Can prophylactic argon plasma coagulation reduce delayed post-papillectomy bleeding? A prospective multicenter trial.

BACKGROUND AND AIM: Endoscopic post-papillectomy bleeding occurs in 3% to 20% of the cases, and delayed bleeding is also problematic. However, there is no consensus on how to reduce delayed post-papillectomy bleeding. The aim of this study was to evaluate the efficacy of prophylactic argon plasma coagulation (APC) to minimize delayed bleeding and reduce the persistence of residual tumors after endoscopic papillectomy. METHODS: In a prospective pilot study of patients with benign ampullary tumors, the prophylactic APC group underwent APC at the resection margin following a conventional snaring papillectomy. Then, 24 h later after the papillectomy, all patients underwent a follow-up duodenoscopy to identify post-papillectomy bleeding and were followed up until 12 months. The main outcomes were the delayed (≥24 h) post-papillectomy bleeding rate and the tumor persistence rate. RESULTS: The delayed post-papillectomy bleeding rate was 30.8% (8/26) in the prophylactic APC group and 21.4% (6/28) in the non-APC group (P = 0.434). The post-procedure pancreatitis rates were 23.1% (6/26) and 35.7% (10/28), respectively (P = 0.310). The rate of tumor persistence did not differ between the two groups at 1 month (12.5% vs 7.4%, P = 0.656), 3 months (4.2% vs 3.7%, P = 1.00), 6 months (8.3% vs 3.7%, P = 0.595), and 12 months (0% vs 3.7%, P = 1.00). There were no procedure-related mortalities or serious complications. CONCLUSION: Prophylactic APC may not be effective in reducing delayed post-papillectomy bleeding or remnant tumor ablation immediately after conventional papillectomy (Clinical trial registration-cris.nih.go.kr; KCT0001955).

Vigorous Periprocedural Hydration With Lactated Ringer's Solution Reduces the Risk of Pancreatitis After Retrograde Cholangiopancreatography in Hospitalized Patients.

BACKGROUND & AIMS: Vigorous intravenous fluid resuscitation (IVFR) was reported to reduce post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in a pilot study. We performed a randomized, double-blind controlled trial to establish whether periprocedural vigorous IVFR reduces the risk of post-ERCP pancreatitis. METHODS: A total of 510 patients with native papilla at 3 tertiary referral centers in Korea were randomly assigned (1:1) to groups given vigorous IVFR (lactated Ringer's solution in an initial bolus of 10 mL/kg before the procedure, 3 mL/kg/h during the procedure, for 8 hours after the procedure, and a post-procedure bolus of 10 mL/kg) or a standard IVFR (lactated Ringer's solution at 1.5 mL/kg/h during and for 8 hours after the procedure). The primary end point of the study was the development of post-ERCP pancreatitis, and the secondary end point was severity of pancreatitis, hyperamylasemia, and fluid overload. RESULTS: The main indications for ERCP were choledocholithiasis (58%) and malignant biliary stricture (27%). Post-ERCP pancreatitis developed in 11 patients in the vigorous IVFR group (4.3%) and 25 patients in the standard IVFR group (9.8%) (relative risk, 0.41; 95% CI, 0.20-0.86; P = .016). Moderate or severe acute pancreatitis occurred in a significantly smaller proportion of patients in the vigorous IVFR group (0.4%) than in the standard IVFR group (2.0%; P = .040). One patient in the vigorous IVFR group developed peripheral edema. CONCLUSIONS: In a double-blind, randomized controlled trial, we found vigorous periprocedural intravenous hydration with lactated Ringer's solution to reduce the incidence and severity of post-ERCP pancreatitis in average-risk and high-risk cases. IVFR is not associated with increased adverse events. ClinicalTrials.gov number: NCT02308891.

Predictors of malignancy in pure branch duct type intraductal papillary mucinous neoplasm of the pancreas: A nationwide multicenter study.

BACKGROUND/OBJECTIVES: Prediction of malignancy in patients with BD-IPMNs is critical for the management. The aim of this study was to elucidate predictors of malignancy in patients with 'pure' BD-IPMNs who had a main pancreatic duct (MPD) diameter of ≤5 mm according to the most recent international consensus criteria and in whom MPD involvement was excluded on postoperative histology. METHODS: We identified 177 patients with 'pure' BD-IPMNs based on preoperative imaging and postoperative histology from 15 tertiary referral centers in Korea. BD-IPMNs with low-grade (n = 72) and moderate-grade (n = 66) dysplasia were grouped as benign and BD-IPMNs with high-grade dysplasia (n = 10) and invasive carcinoma (n = 29) were grouped as malignancy. RESULTS: On univariate analysis, particular symptoms (jaundice and clinical pancreatitis), CT findings (cyst size > 3 cm, the presence of enhancing mural nodules) and EUS features (the presence of mural nodules, the mural nodule size > 5 mm) were significant risk factors predicting malignant BD-IPMNs. Multivariate analysis revealed that the cyst size > 3 cm (odds ratio = 9.9), the presence of enhancing mural nodules on CT (odds ratio = 19.3) and the mural nodule size > 5 mm on EUS (odds ratio = 14.9) were the independent risk factors for the presence of malignancy in BD-IPMNs (p < 0.001). CONCLUSIONS: The cyst size > 3 cm, the presence of enhancing mural nodules on CT, the mural nodule size > 5 mm on EUS are three independent predictors of malignancy in patients with 'pure' BD-IPMNs.

Incremental value of cell block preparations over conventional smears alone in the evaluation of EUS-FNA for pancreatic masses.

BACKGROUND/AIMS: The effectiveness of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been established for a definite pathological diagnosis of pancreatic solid masses. We investigated the usefulness of cell block preparations in EUS-FNA, by evaluating the added value of cell block preparations over conventional smears alone. METHODOLOGY: Between March 2011 and June 2013, 61 patients were retrospectively evaluated who underwent EUS-FNA for pancreatic solid masses. Diagnostic values for diagnosing pancreatic malignancy were compared for a combination of the conventional smear and cell block (CSCB) and the conventional smear alone (CS). RESULTS: The addition of the cell block technique increased the sensitivity of conventional smear for diagnosing the pancreatic malignancy from 79% (CS) to 90% (CSCB, p=0.0313) and the accuracy from 81% to 91% (p=0.0313). The specificity and positive predictive value were 100% in both methods. The negative predictive value was increased from 33% (CS) to 50% (CSCB), but this difference was not statistically significant (p=0.0833). CONCLUSION: The addition of the cell block method after a conventional smear may increase the sensitivity and negative predictive value for diagnosing the pancreatic malignancy in patients with pancreatic masses who undergo EUS-FNA. Further study may be warranted to determine whether the cell block method can replace the conventional smear.

Three cases of Diphyllobothrium nihonkaiense infection in Korea.

Until 2012, a total of 48 cases of diphyllobothriasis had been reported in Korea, all of which were morphologically identified as Diphyllobothrium latum. However, some of these specimens were analyzed by nucleotide sequencing of the mitochondrial cox1 gene, which showed that all were D. nihonkaiense, not D. latum. After that, 3 further cases of diphyllobothriasis were confirmed as D. nihonkaiense. In the present study, 3 new cases of D. nihonkaiense were detected from 2011 through 2013. The hosts were infected through consumption of salmonid fishes, such as the trout or salmon, and 2 of them experienced severe diarrhea prior to proglottid passage. All of the tapeworms were confirmed to be D. nihonkaiense by genetic identification. This proved again that most diphyllobothriasis in Korea have been caused by D. nihonkaiense.

Factors predictive of adverse events following endoscopic papillary large balloon dilation: results from a multicenter series.

BACKGROUND: Lack of established guidelines for endoscopic papillary large balloon dilation (EPLBD) may be a reason for aversion of its use in removal of large common bile duct (CBD) stones. AIMS: We sought to identify factors predictive of adverse events (AEs) following EPLBD. METHODS: This multicenter retrospective study investigated 946 consecutive patients who underwent attempted removal of CBD stones ≥10 mm in size using EPLBD (balloon size 12-20 mm) with or without endoscopic sphincterotomy (EST) at 12 academic medical centers in Korea and Japan. RESULTS: Ninety-five (10.0 %) patients exhibited AEs including bleeding in 56, pancreatitis in 24, perforation in nine, and cholangitis in six; 90 (94.7 %) of these were classified as mild or moderate in severity. There were four deaths, three as a result of perforation and one due to delayed massive bleeding. Causative factors identified in fatal cases were full-EST and continued balloon inflation despite a persistent waist seen fluoroscopically. Multivariate analyses showed that cirrhosis (OR 8.03, p = 0.003), length of EST (full-EST: OR 6.22, p < 0.001) and stone size (≥16 mm: OR 4.00, p < 0.001) were associated with increased bleeding, and distal CBD stricture (OR 17.08, p < 0.001) was an independent predictor for perforation. On the other hand, balloon size was associated with deceased pancreatitis (≥14 mm: OR 0.27, p = 0.015). CONCLUSIONS: EPLBD appears to be a safe and effective therapeutic approach for retrieval of large stones in patients without distal CBD strictures and when performed without full-EST.

Successful removal of remnant cystic duct stump stone using single-operator cholangioscopy-guided electrohydraulic lithotripsy: two case reports.

Cholecystectomy is the best method for treating gallstone diseases. However, 10%-30% of patients who undergo a cholecystectomy continue to complain of upper abdominal pain, dyspepsia, or jaundice-this is referred to as postcholecystectomy syndrome. Cystic duct stump stones are a troublesome cause of postcholecystectomy syndrome. Conventionally, surgery is mainly performed to remove cystic duct stump stones. However, repeated surgery can cause complications, such as postoperative bleeding, biliary injury, and wound infection. As an alternative method of surgery, endoscopic retrograde cholangiopancreatography is sometimes used to remove cystic duct stump stones, although the success rate is not high due to technical difficulties. Recently, peroral cholangioscopy, which can directly observe the bile duct, has been suggested as an alternative method. We report two cases in which a cystic duct stump stone was successfully removed via a single-operator cholangioscopy, after failure with an endoscopic retrograde cholangiopancreatography.

Instructor factors associated with medical students' lecture evaluation: a longitudinal analysis.

PURPOSE: This study identified factors that affect lecture evaluation by analyzing sophomores from Dankook University, examining each cluster's characteristics, and comparing differences among trajectories. METHODS: This study identified factors that affect lecture evaluation by analyzing sophomores from Dankook University, examining each cluster's characteristics, and comparing differences among trajectories. RESULTS: The lecture evaluation score decreased as the teaching hours per instructor in a year increased by an hour, and the number of instructors per lecture increased by one individual. During trajectory analysis, the first trajectory had lower lecture evaluation scores overall but relatively high appropriateness of the textbook and punctuality of class, whereas the second trajectory had higher lecture evaluation scores overall for all four items. CONCLUSION: The two trajectories showed differences in teaching methods (understanding of lecture content and usefulness of the lecture) rather than in external factors (appropriateness of the textbook and punctuality of class). Therefore, to improve lecture satisfaction, enhancing instructors' instructional competencies through lectures and adjusting the teaching hours by assigning an adequate number of instructors per lecture are recommended.

Current Practice Patterns of Endoscopic Ultrasound-Guided Tissue Sampling for Pancreatic Solid Mass in Korea: Outcomes of a National Survey.

Background/Aims: Although endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) and fine needle biopsy (FNB) are widely used for tissue acquisition of pancreatic solid mass, the optimal strategy of this procedure has not been established yet. The aim of this nationwide study was to investigate the current practice patterns of EUS-FNA/FNB for pancreatic solid mass in Korea. Methods: The Policy-Quality Management of the Korean Pancreatobiliary Association (KPBA) developed a questionnaire containing 22 questions. An electronic survey consisting of the questionnaire was distributed by e-mail to members registered to the KPBA. Results: A total of 101 respondents completed the survey. Eighty respondents (79.2%) performed preoperative EUS-FNA/FNB for operable pancreatic solid mass. Acquire needles (60.4%) were used the most, followed by ProCore needles (47.5%). In terms of need size, most respondents (>80%) preferred 22-gauge needles regardless of the location of the mass. Negative suction with a 10-mL syringe (71.3%) as sampling technique was followed by stylet slow-pull (41.6%). More than three needle passes for EUS-FNA/FNB was performed by most respondents (>80%). The frequency of requiring repeated procedure was significantly higher in respondents with a low individual volume (<5 per month, p=0.001). Prophylactic antibiotics were routinely used in 39 respondents (38.6%); rapid on-site pathologic evaluation was used in 6.1%. Conclusions: According to this survey, practices of EUS-FNA/FNB for pancreatic solid mass varied substantially, some of which differed considerably from the recommendations present in existing guidelines. These results suggest that the development of evidence-based quality guidelines fitting Korean clinical practice is needed to establish the optimal strategy for this procedure.

Is the addition of choleretic agents in multiple double-pigtail biliary stents effective for difficult common bile duct stones in elderly patients? A prospective, multicenter study.

BACKGROUND: Temporary biliary stenting is both technically easy and feasible, and choleretic agents such as ursodeoxycholic acid (UDCA) and a terpene preparation may promote a reduction in stone size. However, there are few comparative data on the effectiveness of choleretic agents available. OBJECTIVE: To investigate the efficacy of multiple double-pigtail stents with or without UDCA and terpene on difficult common bile duct (CBD) stones. DESIGN: A prospective, multicenter study. SETTING: Four tertiary-care referral centers. PATIENTS: This study involved 51 patients. INTERVENTION: In total, 51 elderly patients with comorbidities who had difficult CBD stones refractory to conventional methods were randomized to receive either multiple 7F double-pigtail stents (group A) or stents in combination with UDCA and terpene (group B) for a period of 6 months. MAIN OUTCOME MEASUREMENTS: Stone size reduction, successful duct clearance, and complications. RESULTS: Complete endoscopic duct clearance was achieved in 14 patients (73.7%) in group A and 19 patients (86.4%) in group B (P = .826). The mean size of CBD stones (transverse/longitudinal diameter, mean ± SD) was 19.12 ± 4.48 mm/20.47 ± 3.86 mm in group A and 21.30 ± 7.08 mm/22.58 ± 7.61 mm in group B. Stone size decreased significantly to 12.04 ± 3.26 mm/13.31 ± 5.12 mm and 13.67 ± 5.40 mm/14.04 ± 6.12 mm, respectively (P < .01). However, there was no statistical difference in stone size reduction between the two groups (P = .685, P = .289). No serious complications related to the stent or endoscopic procedures were observed, except for cholangitis (n = 1, group A) and distal stent migration (n = 2, group B). LIMITATIONS: Small number of patients in East Asia. CONCLUSION: Temporary multiple double-pigtail biliary stenting was a safe and feasible method of treating difficult and large CBD stones in elderly patients and contributed to a reduction in stone size and successful duct clearance. However, the addition of choleretic agents did not result in a statistical difference in stone size or rate of successful duct clearance.

RNA interference mediated knockdown of apolipophorin-III leads to knockdown of manganese superoxide dismutase in Hyphantria cunea.

Apolipophorin-III (apoLp-III), a hemolymph protein that facilitates lipid transport in aqueous media in insects was recently shown to play a role in insect immune activation. Here, we report another novel possible function of apoLp-III in insects. To identify genes affected by apoLp-III expression in larvae, we decreased endogenous apoLp-III mRNA in Hyphantria cunea (Hc) through RNA interference; subsequently, we observed lower levels of antioxidant enzymes, including manganese superoxide dismutase (MnSOD), glutathione S-transferase, and immune proteins. Knockdown of Hc apoLp-III led to decreased MnSOD expression in fat body tissues and elevated superoxide anion levels in Hc fat body cells, suggesting that Hc apoLp-III is involved in the action and/or expression of antioxidant enzymes, especially MnSOD.

Identification of CDK7 Inhibitors from Natural Sources Using Pharmacoinformatics and Molecular Dynamics Simulations.

The cyclin-dependent kinase 7 (CDK7) plays a crucial role in regulating the cell cycle and RNA polymerase-based transcription. Overexpression of this kinase is linked with various cancers in humans due to its dual involvement in cell development. Furthermore, emerging evidence has revealed that inhibiting CDK7 has anti-cancer effects, driving the development of novel and more cost-effective inhibitors with enhanced selectivity for CDK7 over other CDKs. In the present investigation, a pharmacophore-based approach was utilized to identify potential hit compounds against CDK7. The generated pharmacophore models were validated and used as 3D queries to screen 55,578 natural drug-like compounds. The obtained compounds were then subjected to molecular docking and molecular dynamics simulations to predict their binding mode with CDK7. The molecular dynamics simulation trajectories were subsequently used to calculate binding affinity, revealing four hits-ZINC20392430, SN00112175, SN00004718, and SN00262261-having a better binding affinity towards CDK7 than the reference inhibitors (CT7001 and THZ1). The binding mode analysis displayed hydrogen bond interactions with the hinge region residues Met94 and Glu95, DFG motif residue Asp155, ATP-binding site residues Thr96, Asp97, and Gln141, and quintessential residue outside the kinase domain, Cys312 of CDK7. The in silico selectivity of the hits was further checked by docking with CDK2, the close homolog structure of CDK7. Additionally, the detailed pharmacokinetic properties were predicted, revealing that our hits have better properties than established CDK7 inhibitors CT7001 and THZ1. Hence, we argue that proposed hits may be crucial against CDK7-related malignancies.

Catalase from the white-spotted flower chafer, Protaetia brevitarsis: cDNA sequence, expression, and functional characterization.

Catalase, which is one of the key enzymes of the cellular antioxidant defense system, prevents free hydroxyl radical formation by breaking down hydrogen peroxide into oxygen and water. Here, we show the cloning and characterization of a catalase gene in a coleopteran insect. This gene was isolated by searching the white-spotted flower chafer Protaetia brevitarsis cDNA library, and the gene itself encodes a protein of 505 amino acids in length, named PbCat. PbCat shows high similarities to the insect catalase genes known to date. The recombinant PbCat, which is expressed as a 56-kDa polypeptide in baculovirus-infected insect Sf9 cells, shows the highest activity at 30 degrees C and pH 7.0. Northern and Western blot analyses revealed the presence of PbCat in all tissues examined, showing its ubiquitous expression. P. brevitarsis larvae in which H(2)O(2) was overloaded, showed a marked up-regulation in PbCat expression. Moreover, P. brevitarsis larvae showed an apparent increase in PbCat expression even after a wounding through injection. These results indicate that PbCat is up-regulated after wounding and oxidative pressure induced by H(2)O(2), reflecting an important role of PbCat in H(2)O(2) scavenging.

[Clinical, radiological and pathological exploration of focal nodular hyperplasia of liver reported in Korea].

BACKGROUND/AIMS: Focal nodular hyperplasia (FNH) is mandatory to be differentiated from other hepatic tumorous conditions such as hepatocellular carcinoma and adenoma. The purpose of this study was to explore the clinical, radiological and pathological features of FNH cases reported in Korea. METHODS: We have searched the journals from the web site "http://koreamed.org" using keywords "focal nodular hyperplasia" and "liver" - total of 38 cases of FNH, 37 cases from 17 published articles and one case from our experience confirmed histologically, were reviewed and analyzed. RESULTS: Thirty eight cases were diagnosed between gestational age of 36 weeks and 67 years. Seventeen female patients (45%) had no history of taking oral contraceptives. Twenty cases (52.6%) experienced clinical symptoms such as abdominal pain and palpable mass. Computed tomography revealed contrast-enhancement in 34 nodules (85%) and typical central stellate scar in 9 (22.5%) of 40 nodules. Magnetic resonance imaging showed T1 weighted low signal in 18 (60%) and T2 weighted high signal in 22 (73.3%) of 30 nodules. Six (60%) of 10 cases showed hypervascular staining on hepatic angiography. Among 38 cases, 32 (84.2%) cases had single nodule and their mean size was 3.9 cm (0.5-16 cm). Pathologically, fibrous septa, proliferation of bile ductules and arterial wall thickening were seen in most cases. CONCLUSIONS: Of all the FNH cases reported in Korea, there were some differences in clinical aspects of sex ratio, accompanying clinical symptoms, and relationship with oral contraceptives, compared with previous reports. Further prospective studies are needed by means of nation-wide clinical survey and analysis.

[Down-regulation of survivin in growth inhibition of hepatoma cells induced by a selective cyclooxygenase-2 inhibitor].

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) inhibitors reportedly inhibit the growth of hepatocellular carcinoma (HCC) via caspase-dependent or caspase-independent apoptosis, which is due to COX-2 being associated with hepatocarcinogenesis. Survivin is highly expressed in most human cancers, but the mechanism regulating survivin expression remains unclear. We investigated the regulatory expression of survivin in selective-COX-2-inhibitor-induced growth inhibition of hepatoma cells. METHODS: After treatment with NS-398 (a selective COX-2 inhibitor) at various concentrations (10, 50, 100, 150, and 200 micrometer), the growth inhibition of Hep3B hepatoma cells was assessed by an MTT cell-viability assay, DNA fragmentation gel analysis, and flow cytometry. The expression of survivin transcript was analyzed by reverse-transcription polymerase chain reactions. RESULTS: NS-398 inhibited the growth of hepatoma cells by an amount dependent on the concentration and the time since treatment. Apoptotic DNA ladder and flow-cytometry shifting to the sub-G1 phase were revealed in NS-398-induced growth inhibition of hepatoma cells. NS-398 suppressed the expression of the survivin gene in a concentration- and time-dependent manner. CONCLUSIONS: Survivin was down-regulated in the growth inhibition of hepatoma cells induced by a selective COX-2 inhibitor, NS-398, in a concentration- and time-dependent manner. These results suggest the therapeutic inhibition of COX-2 via suppression of survivin in HCC.

Predictors of Malignancy in "Pure" Branch-Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas without Enhancing Mural Nodules on CT Imaging: A Nationwide Multicenter Study.

Background/Aims: Presence of enhanced mural nodules, which can be visualized using computed tomography (CT), is one of high-risk stigmata in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs). Conversely, the absence of enhanced mural nodules on preoperative imaging does not exclude malignant risk. The present study aimed to investigate other morphological features as predictors of malignancy in "pure" BD-IPMNs without enhanced mural nodules on CT. Methods: This retrospective study included 180 patients with surgically confirmed "pure" BD-IPMNs of the pancreas and no enhanced mural nodules on preoperative CT. The study was conducted at 15 tertiary referral centers throughout South Korea. Univariate and multivariate analyses were used to identify significant predictors of malignancy. Results: BD-IPMNs with low-grade (n=84) or moderate-grade (n=76) dysplasia were classified as benign; those with high-grade dysplasia (n=8) or invasive carcinoma (n=12) were classified as malignant. The multivariate analysis revealed that cyst size ≥30 mm (odds ratio, 8.6; p=0.001) and main pancreatic duct diameter ≥5 mm (odds ratio, 4.1; p=0.01) were independent risk factors for malignancy in "pure" BD-IPMNs without enhanced mural nodules on CT. Endoscopic ultrasound detected enhanced mural nodules (6/82) that had been missed on CT, and two IPMNs with enhanced mural nodules were malignant. Conclusions: In patients with "pure" BD-IPMNs who have no enhanced mural nodules on CT, cyst size ≥30 mm and main pancreatic duct diameter ≥5 mm may be associated with malignancy.

Transferrin inhibits stress-induced apoptosis in a beetle.

Transferrin in insects is known as an iron transporter, an antibiotic agent, a vitellogenin, and a juvenile hormone-regulated protein. We show here a novel functional role for insect transferrin. Stresses, such as iron overload, bacterial or fungal challenge, cold or heat shock, wounding, and H2O2 or paraquat exposure, cause upregulation of the beetle Apriona germari transferrin (AgTf) gene in the fat body and epidermis, and they cause increased AgTf protein levels. RNA interference (RNAi)-mediated AgTf reduction results in rapid induction of apoptotic cell death in the fat body during exposure to heat stress. The observed effect of AgTf RNAi indicates that AgTf inhibits heat stress-induced apoptotic cell death, suggesting a functional role for AgTf in defense and stress responses in the beetle.

cDNA sequences of two biliproteins, BP1 and BP2, from the cabbage white butterfly, Pieris rapae and their tissue- and stage-specific accumulation.

Two similar full-length cDNAs of biliprotein were isolated and shown to encode the two isoelectric forms of biliverdin-binding proteins (BPs): BP1 and BP2 in Pieris rapae. Sequence analysis of two cDNA clones shows that both BPs contain a 567-bp open reading frame which predicts a 189-amino acid protein and a 15-amino acid signal peptide. The calculated isoelectric points are pI=7.25 (BP1) and 6.74 (BP2), respectively. Comparison of two sequences of BP1 and BP2 reveals 12 base differences in the open reading frame, of which three nucleotide changes lead to two amino acid substitutions. The 5'-UTR from the two clones shows no difference, but an additional 45-bp fragment is inserted in the 3'-UTR of BP2 making its message a little longer than that of BP1. Northern blot analysis confirmed that the BP mRNAs are expressed from the late 4th instar to the adult stage with exception of prepupae and newly ecdysed pupae. While the BP1 transcript was prevalent in the larval stage, the BP2 transcript was abundant in the whole body only after the pupal stage in P. rapae. Both BPs were detected in a stage-specific pattern in the epidermis, testis, hindgut, wing, brain, and egg, with a lesser amount in the fat body. Two-dimensional gel electrophoresis and Western blot analyses revealed that BP1 was dominant in tissues from larvae, BP2 was dominant in tissues from pupal stages, and both BPs appeared in tissues from the adult stage, though BP2 was predominant.

[A case of severe skin eruption caused by lamivudine in a patient with chronic hepatitis B].

Lamivudine is widely used for the treatment of chronic hepatitis B infection because of it's remarkable antiviral efficacy and safety. We report a case of severe skin eruption caused by lamivudine. A 47-year-old female was admitted because of jaundice and itching sensation. She was diagnosed as chronic hepatitis B infection a few years ago but did not receive any specific treatment. Laboratory data showed acute deterioration of chronic hepatitis B infection. We prescribed lamivudine as a rescue therapy. Her general condition improved and lab data showed improvement in liver function test thereafter. However, she complained of severe skin eruption and itching sensation a few days after the discharge. We stopped lamivudine because the symptoms did not improve despite the use of anti-histamine. Skin biopsy showed interface dermatitis. After stopping lamivudine, her symptoms improved. However, the skin eruption developed again after lamivudine was restarted. Adefovir was used instead, and the patient did not experience any further skin problems since then.