Anti-Inflammatory and Anti-Bacterial Potential of Mulberry Leaf Extract on Oral Microorganisms.

Mulberry leaves extract (Morus alba extracts; MAE) is known to have therapeutic potentials for numerous human diseases, including diabetes, neurological disorders, cardiovascular diseases, and cancers. However, there has not been sufficient research proving therapeutic effects on oral disease and its related oral risk factors. Thus, we investigated whether MAE has any anti-inflammatory and anti-bacterial effects on risk factors causing oral infectious diseases. To examine the anti-inflammatory response and bacterial inhibition of MAE, we measured intracellular reactive oxygen species (ROS) generation, production of pro-inflammatory cytokines, and the bacterial growth rate. Our study showed that MAE has anti-inflammatory activities, which inhibit the ROS generation and suppressed the production of pro-inflammatory cytokines (TNF-α and IL-6) in human monocyte THP-1 cells by stimulating lipopolysaccharide (LPS) and/or F. nucleatum, which are the virulent factors in periodontal diseases. Furthermore, MAE inhibited the bacterial growth on oral microorganisms (F. nucleatum and S. mutans) infected THP-1 cells. These findings suggested that MAE could be a potential natural source for therapeutic drugs in oral infectious disease.

Level of professional ethics awareness and medical ethics competency of dental hygienists and dental hygiene students: the need to add ethics items to the Korean Dental Hygienist Licensing Examination

PURPOSE: This study aimed to evaluate the level of professional ethics awareness and medical ethics competency in order to assess the potential need for ethics items to be included on the Korean Dental Hygienist Licensing Examination. METHODS: In total, 358 clinical dental hygienists and dental hygiene students completed a structured questionnaire to evaluate their level of ethical awareness and medical ethics competency. The sub-factors of medical ethics were classified into relationships with patients, medical and social relations, and individual specialized fields. RESULTS: Only 32.1% of participants indicated that they had taken a course on professional ethics in the university curriculum, but 95.2% of respondents considered professional ethics to be important. The overall score for medical ethics competency was average (3.37 out of 5). The score for relationships with patients was 3.75 points, followed by medical and social relations (3.19 points) and individual specialized fields (3.16 points). The level of professional ethics awareness was higher among participants who had taken a course on professional ethics than among those who had not done so or who did not remember whether they had done so. CONCLUSION: Dental hygienists were aware of the importance of professional ethics, but their medical ethics competency was moderate. Therefore, medical ethics should be treated as a required subject in the university curriculum, and medical ethics competency evaluations should be strengthened by adding ethics items to the Korean Dental Hygienist Licensing Examination.

Impact of Endoplasmic Reticulum Stress Sensors on Pectolinarin Induced Apoptosis.

Pectolinarin, [5,7-Dihydroxy 4',6-dimethoxyflavone 7-rutinoside, 7-[[6-O-(6-Deoxy-α-L-mannopyranosyl)-ß-D-glucopyranosyl] oxy]-5-hydroxy-6-methoxy-2-(4-ethoxyphenyl)-4H-1-benzopyran-4-one], has been stated one of the major compounds in Cirsium nipponicum (Maxim.) Makino. It is characterized by biological functions of hepatoprotective, anti-inflammatory and antiobesity activities. In this research, it was explained that pectolinarin causes apoptosis in PC12 cells conducted by DNA fragmentation and formation on apoptotic bodies through the activation of ER stress sensors (ATF6 fragmentation and eIF2α phosphorylation). The result of treating the PC12 cells with 50 µM pectolinarin for 24 h has come to increase ATF6 mRNA expression up to 1.6 times, PERK expression up to 1.7 times and IRE1 expression up to 1.4 times, respectively, compared to those of the control. ATF6 fragmentation by pectolinarin treatment was increased about 2 times compared with its control, and phosphorylation of eIF2α was increased 2.5 times. The results proposed that the perception of the molecular mechanisms underlying pectolinarin-caused apoptosis may be useful in new natural medicinal products and health supplements for the apoptosis-related diseases.

Identification of Differentially Expressed Genes Associated with Litter Size in Berkshire Pig Placenta.

Improvement in litter size has become of great interest in the pig industry because fecundity is directly related to sow reproductive life. Improved reproduction has thus been achieved by elucidating the molecular functions of genes associated with fecundity. In the present study, we identified differentially expressed genes (DEGs) via transcriptomic analysis using RNA-sequencing (RNA-Seq) in Berkshire pig placentas from larger (LLG, mean litter size >12) and smaller (SLG, mean litter size < 6.5) litter size groups. In total 588 DEGs were identified (p < 0.05, > 1.5-fold change), of which 98 were upregulated, while 490 were downregulated in the LLG compared with the SLG. Gene Ontology (GO) enrichment was also performed. We concluded that 129 of the 588 DEGs were closely related to litter size according to reproduction related genes selected based on previous reports, as 110 genes were downregulated and 19 upregulated in the LLG compared with the SLG. RT-qPCR utilizing specific primers targeting the early growth response 2 (EGR2), pheromaxein c subunit (PHEROC) and endothelial lipase (LIPG) genes showed high accordance with RNA-Seq results. Furthermore, we investigated the upstream regulators of these three genes in the placenta. We found that WNT9B, a Wnt signaling pathway molecule, and IL-6, known inducers of EGR2 and LIPG, respectively, were significantly increased in LLG compared with SLG. We believe that the induction of IL-6 and LIPG may play an important role in increasing nutrition supply through the placenta from the sow to the piglet during gestation. These results provide novel molecular insights into pig reproduction.

Postoperative Clinical Outcome and Risk Factors for Poor Outcome of Foraminal and Extraforaminal Lumbar Disc Herniation.

OBJECTIVE: We evaluated postoperative outcomes in patients who have lumbar foraminal or extraforaminal disc herniation (FELDH) and suggested the risk factors for poor outcomes. METHODS: A total of 234 patients were selected for this study. Pre- and post-operative Visual Analogue Scale (VAS) and Korean version Oswestry Disability Index (KODI) were evaluated and the changes of both score were calculated. Outcome was defined as excellent, good, fair, and poor based on Mcnab classification. The percentage of superior facetectomy was calculated by using the Maro-view 5.4 Picture Archiving Communication System (PACS). RESULTS: Paramedian lumbar discectomy was performed in 180 patients and combined lumbar discectomy was performed in 54 patients. Paramedian lumbar discectomy group showed better outcome compared with combined discectomy group. p value of VAS change was 0.009 and KODI was 0.013. The average percentage of superior facetectomy was 33% (range, 0-79%) and it showed negative correlation with VAS and KODI changes (Pearson coefficient : -0.446 and -0.498, respectively). Excellent or good outcome cases (Group I) were 136 (58.1%) and fair or poor outcome cases (Group II) were 98 (41.9%). The percentage of superior facetectomy was 26.5% at Group I and 42.5% at Group II. There was significant difference in superior facetectomy percentage between Group I and II (p=0.000). CONCLUSION: This study demonstrated that paramedian lumbar discectomy with preservation of facet joints is an effective and good procedure for FELDH. At least 60% of facet should be preserved for excellent or good outcomes.

Effect of burdock extracts upon inflammatory mediator production.

We investigated the burdock extract on the inhibitions of NO generation, COX-2 expression, and the generations of IL-6 and TNF-α , to find out its anti-inflammatory effect in this study. After the treatment of the burdock extract in the cells, we measured the amount of NO generated in the inflammatory cells developed by LPS and UVB, and confirmed the developments of inflammatory mediators by RT-PCR. Upon the results on the NO generation after the development of inflammation by LPS in Raw 264.7 cell, we found approximately 50% of inhibitory effect at 200 µg/ml concentrations of the burdock extract. It was confirmed that the expression levels of TNF-α, COX-2, and IL-6 were declined to the levels of control by LPS and UVB stimulated inflammation in HaCat cell. This means the anti-inflammatory effect of the burdock extract.

Naloxone induces endoplasmic reticulum stress in PC12 cells.

Naloxone is an opioid inverse agonist used in the treatment of opiate overdose, with well known pharmacology. In the present study, we determined the effects of naloxone on the unfolded protein response (UPR) in PC12 cells. Data from a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that naloxone may accelerate PC12 cell apoptosis in a dose-dependent manner. We also demonstrated that naloxone upregulated gene expression of endoplasmic reticulum (ER) chaperones, including binding immunoglobulin protein (Bip), calnexin, ER protein 29 (ERp29) and protein disulfide isomerase (PDI), and ER stress sensors, including activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1) and protein kinase-like ER kinase (PERK). In addition, naloxone also induced typical ER stress phenomena, including ART6 proteolytic cleavage, eIF2α phosphorylation and XBP1 mRNA splicing. Furthermore, naloxone upregulated gene expression of ER chaperones and ER stress sensors in in vivo experiments. To the best of our knowledge, these results are the first to indicate that naloxone induces ER stress in vitro and in vivo.

Human papillomavirus immunogen that provides protective tumor immunity and induces tumor regression.

Human papillomavirus (HPV) is associated with premalignant lesions such as high-grade cervical intraepithelial neoplasia (CIN-III) with potential progression to cervical carcinoma. There are now preventive vaccines against HPV. However, no effective therapeutic vaccine or immunological treatment exists for individuals already infected or for the 470,000 women that develop high-grade dysplasia, carcinoma in situ, and cervical cancer each year. More than half of these women die from cervical cancer. Relative non-immunogenicity of HPV infection is one of the main reasons for the difficulty in designing a comprehensive therapeutic vaccine against HPV-induced premalignant lesions and cervical carcinoma. HPV E6 and E7 proteins, the major HPV oncogenes, are highly immunogenic but fail to induce cross-reactive and protective immune responses against heterologous strains. We designed and synthesized a therapeutic peptide vaccine comprised of multivalent peptide mixtures called hypervariable epitope constructs (HECs) that represent the major epitope variants of the oncogenic E7 structural protein, and assessed their immunogenicity and in vivo efficacy in mice. Our results show that this peptide vaccine can induce strong, HPV-specific, T-helper cell and CTL responses. More significantly, we have demonstrated that the vaccine is efficacious as a therapeutic agent in a mouse HPV tumor model. Therefore, the HPV HEC vaccine approach described herein can potentially prevent progression of HPV-associated premalignant lesions, and may also be therapeutic against tumors associated with HPV.

Production of interferon α by human immunodeficiency virus type 1 in human plasmacytoid dendritic cells is dependent on induction of autophagy.

BACKGROUND: The mechanisms responsible for interferon α (IFN-α) production by plasmacytoid dendritic cells (pDCs) during human immunodeficiency virus type 1 (HIV-1) infection are unknown. This research examined the roles of Toll-like receptor 7 (TLR7) and autophagy in IFN-α production by pDCs during HIV-1 infection. METHODS: pDCs from human peripheral blood mononuclear cells were incubated with infectious or aldrithiol 2 (AT-2)-inactivated HIV-1 or with uridine-rich single-stranded RNA40 (ssRNA40) from the HIV-1 long terminal repeat. IFN-α was quantified by enzyme-linked immunosorbant assay. Autophagic proteins were detected by Western blot, and autophagosomes were identified using immunofluorescent and confocal microscopy. To inhibit autophagy, pDCs were treated with the phosphoinositide-3 kinase inhibitor 3-methyladenine (3-MA) or were transfected with autophagy-related protein 7 or TLR7 small interfering RNA (siRNA). RESULTS: Increased levels of IFN-α were present in culture supernatants following 16-hour incubation of pDCs with infectious or AT-2-inactivated HIV-1. Treatment of pDCs with ssRNA40 but not ssRNA41 resulted in high levels of IFN-α. pDCs exposed to HIV-1 gp120, rapamycin, or 3-MA alone failed to induce IFN-α. Pretreatment of pDCs with 3-MA significantly reduced the induction of IFN-α by ssRNA40. Similarly, knock down of autophagy-related protein 7 and TLR7 by use of siRNA significantly reduced the induction of IFN-α by ssRNA40 or HIV-1. CONCLUSIONS: These findings demonstrate that IFN-α production by pDCs exposed to infectious or noninfectious HIV-1 and ssRNA40 occurs through induction of autophagy following TLR7 signaling.

Mental Health and Coping Strategies among Medical Students.

PURPOSE: Recently, concern of the college students' mental health has increased due to their continuous psychologic problems such as suicidal attempt. This study aimed to examine the correlation among depression, stress, self-esteem, and coping strategies of the medical students and also according to the academic year. METHODS: The subject was 384 medical students of K medical school in Korea. Self-rating depression scale, stress scale, self-esteem scale was used for the survey, and academic stress and coping strategies of the students were asked. Frequency analysis, one-way ANOVA, t-test, correlation analysis was carried out. RESULTS: Third year students were under most stress (F=5.67, p=0.000) and had the most students who were moderately (22.9%) and mildly depressed (6.3%). Stress form academic studies and grade was also the highest in third year students. For English fluency, freshmen students scored the top. Academic career stress and school culture stress were higher for year 3, 4, 5, 6 than year 1, 2 students. Differences of the coping strategies by academic year was significant in emotional display. Students who showed high level of depression and stress, also students with low self-esteem used emotional display as their major coping strategy. CONCLUSION: Depending on their academic year medical students' level of depression and stress was different, and they did not use a variety of coping strategies. Therefore, a program which can give a diverse access to variety of coping strategies to relieve students' stress should be developed taking their characteristics of academic year into consideration.

Preparation of chitin butyrate by using phosphoryl mixed anhydride system.

Acylation of chitin with butyric acid was performed in the presence of trifluoroacetic anhydride/phosphoric acid mediated system. The products were characterized by (1)H NMR and FT-IR spectroscopy and their solubility was tested in different organic solvents. Inclusion of butyric acid moieties into the parent molecule was confirmed from the (1)H NMR and FT-IR spectra. FT-IR analysis revealed that the degree of acid substitution (DS) of the products was in a range of 1.9-2.38, which increased with increasing the amounts of butyric acid added to the reaction system. Degree of N-deacetylation (DD) of the products, as determined by (1)H NMR was between 54.2% and 65.6%. The products with DS >2.0 were soluble in dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, methanol, acetone, chloroform, and acetic acid.

Pulmonary manifestations in Proteus syndrome: pulmonary varicosities and bullous lung disease.

We report on two patients with Proteus syndrome (PS), with emphasis on its pulmonary manifestations. The first patient was a 6-year-old girl diagnosed with PS at 5 years of age. The pulmonary abnormalities first observed at age 3 years and included streaky densities with accentuated vascular markings detected by chest radiography. The patient had persistent abnormalities on follow-up chest radiographs. Chest computed tomography (CT) scans showed diffuse pulmonary venous dilatations. The second patient was a 10-year-old boy diagnosed with PS at age 4 years. Chest radiography and CT scans showed patchy and streaky densities intermixed with small bullae, which were interpreted as pneumonia with post-inflammatory pneumatoceles. The patient developed diffuse enlargement of air spaces of the lungs at age 10 years with severe respiratory compromise. Although pulmonary manifestations in PS are uncommon, recognition of pulmonary vein malformation and the presentation of enlarged air spaces in the lungs at an earlier age are important for accurate diagnosis. The plain radiograph findings of accentuated vascular markings seen in patients with PS may appear similar to interstitial or chronic pneumonia. This report emphasizes the features of lung involvement in children with PS and suggests that specific attention be paid to pulmonary manifestations using chest CT scans. © 2011 Wiley-Liss, Inc.

Synthetic antigens representing the antigenic variation of human hepatitis C virus.

Immune responses against hepatitis C virus (HCV) have been studied by numerous groups. However, details concerning the production of antibodies to antigenically variable epitopes remain to be elucidated. Since the sequences of the variable regions of several HCV proteins are different among the virus strains infecting patients, we decided to design peptide combinations that represent the theoretical maximum antigenic variation of each epitope to be used as capture antigens. We prepared six peptide mixtures (hypervariable epitope constructs; HECs) representing six different epitopes from structural and non-structural proteins of HCV from genotypes 1-6. Plasma from 300 HCV patients was tested to determine if their antibodies recognize the synthetic constructs. All the patients were chronically infected with diverse HCV genotypes and did not receive antiviral treatment. Antibodies to one or more of the HECs were detected in all of the HCV-infected individuals. Immunogenicity of the HCV HECs was also evaluated in outbred and inbred mice. Strong HEC-specific antibodies were produced, and cellular responses were also induced that were Th-1 rather than Th-2. Our results show that HCV HECs are both antigens that can be used to detect the broad cross-reactivity of antibodies from HCV-infected patients, and strong immunogens that can induce antigen-specific humoral and cellular immune responses in mice.

The influence of HtrA expression on the growth of Streptococcus mutans during acid stress.

When proteins are damaged under stresses conditions, these proteins are either refolded or degraded by quality control system of molecular chaperones and protease. High-temperature requirement A (htrA) is of particular interest because it can perform the roles of both protease and a chaperone. HtrA plays an important role in maintaining the physiological homeostasis of bacteria against environmental stress such as elevated temperature, oxidative and osmotic stress. Inactivation of htrA genes can thus restrict the survival ability of bacteria. These observations suggested that htrA might be responsible for acid tolerance of Streptococcus mutans. In this study, we have generated an htrA mutant and an htrA-complemented strain of S. mutans K7 isolated from a Korean in order to investigate the role of htrA in growth under acidic conditions. In terms of growth under cidic conditions, the htrA mutant exhibited 20% to 23% lower growth than the control group. In addition, glucosyltransferase B and glucosyltransferase C expression levels significantly decreased. When the htrA expression level was restored by adding the htrA gene to the htrA mutant strain, the normal growth phenotype was restored under acid stress. Further, similar results were obtained for S. mutans UA159. Thus, htrA in S. mutans K7, as well as S. mutans UA159, can be concluded to play an important role during acid stress.

Polymorphisms in the survivin gene and the risk of lung cancer.

BACKGROUND: Survivin is an apoptosis inhibitor and plays an important role in the development and progression of cancer. Polymorphisms in the survivin gene may influence survivin production or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between survivin polymorphisms and the risk of lung cancer in a Korean population. METHODS: We first screened for polymorphisms in the survivin gene by direct sequencing of genomic DNA samples from 27 healthy Koreans. We selected identified SNPs based on their frequency, linkage disequilibrium status and haplotype tagging status, and then genotyped the selected SNPs in 582 lung cancer patients and 582 healthy controls who were frequency matched for age and gender. RESULTS: We identified 8 single nucleotide polymorphisms (SNPs): 6 known SNPs [-644T>C, -625G>C, -31C>G, 9194A>G (K129E), 9386T>C and 9809T>C] and 2 novel SNPs (9974C>T and 10347G>A). Among the SNPs studied, only the -31C>G genotype distribution was significantly different between the cases and controls (P=0.04). Individuals with at least one -31G allele were at a significantly decreased risk of lung cancer compared to those individuals with the -31CC genotype [adjusted odds ratio (OR)=0.74, 95% confidence interval (CI)=0.57-0.96, P=0.02]. When the lung cancer cases were categorized by tumor histology, the -31G allele was associated with a significantly decreased risk of adenocarcinoma (adjusted OR=0.59, 95% CI=0.41-0.84, P=0.003). Consistent with the results of the genotyping analysis, the -625G/-31G/9194A/9809T haplotype carrying the -31G allele was associated with a significantly decreased risk of adenocarcinoma (adjusted OR=0.56, 95% CI=0.40-0.77, P=0.0004). The promoter assay revealed the -31G allele to have a significantly lower promoter activity than the -31C allele. CONCLUSION: These results suggest that the survivin -31C>G polymorphism influences survivin expression, thus contributing to the genetic susceptibility to lung cancer.

Timing of retroviral infection influences anamnestic immune response in vaccinated primates.

Using simian immunodeficiency virus (SIV) infection of rhesus macaques to model human immunodeficiency virus (HIV) infection of humans, we assessed whether broadly reactive vaccine-induced humoral immunity would remain broadly reactive after viral challenge, and whether there would be significant differences in anamnestic antibody responses if animals were challenged when predominately effector or memory lymphocyte populations were present. Animals immunized over a prolonged period and challenged 11 months after vaccination mounted more broadly reactive and stronger humoral immunity than those rapidly vaccinated and challenged 2 weeks after their final vaccinations. These data suggest that vaccination schedule and the timing of virus challenge should be considered when evaluating future candidate HIV vaccines.

Expression of Cyclooxygenase-2 and Bcl-2 in human gastric adenomas.

BACKGROUND: Cyclooxygenase (COX)-2 is the rate-limiting enzyme in prostaglandin synthesis. An increased expression has been implicated in the development and progression of human gastric cancers and colorectal adenomas and cancers. This study aimed to determine the involvement and association of COX-2 and Bcl-2 in precancerous gastric adenomas. METHODS: Seventy-nine gastric polyps were obtained by endoscopic mucosal resection or polypectomy from January, 2000 to July, 2003. Immunohistochemical expression of COX-2 and Bcl-2 was observed, and their relationships with various clinicopathological factors were analyzed. RESULTS: Histologically, 13 hyperplastic polyps and 66 tubular adenomas, of which 17 showed high-grade dysplasia, were observed. Increased COX-2 expression was observed in low-grade and high-grade tubular adenomas compared to hyperplastic polyps (p=0.004 and p=0.001, respectively). COX-2 expression was significantly higher in larger (>1 cm) compared with smaller (<1 cm) tubular adenomas (o=0.034), but no relation was observed in hyperplastic polyps. While Bcl-2 expression differed significantly according to histology, increased Bcl-2 expression was observed especially in COX-2 positive low-grade tubular adenomas. CONCLUSION: COX-2 expression increased in a size-dependent manner in tubular adenomas, suggesting a role in polyp growth. The increased expression of Bcl-2 in tubular adenomas, especially in COX-2 positive tubular adenomas, suggests that COX-2 action may be related to Bcl-2 expression.

[Cyclooxygenase-2 expression according to size and location of gastric and colorectal tubular adenomas].

BACKGROUND/AIMS: Recent studies have shown that cyclooxygenase-2 (COX-2) may be involved in the process of invasion, growth and apoptosis in colorectal carcinoma and in the growth and tumorigenesis in familial adenomatous polyposis. This study was conducted to determine the significance of the expression of COX-2 in gastric and colorectal adenomas. METHODS: Forty-nine samples of gastric adenoma and fifty-seven samples of colorectal adenoma were obtained by endoscopic mucosal resection or polypectomy from 106 patients from January 2000 to July 2003. COX-2 expression was determined by immunohistochemistry. Correlation between COX-2 expression and several clinical factors were compared in each gastric and colorectal adenomas. RESULTS: The expression of COX-2 in epithelial cells was significantly higher in the group with large adenoma (>1 cm) compared with the group with small adenoma (< or =1 cm) in gastric (76.5% vs. 46.7%, p=0.04) and colorectal adenomas (75% vs. 41.5%, p=0.023). Moreover, increased COX-2 expression was shown in distal compared to proximal colorectal adenoma (64.3% vs. 37.9%, p=0.047). CONCLUSIONS: COX-2 was expressed in a size-dependent manner in gastric and colorectal tubular adenomas. The expression of COX-2 was different according to the location of colorectal adenoma. The association of COX-2 expression with the size of adenoma may suggest that the role of COX-2 is not related to the early development of adenoma, but related to the progression of adenoma.

[Pretreatment ALT level and histologic activity as predictors of HBeAg loss in lamivudine treatment for chronic hepatitis B].

BACKGROUND/AIMS: Lamivudine is a potent inhibitor of hepatitis B virus replication, but an increased incidence of YMDD mutation may be associated with its long term use. Thus, the decision to initiate therapy should be based on variables that are predictive of lamivudine-induced HBeAg loss. The objective of this analysis was to determine patient-dependent or laboratory variables that predict HBeAg loss. METHODS: We retrospectively analyzed 99 HBeAg-positive patients with chronic hepatitis B who were treated with lamivudine and followed up for more than 52 weeks. All patients had a liver biopsy before starting lamivudine therapy. HBeAg loss and HBeAg seroconversion after 52 weeks of treatment were defined as endpoints. RESULTS: The overall rates of HBeAg loss and HBeAg seroconversion were 41.4% (41/99) and 37.4% (37/99), respectively. The rates of HBeAg loss increased as pretreatment ALT levels increased (P=0.013) and were highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal, occurring in 56.8% of those patients. The rate of HBeAg loss was higher in patients with more active histologic disease on pretreatment liver biopsy (Grade 1 and 2 vs. Grade 3 and 4, 28.3% vs 56.5%, P=0.004). Similar results were seen with HBeAg seroconversion, though seroconversion occurred less frequently than HBeAg loss. Multivariate analysis showed that elevated baseline ALT levels (P<0.05) and histologic activity (P<0.05) were the best independent predictors of HBeAg loss and seroconversion in response to lamivudine. CONCLUSIONS: Pretreatment ALT levels and histologic activity were the most important predictors for response to lamivudine.