The association between N-acetyltransferase 2 gene polymorphisms and pancreatic cancer

Pancreatic cancer has been linked with exposure to environmental chemicals, which generally require metabolic activation to highly reactive toxic or carcinogenic intermediates. N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2) are expressed primarily in extrahepatic and hepatic tissues, respectively. Both enzymes catalyze N- and O-acetylation of aromatic and heterocyclic amines. It is believed that these compounds are activated via O-acetylation and detoxified by N-acetylation. Several polymorphisms of these two genes have been associated with an increased risk of cancer. Twenty-seven cases of pancreatic cancer and 104 controls were included in this study. Blood was collected in EDTA-containing tubes, and genomic DNA was extracted from the white blood cells by using a high pure PCR template preparation kit. Genotyping of NAT2 polymorphisms was detected by a real time PCR instrument. There was a significant difference in the distribution of the NAT2*6A acetylators phenotype between cases and the controls. The odds ratio of pancreatic cancer for the NAT2*6A slow phenotype was 5.7 (95% CI = 1.27-25.55; p = 0.023) compared with the fast type. Our results suggest that slow acetylators have higher risk of developing pancreatic cancer than fast acetylators. NAT2 gene polymorphisms may be associated with genetic susceptibility to pancreatic cancer.     

Diet composition and prey selection of the pike,Esox lucius,in Çivril Lake,Turkey

Diet composition and prey selection of pike (Esox lucius) were studied in Çivril Lake, Turkey. The lake is eutrophic in character with a surface area of ca. 64 km^?2 and mean depth of 3 m. Stomach contents of 409 specimens were collected between October 2003 and April 2005. Pike diet included 10 prey fish species, two Crustaceae, four Insecta, one Hirudinae and one Amphibia. Feeding was homogeneous, with most pike specializing in prey fish and a few pike specializing on miscellaneous items. Feeding activity varied by season and ontogeny. Stomach fullness and the percentage of fish with prey were highest in spring and in small pike, while feeding intensity was lowest in winter and in large sized pike. Diet composition was dominated by fish, including Carasius gibelio, Chondrostoma meandrense, Esox lucius, Gambusia affinis, Gobio gobio, Hemigrammocapoeta kemali, Leuciscus cephalus, and Tinca tinca. Crustacea were also a significant component in spring and in small sized pike. The most important prey items were C. meandrense, Gammarus sp., H. kemali, and L. cephalus. Pike feeding in winter and summer was homogeneous, specializing mainly on fish as prey, while the diet in spring and autumn was heterogeneous with some pike specializing on Gammarus sp. Cannibalism at 8.7% was observed only in the large sized pike (>40 cm). Pike strongly preferred C. meandrense (Selectivity index V = 0.372; χ² = 27.739; P < 0.01), G. gobio (V = 0.192; χ² = 7.350; P < 0.01) and T. tinca (V = 0.146; χ² = 4.257; P < 0.05) despite their low abundance in the lake. Hemigrammocapoeta kemali was the most abundant prey fish in the environment; however, it was a negatively selected food item (V = ?0.358; χ² = 25.642; P < 0.01). Cyprinus carpio also inhabits the lake, but was not preferred by pike (V = ?0.056; χ² = 0.625; P > 0.05).     

Resilience of the iron environment in heme proteins

Conformational flexibility is essential to the functional behavior of proteins. We use an effective force constant introduced by Zaccai, the resilience, to quantify this flexibility. Site-selective experimental and computational methods allow us to determine the resilience of heme protein active sites. The vibrational density of states of the heme Fe determined using nuclear resonance vibrational spectroscopy provides a direct experimental measure of the resilience of the Fe environment, which we compare quantitatively with values derived from the temperature dependence of atomic mean-squared displacements in molecular dynamics simulations. Vibrational normal modes in the THz frequency range dominate the resilience. Both experimental and computational methods find a higher resilience for cytochrome c than for myoglobin, which we attribute to the increased number of covalent links to the peptide in the former protein. For myoglobin, the resilience of the iron environment is larger than the average resilience previously determined for hydrogen sites using neutron scattering. Experimental results suggest a slightly reduced resilience for cytochrome c upon oxidation, although the change is smaller than reported in previous Mössbauer investigations on a bacterial cytochrome c, and is not reproduced by the simulations. Oxidation state also has no significant influence on the compressibility calculated for cyt c, although a slightly larger compressibility is predicted for myoglobin.     

Renal responses to hemorrhage are age dependent in conscious sheep.

Experiments were carried out in conscious, chronically instrumented lambs (n = 8) and young adult sheep (n = 11) to investigate age-dependent renal responses to hemorrhage. Various parameters of renal function were measured for 1 h before and 1 h after either 10% hemorrhage (experiment 1) or 20% hemorrhage (experiment 2). The two experiments were carried out in random order at intervals of 2-5 days. There were no effects of 10-20% hemorrhage on renal plasma flow in either age group. Blood pressure decreased after 20% but not 10% hemorrhage in both age groups. Glomerular filtration rate and filtration fraction decreased after 20% hemorrhage in both age groups, the decrease being greater in lambs than young adult sheep. In response to 20% hemorrhage, urinary flow rate and urinary Na+ excretion rate decreased by 40 min after hemorrhage in young adult sheep but not lambs and remained decreased for 60 min; urinary chloride excretion rate showed a similar response. In lambs but not young adult sheep, free water clearance increased by 20 min after 20% hemorrhage and remained above control at 60 min. Urinary osmolality decreased at 20 min after 20% hemorrhage in young adult sheep but not lambs, returning to control levels by 40 min. These data provide new information that renal responses to hypotensive hemorrhage appear to be developmentally regulated.     

Noscapine,a Non-addictive Opioid and Microtubule-Inhibitor in Potential Treatment of Glioblastoma

Neurochemical Research - Noscapine is a phthalide isoquinoline alkaloid that easily traverses the blood brain barrier and has been used for years as an antitussive agent with high safety. Despite...     

Fine specificity of cellular immune responses in humans to human cytomegalovirus immediate-early 1 protein.

Cell-mediated immunity is important in maintaining the virus-host equilibrium in persistent human cytomegalovirus (HCMV) infection. The HCMV 72-kDa major immediate early 1 protein (IE1) is a target for CD8+ cytotoxic T cells in humans, as is the equivalent 89-kDa protein in mouse. Less is known about responses against this protein by CD4+ T cells, which may be important as direct effector cells or helper cells for antibody and CD8+ responses. Proliferative-T-cell responses to HCMV IE1 were studied in normal seropositive subjects. Peripheral blood mononuclear cells from 85% of seropositive subjects proliferated in response to HCMV from infected fibroblasts, and of these, 73% responded to recombinant baculovirus IE1. Responding cells were predominantly CD3+ CD4+. IE1 antigen preparations, including baculovirus recombinant protein, transfected rat cell nuclei, and synthetic peptides, induced IE1-specific T-cell lines which cross-reacted between the preparations. The fine specificity of these IE1-specific T-cell lines was studied by using overlapping synthetic peptides encompassing the entire sequence of the IE1 protein. The regions of the IE1 molecule recognized were identified and these varied between individuals, possibly reflecting differences in major histocompatibility complex (MHC) class II haplotype. In one subject, the peptide specificities of proliferative and MHC class I-restricted cytotoxic determinants on IE1 were spatially distinct. Thus, no single immunodominant T-cell determinant within HCMV IE1 was identified, suggesting that multiple peptides or a region of the 72-kDa IE1 protein would be required to induce specific T-cell responses in humans.     

Impact of xylanase pretreatment on peroxide bleaching stage of hemp pulp

Pretreatment of hemp pulp with xylanase was investigated. Unbleached hemp pulp was treated with commercial xylanase, and then bleached with hydrogen peroxide. Control pulp bleached with out xylanase was compared with xylanase bleached pulp. Application of xylanase was found to have a positive effect on followed peroxide stage in terms of low kappa number and high brightness of pulp.     

Combined point mutations in codon 12 and 13 of KRAS oncogene in prostate carcinomas

Prostate cancer is a common malignancy that develops by structural mutation(s) and/or other genetic alterations in specific genes.The G to T transversions in codon 12 and C to T transitions in codon 13 of KRAS proto-oncogene are predominant point mutations that occur in about 20% of different cancers in human. In the current study it was aimed to investigate the prevalence and predictive significance of KRAS mutations in patients with prostate carcinomas. In a total of 30 fresh tumoural tissue specimens were investigated in patients with prostate carcinoma. All tumoural specimens were histo-pathologically diagnosed and genotyped for codon 12, 13 KRAS point mutations by reverse hybridisation and direct sequencing methods. KRAS mutations were found in 12 (40%) samples with 29 samples deriving from adenocarcinomas and 1 sample was small cell prostate carcinoma. In 1 (3.44%) sample codon 12 was found to be mutated and in 2 (6.8%) samples codon 13 and in 9 (31%) samples combined codon 12 and 13 were found to be mutated particularly in higher grade of tumoural tissues. Our study, based on representative collection of human prostate tumours, indicates that combined mutations in codons 12 and 13 KRAS are relatively infrequent and most commonly occur in prostate carcinomas.     

Trace Metal Levels in Rainbow Trout (Oncorhynchus mykiss) Cultured in Net Cages in a Reservoir and Evaluation of Human Health Risks from Consumption

Although fish consumption has positive health effects, metals accumulated in fish can cause human health risks. In this study, the levels of ten metals in rainbow trout (Oncorhynchus mykiss) farmed in the Keban Dam Reservoir, which has the biggest rainbow trout production capacity in Turkey, were determined and compared with the maximum permissible levels (MPLs). Also, human health risks associated with rainbow trout consumption were assessed. The metal concentrations in rainbow trout were found below the MPLs. The estimated daily intake of each metal was much lower than the respective tolerable daily intake. The target hazard quotient (THQ) for individual metal and total THQ for combined metals did not exceed 1, indicating no health risk for consumers. The cancer risk (CR) value for inorganic arsenic was within the acceptable lifetime risk range of 10⁻⁶ and 10⁻⁴. For carcinogenic and non-carcinogenic effects, the maximum allowable fish consumption rates were high enough to ensure the human health. According to these results, the consumption of rainbow trout farmed in the Keban Dam Reservoir does not pose a risk on human health.

     

Automated fluorescent in situ hybridization (FISH) analysis of t(9;22)(q34;q11) in interphase nuclei.

BACKGROUND: For chronic myeloid leukemia, the FISH detection of t(9;22)(q34;q11) in interphase nuclei of peripheral leukocytes is an alternative method to bone marrow karyotyping for monitoring treatment. With automation, several drawbacks of manual analysis may be circumvented. In this article, the capabilities of a commercially available automated image acquisition and analysis system were determined by detecting t(9;22)(q34;q11) in interphase nuclei of peripheral leukocytes. METHODS: Three peripheral blood samples of normal adults, 21 samples of CML patients, and one sample of a t(9;22)(q34;q11) positive cell-line were used. RESULTS: Single nuclei with correctly detected signals amounted to 99.6% of nuclei analyzed after exclusion of overlapping nuclei and nuclei with incorrect signal detection. A cut-off value of 0.84 mum was defined to discriminate between translocation positive and negative nuclei based on the shortest distance between signals. Using this value, the false positive rate of the automated analysis for negative samples was 7.0%, whereas that of the manual analysis was 5.8%. Automated and manual results showed strong correlation (R(2) = 0.985), the mean difference of results was only 3.7%. CONCLUSIONS: A reliable and objective automated analysis of large numbers of cells is possible, avoiding interobserver variability and producing statistically more accurate results than manual evaluation.