Biomedical subjects

J Lay

Publications and source records attributed to J Lay.

12 recordsLinked to original sources

PubMed2006

Differential expression of mitochondrial and extramitochondrial proteins in lymphocytes of male broilers with low and high feed efficiency.

Studies were conducted to investigate relationships between mitochondrial and extramitochondrial protein expression, and protein oxidation in lymphocytes obtained from broilers in which individual feed efficiencies were obtained. Lymphocytes were isolated from male broilers from a single line that were shown to exhibit either low (0.48 +/- 0.02, n = 8) or high (0.68 +/- 0.01, n = 7) feed efficiency (FE). Western blot analysis showed that, compared with lymphocytes from high FE broilers, lymphocytes from low FE broilers exhibited a) higher amounts of oxidized proteins (protein carbonyls), b) lower amounts of 3 mitochondrial proteins [core I, cyt c 1 (complex III), and ATP synthase (complex V)], and c) higher amounts of 2 proteins [30 S (complex II) and COX II (complex IV)]. Two-dimensional gel electrophoresis revealed that the intensities of 25 protein spots from pooled samples of lymphocytes from high and low FE broilers differed by 5-fold or more. Three of these protein spots were picked from the gel and subjected to matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry analysis. One protein spot of ~33 kDa was tentatively identified by MALDI-TOF as a fragment of collapsin-2, a component of semaphorin 3D. The results of this study provide further evidence of increased oxidation associated with low FE and further evidence of differential protein expression associated with the phenotypic expression of feed efficiency.

Animal Feed↗

PubMed2005

Contamination of the alluvial plain, feeding-stuffs and foodstuffs with polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (DL-PCBs) and mercury from the River Elbe in the light of the flood event in August 2002.

Meadow soils, feeding-stuffs and foodstuffs from the alluvial plain of the river Elbe were analyzed in respect of PCDD/Fs, DL-PCBs and mercury with a view to assessing the consequences of the extreme flood of August 2002. The PCDD/F concentrations in the soils range from 3 to 2100 ng WHO-TEQ/kg dm, and for the DL-PCBs the range was 0.32 to 28 ng WHO-TEQ/kg dm. On the basis of established threshold values >40% of the areas are only fit for restricted usage. Mercury concentrations range from 0.11 to 17 mg/kg dm, whereby the action value of 2 mg/kg dm is exceeded in about 50% of the soil samples. A cumulative memory effect from past floods rather than a recent contamination from August 2002 is documented. Soils taken from behind broken dykes showed significantly lower concentrations. Grass, hay and grass silage originating from pasture land in Lower Saxony were taken before and immediately after the flooding. PCDD/Fs range from 0.29 to 16 ng WHO-TEQ/kg, the maximum permitted value of 0.75 ng WHO-TEQ/kg was exceeded in about 50% of the samples. Muscle-tissue from cattle, sheep, lamb and a roe deer as well as untreated milk from individual cows returned values ranging from 0.76 to 5.9 pg WHO-PCDD/F-TEQ/g fat, and 10% of the samples returned values higher than the permitted maximum of 3 pg WHO-PCDD/F-TEQ/g fat. The action value of 2 pg WHO-PCDD/F-TEQ/g fat was exceeded in 33% of the samples. No direct connection between these results and the effects of the flood could be established. A major input path for PCDD/Fs is the tributary Mulde, which discharges contaminated sediments from its catchment area into the Elbe.

Animal Feed↗

PubMed1998

Altered expression of selectable marker URA3 in gene-disrupted Candida albicans strains complicates interpretation of virulence studies.

The ura-blaster technique for the disruption of Candida albicans genes has been employed in a number of studies to identify possible genes encoding virulence factors of this fungal pathogen. In this study, the URA3-encoded orotidine 5'-monophosphate (OMP) decarboxylase enzyme activities of C. albicans strains with ura-blaster-mediated genetic disruptions were measured. All strains harboring genetic lesions via the ura-blaster construct showed reduced OMP decarboxylase activities compared to that of the wild type when assayed. The activity levels in different gene disruptions varied, suggesting a positional effect on the level of gene expression. Because the URA3 gene of C. albicans has previously been identified as a virulence factor for this microorganism, our results suggest that decreased virulence observed in strains constructed with the ura-blaster cassette cannot accurately be attributed, in all cases, to the targeted genetic disruption. Although revised methods for validating a URA3-disrupted gene as a target for antifungal drug development could be devised, it is clearly desirable to replace URA3 with a different selectable marker that does not influence virulence.

Animals↗

PubMed1994

Identification of a novel, N7-deoxyguanosine adduct as the major DNA adduct formed by a non-bay-region diol epoxide of benzo[a]pyrene with low mutagenic potential.

A metabolite of benzo[a]pyrene, 9-r,10-t-dihydroxy-7,8-c-oxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE-III), that is not thought to be involved in carcinogenesis has nevertheless been shown to bind extensively to DNA in vitro. The adducts formed by this non-bay-region diol epoxide in Chinese hamster ovary cells are much less mutagenic than those formed by an isomeric diol epoxide that is carcinogenic. We have isolated and characterized three major adducts formed by in vitro reaction of BPDE-III with DNA. The major adduct, accounting for over half of the total is formed by reaction of BPDE-III with the N7 position of dGuo and is recovered after enzymatic digestion as an N7-Gua adduct. A second major adduct involves the N2 position of dGuo, while the third adduct is tentatively identified as a C8-substituted dGuo. Little or no reaction with deoxyadenosine residues is detected. The N7 adduct is unstable in DNA at 37 degrees C and is released as the modified base with a half-life of about 24 h. This adduct lability apparently leads to single-strand breaks and alkali-sensitive sites in the DNA and may account in part for some of the biological properties of BPDE-III adducts. This represents the first description of an N7-dGuo adduct that is formed in DNA as the major adduct by a diol epoxide derived from a carcinogenic polycyclic aromatic hydrocarbon.

Animals↗

PubMed1994

Serum albumin and CA125 are powerful predictors of survival in epithelial ovarian cancer.

OBJECTIVE: To assess the prognostic significance of presentation serum albumin, clinical stage and CA125 levels in ovarian cancer. DESIGN: Retrospective analysis of data using a Cox proportional hazards model. SETTING: A district general hospital oncology unit. SUBJECTS: One hundred and fourteen consecutive patients with epithelial ovarian cancer. INTERVENTIONS: Cytotoxic chemotherapy and surgery. MAIN OUTCOME MEASURE: Survival. RESULTS: A linear increase in risk was observed with high log CA125 (P < 0.0001) and with low albumin (P < 0.0001). In late stage patients (III and IV) albumin is the best predictor of survival (P = 0.0006). The presence of ascites, blood transfusion, type of surgery or chemotherapy did not improve the predictive model. CONCLUSIONS: CA125 and albumin can be used to identify prognostic subgroups independently of stage. Albumin alone can also be used as a predictor of survival. A simple classification of patients into three groups based on serum albumin of 41 g/l or more, 35 to 40 g/l and 34 g/l or less provides a clear separation of survival curves in the present group of patients.

Adult↗

PubMed1987

The binding of an aminoazo dye carcinogen to a specific methionine residue in rat liver alcohol dehydrogenase in vivo.

On the administration of 3'-methyl-N,N-dimethyl-4-aminoazobenzene to rats pure aminoazo dye-bound alcohol dehydrogenase accounting for 45% of the total soluble protein bound aminoazo dye is isolated from the liver soluble supernatant. Tryptic digestion of that purified aminoazo dye-bound enzyme yields an aminoazo dye-bound nonapeptide which has a sequence identical to amino acids 301-309 in the known sequence of alcohol dehydrogenase (H. Jornvall and O. Markovic, Eur. J. Biochem., 29 (1972) 167-174) with the exception of methionine 306 which is replaced by an aminoazo dye modified amino acid. The nature of the aminoazo dye adduct was determined by studying the structure of the related tetrapeptide obtained by Pronase B digestion and shown by proton NMR spectroscopy and fast atom bombardment mass spectroscopy to have the structure 3-(Val. Asn. Pro. Homocystein-S-yl)-4-methylamino-3'-methylazobenzene. This carcinogen-protein adduct is assumed to arise from attack of the ultimate carcinogenic metabolite, N-sulphonyloxy-4-methylamino-3'-methylazobenzene (FF. Kadlubar, J.A. Miller and E.C. Miller, Cancer Res., 36 (1976) 2350-2359) at the sulphur of methionine 306 followed by spontaneous S-demethylation. This highly specific reaction of carcinogen with alcohol dehydrogenase lowers its Vmax and increases its Km with cyclohexanone thereby reducing its catalytic efficiency for this substrate. This highly specific reaction of the carcinogen with alcohol dehydrogenase may be regarded as a major detoxication reaction.

Alcohol Dehydrogenase↗

PubMed1983