Downregulated ECRG4 is correlated with lymph node metastasis and predicts poor outcome for nasopharyngeal carcinoma patients.

OBJECTIVE: Esophageal cancer-related gene 4 (ECRG4) is a new candidate tumor suppressor gene. In this retrospective study, we evaluated ECRG4 protein expression in patients with nasopharyngeal carcinoma (NPC) under curative treatment and examined its association with pathological features and clinical outcomes as a possible biomarker for diagnosis and prognosis of NPC. METHODS: We enrolled 122 patients with a first diagnosis between January 2001 and December 2003. Tumor tissue and control tissue from biopsies underwent immunohistochemical staining for ECRG4. ECRG4 expression was analyzed by clinicopathological variables. After Kaplan-Meier survival analysis, we used Cox proportional hazards regression to estimate the predictive effect of ECRG4 expression on overall survival. RESULTS: ECRG4 protein level was lower in NPC than control tissue (P < 0.01). It was inversely related to node status (P < 0.001) and clinical stage (P = 0.027). ECRG4 expression was associated with overall survival, and downregulated ECRG4 expression was an independent prognostic factor of poor survival (hazard ratio = 0.677, 95 % confidence interval 0.463-0.989, P = 0.044). CONCLUSIONS: A significant NPC patients showed downregulated ECRG4 expression, which is correlated with lymph node metastasis. The marker could be an independent prognostic factor for NPC patients. The precise function of ECRG4 in the progression of NPC, especially for lymphatic metastasis, deserves further investigation, which would bring a new target for personalized therapy.

Lepra lepromatosa peneal en paciente con enfermedad de chagas. Reporte de un caso / Penile lepromatous leprosy in a patient with chagas disease. a case report

Se presenta el caso de un paciente masculino de 52 años con fimosis secundaria a una masa pseudotumoral prepucial. El paciente presentaba una historia de enfermedad de Hansen con afectación de piel, laringe y bronquios. Previa a la circuncisión, el examen físico revelaba, además de las alteraciones lepromatosas, un mega esófago secundario a estenosis en la porción distal. El análisis laboratorial mediante la técnica de ELISA dio positivo para Trypanosoma cruzi, patógeno responsable de la enfermedad de Chagas. Sólo pudimos encontrar un caso previo reportado de lepra lepromatosa con afectación prepucial. La coexistencia de lepra y miocardiopatía chagásica es inusual pero bien conocida por casos reportados en Brasil e India. Sin embargo, de acuerdo a nuestros conocimientos, éste es el primer caso reportado de una asociación entre lepra lepromatosa y mega esófago chagásico en un paciente con fimosis.

We are presenting a 52-year-old patient with phimosis due a tumor like mass, which on pathological evaluation was diagnosed as lepromatous leprosy. The patient had a history of Hansen's disease involving the skin, the larynx and the bronchial tree. Before a circumcision, a physical examination revealed in addition to the lepromatous changes the presence of megaesophagus secondary to stenosis of the distal portion. Laboratory analysis for Tripanosomacruzii using ELISA technique was positive for Chagas Disease. We could find only one previous report of lepromatous leprosy affecting the foreskin. The coexistence of leprosy and myocardial Chagas disease is unusual but well known in reports from Brazil and India. However, this is, to our knowledge, the first case reported of an association of lepromatous leprosy and chagasicmegaesophagus in a patient with phimosis.

Comparison of genetic diversity between wild-caught broodstock and hatchery-produced offspring populations of the vulnerable Korean kelp grouper (Epinephelus bruneus) by microsatellites.

The kelp grouper Epinephelus bruneus (Perciformes: Haemulidae), is one of the most economically important fishery resources in Korea. This fish is regarded as a target for prospective aquaculture diversification; therefore, maintenance of stock quality is important. To investigate the effects of current artificial reproduction in a hatchery facility, genetic variation in wild-caught broodstock and hatchery-produced offspring of kelp grouper was analyzed using eight polymorphic nuclear microsatellite DNA loci; 77 alleles were identified. Allelic variability ranged from 2 to 22 in the broodstock and from 1 to 10 in the offspring. The average observed and expected heterozygosities were 0.620 and 0.623 in the broodstock and 0.600 and 0.513 in the offspring, respectively. The possibility of a recent genetic bottleneck was suggested in both populations of E. bruneus. The minor, but significant, genetic differentiation (FST = 0.047, P < 0.05) observed was mainly due to statistically significant reductions in the number of alleles in the offspring compared with the broodstock, suggesting that these genetic changes could be related to genetic drift. Our results demonstrate the usefulness of microsatellite markers to monitor genetic variation and raise concerns about potential harmful genetic effects of inappropriate hatchery procedures. Therefore, genetic variation between broodstock and offspring in a hatchery should be monitored in both breeding and release programs as a routine hatchery operation, and inbreeding should ideally be controlled to improve kelp grouper hatchery management. Our data provide a useful genetic basis for future planning of sustainable culture and management of E. bruneus in fisheries.

Genetic differences between the wild and hatchery-produced populations of Korean short barbeled grunter (Hapalogenys nitens) determined with microsatellite markers.

Short barbeled grunter, Hapalogenys nitens, is an economically important fishery resource. In Korea, this fish is in the early stage of domestication, and it has been regarded as the candidate marine fish species for prospective aquaculture diversification. This study presents a preliminary investigation of the future viability of sustainable fry production from short barbeled grunter. We used 12 polymorphic nuclear microsatellite DNA loci to analyze the possible genetic variability between the wild and hatchery-produced populations of short barbeled grunter from Korea and identified 91 alleles. Compared to the wild population, significant genetic changes including reduced genetic diversity (average allele number: 7.42 vs 3.75; average expected heterozygosity: 0.713 vs 0.598, Wilcoxon signed-rank test; P < 0.05) and differentiation [overall fixation index (FST) = 0.088, P < 0.01] occurred in the hatchery-produced population, as indicated by the observation of allele richness, unique allele, heterozygosity, FST, and results of molecular analysis of variance. These findings indicate that genetic drift may have promoted the differentiation between these 2 populations, which may have negative effects on sustainable fry production. Therefore, genetic variations of the wild and hatchery-produced populations should be monitored and subjected to control inbreeding through a commercial breeding program. The information presented by this paper would provide a useful genetic basis for future sustainable culturing planning and management of H. nitens.

Up-regulation of nuclear receptor coactivator amplified in breast cancer-1 in papillary thyroid carcinoma correlates with lymph node metastasis.

INTRODUCTION: Nuclear receptor coactivator amplified in breast cancer-1 (AIB1), a new oncogenic coactivator, is commonly overexpressed and amplified in variety of human cancers. However, the expression of AIB1 in papillary thyroid carcinoma (PTC), the major histologic type of thyroid cancer, and its clinical significance are still unclear. MATERIALS AND METHODS: AIB1 expression in PTC was examined by immunohistochemistry using tissue microarrays comprised of 90 primary PTC, 46 matched lymph node, and 20 normal thyroid tissue specimens in this study. RESULTS: In the normal thyroid specimens, AIB1 expression was either absent or at low levels. In contrast, AIB1 overexpression was detected in 50 of 83 (60.2 %) primary PTC specimens. Up-regulated AIB1 was evident in 39 of 46 (73.5 %) matched lymph nodes. Overexpression of AIB1 was observed more frequently in PTCs with lymph node metastasis [N1a/N1b, 39/46 (73.5 %)] versus PTCs without lymph node metastasis [N0, 14/34 (41.2 %)]. Furthermore, high-level AIB1 expression was only observed in the lymph node-positive specimens. Moreover, we found no correlation between AIB1 expression and ER expression in PTC tissues. CONCLUSIONS: Our findings suggest that overexpression of AIB1 may be a biomarker for tumorigenesis and progression of PTC and may play an important role in its acquisition of a metastatic phenotype.

A follow-up study of preterm infants given budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants.

OBJECTIVE: Our study of early intratracheal instillation of budesonide using surfactant as vehicle showed a significant decrease in death or chronic lung disease (CLD) in preterm infants with severe respiratory distress syndrome (RDS). We now report the long-term outcome at about 2 to 3 years of age. STUDY DESIGN: Of the 75 potential survivors, 67 (90%) were studied (35 budesonide-treated, 32 control). All infants had birth weight <1500 g and had severe RDS requiring intermittent mechanical ventilation shortly after birth. The treated group received a mixture of budesonide and surfactant every 8 hours. The control group received only surfactant. RESULTS: The physical growth and the neurological examinations were comparable between the groups at follow-up. Infants in the group treated with budesonide tended to have higher PDI and MDI scores than infants in the control group (79 +/- 20 vs 74 +/- 18 and 80 +/- 19 vs 75 +/- 20), but these differences were not statistically significant. The incidence of neurodevelopmental impairment was 11 (31%) in the treated group and 13 (40%) in the control group (P = .367). CONCLUSIONS: Early intratracheal instillation of budesonide using surfactant as a vehicle significantly improved pulmonary outcome without causing long-term adverse effects.

Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro.

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 microM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 +/- 3.9% in HNE1-LMP1 cells vs 37.89 +/- 4.9% in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 +/- 3.5 vs 65.87 +/- 5.9%), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 +/- 3.7 and 27.91 +/- 2.1%), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 +/- 3.9 vs 29.19 +/- 6.27%) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.

Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 æM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 ± 3.9 percent in HNE1-LMP1 cells vs 37.89 ± 4.9 percent in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 ± 3.5 vs 65.87 ± 5.9 percent), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 ± 3.7 and 27.91 ± 2.1 percent), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 ± 3.9 vs 29.19 ± 6.27 percent) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.

Adiposity in childhood predicts obesity and insulin resistance in young adulthood.

OBJECTIVE: To determine whether adiposity in children predicts adiposity, insulin resistance, and abnormal lipid levels in young adults. STUDY DESIGN: Children (n = 31) were recruited into an epidemiologic study at age 13.3 +/- 0.3 years and had blood pressure, weight, and height measured. They were reevaluated at age 21.8 +/- 0.3 years at which time the measurements were repeated, a euglycemic insulin clamp was performed, and fasting lipid levels were measured. All values are expressed as mean +/- SEM. Data were analyzed by analysis of variance and linear regression analysis. RESULTS: Body mass index (BMI) in childhood (22.6 +/- 0.6) was highly correlated with BMI in young adulthood (26.9 +/- 0.9). Childhood BMI was also inversely correlated with young adult glucose utilization (r = -0.5, P = .006) and positively correlated with total cholesterol (r = 0.37, P = .05), and low-density lipoprotein (LDL) cholesterol (r = 0.48, P = .01). CONCLUSIONS: These data confirm that adiposity in childhood is a strong predictor of young adult adiposity. In addition, these results demonstrate that cardiovascular risk in young adulthood is highly related to the degree of adiposity as early as age 13.

Very long chain acyl coenzyme A dehydrogenase deficiency in a 5-month-old Korean boy: identification of a novel mutation.

A 5-month-old Korean boy who presented with lethargy and cardiomyopathy was diagnosed with very long chain acyl coenzyme A dehydrogenase (VLCAD) deficiency by organic acid, fatty acid, acylcarnitine, and molecular genetic analysis. The patient was a compound heterozygote for mutations in the VLCAD gene. One allele contains a 3-bp deletion in exon 6, deleting glutamic acid in codon 130 (E130del ); this allele is of paternal origin. The patient's maternally derived allele is a novel mutation, C1843T in exon 20, which creates a premature termination codon (R615stop ). Although molecular genetic characterization of VLCAD deficiency is limited to a few patients, heterogeneity of mutations is already apparent. However, the E130del is a relatively frequent mutant allele, which has been noted in 2 previously identified patients. The 2 mutant alleles in our patient appear to be responsible for his severe and fatal clinical manifestations.

Histomorphologic changes in expanded skeletal muscle in rats.

Tissue expansion is one of the powerful tools for various reconstructive procedures and has proven to provide more available local tissues. However, limited attention has been given to the characteristics of expanded skeletal muscle. Using a rat model (n = 41), we expanded the rat gracilis muscle and investigated the histomorphologic changes in the expanded skeletal muscle. By expansion, the gracilis muscle after 3 weeks increased 50.4 to 58.4 percent in length and 60.5 percent in width and decreased 39.0 to 42.0 percent in thickness. Histologically, the expanded muscle demonstrated a normal striation and no signs of inflammation or necrosis. The cross-sectional areas of muscle fibers indicated that expanded muscle consisted of predominantly smaller fibers. Vasculature in the expanded muscle demonstrated a longer network of arteries and a more obvious and developed arterial arcade. The average number of sarcomeres in a fiber estimated from the sarcomere length and fiber length was significantly greater (46.5 percent) in the expanded muscle. These findings suggest that the expansion of skeletal muscle is not a "stretching" process of muscle but rather a growth process of the muscle accompanied by an increase in the number of sarcomeres per fiber. Furthermore, the expanded skeletal muscle appears to preserve normal skeletal muscle architecture, vasculature, and function while undergoing the ischemic stress of expansion.

Artificial microvascular graft thrombosis: the consequences of platelet membrane glycoprotein Ib inhibition and thrombin inhibition.

Early thrombosis of artificial microvascular grafts (AMG, grafts < or = 2 mm internal diameter) prevents their reliable clinical use. The present studies were undertaken to examine the effect of hirudin, a thrombin-specific inhibitor, and of the F(ab')2 fragment of PG-1, a monoclonal antibody (MoAb) directed against guinea pig platelet membrane glycoprotein Ib (GPIb), on AMG patency in an animal model. One-centimeter long segments of expanded polytetrafluoroethylene (ePTFE), 0.88 mm internal diameter, were serially implanted as interposition grafts in the guinea pig femoral arterial systems bilaterally. A control group was treated with 0.5 mL saline intravenously (IV) 30 minutes before limb 1 and limb 2 graft implantation. Three experimental groups were treated with 0.5 mL saline IV before limb 1 graft implantation as an animal control and with either 0.5 mL saline containing 1.25 mg/kg IV PG-1 F(ab')2, (which inhibits ristocetin-induced platelet agglutination and von Willebrand factor binding), hirudin 1 mg/kg IV, or a combination of both agents before limb 2 graft implantation. GPIb inhibition, thrombin inhibition, and the combination resulted in a significant prolongation of AMG patency (P < .005). Whereas thrombin inhibition with hirudin prolonged AMG patency similar to that observed with GPIb inhibition, the combination of GPIb and thrombin inhibition provided the overall longest prolongation of AMG patency. These results indicate that both platelet membrane GPIb and thrombin play a role in AMG thrombosis.