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Biomedical subjects

M Payton

Publications and source records attributed to M Payton.

At least 19 recordsLinked to original sources
PubMed2005

Maternally and naturally acquired antibodies to Mannheimia haemolytica and Pasteurella multocida in beef calves.

The dynamics and duration of maternally derived antibodies as well as the onset of acquired immunity against Mannheimia haemolytica and Pasteurella multocida in range-pastured beef calves were investigated. Two groups of unvaccinated cattle were used in this study. Serum antibody responses were measured by enzyme-linked immunoassay for antibodies of the IgG1, IgG2 and IgM isotypes binding M. haemolytica whole cells (WC) or leukotoxin (LKT) and P. multocida outer membrane proteins (OMPs). Comparisons of mean antibody responses to M. haemolytica LKT and WC and P. multocida OMPs were made within each group. Maternally derived antibodies against M. haemolytica and P. multocida reached lowest levels at 30-90 days after birth. Calves began production of antibodies against M. haemolytica and P. multocida between 60 and 90 days of age in both groups. Based on the results of this study, in beef herds vaccinated against M. haemolytica and/or P. multocida, it may be best to vaccinate calves around 3 months of age. In contrast, beef calves from unvaccinated herds might benefit from vaccination at 4 months of age.

Animals↗
PubMed2005

Economic evaluation of the effects of planting date and application rate of imidacloprid for management of cereal aphids and barley yellow dwarf in winter wheat.

The effects of planting date and application rate of imidacloprid for control of Schizaphis graminum Rondani, Rhopalosiphum padi L. (Homoptera: Aphididae), and barley yellow dwarf virus (BYDV) in hard red winter wheat were studied. The first experiment was conducted from 1997 to 1999 at two locations and consisted of three planting dates and four rates of imidacloprid-treated seed. The second experiment was conducted from 2001 to 2002 in Stillwater, OK, and consisted of two varieties of hard red winter wheat seed and four rates of imidacloprid. Aphid densities, occurrence of BYDV, yield components, and final grain yield were measured, and yield differences were used to estimate the economic return obtained from using imidacloprid. In the first study, aphid populations responded to insecticide rate in the early and middle plantings, but the response was reduced in the late planting. Yields increased as insecticide rate increased but did not always result in a positive economic return. In the second study, imidacloprid seed treatments reduced aphid numbers and BYD occurrence, protected yield, and resulted in a positive economic return. The presence of aphids and BYDV lowered yield by reducing fertile head density, total kernel weight, and test weight. Whereas the application of imidacloprid seed treatments often provided positive yield protection, it did not did not consistently provide a positive economic return. A positive economic return was consistently obtained if the cereal aphid was carrying and transmitting BYDV and was more likely to occur if wheat was treated with a low rate if imidacloprid and planted in a "dual purpose" planting date window.

Agriculture↗
PubMed2003

Generation and analysis of mice with a targeted disruption of the arylamine N-acetyltransferase type 2 gene.

Arylamine N-acetyltransferases (NATs) are polymorphic xenobiotic metabolising enzymes, linked to cancer susceptibility in a variety of tissues. In humans and in mice there are multiple NAT isoforms. To identify whether the different isoforms represent inbuilt redundancy or whether they have unique roles, we have generated mice with a null allele of Nat2 by gene targeting. This mouse line conclusively demonstrates that the different isoforms have distinct functions with no compensatory expression in the Nat2 null animals of the other isoforms. In addition, we have used the transgenic line to show the pattern of Nat2 expression during development. Although Nat2 is not essential for embryonic development, it has a widespread tissue distribution from at least embryonic day 9.5. This mouse line now paves the way for the teratological role of Nat2 to be tested.

Amino Acid Transport System A↗
PubMed2001

Evidence towards the role of arylamine N-acetyltransferase in Mycobacterium smegmatis and development of a specific antiserum against the homologous enzyme of Mycobacterium tuberculosis.

Arylamine N-acetyltransferase (NAT) in humans inactivates the anti-tubercular drug isoniazid (INH). Homologues of human NAT are present in Mycobacterium tuberculosis and Mycobacterium smegmatis, where they can acetylate, and hence inactivate, INH. The in vivo role of mycobacterial NAT is not known but heterologous expression of the M. tuberculosis gene increases the INH resistance. The 0.85 kb nat gene is part of a gene cluster in M. smegmatis. The gene is transcribed as a large, 7.5 kb mRNA as demonstrated by Northern analysis. A nat knockout strain of M. smegmatis was generated by targeted disruption. The new strain was confirmed to be devoid of NAT activity. The growth of the knockout strain is considerably delayed compared with the wild-type, due to an extended lag phase. The knockout mutant has an increased sensitivity to INH as would be predicted. The NATs from M. smegmatis and M. tuberculosis have a high degree of homology, except in the region of the C terminus. A specific polyclonal antiserum raised against recombinant NAT protein from M. tuberculosis is described that recognizes a stretch of about twenty residues within the C terminus of M. tuberculosis NAT. This highly specific antiserum will enable comparison of nat expression between isolates of M. tuberculosis.

Acebutolol↗
PubMed2000

An update on genetic, structural and functional studies of arylamine N-acetyltransferases in eucaryotes and procaryotes.

Arylamine N:-acetyltransferase (NAT) was first identified as the inactivator of the anti-tubercular drug isoniazid. The enzyme was shown to catalyse the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of the hydrazine drug. The rate of inactivation of isoniazid was polymorphically distributed in the population and was one of the first examples of pharmacogenetic variation. NAT was identified recently in Mycobacterium tuberculosis and is a candidate for modulating the response to isoniazid. Genome sequences have revealed many homologous members of this unique family of enzymes. The first three-dimensional structure of a member of the NAT family identifies a catalytic triad consisting of aspartate, histidine and cysteine proposed to form the activation mechanism. So far, all procaryotic NATs resemble the human enzyme which acetylates isoniazid (NAT2). Human NAT2 is characteristic of drug-metabolizing enzymes: it is found in liver and intestine. In humans and other mammals, there are up to three different isoenzymes. If only one isoenzyme is present, it is like human NAT1. Human NAT1 and its murine equivalent specifically acetylate the folate catabolite p-aminobenzoylglutamate. NAT1 and its murine homologue each have a ubiquitous tissue distribution and are expressed early in development at the blastocyst stage. During murine embryonic development, NAT is expressed in the developing neural tube. The proposed endogenous role of NAT in folate metabolism, and its multi-allelic nature, indicate that its role in development should be assessed further.

Animals↗
PubMed2000

Chromosome mapping of the genes for murine arylamine N-acetyltransferases (NATs), enzymes involved in the metabolism of carcinogens: identification of a novel upstream noncoding exon for murine Nat2.

Arylamine N-acetyltransferases (NATs) catalyse acetylation reactions which can result in either detoxification or activation of arylamine carcinogens. The human NAT loci (NAT1, NAT2, and a pseudogene, NATP) have been mapped to human chromosome 8p22, a region frequently deleted in tumours. There are three functional genes in mice (Nat1, Nat2, and Nat3) encoding for three NAT isoenzymes. Different alleles at the Nat2 locus are responsible for the acetylation polymorphism identified in different mouse strains. We show that Nat3 is close to Nat1 and Nat2, by screening of a P1 artificial chromosome (PAC) library and provide cytogenetic evidence for co-localisation of the three genes in chromosome region 8 B3.1-B3.3. The Nat region of mouse and human is homologous. We also provide sequence information and a restriction map in the vicinity of Nat1 and Nat2 and describe a noncoding exon located 6 kb upstream of the Nat2 coding region.

5' Untranslated Regions↗
PubMed1999

A rapid novel method for the extraction of RNA from wild-type and genetically modified kanamycin resistant mycobacteria.

RNA extraction from mycobacteria can be a difficult and time consuming process due to their unique mycolic acid cell wall composition and the short half life of RNA. Rapid cell wall disruption is essential to isolate intact high quality RNA. Genetically modified Mycobacteria smegmatis resistant to kanamycin demonstrate an altered cell wall composition which impairs the quality of RNA obtained from these mycobacteria. In this report we describe a method of RNA extraction using the detergent Catrimox-14 resulting in high yields of pure, undegraded RNA in less than 1 h. Yields of 25-30 microg RNA per 1x10(9) cells were consistently obtained from both wild-type and genetically modified M. smegmatis. The integrity of this RNA is demonstrated by gel electrophoresis, Northern blot and cDNA analysis.

Blotting, Northern↗
PubMed1999

A method for genotyping murine arylamine N-acetyltransferase type 2 (NAT2): a gene expressed in preimplantation embryonic stem cells encoding an enzyme acetylating the folate catabolite p-aminobenzoylglutamate.

Mice have three arylamine N-acetyltransferase (NAT) isoenzymes (NAT1, NAT2, and NAT3) of which NAT2 is known to be polymorphic. Humans have two polymorphic isoenzymes, NAT1 and NAT2. The isoenzymes mouse NAT1 and human NAT2 are expressed predominantly in the liver and intestine and are involved in drug and xenobiotic metabolism. Mouse NAT2 and human NAT1 have a widespread tissue distribution and the folate catabolite p-aminobenzoylglutamate (pAB-Glu) has been proposed as a candidate endogenous substrate. All mice have detectable NAT2 activity, although inbred mouse strains have either a fast or slow acetylator phenotype conferred by the presence of either NAT2*8 (fast) or NAT2*9 (slow) alleles at the NAT2 locus. In this report, we describe a simple method for distinguishing these murine alleles by polymerase chain reaction followed by restriction fragment length polymorphism analysis. We compared the tissue distribution of the acetylation activity found in both fast (C57BL/6J) and slow (A/J) acetylating strains of mice using pAB-Glu and p-aminobenzoic acid as probe substrates. It has previously been demonstrated that murine NAT2 is expressed in the neural tube prior to closure (Stanley L, Copp A, Rolls S, Smelt V, Perry VH and Sim E, Teratology 58: 174-182, 1998). We demonstrate here that murine NAT2 is expressed in preimplantation embryonic stem cells. Murine NAT2 is likely to be expressed prior to neurulation and this may be important in view of the protective role of folate in neural tube development.

4-Aminobenzoic Acid↗
PubMed1999

Arylamine N-acetyltransferase type 2 (NAT2), chromosome 8 aneuploidy, and identification of a novel NAT1 cosmid clone: an investigation in bladder cancer by interphase FISH.

Two genes (arylamine N-acetyltransferase types 1 and 2, NAT1 and NAT2), which are known to metabolize bladder carcinogens, are located on chromosome band 8p22. Alterations in chromosome 8, including deletions of 8p, occur frequently in many epithelium-derived tumors. In this study, fluorescence in situ hybridization (FISH) was used for study of the relationship between chromosome 8 deletions in the region of NAT1 and NAT2 and grade and stage of tumor in bladder cancer. Cells from 52 bladder tumors were examined by dual-labeling FISH with a centromere 8-specific probe and a cosmid probe for NAT2. A more limited number were examined for loss with both the NAT2 probe and a newly constructed NAT1-specific cosmid. Loss of NAT2 was found in 6/52 patients in more than 30% of cells, and in 10/52 in 10%-30% of cells examined. Six samples also showed loss of NAT1, indicating that the region of deletion spans at least the distance of the two genes. No obvious correlation between loss of NAT genes with grade and stage of tumor was evident. Interestingly, 17/52 (32%) tumors showed an increased copy number of chromosome 8, with tumors of low stage showing relatively smaller increases of chromosome 8. Loss of 8p22 and genetic instability involving chromosome 8 indicate that this chromosome is important in bladder cancer and that NAT genes will act as important genetic landmarks in defining deletions in this disease. Genes Chromosomes Cancer 25:376-383, 1999.

Acetyltransferases↗
PubMed1999

Cloning and characterization of arylamine N-acetyltransferase genes from Mycobacterium smegmatis and Mycobacterium tuberculosis: increased expression results in isoniazid resistance.

Arylamine N-acetyltransferases (NATs) are found in many eukaryotic organisms, including humans, and have previously been identified in the prokaryote Salmonella typhimurium. NATs from many sources acetylate the antitubercular drug isoniazid and so inactivate it. nat genes were cloned from Mycobacterium smegmatis and Mycobacterium tuberculosis, and expressed in Escherichia coli and M. smegmatis. The induced M. smegmatis NAT catalyzes the acetylation of isoniazid. A monospecific antiserum raised against pure NAT from S. typhimurium recognizes NAT from M. smegmatis and cross-reacts with recombinant NAT from M. tuberculosis. Overexpression of mycobacterial nat genes in E. coli results in predominantly insoluble recombinant protein; however, with M. smegmatis as the host using the vector pACE-1, NAT proteins from M. tuberculosis and M. smegmatis are soluble. M. smegmatis transformants induced to express the M. tuberculosis nat gene in culture demonstrated a threefold higher resistance to isoniazid. We propose that NAT in mycobacteria could have a role in acetylating, and hence inactivating, isoniazid.

Amino Acid Sequence↗
PubMed1999

Cyclin E2, a novel G1 cyclin that binds Cdk2 and is aberrantly expressed in human cancers.

A novel cyclin gene was discovered by searching an expressed sequence tag database with a cyclin box profile. The human cyclin E2 gene encodes a 404-amino-acid protein that is most closely related to cyclin E. Cyclin E2 associates with Cdk2 in a functional kinase complex that is inhibited by both p27(Kip1) and p21(Cip1). The catalytic activity associated with cyclin E2 complexes is cell cycle regulated and peaks at the G1/S transition. Overexpression of cyclin E2 in mammalian cells accelerates G1, demonstrating that cyclin E2 may be rate limiting for G1 progression. Unlike cyclin E1, which is expressed in most proliferating normal and tumor cells, cyclin E2 levels were low to undetectable in nontransformed cells and increased significantly in tumor-derived cells. The discovery of a novel second cyclin E family member suggests that multiple unique cyclin E-CDK complexes regulate cell cycle progression.

Amino Acid Sequence↗
PubMed1999

N-acetylation of the heterocyclic amine batracylin by human liver.

Batracylin (8-aminoisoindolo[1,2-b]quinazolin-12(10 H)-one; BAT) is a heterocyclic amine that exhibits antitumor activity in a number of in vivo and in vitro models. The acetyl product has been implicated in BAT toxicity in animals, cells, and bacteria. The ability of human N-acetyltransferase (NAT) to form this product was investigated. Nine human liver samples were analyzed for NAT1 and NAT2 genotypes. Seven of the samples possessed at least one NAT1*4 allele. Three samples contained one or more NAT2*4 allele and were classified as rapid acetylators. The remaining six had two alleles associated with the slow phenotype. NAT activities were evaluated with BAT, sulfamethazine (SMZ), a preferential substrate for human NAT2, and p-aminobenzoic acid, a substrate for NAT1. BAT activities in the nine donor samples ranged from 14.9 to 0.56 nmol/min/mg. The mean apparent K(m) values in rapid acetylators for BAT, SMZ, and p-aminobenzoic acid were 6.59 +/- 3.21, 278 +/- 69.4, and 31.2 +/- 12.5 microM, respectively. The apparent K(m) values for slow acetylators did not differ from the rapid acetylator phenotype. However, a significant difference in the apparent V(max) for BAT and SMZ was observed between rapid and slow acetylators. Comparing the apparent intrinsic clearance (V(max)/K(m)) for BAT and SMZ, a significant correlation (r(2) = 0.97, p <.001) was observed. These data demonstrate that BAT N-acetylation is similar to SMZ, and suggests that BAT is a preferential substrate for human NAT2. Thus, rapid acetylators would be more likely to develop toxicity when exposed to this drug.

4-Aminobenzoic Acid↗
PubMed1998

Expression of arylamine N-acetyltransferase in human intestine.

BACKGROUND: Arylamine N-acetyltransferases in humans (NAT1 and NAT2) catalyse the acetylation of arylamines including food derived heterocyclic arylamine carcinogens. Other substrates include the sulphonamide 5-aminosalicylic acid (5-ASA), which is an NAT1 specific substrate; N-acetylation of 5-ASA is a major route of metabolism. NAT1 and NAT2 are both polymorphic. AIMS: To investigate NAT expression in apparently healthy human intestines in order to understand the possible role of NAT in colorectal cancer and in the therapeutic response to 5-ASA. METHODS: The intestines of four organ donors were divided into eight sections. DNA was prepared for genotyping NAT1 and NAT2 and enzymic activities of NAT1 and NAT2 were determined in cytosols prepared from each section. Tissue was fixed for immunohistochemistry with specific NAT antibodies. Western blotting was carried out on all samples of cytosol and on homogenates of separated muscle and villi after microdissection. RESULTS: NAT1 activity of all cytosols was greater than NAT2 activity. NAT1 and NAT2 activities correlated with the genotypes of NAT1 and NAT2 and with the levels of NAT1 staining determined by western blotting. The ratio of NAT1:NAT2 activities showed interindividual variations from 2 to 70. NAT1 antigenic activity was greater in villi than in muscle. NAT1 was detected along the length of the villi in the small intestine. In colon samples there was less NAT1 at the base of the crypts with intense staining at the tips. CONCLUSIONS: The interindividual variation in NAT1 and NAT2 in the colon could affect how individuals respond to exposure to specific NAT substrates including carcinogens and 5-ASA.

Arylamine N-Acetyltransferase↗
PubMed1998

Height, weight, and body fat: assessments of covariation based on visual information or reported correlations.

College students' intuitive judgments about covariations between height, weight, and body fat were assessed in three experiments using responses to a series of propositional statements as the dependent variable. In Exp. 1, judgments were rendered without explicit exposure to a prior database. In Exps. 2 and 3, however, databases were studied prior to these judgments. Remarkable consistencies in judgments of weight and body fat, height and weight as well as of height and body fat were obtained across experiments. At best, there was little evidence that the databases influenced the judged covariations among these variables. Whereas judgments about weight and body fat were unambiguous and consistent with the actual positive correlation between weight and body fat, judgments about height and weight as well as height and body fat were less clearcut. What was clear, however, was that these judgments were highly similar. Implications of these findings from previous research that suggest that presence of a perceived negative correlation between height and body fat are discussed.

Adipose Tissue↗
PubMed1997

Antibodies to the tyrosine phosphatase-like protein IA-2 are highly associated with IDDM, but not with autoimmune endocrine diseases or stiff man syndrome.

Antibodies to the 40 kD antigen (identified as tyrosine phosphatase IA-2) and glutamate decarboxylase (GAD65) are strongly associated with insulin dependent diabetes mellitus (IDDM). However, antibodies to GAD (GADA) can appear in the absence of IDDM, particularly in stiff man syndrome (SMS) and in some individuals with autoimmune polyendocrine syndrome type II (APS II) and organ specific autoimmune diseases. The aim of this study was to compare the specificity of IA-2 antibodies (IA-2A) and GADA for IDDM by determining their frequency in different patient groups. IA-2A were present in 64/114 (56%) IDDM patients and 9/19 (47%) APS II patients with IDDM but in only 4/28 (14%) SMS patients. 1/24 (4%) APS II patients without IDDM and 1/113 (0.9%) patients with organ specific autoimmune disease had low level IA-2A. In contrast GADA were present in 77/114 (68%) IDDM patients and 17/19 (89%) APS II patients with IDDM, but also in 25/28 (89%) SMS patients, 5/24 (21%) APS II patients without IDDM and 22/113 (19%) patients with organ specific autoimmune diseases. Furthermore, within the group of new onset IDDM, IA-2A seemed to be associated with ICA and age: 63% of ICA positive IDDM patients had IA-2A (74% had GADA) increasing to 77% in the group below 20 years of age (69% for GADA). Our results demonstrate that IA-2A may be more specific for IDDM than GADA, as the latter are also present in patients with SMS, APS II without IDDM and organ specific autoimmune diseases. IA-2A were less frequent in older patients with IDDM than GADA or ICA. A combination of IA-2A and GADA detected 84% of total and 93% of ICA positive IDDM patients.

Adolescent↗
PubMed1996

Determinants of bone and blood lead levels among community-exposed middle-aged to elderly men. The normative aging study.

Levels of lead in bone serve as a dosimeter for cumulative exposure to lead; moreover, lead in bone may serve as an internal source of circulating lead many years after environmental exposure has ceased. The authors measured lead in blood and used a K-x-ray fluorescence instrument to measure lead in the tibia (cortical) and patella (trabecular) bones in a cross-sectional survey of 719 middle-aged to elderly male participants in the Normative Aging Study who were without unusual occupational exposures to lead and who were healthy when enrolled in 1962-1965. Blood lead levels ranged from < 1 to 27.9 micrograms/dl, with a geometric mean of 5.7 micrograms/dl. Tibia and patella lead level ranges (geometric means) were < 1-51 (20.8) micrograms/g and 3-77 (29.8) micrograms/g, respectively. In backwards elimination multivariate regression models that considered age, race, education, retirement status, measures of both current and cumulative smoking, and alcohol consumption, the factors that remained significantly related to higher levels of both tibia and patella lead were higher age and measures of cumulative smoking, and lower levels of education. In the final model predicting blood lead that began with these same covariates and also included tibia and patella lead, the factor that accounted for the dominant portion of the variance in blood lead was patella lead. After adjustment for measurement error, a rise in patella lead from the median of the lowest to the median of the highest quintiles (13-56 micrograms/g) corresponded to a rise in blood lead of 4.3 micrograms/dl. The authors conclude that bone lead levels are substantial and comprise the major source of circulating lead in these men.

Adult↗
PubMed1996

The relationship of bone and blood lead to hypertension. The Normative Aging Study.

OBJECTIVE: To test the hypothesis that long-term lead accumulation, as reflected by levels of lead in bone (as opposed to blood which reflects recent lead exposure), is associated with an increased odds of developing hypertension. DESIGN: Case-control study of participants in the Veterans Administration (now Department of Veterans Affairs) Normative Aging Study, a 30-year longitudinal study of men. PARTICIPANTS: Of 1171 active subjects who were seen between August 1991 and December 1994, 590 (50%) participated in this investigation and had data on all variables of interest. MAIN OUTCOME MEASURES: Hypertension was defined as taking daily medication for the treatment of hypertension or systolic blood pressure higher than 160 mm Hg or diastolic blood pressure of 96 mm Hg or higher during the time of examination. Levels of lead in the tibia (representing cortical bone) and the patella (representing trabecular bone) were measured in vivo with a K x-ray fluorescence (KXRF) instrument. Levels of lead in blood were measured by graphite furnace atomic absorption spectroscopy. RESULTS: Blood lead levels were low, ranging from less than 0.05 to 1.35 micromol/L (<1 to 28 microgram/dL), with a mean (SD) of 0.30 (0.20) micromol/L (6.3[4.1] microgram/dL). Bone lead levels were similar to those described in other general populations. In comparison to nonhypertensives, mean levels of lead in blood and both tibia and patella bone lead levels were significantly higher in hypertensive subjects. In a logistic regression model of hypertensive status that began with age, race, body mass index, family history of hypertension, history of ethanol ingestion, pack-years of smoking, dietary sodium intake, dietary calcium intake, blood lead, tibia lead, and patella lead, the variables that remained after backward elimination were body mass index, family history of hypertension, and level of lead in the tibia. An increase from the midpoint of the lowest quintile to the midpoint of the highest quintile of tibia lead from 3 to 37 micrograms per gram of bone mineral was associated with an increased odds ratio of hypertension of 1.5. CONCLUSION: Our findings suggest that long-term lead accumulation, as reflected by levels of lead in bone, may be an independent risk factor for developing hypertension in men in the general population.

Age Factors↗