ß-1,4-Galactosyltransferase III suppresses extravillous trophoblast invasion through modifying ß1-integrin glycosylation.

INTRODUCTION: Glycosylation controls diverse protein functions and regulates various cellular phenotypes. Trophoblast invasion is essential for normal placental development. However, the role of glycosylation in human placenta throughout pregnancy is still unclear. The ß-1,4-galactosyltransferase III (B4GALT3) has been found to regulate cancer cell invasion. We therefore investigated the expression of B4GALT3 in placenta and its roles in trophoblast. METHODS: B4GALT3 protein expression was examined by quantitative Western blotting analysis in human placentas. For identification of B4GALT3-positive cells in normal human placenta, immunohistochemistry and immunofluorescence methods were used. To investigate effects of B4GALT3 on extravillous trophoblast (EVT)-like cell and primary EVT cells, we analyzed cell growth, adhesion, migration, and invasion in mock and B4GALT3-transfected cell. RESULTS: B4GALT3 expression significantly increased in third trimester human placenta. Immunostaining revealed that B4GALT3 expressed in placental villous cytotrophoblast, syncytiotrophoblast, and a subpopulation of EVT cells throughout pregnancy. Interestingly, we found increases in the expression level and percentage of B4GALT3-positive cells in third trimester EVT, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. Overexpression of B4GALT3 in HTR8/SVneo cells and primary trophoblast cells significantly suppressed cell migration. In addition, B4GALT3 suppressed cell invasion, and enhanced cell adhesion to laminin in HTR8/SVneo cells. Notably, we found that B4GALT3 modified glycans on ß1-integrin, suppressed focal adhesion kinase (FAK) signaling, and enhanced ß1-integrin degradation. DISCUSSION: We propose that B4GALT3-mediated glycosylation change not only enhances ß1-integrin binding to laminin, but also attenuates ß1-integrin stability. Our findings suggest that B4GALT3 is a critical regulator for suppressing EVT invasion in the late stages of pregnancy.

Use of retrograde esophagoscopy in delayed primary esophageal anastomosis for isolated esophageal atresia.

INTRODUCTION: Preserving the native esophagus is critical for long-term swallowing function in patients with esophageal atresia (EA). However, long esophageal gaps and hidden distal esophageal pouches are frequently encountered, making primary esophageal anastomosis very difficult in cases with isolated EA. This study evaluates the efficacy of retrograde esophagoscopy for the identification of distal esophageal pouches to aid primary esophageal anastomosis in patients with isolated EA. MATERIAL AND METHODS: From January 1995 to January 2007, five patients with isolated EA out of 30 patients with EA treated in our hospital were included in this study. All patients initially received a gastrostomy and distal esophagogram to evaluate distal esophageal pouches and esophageal gaps. Delayed esophageal reconstruction was performed 3 to 4 months later. During surgery for esophageal reconstruction, a 0.5 cm diameter endoscope was inserted through the gastrostomy to identify the distal esophageal pouch. RESULTS: Distal esophagograms found no distal esophageal pouch in 3 patients. Retrograde esophagoscopy and exploratory surgery found no distal esophageal pouch in only 1 patient. The esophageal gap ranged from 4 to 7 cm. All patients successfully received primary esophageal anastomosis except for one without a distal pouch who received colon interposition. Postoperative complications included esophageal stricture in 4 patients and gastroesophageal reflux (GER) in 3. All esophageal strictures resolved after esophageal dilatation. One patient required further fundoplication for GER. CONCLUSIONS: Retrograde esophagoscopy is superior to distal esophagogram for the identification of distal esophageal pouches in isolated EA. In addition, retrograde esophagoscopy is excellent for the localization of distal esophageal pouches to facilitate primary end-to-end esophageal anastomosis.

Retinoblastoma in Taiwan: incidence and survival characteristics from 1979 to 2003.

PURPOSE: To describe the incidence and survival rate of patients with retinoblastoma in Taiwan over a 25-year period, from 1979 to 2003. METHODS: Cases of retinoblastoma have been reported to the Taiwan National Cancer Registry (TNCR) since 1979. Retinoblastoma data from 1979 to 2003 were retrieved from the TNCR databank for analysis of both the incidence and survival rate. Trends in the incidence rate were estimated by calculating the annual percentage change (APC). RESULTS: From 1979 to 2003, a total of 380 patients (182 [47.9%] females) with retinoblastoma were identified. Of the 380 cases, 359 patients (94.5%) were diagnosed before 5 years of age. The average annual age-standardized incidence rate was 4.45 per million in children under 10 years of age and 8.58 per million in children under 5 years of age. There was a significant increasing trend in the incidence rate over the study period with an APC of 2.3% (P=0.035). Before the implementation of Taiwan's National Health Insurance (NHI) Program in 1995, the mean age at diagnosis was 4.8+/-13.3 years and the 5-year survival rate was 74.7%. After implementation of the NIH Program, the mean age at diagnosis decreased to 1.6+/-2.1 years (P<0.001) and the 5-year survival rate increased to 84.7% (P=0.063). CONCLUSIONS: We report the first population-based study on retinoblastoma in Taiwan. There was a significant increasing trend in the incidence rate from 1979 to 2003. Since the implementation of Taiwan's NHI, the mean diagnostic age decreased.

Oxidative stress in patients with Graves' ophthalmopathy: relationship between oxidative DNA damage and clinical evolution.

PURPOSE: To evaluate the relationship between oxidative stress and clinical evolution in patients with Graves' ophthalmopathy (GO). METHODS: Thirty-one euthyroid GO patients and 25 healthy subjects participated in this study. Oxidative DNA damage was assessed by determination of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in urine by ELISA. The relationship of oxidative DNA damage to the clinical evolutions of GO, especially the smoking status, clinical activity scores (CAS), and ophthalmopathy index was examined. RESULTS: The mean 8-OHdG was significantly higher in GO patients than that of normal controls (12.6+/-5.7 vs 6.7+/-2.5 ng/mg creatinine, P<0.001). Smokers had significant higher 8-OHdG than did never smokers in GO patients (P=0.029), but not in healthy controls (P=0.374). Among GO patients, only CAS remained significantly correlated with 8-OHdG (P=0.001) after adjusting for age, sex, disease duration, the status of antithyroid drug and smoking, and thyroid-stimulating hormone level. Patients with active GO (CAS>3) had higher 8-OHdG than did the patients with CAS

Cytotoxicity of silicone oil on cultivated human corneal endothelium.

BACKGROUND AND OBJECTIVE: To investigate the cytotoxic effects of silicone oil on the cultivated human corneal endothelial cells (CEs). METHODS: We cultured human CE and passed them in insert wells that allowed the apical side of CE monolayer in contact with the silicone oil. The tested silicone oils were of two different viscosities, 1,000 and 5,000 centistoke (CS). MTS proliferation bioassay and calcein-acetoxymethyl ester (CAM)-ethidium homodimer staining were performed to evaluate cell viability after CEs were co-cultured with silicone oils for 48 h. Apoptosis of CEs was evaluated by TdT-mediated dUTP nick-end labelling (TUNEL) stain. RESULTS: The MTS bioassay showed that contact of silicone oil inhibited CE proliferation. The higher viscosity (5,000 CS) silicone oil suppressed cell cycling significantly more than the lower viscosity (1,000 CS) silicone oil. CAM-ethidium homodimer staining revealed CE death, 9.1+/-0.1% (1,000 CS silicone oil) and 41.6+/-0.4% (5,000 CS), but apoptosis played only minor role in silicone oil toxicity, 1.7+/-0.1% (1,000 CS silicone oil) and 9.4+/-0.1% (5,000 CS). CONCLUSIONS: Silicone oil is cytotoxic to cultivated human CEs. Avoiding the forward migration of silicone oil to the anterior chamber and corneal CE contact is critical in preventing silicone oil-associated keratopathy. Silicone oil should be removed as early as possible once the goal of tamponade has been achieved.

Calreticulin expression in neuroblastoma--a novel independent prognostic factor.

BACKGROUND: Calreticulin (CRT), an endoplasmic reticulum protein, has been reported to be essential for the differentiation of neuroblastoma (NB) cells, suggesting that CRT may affect the tumor behavior of neuroblastoma. The aim of this study was to evaluate the association of clinicopathologic factors and patient survival with the expression of CRT in patients with NB. PATIENTS AND METHODS: Sixty-eight NBs were investigated by immunohistochemical staining against CRT, and were divided into positive and negative immunostaining groups. Correlations between calreticulin expression, various clinicopathologic and biologic factors, and patient survival were studied. In seven tumor samples, CRT mRNAs and proteins were evaluated with real-time PCR and western blot, respectively, and correlated with immunohistochemical findings. RESULTS: Among 68 NBs, 32 (47.1%) showed positive CRT expression. Positive CRT immunostaining strongly correlated with differentiated histologies, as well as known favorable prognostic factors such as detected from mass screening, younger age (< or =1 year) at diagnosis and early clinical stages, but inversely correlated with MYCN amplification. Kaplan-Meier analysis revealed that NB patients with CRT expression did have better survival. Multivariate analysis demonstrated CRT expression to be an independent prognostic factor. Moreover, CRT expression also predicted better survival in patients with advanced-stage NBs, and its absence predicted poorer survival in patients whose tumor had no MYCN amplification. The amount of CRT mRNAs and proteins in NB tumor samples tested correlated well with the immunohistochemical expressions. CONCLUSIONS: CRT expression correlates with the differentiation of NB and predicts favorable survival, thereby suggesting CRT to be a useful indicator for planning treatment of NB.

Incidence and severity of iris pigmentation on latanoprost-treated glaucoma eyes.

PURPOSE: The purpose of the present study was to investigate the incidence and severity of iridial pigmentation under latanoprost topical use on brown eyes in Taiwan. METHODS: Retrospective review study was conducted from April 1999 to October 2001 in the Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan, for glaucoma clinic monthly follow-up patients; 140 open-angle glaucoma patients on 0.005% latanoprost were enrolled. Analyses of iridial pigmentation incidence, grading, patient age distribution, side effect, and time course were performed. Boys-Smith pigment gradation lens was used as standard for semiquantitative iris pigmentation grading. RESULT: Before 0.005% latanoprost use, 90% of the patients enrolled were noted with iridial pigmentation grade I, and 10% were with grade I-II, but not reaching grade II scale standard. A total of 60 patients on 0.005% latanoprost developed increased pigmentation of the iris during the follow-up period. An increase of iris pigmentation was noted after an average of 7.27 months use of latanoprost (range 1-19 months, SD 2.65 months). For iridial pigmentation grading, 57.1, 30.7, 10.0, and 2.1% of our patients were noted to have grade I, II, III, and IV respectively. Most patients with latanoprost-induced iris hyperpigmentation were with grade II iridial pigmentation. There were 15 patients (10.7%) (10 female and five male) with hypertrichosis in the study group who were not compatible with the iridial pigmentation status. Among these patients, female patients had higher incidence of hypertrichosis than males, but this did not bother them. Only four patients (2.8%) were with conjunctiva chemosis and three patients (2.1%) with lid margin hyperpigmentation. CONCLUSION: Contrary to the belief that latanoprost rarely caused iris hyperpigmentation in yellow-brown eyes, our study showed that 42.8% iris hyperpigmentation did occur, especially after continual use for around 7 months. Higher hyperpigmentation incidence were noted in male than in female patients. This might be due to stronger adrenergic incidence in male than in female patients. Although hypertrichosis and increasing eyelid pigmentation together with iridial pigmentation represented a potentially permanent cosmetic side effect, they are very rare and occurred in no more than 3% in our patients. It is a good way to take Boys-Smith pigment gradation lens for iridial pigmentation grading and for long-term continual evaluation. The doctors should exert great care in differentiating drug-induced iris pigmentation and iris nevi from early stage uveal melanoma.

Nasopharyngeal carcinoma with orbital invasion.

PURPOSE: To review the clinical profiles of patients having nasopharyngeal carcinoma (NPC) with orbital invasion, which occurs more frequently in patients with Chinese and south-east Asian racial backgrounds. Although this disease frequently spreads superiorly to the skull base and intracranium, it rarely invades the orbit and we wish to examine some cases in which it has. METHODS: In this observational case series, we examined 406 patients, who were diagnosed with orbital tumour at Taipei Veterans General Hospital between January 1974 and December 2001. In all, 13 of the patients (11 males, two females) were found to have NPC with orbital invasion. Neuroimaging studies, pathologic reports, and clinical courses of these 13 patients were then reviewed retrospectively and survival analysis was carried out using a Kaplan-Meier estimate. RESULTS: One patient presented with eyelid tumour and three other patients presented with proptosis as the initial manifestation of NPC. The other nine cases, already diagnosed to have NPC, visited our department with a variety of ocular symptoms and signs, such as proptosis, diplopia, visual impairment, and orbital pain. Palliative treatment with radiotherapy alone or in combination with chemotherapy was given in 12 cases. During the follow-up period ranging from 4 to 64 months, six patients died, one was lost during follow-up, and six were still alive. CONCLUSIONS: Although orbital invasion in NPC is rare, we found a 5-year survival rate of 28% in our patients, indicating that orbital invasion with NPC confers a particularly poor prognosis.

Incidence of eye cancer in Taiwan: an 18-year review.

PURPOSE: To describe the incidence and histologic patterns of eye cancers in Chinese in Taiwan. METHODS: Beginning in 1979, cases of cancer in Taiwan were reported to the Taiwan National Cancer Registry. Information on all Chinese patients diagnosed with eye malignancies under the International Classification of Disease, Ninth Revision, site 190, was retrieved for analysis from the data bank of the Taiwan National Cancer Registry. RESULTS: In all, 733 cases with primary eye cancers were identified from 1979 to 1996, an 18-year period. The average annual age-standardized incidence of eye cancers was 2.46 per million population (2.57 for male and 2.33 for female). For cases less than 15 years of age, the most common eye malignancy was retinoblastoma (86.0%), followed by rhabdomyosarcoma (3.9%) and lymphoma (2.8%). For cases 15 years of age or older, the most common eye malignancy was melanoma (28.6%), followed by squamous cell sarcoma (21.0%) and lymphoma (20.8%). CONCLUSIONS: The time trends of the incidence of eye cancers were relatively stable over the 18-year period in Taiwan. Retinobalstoma, melanoma, and lymphoma were the three most common eye cancers in this Chinese population.

Genetic polymorphism of hOGG1 and risk of pterygium in Chinese.

PURPOSE: Ultraviolet irradiation is known to cause oxidative DNA damage and is thought to be a major factor implicated in the pathogenesis of pterygium. The highly mutagenic 8-hydroxy-2'-deoxyguanosine, a marker for the evaluation of photo-oxidative DNA damage, can be repaired by human 8-oxoguanine glycosylase I (hOGG1). A transition of C to G at nucleotide position 1245 in exon 7 of the hOGG1 gene is associated with the substitution of cysteine for serine at codon 326. In this study, we investigated the association of the hOGG1 Ser326Cys polymorphism with pterygium in a Chinese population. METHODS: In all, 70 patients and 86 controls were enrolled in this study. The Ser326Cys polymorphism was determined by the polymerase chain reaction-restriction fragment-length polymorphism analysis. The association between this genetic polymorphism and risk of pterygium was examined by chi(2)-test and logistic regression. RESULTS: The allelic frequencies for the Ser and Cys variants of hOGG1 gene were not significantly different between the two groups. However, when compared with Ser/Ser and Ser/Cys genotypes combined, we found that the homozygous Cys/Cys genotype was more prevalent in pterygium patients than controls (P=0.024) with the odds ratio being 2.2 (95% CI: 1.1-4.5). In the pterygium group, the mean age of patients with the Cys/Cys genotype was younger than those with the other two genotypes (P=0.025). CONCLUSIONS: Our findings suggest that the 1245C --> G transition in exon 7 of the hOGG1 gene, which results in Ser326Cys substitution of the enzyme, might play a role in the susceptibility of humans to pterygium.