The clinical significance of MAGEA3 expression in pancreatic cancer

The MAGEA gene family that encodes cancer testis antigens is differentially expressed in many cancers. Though MAGEA3 expression has been detected in gastrointestinal malignancies, its role in pancreatic ductal adenocarcinoma (PDAC) has not been well established. We assessed 57 patients who underwent intent-to-cure surgery for PDAC. Total RNA from paraffin-embedded pancreatic tumors was extracted and assessed for MAGEA3 gene expression by an optimized probe-based quantitative real-time RT-PCR (qRT) assay. MAGEA3 gene expression was detected by qRT in 25 (44%) patients. For the entire cohort, detection of MAGEA3 expression was associated with significantly decreased overall survival (median, 16 vs 33 months; log-rank, p = 0.032). When clinicopathologic factors, including age, gender, stage, tumor extent, lymph node metastasis, tumor grade, perineural invasion and lymphovascular invasion were assessed by univariate analysis, MAGEA3 gene expression and tumor grade were significant prognostic factors for poor survival (HR 2.1, 95% CI: 1.0-4.4, p = 0.041; and HR 3.7, 95% CI: 1.8-7.6, p = 0.0004, respectively). Immunohistochemistry (IHC) was performed and confirmed MAGEA3 protein in PDAC specimens. In conclusion, MAGEA3 is differentially expressed in patients with PDAC; its expression correlates with significantly worse survival. Molecular assessment for MAGEA3 should be considered to improve prognostic evaluation and to identify eligible patients for potential immune-based therapy.     

Estrogen receptor-alpha methylation predicts melanoma progression

The role of estrogen receptor alpha (ER-alpha) in melanoma is unknown. ER-alpha expression may be regulated in melanoma via hypermethylation of promoter CpG islands. We assessed ER-alpha hypermethylation in primary and metastatic melanomas and sera as a potential tumor progression marker. ER-alpha methylation status in tumor (n = 107) and sera (n = 109) from American Joint Committee on Cancer (AJCC) stage I to IV melanoma patients was examined by methylation-specific PCR. The clinical significance of serum methylated ER-alpha was assessed among AJCC stage IV melanoma patients receiving biochemotherapy with tamoxifen. Rates of ER-alpha methylation in AJCC stage I, II, and III primary melanomas were 36% (4 of 11), 26% (5 of 19), and 35% (8 of 23), respectively. Methylated ER-alpha was detected in 42% (8 of 19) of stage III and 86% (30 of 35) of stage IV metastatic melanomas. ER-alpha was methylated more frequently in metastatic than primary melanomas (P = 0.0003). Of 109 melanoma patients' sera in AJCC stage I, II, III, and IV, methylated ER-alpha was detected in 10% (2 of 20), 15% (3 of 20), 26% (5 of 19), and 32% (16 of 50), respectively. Serum methylated ER-alpha was detected more frequently in advanced than localized melanomas (P = 0.03) and was the only factor predicting progression-free [risk ratio (RR), 2.64; 95% confidence interval (95% CI), 1.36-5.13; P = 0.004] and overall survival (RR, 2.31; 95% CI, 1.41-5.58; P = 0.003) in biochemotherapy patients. Hypermethylated ER-alpha is a significant factor in melanoma progression. Serum methylated ER-alpha is an unfavorable prognostic factor.     

Toxicity Identification Evaluation of Five Metals Performed with Two Organisms (Daphnia magna and Lactuca sativa)

When trying to identify the main toxicants in effluents, natural waters, sediments, soil leachates, and leachates from products, the Toxicity Identification Evaluation (TIE) procedure has proven useful. To enhance the use of this procedure for soil, sewage, and sediment samples, we wanted to evaluate this TIE procedure, regarding metal toxicity, for the 96-h root elongation test performed with Lactuca sativa (lettuce) seeds. We also wanted to evaluate the effect of TIE treatment on the toxicity of Mn and Fe to Daphnia magna. Bioassays were performed with Daphnia magna (48-h immobility) and lettuce seeds (96-h root elongation) to determine the effect concentrations for both organisms of Ag, Cu, Fe, Mn, and Zn. The TIE was then performed at the determined Daphnia 48-h EC₈₄ and Lactuca 96-h EC₅₀ for each metal. Our results showed that the order of the metal toxicity was Ag>Cu>Zn>Fe>Mn, for Daphnia and Ag = Zn = Fe = Cu > Mn for lettuce seeds. We also found that toxicity of the metals for Daphnia magna was reduced according to the prevailing knowledge regarding Cu, Zn, and Ag. However, the toxicity of Ag and Cu for Daphnia was also reduced by filtration through a C18 resin. Toxicity of Mn and Fe was reduced by filtration through a CM resin and increase of pH. For lettuce seeds, toxicity of the metals was reduced by the same treatments as for Daphnia magna with the exception of EDTA addition, which did not affect Cu toxicity to lettuce seeds. No effects were found for filtration through a C18 resin. We suggest that the TIE procedure using lettuce seeds can be used in toxicity identification of metals. However, the effects of pH manipulations were often stronger with lettuce and should be interpreted with care.     

Changing the home nutrition environment: effects of a nutrition and media literacy pilot intervention

The specific aim for this pilot study was to evaluate the effectiveness of a nutrition and media literacy intervention targeting elementary students and their parents. The purpose of the intervention was to increase child fruit and vegetables (FV) consumption and change the home nutrition environment (measured with FV availability and accessibility and parental social support). During the intervention, students learned about nutrition, the role media plays in shaping values concerning nutrition, and developed a media campaign for their parents. A quasi-experimental research design was used to evaluate the effectiveness of the intervention. The media intervention was effective in changing the home environment.     

Molecular immunophenotyping of lungs and spleens in naive and vaccinated chickens early after pulmonary avian influenza A (H9N2) virus infection

In a respiratory-infection-model with the avian influenza A H9N2 virus we studied lung and splenic immune reactions in chickens using a recently developed 5K chicken immuno-microarray. Groups of chickens were either mock-immunized (referred to as non-immune), vaccinated with inactivated viral antigen only (immune) or with viral antigen in a water-in-oil (W/O) immunopotentiator (immune potentiated). Three weeks after vaccination all animals were given a respiratory infection. Immune potentiated birds developed inhibitory antiviral antibodies, showed minimal lung histopathology and no detectable viral sequences, while non-immune animals showed microscopic immunopathology and detectable virus. Immune birds, receiving antigen in saline only, showed minimal microscopic histopathology, and intermediate levels of virus detection. These classical features in the different groups were mirrored by overlapping or specific mRNA gene expression profiles in lungs and spleen using microarray analysis. To our knowledge this is the first study demonstrating pneumonia-associated lung pathology of the low pathogenic avian influenza H9N2 virus. Our data provide insights into the molecular interaction of this virus with its natural host when naive or primed by vaccination.     

A comparison of lung function methods for assessing dose-response effects of salbutamol

Pulmonary function methods which are able to detect small pharmacological effects may be useful for assessing the full dose-response curve of bronchodilatators. We compared the ability of impulse oscillometry (R5, R20, X5, RF), plethysmography (sGaw) and spirometry [forced expiratory volume in 1 s (FEV(1)), maximal mid expiratory flow rate (MMEF)] to measure the dose-response effects of salbutamol in 12 healthy subjects, 12 mild asthmatics (mean FEV(1) 96% predicted) and 12 moderate asthmatics (mean FEV(1) 63% predicted). The techniques were performed twice to assess variability. Then salbutamol 10, 20, 100, 200 and 800 microg was administered. The sensitivity of the methods were compared by determining the lowest dose that caused changes greater than variability. In healthy subjects significant changes (p < or = 0.05) were observed only in FEV(1) (4.1%) and MMEF (14.6%) at 100 microg and sGaw (25.6%) and R20 (8.3%) at 200 microg. In mild asthmatics significant changes were observed in sGaw (15.9%) at 10 microg, X5 (23%), RF (20.3%) and MMEF (15.7%) at 20 microg, R5 (13.9%) and R20 (9.4%) at 100 microg and FEV(1) (7.1%) at 200 microg. All measurements except R20 demonstrated significant changes at 10 micro g in moderate asthmatics. The most sensitive test for assessing bronchodilatation is different in healthy subjects and asthmatics, and varies with severity of airflow obstruction.     

The role of family history in addiction severity and treatment response

This study examined the relationship between familial history of substance use and addiction severity and treatment outcomes of opiate-dependent patients. The sample was comprised of 281 methadone maintenance patients at a VA or community-based clinic. Using the family history section of the Renard Diagnostic Interview, three familial risk groups were identified based on patients' self-report of their relatives' substance use. The three groups considered both the number and type (e.g., first vs. second degree) of biological relatives with a substance use problem. These three risk groups included: (1) high risk (HR, n = 111), (2) medium risk (MR, n = 80), and (3) low risk (LR, n = 90). HR patients reported a history of more severe asocial behavior at baseline and they reported more medical problems and a greater degree of concurrent alcohol use both prior to and after 6 months of treatment compared to LR patients. In addition, the HR group reported more family/social problems at baseline compared to the MR and LR group and both HR and MR patients reported more psychological problems than LR patients after 6 months of treatment. However, when accounting for baseline differences, the regression analyses demonstrated that familial risk was not predictive of drug treatment outcomes after 6 months of methadone maintenance treatment.     

Ambient hydrogen sulfide, total reduced sulfur, and hospital visits for respiratory diseases in northeast Nebraska, 1998-2000

This analysis examined associations between total reduced sulfur (TRS) and hydrogen sulfide (H(2)S) levels, and hospital visits for respiratory disease among residents of Dakota City and South Sioux City, Nebraska, from January 1998 to May 2000. For reference, the association between TRS, H(2)S, and digestive diseases was also examined. Time-series analyses of daily hospital visits in the selected outcome categories and measures of TRS and H(2)S were performed using generalized additive models with a Poisson link. TRS and H(2)S levels were categorized as high if at least one of the daily 30-min rolling averages was > or =30 ppb and as low if every rolling average was <30 ppb. Loess smoothers allowed for flexible modeling of the time effect and the effect of temperature and relative humidity. The measure of association used was the mean percent change in the average number of hospital visits recorded following a day with a high exposure versus a day with a low exposure. For children less than 18 years of age, a positive association was found between asthma hospital visits and 1-day lagged TRS levels. For adults, a positive association was found between asthma hospital visits and H(2)S levels on the previous day. A positive association also was found between hospital visits for all respiratory diseases, and H(2)S and TRS levels on the previous day for children but not for adults. No association was found between contaminant levels and hospital visits for all digestive diseases. These findings suggest that TRS or H(2)S levels may be associated with exacerbations of asthma or other respiratory diseases among the residents of Dakota City and South Sioux City.