PURPOSE: Transforming growth factor-β-induced protein (TGFBIp) is highly expressed in the cornea, and mutant TGFBIp induces corneal diseases. However, the function of TGFBIp in cornea epithelium is not fully investigated. Here, we tested the importance of TGFBIp in regulation of gene expression and corneal epithelial cell (CEC) activity. MATERIALS AND METHODS: The effect of TGFBIp on CEC activity was analyzed by cell migration, adhesion, proliferation and wound healing assay. Analysis of gene expression was examined by western blot and quantitative reverse transcription PCR. RESULTS: The results demonstrated that TGFBIp increased adhesion, migration, proliferation, and wound healing of CECs. Analysis of gene expression presented that TGFBIp-stimulated CECs exhibited increased expression of mucin family genes, such as MUC1, -4, -5AC, and -16. Furthermore, TGFBIp treatment increased the expression of MUC1, -4, -5AC, -7, and -16 in conjunctival epithelial cells. TGFBIp also increased the activity of intracellular signaling molecules ERK and AKT in CECs. Using pharmacologic inhibitors of ERK and AKT, we showed that the expression of mucin genes by TGFBIp is mediated by the activation of ERK and AKT signaling. CONCLUSION: Our findings demonstrate that the locally generated TGFBIp in the cornea may contribute to wound healing of CECs by enhancing the migration, adhesion, and proliferation of CECs. In addition, our results suggest that TGFBIp has a protective effect on ocular surfaces by inducing the expression of mucin genes in corneal and conjunctival epithelial cells. These data suggest that TGFBIp is a useful therapeutic target for patients with corneal wounds.
Blotting, Western ; Cell Movement ; Cornea ; Corneal Diseases ; Epithelial Cells* ; Epithelium ; Gene Expression ; Gene Expression Regulation ; Humans ; Mucins* ; Polymerase Chain Reaction ; Reverse Transcription ; Wound Healing* ; Wounds and Injuries*

PURPOSE: While the Trastuzumab for Gastric Cancer (ToGA) trial demonstrated the efficacy and safety of trastuzumab-based chemotherapy in HER2-positive metastatic gastric cancer, the overall survival (OS) benefit was not found in Asian and diffuse-type cancer patients. The aim of the study is to investigate predictive markers for trastuzumab-based chemotherapy. MATERIALS AND METHODS: Data of patients with HER2-positive gastric cancer treated with trastuzumab-based chemotherapy were analyzed retrospectively. RESULTS: A total of 168 Asian patients were included. The median age was 60 years (range, 27 to 85 years) and the male:female ratio was 118 (70.2%):50 (29.8%). Fourteen (8.3%), 63 (37.5%), 75 (44.6%), and 11 (6.5%) patients had well, moderately, poorly-differentiated tubular adenocarcinoma and signet ring cell carcinoma, respectively. With 14 complete responses and 73 partial responses, the response rate was 50.6%. The median progression-free survival (PFS) was 10.2 months (95% confidence interval [CI], 8.7 to 11.7), and the median OS was 18.5 months (95% CI, 16.4 to 50.6). Next, we investigated the effect of poorly-differentiated histology (PDH, poorly-differentiated tubular adenocarcinoma+signet ring cell carcinoma) on clinical outcomes. The median PFS (8.9 months vs. 11.5 months, p=0.16) was slightly inferior in PDH patients, and the median OS was significantly shorter in PDH patients (14.6 months vs. 19.0 months, p=0.025). CONCLUSION: While subset analysis of the ToGA trial demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asians and patients with PDH, our data may suggest that even in Asian patients and patients with PDH, trastuzumab-based chemotherapy could be associated with improved clinical outcomes in patients with HER2-positive gastric cancer.
Adenocarcinoma ; Asian Continental Ancestry Group ; Carcinoma, Signet Ring Cell ; Disease-Free Survival ; Drug Therapy* ; Ethnic Groups ; Humans ; Receptor, erbB-2 ; Retrospective Studies* ; Stomach Neoplasms*

Artemisia princeps (AP) is a flowering perennial used as a traditional medicine and dietary supplement across East Asia. No study has yet assessed its effects on synaptic plasticity in hippocampus and much less in a model of ovarian hormone deficiency. We examined the influence of chronic oral AP ethanol extract treatment in ovariectomized rats on the induction of long-term depression in a representative synapse (CA3-CA1) of the hippocampus. Ovariectomized rats demonstrated lower trabecular mean bone mineral densities than sham, validating the establishment of pathology. Against this background of pathology, AP-treated ovariectomized rats exhibited attenuated long-term depression (LTD) in CA1 relative to water-treated controls as measured by increased field excitatory post-synaptic potentials (fEPSP) activation averages over the post-stimulation period. While pathological significance of long-term depression (LTD) in ovariectomized rats is conflicting, that AP treatment significantly affected its induction offers justification for further study of its influences on plasticity and its related disorders.
Animals ; Artemisia* ; Bone Density ; Depression ; Dietary Supplements ; Ethanol ; Far East ; Female ; Flowers ; Hippocampus ; Medicine, East Asian Traditional ; Medicine, Traditional ; Models, Animal* ; Neuronal Plasticity* ; Ovariectomy ; Pathology ; Plants, Medicinal* ; Plastics ; Rats ; Synapses

Msi1-like (MSIL) proteins, which are eukaryote-specific and contain a series of WD40 repeats, have pleiotropic roles in chromatin assembly, DNA damage repair, and regulation of nutrient/stress-sensing signaling pathways. In the fungal kingdom, the functions of MSIL proteins have been studied most intensively in the budding yeast model Saccharomyces cerevisiae, an ascomycete. Yet their functions are largely unknown in other fungi. Recently, an MSIL protein, Msl1, was discovered and functionally characterized in the pathogenic yeast Cryptococcus neoformans, a basidiomycete. Interestingly, MSIL proteins appear to have redundant and unique roles in both fungi, suggesting that MSIL proteins may have evolutionarily divergent roles in different parts of the fungal kingdom. In this review, we will describe the current findings regarding the role of MSIL proteins in fungi and discuss future directions for research on this topic.
Ascomycota ; Basidiomycota ; Chromatin Assembly and Disassembly ; Cryptococcus neoformans ; DNA Damage ; Fungi ; Histones ; Proteins ; Retinoblastoma ; Saccharomyces cerevisiae ; Saccharomycetales ; Yeasts

BACKGROUND/AIMS: There is an ongoing debate on the relationship between gastric fundic gland polyps and increased incidence of colorectal neoplasia in Caucasians. However, there was no report on the relationship between gastric fundic gland polyp and colorectal neoplasia in Korea. The aim of this study was to identify the characteristics of gastric fundic gland polyps and whether a relationship exists between fundic gland polyps and colorectal neoplasia in Korean population. METHODS: Persons who underwent an esophagogastroduodenoscopy and colonoscopy from 1992 to 2007 at the Health Promotion Center of Incheon St. Mary's Hospital, The Catholic University of Korea were reviewed retrospectively. The relationship between gastric fundic gland polyps and colorectal neoplasia were analyzed. RESULTS: Among 22,451 subjects, fundic gland polyps were found in 328 subjects (1.5%). Fundic gland polyps were more common in women than in men (odds ratio of 6.25; 95% CI of 4.68-8.34). The odds ratios for colorectal neoplasia in all subjects with gastric fundic gland polyps were 0.56 (95% CI of 0.33-0.95) and men who were 50 years of age or older had an odds ratio of 2.81 (95% CI of 1.03-7.66) as compared to the control group. However, age and sex-adjusted odds ratios for all gastric fundic gland polyps were 0.73 (95% CI of 0.42-1.26), for men 1.78 (95% CI of 0.80-3.98), and for women 0.37 (95% CI of 0.16-0.87). CONCLUSIONS: Surveillance colonoscopy in patients with fundic gland polyps can be performed in the same manner as general population in Korea.
Adult ; Age Factors ; Colorectal Neoplasms/*epidemiology/pathology ; Endoscopy, Gastrointestinal ; Female ; Gastric Fundus/pathology ; Humans ; Male ; Middle Aged ; Odds Ratio ; Polyps/*epidemiology/pathology ; Republic of Korea ; Retrospective Studies ; Sex Factors

Hypoglycemia is caused by poor oral intake, excessive exercise, alcohol abuse and inaccurate use of a hypoglycemic agent or insulin in patients that have history of diabetes mellitus (DM), especially in the elderly. Severe hypoglycemia has a variety of different symptoms or signs from focal neurologic deficits to severe coma, or death. It can be difficult to differentiate hypoglycemia-induced symptoms or signs, and stroke or cardiovascular disease in acute setting. Transient hypoglycemic hemiparesis is an infrequent case in the emergency department (ED), which is frequently misdiagnosed for stroke. When patients with decreased mental status or hemiparesis are admitted to the ED, a routine blood sugar test is essential. Hypoglycemic hemiparesis if unrecognized can result in permanent neurological damage. Therefore, it is important to detect hypoglycemia early and treat it appropriately.
Aged ; Alcoholism ; Blood Glucose ; Cardiovascular Diseases ; Coma ; Diabetes Mellitus ; Emergencies ; Humans ; Hypoglycemia ; Insulin ; Neurologic Manifestations ; Paresis ; Stroke

The cyclic AMP (cAMP) pathway plays a major role in growth, sexual differentiation, and virulence factor synthesis of pathogenic fungi. In Cryptococcus neoformans, perturbation of the cAMP pathway, such as a deletion in the gene encoding adenylyl cyclase (CAC1), causes defects in the production of virulence factors, including capsule and melanin production, as well as mating. Previously, we performed a comparative transcriptome analysis of the Ras- and cAMP- pathway mutants, which revealed 163 potential cAMP-regulated genes (38 genes at a 2-fold cutoff). The present study characterized the role of one of the cAMP pathway-dependent genes (serotype A identification number CNAG_ 06576.2). The expression patterns were confirmed by Northern blot analysis and the gene was designated cAMP-regulated gene 1 (CAR1). Interestingly, deletion of CAR1 did not affect biosynthesis of any virulence factors and the mating process, unlike the cAMP-signaling deficient cac1Delta mutant. Furthermore, the cac1Delta mutant exhibited wild-type levels of the stress-response phenotype against diverse environmental cues, indicating that Car1, albeit regulated by the cAMP-pathway, is not essential to confer a cAMP-dependent phenotype in C. neoformans.
Adenylyl Cyclases ; Blotting, Northern ; Cryptococcus ; Cryptococcus neoformans ; Cues ; Cyclic AMP ; Fungi ; Gene Expression Profiling ; Melanins ; Phenotype ; Sex Differentiation ; Virulence Factors

Protein phosphatase-1 (PP1) nuclear targeting subunit (PNUTS), also called PP1R10, p99, or CAT 53 was originally isolated as a mammalian nuclear PP1-binding protein. In this study, we performed yeast two-hybrid screens to identify PNUTS-interacting proteins. Here, we report that LCP1 (epidermal Langerhans cell protein 1), a novel member of the HMG-box protein family, binds tightly to PNUTS. Co-immunoprecipitation of deletion constructs revealed that the C-terminus of LCP1 is sufficient for the interaction with an N-terminal region of PNUTS that is distinct from its PP1-binding domain. Furthermore, immunofluorescence studies showed that a subpopulation of LCP1 co-localizes with PNUTS in nuclear speckles. Importantly, we found that the N-terminus of LCP1 has a strong trans-activation activity in a GAL4-based heterologous transcription assay. The transcriptional activity of LCP1 is markedly suppressed by its interaction with PNUTS, in a PP1-independent manner. These findings suggest that the coordinated spatial and temporal regulation of LCP1 and PNUTS may be a novel mechanism to control the expression of genes that are critical for certain physiological and pathological processes.
Amino Acid Sequence ; Cell Line ; Cell Nucleus/*metabolism ; DNA-Binding Proteins/*metabolism ; HMGB Proteins/*metabolism ; Humans ; Molecular Sequence Data ; Nuclear Proteins/*metabolism ; Protein Binding ; Protein Interaction Mapping ; RNA-Binding Proteins/*metabolism ; Transcriptional Activation ; Two-Hybrid System Techniques

PURPOSE: The purpose of this study was to find out what clinicopathologic or immunohistochemical parameter that may affect FDG uptake of primary tumor in PET/CT scan of the gastric carcinoma patient. MATERIALS AND METHODS: Eighty-nine patients with stomach cancer who underwent pre-operative FDG PET/CT scans were included. In cases with perceptible FDG uptake in primary tumor, the maximum standardized uptake value (SUVmax) was calculated. The clinicopathologic results such as depth of invasion (T stage), tumor size, lymph node metastasis, tumor differentiation and Lauren's classification and immunohistochemical markers such as Ki-67 index, expression of p53, EGFR, Cathepsin D, c-erb-B2 and COX-2 were reviewed. RESULTS: Nineteen out of 89 gastric carcinomas showed imperceptible FDG uptake on PET/CT images. In cases with perceptible FDG uptake in primary tumor, SUVmax was significantly higher in T2, T3 and T4 tumors than T1 tumors (5.8+/-3.1 vs. 3.7+/-2.1, p=0.002). SUVmax of large tumors (above or equal to 3 cm) was also significantly higher than SUVmax of small ones (less than 3 cm) (5.7+/-3.2 vs. 3.7+/-2.0, p=0.002). The intestinal types of gastric carcinomas according to Lauren showed higher FDG uptake compared to the non-intestinal types (5.4+/-2.8 vs. 3.7+/-1.3, p=0.003). SUVmax between p53 positive group and negative group was significantly different (6.0+/-2.8 vs. 4.4+/-3.0, p=0.035). No significant difference was found in presence of LN metastasis, tumor differentiation, Ki-67 index, and expression of EGFR, Cathepsin D, c-erb-B2 and COX-2. CONCLUSION: T stage of gastric carcinoma influenced the detectability of gastric cancer on FDG PET/CT scan. When gastric carcinoma was perceptible on PET/CT scan, T stage, size of primary tumor, Lauren's classification and p53 expression were related to degree of FDG uptake in primary tumor.
Cathepsin D ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Stomach Neoplasms

OBJECTIVE: To investigate the differential expression of junctional proteins in the normal and preeclamptic human placenta and the effect of ginsenoside Rk1 in junctional proteins. METHODS: Placental tissues from 10 women with severe preeclampsia and 5 normal women were collected at the time of their cesarean section. Five of 10 preeclamptic women were complicated with intrauterine growth restriction (IUGR). Immunohistochemistry and Western blotting was employed to localize junctional proteins (zo-1, occludin and plakoglobin) positive cells. The placental explant culture was performed to investigate if Rk1 can attenuate the expression of junctional proteins (zo-1, occluding and plakoglobin) induced by deferoxamine-induced hypoxia. Rk1 was treated at the day 3 and Western blot analysis was performed for protein quantification. RESULTS: There was no different expression of zo-1 and plakoglobin among all the study groups. Occludin showed negative at the endothelial cells of the terminal villi in both normal and preeclampsia groups. At the endothelial cells of the stem villi, occludin was detected in both normal and severe preeclamptic placenta with normal fetal growth. However, severe preeclampsia with IUGR were decreased expression of occludin at the endothelial cells of the stem villi. When we administered Rk1 to the placenta treated with DFO, expression of occludin was not different. CONCLUSION: The placental expression of zo-1 and plakoglobin were not different among the study groups, while that of occludin was significantly decreased at the endothelium of stem villi in severe preeclampsia with IUGR. Rk-1 showed no effect on the placental junctional proteins. These results suggest that occludin may play a role in pathophysiology of fetal growth restriction in utero.
Anoxia ; Blotting, Western ; Cesarean Section ; Endothelial Cells ; Endothelium ; Female ; Fetal Development ; Fetal Growth Retardation ; gamma Catenin ; Ginsenosides ; Humans ; Immunohistochemistry ; Occludin ; Placenta ; Pre-Eclampsia ; Pregnancy ; Proteins