kg as ascites developed, and showed evidence of hepatic insufficiency with prolonged prothrombin time and jaundice. Computed tomography, performed at postoperative day 28 when fever had developed, showed only ascites without bowel perforation or abscess. When paracentesis was performed, the serum-ascites albumin gradient was 2.3 g/dL, indicating portal hypertension, and the ascites' polymorphonuclear cell count was 1,156/mm3. Since the clinical, laboratory, and image findings were compatible with spontaneous bacterial peritonitis, we started empirical antibiotics without additional intervention. Follow-up analysis of the ascites after 48 hours revealed that the polymorphonuclear cell count had decreased markedly to 108/mm3; the fever and leukocytosis had also improved. After 2 weeks of antibiotic treatment, the patient recovered well, and was discharged without any problem.
Spontaneous bacterial peritonitis; Hepatic resection; Cholangiocarcinoma
We report a novel method of increasing both the reaction rate and the sensitivity of low-abundance enzyme assay using a micro/nanofluidic preconcentration chip. The disposable preconcentration device made out of PDMS with a surface-patterned ion-selective membrane increases local enzyme/substrate concentrations for rapid monitoring of enzyme activity. As a model system, we used trypsin as the enzyme and BODIPY FL casein as the fluorogenic substrate. We demonstrated that the reaction rate of trypsin-BODIPY FL was significantly enhanced by increasing the local concentrations of both trypsin and BODIPY FL casein in the preconcentration chip. The reaction time required to turn over substrates at 1 ng/mL was only ~10 min compared to ~1 h without preconcentration, which demonstrates significantly higher reaction rate through the increase of the concentrations of both the enzyme and substrate. Furthermore, trypsin activity can be measured down to a concentration level of 10 pg/mL, which is ~100 fold enhancement in sensitivity compared to the result without the preconcentration step. This micro/nanofluidic preconcentrator chip could be used as a generic micro reaction platform to study any enzyme-substrate systems, or other biochemical reaction systems in low concentration ranges.
In this paper, we report a new method of fabricating a high-throughput protein preconcentrator in poly(dimethylsiloxane) (PDMS) microfluidic chip format. We print a submicron thick ion-selective membrane on the glass substrate by using standard patterning techniques. By simply plasma-bonding a PDMS microfluidic device on top of the printed glass substrate, we can integrate the ion-selective membrane into the device and rapidly prototype a PDMS preconcentrator without complicated microfabrication and cumbersome integration processes. The PDMS preconcentrator shows a concentration factor as high as ~ 104 in 5 min. This printing method even allows fabricating a parallel array of preconcentrators to increase the concentrated sample volume, which can facilitate an integration of our microfluidic preconcentrator chip as signal enhancing tool to various detectors such as mass spectrometer.
A perm-selective nanochannel could initiate concentration polarization near the nanochannel, significantly decreasing (increasing) the ion concentration in the anodic (cathodic) end of the nanochannel. Such strong concentration polarization can be induced even at moderate buffer concentrations because of local ion depletion (therefore thicker local Debye layer) near the nanochannel. In addition, fast fluid vortices were generated at the anodic side of the nanochannel due to the nonequilibrium electro-osmotic flow (EOF), which was at least ∼10X faster than predicted from any equilibrium EOF. This result corroborates the relation among induced EOF, concentration polarization, and limiting-current behavior.
Pneumatosis intestinalis (PI) is an uncommon disorder characterized by an accumulation of gas in the bowel wall, and has been associated with a variety of disorders and procedures. We describe a 35-year-old man who undertook hematopoietic stem cell transplantation due to myelodysplastic syndrome. An abdominal X-ray demonstrated extensive PI with pneumoperitoneum mimicking hollow organ perforation. However, the patient had no abdominal symptoms and there was no evidence of peritoneal inflammation. After two weeks of conservative management, including bowel rest and antibiotics, his pneumoperitoneum resolved spontaneously without any complications. Of the many factors that affect the gastrointestinal tract mucosal integrity, intramural pressure, and bacterial flora-produced intraluminal gas interact to produce PI. If the condition is accompanied by bowel ischemia, portomesenteric venous gas, metabolic acidosis, and abdominal sepsis, or if PI is severe in extent immediate surgical intervention is indicated. The described case supports that a mechanical rather than a bacterial etiology underlies the pathogenesis of PI.
Pneumatosis cystoides intestinalis; Pneumoperitoneum; Hematopoietic stem cell transplantation
To facilitate the establishment of mixed chimerism with limited dose of bone marrow (BM) cells, and to achieve tolerance in skin graft model, combined blocking of costimulatory pathway and IL-2 pathway was used in minimally myeloablative model using busulfan. BM cells (2.5×107) of BALB/c were injected into C57BL/6 mice at day 0 with full thickness skin graft after single dose injection of busulfan (25 mg/kg) on day -1. Recipients were grouped and injected the anti-CD154, CTLA4-Ig, anti-IL-2R at days 0, 2, 4, and 6 according to protocol. Mixed macrochimerism were induced in groups treated with anti-CD154+anti-CTLA4-Ig, anti-CD154+anti-IL-2R, and anti-CD154+anti-CTLA4 Ig+anti-IL-2R. Three groups having chimerism enjoyed prolonged graft survival more than 6 months. Superantigen deletion study revealed deletion of alloreactive T cells in combined blockade treated groups. In graft versus host disease model using CFSE staining, CD4+ T cell and CD8+ T cell proliferation were reduced in groups treated with CTLA4-Ig or anti-IL-2R or both in combination with anti-CD154. However, anti-IL-2R was not so strong as CTLA4-Ig in terms of inhibition of T cell proliferation. In conclusion, IL-2 pathway blocking combined with anti-CD154 can establish macrochimerism with limited dose of BM transplantation and induce specific tolerance to allograft.
ABI1793 monoclonal antibody; Asnti-CD154; abatacept; CTLA4-Ig; Anti-IL-2R; Mixed Chimerism; Transplantation Chimera; Bone Marrow Transplantation; Skin Transplantation; Busulfan
Micro RNAs-371-372-373 (miRNAs-371-373), originating from the same pri-miRNA transcript, are reported to be upregulated in hepatocellular carcinoma (HCC) and to be related to the regulation of hepatitis B virus (HBV) infection. Our study investigated whether pri-miRNAs-371-373 polymorphisms are associated with the risk of HCC occurrence and HBV clearance.
Genetic variations were identified through direct DNA sequencing using TaqMan assay. Three sequence variants of pri-miRNAs-371-373 were identified. Genetic associations of those with HCC occurrence and HBV clearance among patients with HBV infection were analyzed using logistic regression analyses with adjustment for age and gender (n = 1439).
For the occurrence of HCC, polymorphism rs3859501C>A acted as a protective factor both in chronic carriers (OR = 0.75, P = 0.005 in a codominant model; OR = 0.71, P = 0.02 in a dominant model; OR = 0.66, P = 0.03 in recessive model) and liver cirrhosis patients (OR = 0.69, P = 0.001 in a codominant model; OR = 0.60, P = 0.003 in a dominant model; OR = 0.63, P = 0.03 in a recessive model). The pri-miRNAs-371-373_ht2 [C-A-C] also showed a protective effect on HCC occurrence both in the chronic carrier and liver cirrhosis groups (P<0.05 in both). However, there was no significant association between pri-miRNAs-371-373 polymorphisms and HBV clearance.
In conclusion, among chronic carriers and liver cirrhosis patients, the A allele of rs3859501 and the haplotype pri-miRNAs-371-373_ht2 were more protective to HCC than other genotypes and haplotypes. Further studies into the roles of rs3859501 and pri-miRNAs-371-373_ht2 haplotype in hepatocarcinogenesis are needed.