Differential Gene Expression in the Hippocampi of Nonhuman Primates Chronically Exposed to Methamphetamine, Cocaine, or Heroin

Objective@#Methamphetamine (MA), cocaine, and heroin cause severe public health problems as well as impairments in neural plasticity and cognitive function in the hippocampus. This study aimed to identify the genes differentially expressed in the hippocampi of cynomolgus monkeys in response to these drugs. @*Methods@#After the monkeys were chronically exposed to MA, cocaine, and heroin, we performed large-scale gene expression profiling of the hippocampus using RNA-Seq technology and functional annotation of genes differentially expressed. Some genes selected from RNA-Seq analysis data were validated with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). And the expression changes of ADAM10 protein were assessed using immunohistochemistry. @*Results@#The changes in genes related to axonal guidance (PTPRP and KAL1), the cell cycle (TLK2), and the regulation of potassium ions (DPP10) in the drug-treated groups compared to the control group were confirmed using RT-qPCR. Comparative analysis of all groups showed that among genes related to synaptic long-term potentiation, CREBBP and GRIN3A were downregulated in both the MA- and heroin-treated groups compared to the control group. In particular, the mRNA and protein expression levels of ADAM10 were decreased in the MA-treated group but increased in the cocaine-treated group compared to the control group. @*Conclusion@#These results provide insights into the genes that are upregulated and downregulated in the hippocampus by the chronic administration of MA, cocaine, or heroin and basic information for developing novel drugs for the treatment of hippocampal impairments caused by drug abuse.

Development and Validation of a Questionnaire on the Feasibility of a Mobile Dietary Self-Monitoring Application / 대한지역사회영양학회지

Objectives@#This study aimed to develop and assess the content validity and internal consistency of a questionnaire on the feasibility of mobile dietary self-monitoring applications. @*Methods@#We developed a feasibility questionnaire to assess the overall usage, convenience, usefulness, and satisfaction of mobile dietary applications. The initial draft of the questionnaire contained 17 items with yeso, multiple-choice, and open-ended questions and 52 items on 5-point Likert scales. To validate the content, ten experts evaluated the relevance of the items for each subscale using a 5-point scale. We calculated the item-level content validity index (I-CVI) and scale-level content validity index (S-CVI). A total of 102 adults answered the questionnaires which reflected the experts' reviews. We conducted an exploratory factor analysis to determine the underlying structure of responses and categorized convenience, usefulness, and satisfaction. We also calculated Cronbach's alpha coefficient to examine the internal consistency of items in each subscale. @*Results@#The S-CVI score of the items was 0.86, and we removed items with an I-CVI score of 0.40, resulting in a final set of 35 questions (convenience: 15, usefulness: 12, satisfaction: 8 items). The Cronbach's alpha values of the three scales were 0.93, 0.91, and 0.91 for 1) usefulness, 2) convenience, and 3) satisfaction, respectively. @*Conclusions@#We developed a feasibility questionnaire for mobile dietary self-monitoring applications and examined its content validity and internal consistency. Our questionnaire has the potential to measure the feasibility of mobile dietary self-monitoring applications.

Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses

Background@#The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. @*Methods@#We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. @*Results@#We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR, MTRR and MTR, GATA4, NKX2-5, SRD5A2, CFTR, and 1p22 and 20q12 anomalies. @*Conclusion@#This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.

Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses

Background@#The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. @*Methods@#We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. @*Results@#We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR, MTRR and MTR, GATA4, NKX2-5, SRD5A2, CFTR, and 1p22 and 20q12 anomalies. @*Conclusion@#This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.

Differences in Language Ability and Emotional-Behavioral Problems according to Symptom Severity in Children with Autism Spectrum Disorder

Purpose@#The aim of this study was to investigate differences in language ability and emotional-behavioral problems according to the severity of social communication impairments (SCI) and restricted and repetitive behaviors (RRB) in children with autism spectrum disorders (ASD). @*Materials and Methods@#We grouped 113 children with ASD aged 3–12 years according to the severity of SCI and RRB, and investigated language differences and emotional-behavioral problems among the severity groups. If differences in language abilities between the groups were observed, they were further subdivided to examine possible predictors of both receptive and expressive language abilities. @*Results@#In cluster analyses using subdomains of the Autism Diagnostic Interview-revised, severe SCI individuals showed lower language ability than their milder counterparts, while RRB showed no differences. Receptive and expressive language in the severe SCI group was negatively predicted by social communication and social motivation, respectively. The severe RRB group showed significantly higher levels of anxiety/distress, somatic complaints, thought problems, attention problems, and aggressive behavior, while the severe SCI group was reported to be more withdrawn. @*Conclusion@#The results of this study suggest that the severity of SCI greatly affects language ability. In children with severe SCI, social communication and social motivation negatively predicted receptive language and expressive language, respectively. Children with severe RRB may have more emotional-behavioral problems that require active intervention.

Prognostic implications of stromal hyaluronic acid protein expression in resected oropharyngeal and oral cavity cancers

Background/Aims@#Hyaluronic acid (HA) regulates cell adhesion, migration and proliferation in various cancers. The clinical implications of HA in resected head and neck squamous cell carcinoma have not been elucidated. We investigated the clinical significance and prognostic value of the expression of tumoral and stromal HA and its related proteins in oropharyngeal and oral cavity cancer. @*Methods@#Resected tissues from oropharyngeal or oral cavity cancer patients undergoing surgery were analysed in tissue microarrays divided into stroma and cancer panels. The expression levels of HA, HA synthases and hyaluronidases were also assessed by immunohistochemistry. @*Results@#A total of 160 resected oropharyngeal or oral cavity cancer tissues were analysed. Stromal HA expression was observed more frequently in human papilloma virus (HPV)-negative tumors, but other clinicopathological characteristics did not differ. In patients with HPV-negative oral cavity cancers, high stromal HA expression was associated with significantly shorter recurrence-free survival and overall survival compared with low stromal HA expression. The expression of HA in both tumors and stroma was significantly correlated with poorer outcomes than other combinations in patients with HPV-negative oral cavity cancers. However, these prognostic roles of HA were not observed in patients with HPV-negative oropharyngeal cancers. In the HPV-stratified multivariate analysis, high stromal HA expression remained an independent indicator of poor prognosis in terms of recurrence-free survival. @*Conclusions@#High stromal HA and expression of HA in both tumors and stroma were correlated with poor prognosis in HPV-negative oral cavity cancer, but not in HPV-negative oropharyngeal cancers.

Validation of MoCA-MMSE Conversion Scales in Korean Patients with Cognitive Impairments

BACKGROUND AND PURPOSE: Two conversion scales between the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) have been validated for Korean patients with Parkinson's disease. The aim of the present study was to validate these conversion scales for all patients with cognitive impairments regardless of dementia subtype. METHODS: Medical records of 323 subjects who completed both MMSE and MoCA on the same day were retrospectively reviewed. Mean, median, and root mean squared error (RMSE) of the difference between true and equivalent MMSE scores were calculated. Intraclass correlation coefficients (ICCs) between true and equivalent MMSE scores were also calculated. The validity of MoCA-MMSE conversion scales was evaluated according to educational level (low educated: ≤6 years; high educated: ≥7 years) and subtypes of cognitive impairment. RESULTS: The difference between true and equivalent MMSE scores had a median value of 0, a mean value of 0.19 according to the van Steenoven scale, a mean value of 0.57 according to the Lawton scale, RMSE value of 2.2 according to the van Steenoven scale, and RMSE value of 0.42 according to the Lawton scale. Additionally, ICCs between true and equivalent MMSE scores were 0.92 and 0.90 on van Steenovan and Lawton conversion scales, respectively. These results were maintained in subgroup analyses. CONCLUSIONS: Findings of the present study suggest that both van Steenovan and Lawton MoCA-MMSE conversion scales are applicable to transforming MoCA scores into MMSE scores in patients with cognitive impairments regardless of dementia subtype or educational level.

A Case of Posterior Reversible Encephalopathy Syndrome with Similar Symptoms as Transient Global Amnesia

No abstract available.

microRNA-200a-3p increases 5-fluorouracil resistance by regulating dual specificity phosphatase 6 expression

Acquisition of resistance to anti-cancer drugs is a significant obstacle to effective cancer treatment. Although several efforts have been made to overcome drug resistance in cancer cells, the detailed mechanisms have not been fully elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5-FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed that five miRNAs promoted cell survival after 5-FU treatment in human hepatocellular carcinoma Hep3B cells. Among the five different clones, the clone expressing miR-200a-3p (Hep3B-miR-200a-3p) was further characterized as a 5-FU-resistant cell line. The cell viability and growth rate of Hep3B-miR-200a-3p cells were higher than those of control cells after 5-FU treatment. Ectopic expression of a miR-200a-3p mimic increased, while inhibition of miR-200a-3p downregulated, cell viability in response to 5-FU, doxorubicin, and CDDP (cisplatin). We also showed that dual-specificity phosphatase 6 (DUSP6) is a novel target of miR-200a-3p and regulates resistance to 5-FU. Ectopic expression of DUSP6 mitigated the pro-survival effects of miR-200a-3p. Taken together, these results lead us to propose that miR-200a-3p enhances anti-cancer drug resistance by decreasing DUSP6 expression.

Arctiin inhibits adipogenesis in 3T3-L1 cells and decreases adiposity and body weight in mice fed a high-fat diet

BACKGROUND/OBJECTIVES: The purpose of this study was to examine the effects and associated mechanisms of arctiin, a lignan compound found in burdock, on adipogenesis in 3T3-L1 cells. Also, the effects of arctiin supplementation in obese mice fed a high-fat diet on adiposity were examined. MATERIALS/METHODS: 3T3-L1 cells were treated with arctiin (12.5 to 100 microM) during differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining and intracellular triglyceride contents. The expressions of genes related to adipogenesis were measured by real-time RT-PCR and Western blot analyses. For in vivo study, C57BL/6J mice were first fed either a control diet (CON) or high-fat diet (HF) to induce obesity, and then fed CON, HF, or HF with 500 mg/kg BW arctiin (HF + AC) for four weeks. RESULTS: Arctiin treatment to 3T3-L1 pre-adipocytes markedly decreased adipogenesis in a dose-dependent manner. The arctiin treatment significantly decreased the protein levels of the key adipogenic regulators PPARgamma and C/EBPalpha, and also significantly inhibited the expression of SREBP-1c, fatty acid synthase, fatty acid-binding protein and lipoprotein lipase. Also, arctiin greatly increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated-acetyl CoA carboxylase. Furthermore, administration of arctiin significantly decreased the body weight in obese mice fed with the high-fat diet. The epididymal, perirenal or total visceral adipose tissue weights of mice were all significantly lower in the HF + AC than in the HF. Arctiin administration also decreased the sizes of lipid droplets in the epididymal adipose tissue. CONCLUSIONS: Arctiin inhibited adipogenesis in 3T3-L1 adipocytes through the inhibition of PPARgamma and C/EBPalpha and the activation of AMPK signaling pathways. These findings suggest that arctiin has a potential benefit in preventing obesity.

miR-27 regulates mitochondrial networks by directly targeting the mitochondrial fission factor

Mitochondrial morphology is dynamically regulated by forming small, fragmented units or interconnected networks, and this is a pivotal process that is used to maintain mitochondrial homeostasis. Although dysregulation of mitochondrial dynamics is related to the pathogenesis of several human diseases, its molecular mechanism is not fully elucidated. In this study, we demonstrate the potential role of miR-27 in the regulation of mitochondrial dynamics. Mitochondrial fission factor (MFF) mRNA is a direct target of miR-27, whose ectopic expression decreases MFF expression through binding to its 3'-untranslated region. Expression of miR-27 results in the elongation of mitochondria as well as an increased mitochondrial membrane potential and mitochondrial ATP level. Our results suggest that miR-27 is a novel regulator affecting morphological mitochondrial changes by targeting MFF.

Effects of Nutrition Education Promoting Vegetable, Fruit, and Fish Intake on the Severity of Atopic Dermatitis in Children: Results from a One-year Follow Up Study / 대한지역사회영양학회지

Atopic dermatitis (AD) is believed to be associated with the intake of antioxidant nutrients and fatty acids due to its immunological dysfunction. The purpose of this study was to examine the effects of nutrition education promoting vegetable, fruit, and fish intake on the severity of AD in children. Children with AD aged 6 months to 5 years were randomly assigned into education and control groups, and followed for 1 year. Seventy-six children completed the study (38 for control, 38 for education). The education group received education promoting the intakes of antioxidant-rich foods (vegetables, fruits) and n-3 fatty acid foods (fish). A 24-hour food recall was collected for the diet information. After education, all vegetables (p < 0.001), fruits (p < 0.01), and fish (p < 0.05) intakes per 1000 kcal increased significantly in the education group, whereas only vegetable intake increased in the control group (p < 0.001). The SCORAD index, the severity of atopic dermatitis, decreased significantly in the education group (p < 0.05). Increased consumption of dietary vitamin E was significantly associated with reduction in the SCORAD index, after adjusting for age and gender (p < 0.05). A nutritional education program to increase vegetable, fruit, and fish intake may be effective in reducing the severity of AD, and vitamin E intake may be associated with the decreased severity of AD. More controlled studies on the relationship between these intakes and severity of AD, with intensive diet and/or supplement intervention programs, are needed to obtain conclusive results.

Comparison of Maternal Food Intakes during Pregnancy in Children with and without Atopic Dermatitis

The prevalence of atopic dermatitis (AD), chronic cutaneous disease, has increased rapidly worldwide. Since AD is the most common disease affecting infants, maternal food intake during pregnancy as well as lactation is important. The purpose of this research was to examine the difference in maternal food intake during pregnancy between mothers having children with or without AD. One hundred forty-eight mothers with children aged under 2 years with AD (AD group, n=74) or without AD (non-AD group, n=74) were included in the study. Diet during pregnancy was examined using a food frequency questionnaire. There were no differences in the status of mothers' food consumption during pregnancy between the AD and non-AD groups. Mothers in the AD group consumed significantly less white fish (P<0.05), carrot & pumpkin (P<0.01), walnut & pine nut (P<0.05), mandarin & orange (P<0.05), and peach (P<0.05) than those in the non-AD group. As food frequencies were categorized according to <1/month, 1~3/month, 1~6/week, and 1~3/day, lower consumption of carrot & pumpkin (Odds Ratio (OR)=6.67, 95% Confidence Interval (CI)=1.98~22.44), tomato (OR=5.11, 95% CI=1.62~16.08), mandarin & orange (OR=8.64, 95% CI=1.59~46.81), and walnut & pine nut (OR=3.85, 95% CI=1.26~11.77) increased the risk of childhood AD. According to the results, maternal food intakes during pregnancy were significantly different between the AD and non-AD groups. Therefore, further studies are necessary to examine the causal relationship between maternal food intake and prevalence of AD in children.

Excessive Food Restriction in Children with Atopic Dermititis / 대한지역사회영양학회지

The prevalence of Atopic Dermatitis (AD), a non-infective chronic inflammatory skin disease, is increasing worldwide. Avoiding the allergen is the basic principle in the treatment of AD. However, when the allergen is food, excessive restriction can lead to nutrition deficiency. The objective of the study was to examine the status of the dietary restriction and compare the caregiver's restriction practice with doctor's recommendation in Korean children with AD. A total of 158 children diagnosed with Atopic Dermatitis were recruited for this study. Information about foods that aggravate AD symptoms and food restriction were collected from the mothers of 158 children aged 6 month-5 year with AD using questionnaires. Food restriction recommendation by doctor was collected through medical chart. McNemar and Margianl homogeneity tests were used to detect a relationship between food restriction recommended by doctor and current practice by mother. There were significant proportion differences of food restriction for each food between by doctor and mother. We found 75.9% of children were avoiding eggs although only 61.4% were recommended for egg restriction by a doctor. Children with restriction of more than 4 kinds of food were 53.2% compared to 13.3% by doctor. Excessive restrictors tended to be younger and diagnosed at younger age. The caregivers of excessive restrictors had trends of "being older" and "having higher income". Avoidance of common foods in children without food allergy could result in malnutrition or impaired growth. Nutrition education is needed for sound practice and nutrition care in children with Atopic Dermatitis as well as interactive communication between caregivers and experts.

Primary Splenic Vascular Lesions: A Clinicopathologic, Immunophenotypic and Radiopathologic Correlation Study of 40 Cases

BACKGROUND: Primary splenic vascular lesions include the tumor and the inflammatory condition. A primary splenic vascular tumor is rare but is the most common tumor of the benign primary splenic tumors. METHODS: We describe the clinicopathological, radiological, and immunophenotypical findings of 40 cases of primary vascular lesions identified at our hospital from 1996 to 2009. RESULTS: The patients included 18 men and 22 women, aged 12 to 74 years, with a mean of 43.3-years and median of 40-years. They comprised 14 hemangiomas (35%), 13 lymphangiomas (32.5%), three hamartomas (7.5%), three littoral cell angiomas (7.5%), three sclerosing angiomatoid nodular transformations (SANT, 7.5%) and four angiosarcomas (10%). The majority of the patients (65%) were asymptomatic. Some of the patients (32.5%) complained of abdominal pain, and 2.5% of the patients presented with fever. Metastases were identified in 75% of the patients with an angiosarcoma at the initial work-up. One angiosarcoma patient died of the disease despite adjuvant chemoradiotherapy. The radiological findings for hamartoma, littoral cell angioma, and SANT were nonspecific. Microscopically, six types of vascular lesions showed classic morphological and immunophenotypical features of their type. CONCLUSIONS: One should be aware of rare splenic vascular lesions when radiological findings are nonspecific. Histomorphological and immunophenotypical features are helpful for the differential diagnosis.

Splenic Littoral Cell Angioma with Hepatitis C Associated Liver Cirrhosis

Littoral cell angioma (LCA) of spleen is an uncommon vascular neoplasm of littoral cell origin. It is well established that LCA may be associated with other malignancy or autoimmune disorders. We describe a 34-year-old woman with viral hepatitis C associated liver cirrhosis who presented with the incidental finding of LCA. She showed ascites, esophageal varix and drowsy mentality. Abdominal computed tomography (CT) showed multiple benign looking nodules in both hepatic lobes, but no abnormality in spleen. Liver transplantation and splenectomy were performed. Microscopic findings revealed narrow anastomosing vascular channels lined with plump cells that exfoliated into the lumen. Immunohistochemically the lining cells were positive for CD31, CD68 and negative for CD34, consistent with LCA. Herein, a second case of an incidentally detected LCA with cirrhosis, viral hepatitis C associated in Korea is reported.

Intestinal Endometriosis: Clinicopathologic Analysis of 15 Cases Including a Case of Endometrioid Adenocarcinoma

BACKGROUND: Since many patients with intestinal endometriosis present with gastrointestinal symptoms without a history of endometriosis, endoscopic examination of the intestinal tract is initially performed, often leading to a misdiagnosis. METHODS: We reviewed the clinicopathologic findings of 18 samples from 15 patients with intestinal endometriosis who underwent endoscopic biopsy and/or surgical resection to identify diagnostically helpful findings. RESULTS: All 7 biopsy specimens displayed relatively well-defined submucosal lesions, with non-mucinous glands lined by ciliated epithelium and surrounding cellular stroma containing spiral arteriole-like blood vessels. The stroma was immunopositive for CD10 in all cases. All but one specimen exhibited immunopositivity for ER and PR in both glandular and stromal components. In contrast to the overlying normal colonic mucosa, glandular epithelium with endometriosis was immunopositive for cytokeratin (CK) 7, but immunonegative for CK20 in all cases. Three cases were associated with adenocarcinoma in the same or different segments; specifically, two primary rectal adenocarcinomas and one endometrioid adenocarcinoma arising from endometriosis. CONCLUSIONS: The characteristic features of endometrial glands and stroma, including non-mucinous glands without goblet cells, ciliated columnar epithelium, and cellular stroma with spiral arterioles, facilitate the accurate diagnosis of intestinal endometriosis, which can be confirmed by immunohistochemical staining.

The Clinicopathological Parameters for Making the Differential Diagnosis of Neonatal Cholestasis

BACKGROUND: The diseases that cause neonatal cholestasis display several overlapping clinical feature. Making the differential diagnosis using liver biopsy specimens from infants with neonatal cholestasis is important for delivering the proper treatment. METHODS: We assessed the clinical manifestations, laboratory data, and histopathologic features of the pretreatment liver biopsy specimens from patients suffering with biliary atresia (n=66), intrahepatic bile duct paucity (n=15), and neonatal hepatitis (n=21). RESULTS: The gender distribution was nearly equal for the patients with biliary atresia and intrahepatic bile duct paucity, whereas males predominated for the cases of neonatal hepatitis. Only the gamma-glutamyl transferase level differed significantly amongst the groups. The diagnostic features for making the differential diagnosis of bile duct lesions included marked bile ductular proliferation, severe fibrosis, and bile duct loss. The difference of the average percentage of portal tracts with bile duct loss was statistically significant between the patients with intrahepatic bile duct paucity (73.9%) and those patients with neonatal hepatitis (39.1%) (p<0.001). CONCLUSIONS: Bile ductular proliferation, bile duct loss, and advanced fibrosis are useful for the differential diagnosis of neonatal cholestasis. Moreover, stricter diagnostic criteria for bile duct loss (more than 2/3 of bile ducts) should be applied for the definitive diagnosis of intrahepatic bile duct paucity, because bile duct loss also frequently occurs in infants suffering with neonatal hepatitis.