Uptake and disposition of inhaled methanol vapor in humans.

Methanol is a widely used solvent and a potential fuel for motor vehicles. Human kinetic data of methanol are sparse. As a basis for biological exposure monitoring and risk assessment, we studied the inhalation toxicokinetics of methanol vapor in four female and four male human volunteers during light physical exercise (50 W) in an exposure chamber. The relative uptake of methanol was about 50% (range 47-53%). Methanol in blood increased from a background level of about 20 to 116 and 244 microM after 2 h exposure at 0, 100 ppm (131 mg/m3) and 200 ppm (262 mg/m3), respectively. Saliva showed substantially higher levels than blood immediately after exposure. This difference disappeared in a few minutes; thereafter the concentrations and time courses in blood, urine, and saliva were similar, with half times of 1.4, 1.7, and 1.3 h, respectively. The postexposure decrease of methanol in exhaled air was faster, with a half time of 0.8 h. The methanol concentrations were approximately twice as high in all four types of biological samples at 200 compared to 100 ppm. No increase in urinary formic acid was seen in exposed subjects. Our study indicates non-saturated, dose-proportional kinetics of methanol up to 200 ppm for 2 h. No gender differences were detected. Similar, parallel patterns were seen with regard to the methanol time courses in blood, urine, and saliva, whereas the concentration in exhaled air decreased markedly faster. Thus, apart from blood and urine, saliva also seems suitable for biomonitoring of methanol exposure.     

Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer.

PURPOSE: Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors including colorectal cancer. However, there is no study examining the relationship of legumain expression to clinocopathologic and biological variables in colorectal cancers. EXPERIMENTAL DESIGN: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry. We also did Western blotting analysis on three additional colorectal cancers and three colonic cell lines. RESULTS: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05). Legumain expression was positively related to poorer differentiation/mucinous carcinoma (P = 0.04), higher degree of necrosis (P = 0.03) and apoptosis (P < 0.0001), positive proliferating cell nuclear antigen (P < 0.0001) and p53 expression (P = 0.049), and had a positive tendency towards stromelysin 3 (P = 0.058) and PINCH positivity (P = 0.05). The patients with tumors that showed both weak and lower percentage of the legumain expression, either in tumor (P = 0.01) or in stroma (P = 0.04), had a better prognosis. CONCLUSIONS: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients.     

TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

Background  

Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive.     

Gene–environment interactions in the aetiology of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease that displays a multitude of symptoms and a vast array of autoantibodies. The disease course may vary substantially between patients. The current understanding of SLE aetiology includes environmental factors acting on a genetically prone individual during an undetermined time period resulting in autoimmunity and finally surpassing that individual's disease threshold. Genetic differences and environmental factors may interact specifically in the pathogenetic processes and may influence disease development and modify the disease course. Identification of these factors and their interactions in the pathogenesis of SLE is vital in understanding the disease and may contribute to identify new treatment targets and perhaps also aid in disease prevention. However, there are several problems that need to be overcome, such as the protracted time frame of environmental influence, time dependent epigenetic alterations and the possibility that different pathogenetic pathways may result in a similar disease phenotype. This is mirrored by the relatively few studies that suggest specific gene-environment interactions. These include an association between SLE diagnosis and glutathion S-transferase gene variants combined with occupational sun exposure as well as variants of the N-acetyl transferase gene in combination with either aromatic amine exposure or hydralazine. With increased knowledge on SLE pathogenesis, the role of environmental factors and their genetic interactions may be further elucidated.     

Reliability of a multidimensional questionnaire for adults with treated complete cleft lip and palate

The purpose of this study was to evaluate the reliability of a multidimensional questionnaire for Swedish adults with treated complete unilateral or bilateral cleft lip and palate (CLP). The questionnaire was designed to be used in the evaluation of adults with treated CLP after treatment. Before any conclusions were drawn from the results of the study we assessed the test-retest reliability of the questionnaire. The questionnaire included 168 questions and assessed the following domains: aesthetics, functions associated with CLP, satisfaction with treatment and perceived need for treatment, quality of life, depression and non-specific physical symptoms, body image, and jaw function. The subjects answered the questionnaire twice at a 2-3-week interval. Sixty-one adults (38 men, 23 women) mean age 24 years (range 20-29) participated in the study. The response rate for the questionnaire was acceptable at 75%. The test-retest reliability varied among the different domains. The reliability of questions regarding aesthetics, functions associated with CLP, and treatment satisfaction was good to excellent (intraclass correlation coefficient (ICC) = 0.51 to 0.89). Good to excellent (ICC = 0.61 to 1.0) reliability was also found for the quality of life in various life domains and the wellbeing scales. The reliability of the body image scale was moderate (kappa = 0.43-0.60) for most items and lower than that of other scales used in this study. The reliability of the mean depression symptom score (ICC = 0.93) and the mean non-specific physical symptoms score (ICC = 0.85) were excellent. The reliability of the mandibular function impairment was good (ICC = 0.67). The conclusion of the study is that an overall reliability was good for the multidimensional questionnaire.     

Immune parameters in the intestine of wild and reared unvaccinated and vaccinated Atlantic salmon (Salmo salar L.)

Forming a barrier to the outside world, the gut mucosa faces the challenge of absorbing nutrients and fluids while initiating immune reactions towards potential pathogens. As a continuation to our previous publication focusing on the regional intestinal morphology in wild caught post smolt and spawning Atlantic salmon, we here investigate selected immune parameters and compare wild, reared unvaccinated and vaccinated post smolts.