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PubMed1998

Adaptive conjoint analysis to determine perceived risk factors of farmers, veterinarians and AI technicians for introduction of BHV1 to dairy farms.

A study was carried out to determine the possibility of a more-closed farming system for (Dutch) dairy farms. The objective of the study was to provide effective and economically profitable management advice for improving the animal-health status of farms. Management measures will only be successfully applied if supported by farmers and their advisors (such as veterinarians). Therefore, the perception of farmers and advisors of the importance of various risk factors for the introduction of diseases to a farm was determined by using bovine herpes virus type 1 (BHV1) as an example. As part of the study, an evening-long workshop was organized and run thrice. In total, 49 farmers, veterinarians and AI technicians participated in these workshops. The computerized questionnaire technique was based on adaptive conjoint analysis (ACA). ACA has the advantage that participants can work with a large number of risk factors in a relatively short period of time. Another advantage of ACA (compared with standard questionnaires) is that the answers from each participant can be checked with regard to consistency with respect to the importance assigned to them. Data from participants with inconsistent responses can be excluded from further analyses. The results of the ACA interview were compared with the risk factors reported in the literature as being associated with BHV1 status (e.g. purchase of cattle, participation in cattle shows) and with farmers' actual management to prevent the introduction of diseases. The workshop participants were all operating in the dairy sector and they seemed well aware of the risk of direct animal contacts for the introduction of BHV1. Farmers thought visitors to be more risky than did AI technicians and (especially) veterinarians. Farmers who purchased cattle or participated in cattle shows were of the opinion that the risks of direct animal contacts were more important than did farmers who were not involved in those practices. Farmers whose farms were BHV1-positive (and participated in cattle shows more often) thought the risk of participation smaller than did farmers with BHV1-negative farms.

Animal Husbandry↗

PubMed1996

Structural and functional properties of full-length and truncated human proapolipoprotein AI expressed in escherichia coli.

Utilizing the Escherichia coli/pGex vector expression system incorporating a thrombin cleavage site, full-length (residues -6-243) and truncated forms of proapolipoprotein AI (proapoAI), terminating at amino acid residues 222, 210, 150, and 135, were purified to levels of at least 5 mg/L, after thrombin cleavage. Assessed by circular dichroism, the helical contents of L-alpha-dimyristoylphosphatidylcholine-associated forms of human plasma-derived apolipoprotein AI (apoAI) and recombinant proapoAI were comparable, being 69% and 65%, respectively. Circular dichroism measurements of the lipid-associated complexes of the truncated forms showed that between the sequence of residues 150-222 no additional helicity was gained until the carboxyl-terminal sequence was present in the molecule, indicating that the carboxyl terminus of the protein is required for the formation of helix within this central region. While tryptophan residues were more than 86% accessible, as assessed by iodide quenching, in the two truncated forms, proapoAI-6-135 and proapoAI-6-150, for both free and complexed protein, this figure fell to about 50% for full-length recombinant proapoAI, further indicating the influence of the carboxyl terminus on the structure of the whole protein. While cross-linking human plasma apoAI in solution with dithiobis-(succinimidyl propionate) revealed high molecular weight oligomers by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, recombinant proapoAI did not strongly form complexes larger than trimers. None of the truncated proapoAI molecules formed oligomers larger than trimers. The shortest form, proapoAI-6-135, only dimerized. Initial results from lecithin:cholesterol acyltransferase activation (apoAI peptide concentration 0.2 microM) indicated that truncation of the 21 carboxy-terminal amino acids resulted in a drop of approximately 53% in activation and 33 residues a drop of 67% relative to the full-length protein. Overall these results indicate the important influence of the carboxyl terminus on the structure of apoAI.

Apolipoprotein A-I↗

PubMed2001

Stereoselective synthesis of pseudopeptide microbial agent AI-77-B.

[structure: see text]. An efficient and highly stereoselective synthesis of the gastroprotective natural product AI-77-B is described. The stereocenters of the hydroxy amino acid moiety were generated by an ester-derived titanium-enolate-mediated syn-aldol reaction, a Curtius rearrangement, and application of Dondoni's aldehyde homologation. Condensation with the dihydroisocoumarin fragment and subsequent deprotecting transformations furnished optically active AI-77-B.

Anti-Bacterial Agents↗

PubMed2004

Boron binding with the quorum sensing signal AI-2 and analogues.

[reaction: see text] The unstable bacterial metabolic product, DPD, and the related natural product, laurencione, are shown to have a high affinity for borate complexation, through the hydrated analogue. The boron complex of DPD is Vibrio harveyi AI-2, an interspecies quorum sensing signal in bacteria, and an affinity column with a borate resin is effective in providing the first method for concentrating and purifying V. harveyi AI-2 from the biosynthetic product.

Boron↗

PubMed2007

Different isoforms of apolipoprotein AI present heterologous post-translational expression in HIV infected patients.

Human immunodeficiency virus (HIV) is rapidly becoming a global health concern. Proteomics technology was employed to examine HIV infected plasma samples in an attempt to identify disease-associated proteins. By comparison with normal and HIV positive plasma samples, at least eight proteins were significantly changed in HIV infected plasma. In particular, apolipoprotein AI presents a heterogeneous change in expression level with different isoforms. Apolipoprotein AI could be a useful biomarker for HIV diagnosis.

AIDS Serodiagnosis↗

PubMed2001

Apolipoproteins AI, B, and E polymorphisms in severe aortic valve stenosis.

Hypercholesterolemia has been related to aortic valve stenosis (AS). Polymorphisms of apolipoproteins (apo) AI, B, and E are associated with variable levels of plasma lipids, but the association between these polymorphisms and AS is unknown. In a case-control study of groups matched by age, sex, comparable body mass index, hypertension, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol, we analyzed the distribution of apo AI A/G mutation, apo B signal peptide insertion/deletion, apo B XbaI restriction fragment length. and apo E polymorphisms in 62 non-diabetic patients with severe aortic valve stenosis and 62 control subjects. All patients underwent echocardiographic analysis. Univariate analysis showed a higher prevalence of the XbaI X + /X + genotype (p = 0.007) of apo B and the apo E2 allele (p = 0.034) in patients with severe AS. Apo polymorphisms were not associated with lipid levels, left ventricular mass, or the aortic gradient.

Aortic Valve Stenosis↗

PubMed1991

Familial combined hyperlipidaemia linked to the apolipoprotein AI-CII-AIV gene cluster on chromosome 11q23-q24.

Familial combined hyperlipidaemia (FCHL) is a common inherited disorder of lipid metabolism with a prevalence of 0.5-2.0% (refs 1, 2). It is estimated to cause 10% of premature coronary heart disease. The underlying metabolic and genetic defects in FCHL have not been identified, but a population study has suggested an association between FCHL and an XmnI restriction fragment length polymorphism (RFLP) within the apolipoprotein AI-CIII-AIV gene cluster. Here we confirm this association and show that it results from linkage disequilibrium between FCHL and the 6.6-kilobase (kb) allele of the XmnI RFLP. Subsequent analysis in seven FCHL families, ascertained through a proband carrying the 6.6 kb XmnI allele, demonstrated linkage to the AI-CIII-AIV cluster on 11q23-q24, zeta = 6.86 with no recombinants. This assignment will facilitate the identification of the mutation that causes hyperlipidaemia in these families.

Apolipoprotein A-I↗

PubMed2001

Two newly identified SNPs in the APO AI-CIII intergenic region are strongly associated with familial combined hyperlipidaemia.

BACKGROUND: We previously reported linkage and association of the apoAI-CIII-AIV gene region on chromosome 11 with familial combined hyperlipidaemia (FCHL). However, the observed epistasis resulting in an increased susceptibility to FCHL still remains unexplained. We hypothesize that the region between the apo AI and apo CIII genes may harbour functional mutations that might be in linkage disequilibrium with the already identified SstI and MspI polymorphisms, and provide an alternative explanation for the observed relationship. METHODS: Using sequence analysis, we identified four new single nucleotide polymorphisms (SNPs) in the apo AI-CIII intergenic region. These four variants, T(3213)C, A(3235)C, T(3287)C and A(5132)C, were studied in 30 FCHL probands, 159 hyperlipidaemic relatives, 327 normolipidaemic relatives, and 218 spouses from the same families in which the original results were obtained. RESULTS: The allele frequencies were significantly different between probands and spouses (P < 0.05). Transmission/disequilibrium test (TDT) analyses revealed more frequent transmission of the minor alleles to the affected offspring. The minor genotype was associated with elevated plasma cholesterol and triglyceride levels. The T(3213)C and MspI, and the A(3235)C and SstI SNPs were in complete linkage disequilibrium, resulting in two different major haplotypes 2-2-1-2-2-1 and 1-1-2-2-2-2 (MspI-T(3213)C-A(3235)C-T(3287)C-A(5132)C-SstI). Both haplotypes appear to predispose to FCHL independently, and account, together with the wild-type, for almost 90% of those occurring in these FCHL families, extending the high-risk combination of haplotypes that were reported previously. CONCLUSION: These newly identified additional intergenic SNPs therefore provide an alternative explanation for the observed association of the SstI and MspI polymorphisms to the increased susceptibility for FCHL.

Adult↗

PubMed2005

[On the origin of the adaptative immune system (AIS): the hypothesis].

The adaptive immune system (AIS) appears exclusively at the vertebrate ones with jaw. In parallel, the lymphoid tissu associated with the digestive tract, or GALT (gut associated lymphoïd tissu), seems to play an essential part in the development of this response immune with memory. That one could find its origin in the innate immune system of the invertebrates and closer the cyclostomes (vertebrates without jaws). But the transition is brutal since the chondrychtyens (lines, sharks) do have the AIS but the cyclostomes not. Moreover, it is still enigmatic and source of speculations. The gnathostomes (vertebrate with jaw) raise ancestral and adaptive innate defences of which acquisition will be discussed here. We will also discuss the consequences of integration in the genome by rag1 and rag2 genes (recombination activating genes).

Adaptation, Physiological↗

PubMed2002

Serum testosterone associates with lower high-density lipoprotein cholesterol in black and white males, 10 to 15 years of age, through lowered apolipoprotein AI and AII concentrations.

High-density lipoprotein cholesterol (HDL-C) concentrations decrease during adolescence in males in association with increasing pubertal maturation and free testosterone (F-T). To determine whether F-T effects lower HDL-C levels by decreasing the amount of cholesterol associated with the major protein moeities associated with HDL-C (apolipoprotein [apo]AI and AII) or by decreasing the concentrations of these proteins, we studied 251 black and 285 white boys, ages 10 to 15 years. In cross-sectional analysis, advancing puberty associated with decreasing HDL-C, apoAI, and apoAII in boys of each ethnic group. The decreases were greater in white (1.49 to 1.24 mmol/L) than black boys (1.68 to 1.53 mmol/L). Backward stepwise regression analyses indicated that F-T was a significant negative predictor of all 3 lipid parameters--HDL-C, apoAI, and apoAII. Ethnic group was associated with HDL-C (blacks higher) and apoAII (whites higher), but not apoAI. The ratio of HDL-C to apo (AI+AII) varied significantly (and negatively) with body mass index (BMI; kg/m(2)), but not with pubertal stage or F-T. Thus, increased F-T appears to explain decreased HDL-C via decreased apoAI and apoAII, not decreases in the amount of cholesterol associated with these proteins.

Adolescent↗

PubMed2002

Evaluation of a new ultrasound contrast agent (AI-700) using two-dimensional and three-dimensional imaging during acute ischemia.

BACKGROUND: A new intravenous contrast agent, AI-700, was evaluated to determine whether a bolus injection could be used to detect myocardial perfusion abnormalities during acute ischemia by using 2-dimensional (2D) and 3-dimensional (3D) myocardial contrast echocardiography. METHODS: 2D MCE was performed in 14 closed-chest dogs during coronary occlusion by using both continuous and triggered gray scale harmonic imaging and triggered power Doppler imaging. 3D MCE (open-chest) and nuclear perfusion imaging were performed in 10 of the 14 dogs. Postmortem triphenyl tetrazolium chloride (TTC) staining was performed to verify infarction. RESULTS: Thirteen of the 14 dogs had infarct by TTC; all 10 that had nuclear imaging showed a perfusion defect. Of the 13 dogs that had infarction, perfusion defects were detected in all (13 of 13) by gray scale harmonic imaging (sensitivity = 100%), and in 11 of 13 by power Doppler imaging (sensitivity = 85%). All 10 dogs that had nuclear imaging showed perfusion defects by gray scale harmonic imaging (sensitivity = 100%) and 8 of 10 by power Doppler imaging (sensitivity = 80%). The perfusion defect size, derived from 3D imaging (25% +/- 12%) correlated well with that from nuclear imaging (24% +/- 12%) (y = 0.9x + 3.8, r = 0.96, mean difference = 1.3% +/- 2.6%). The perfusion defect mass by 3D (22 +/- 14 g) also correlated well with the infarct mass by TTC staining (24 +/- 16 g) (y = 0.8x + 2.9, r = 0.89, P <.001, mean difference = -2.8 +/- 7.6 g). CONCLUSION: After a single bolus of AI-700, both 2D and 3D MCE could accurately detect perfusion defects representing the area at risk of infarction during acute ischemia compared with nuclear imaging and predicted the size of infarction as verified by TTC staining.

Animals↗

PubMed1991

Methylation changes in the apolipoprotein AI gene during embryonic development of the mouse.

We report here a detailed study of developmental changes in the methylation status of specific sites in a single-copy tissue-specific gene, from the germ cell through the early embryo to adult tissues. Two sites at the 5' end of the mouse apolipoprotein AI gene were unmethylated in the ovulated unfertilized oocytes and methylated in the sperm. In contrast, a third site, located upstream of the gene, was methylated and a CpG island within the gene was unmethylated in both oocyte and sperm. The methylated sites, regardless of maternal or paternal origin, underwent demethylation in the early embryo (8-16 cells) and stayed unmethylated through the late blastocyst stage. During gastrulation, non-CpG island sites underwent methylation, followed by gradual demethylation at specific sites in tissues parallel to expression of the gene (liver and intestine). The formation of the mature tissue-specific methylation pattern of the apolipoprotein AI gene, therefore, involves the following three major events: (i) erasure of the germ-cell methylation pattern (at the 8- to 16-cell stage), (ii) formation of a new methylation pattern by de novo methylation of non-CpG island sites (during gastrulation), and (iii) tissue-specific demethylation associated with the onset of expression of the gene.

Aging↗

PubMed1996

The role of apolipoprotein AI domains in lipid binding.

Apolipoprotein AI (apoAI) is the principal protein constituent of high density lipoproteins and it plays a key role in human cholesterol homeostasis; however, the structure of apoAI is not clearly understood. To test the hypothesis that apoAI is organized into domains, three deletion mutants of human apo AI expressed in Escherichia coli were studied in solution and in reconstituted high density lipoprotein particles. Each mutant lacked one of three specific regions that together encompass almost the entire 243 aa sequence of native apoAI (apoAI delta 44-126, apoAI delta 139-170, and apoAI delta 190-243). Circular dichroism spectroscopy showed that the alpha-helical content of lipid-free apoAI delta 44-126 was 27% while the other mutants and native apoAI averaged 55 +/- 2%, suggesting that the missing N-terminal portion contains most of the alpha-helical structure of lipid-free apoAI. ApoAI delta 44-126 exhibited the largest increase in alpha-helix upon lipid binding (125% increase versus an average of 25% for the others), confirming the importance of the C-terminal half of apoAI in lipid binding. Denaturation studies showed that the N-terminal half of apoAI is primarily responsible for alpha-helix stability in the lipid-free state, whereas the C terminus is required for alpha-helix stability when lipid-bound. We conclude that the N-terminal half (aa 44-126) of apoAI is responsible for most of the alpha-helical structure and the marginal stability of lipid-free apoAI while the C terminus (aa 139-243) is less organized. The increase in alpha-helical content observed when native apoAI binds lipid results from the formation of alpha-helix primarily in the C-terminal half of the molecule.

Apolipoprotein A-I↗

PubMed2006

Curve correction effect of rigid spinal orthosis in different recumbent positions in adolescent idiopathic scoliosis (AIS): a pilot MRI study.

In this pilot cross-sectional study, the effectiveness of rigid spinal orthoses in the correction of spinal curvature of 14 patients with moderate adolescent idiopathic scoliosis (AIS) at different recumbent positions (supine, prone, right and left decubitus) was investigated. Using magnetic resonance (MR) imaging and multi-planar reconstruction technique, evaluation of the scoliotic spine in the coronal, sagittal and axial planes and the effect of spinal orthosis on AIS at different recumbent positions was studied. There was significant reduction of coronal Cobb's angle (p < 0.05) with bracing at all four recumbent positions and the maximal reduction was found in the prone position (18% reduction). The sagittal Cobb's angle was only significantly reduced at the supine position while the axial rotation did not change significantly in all positions.

Adolescent↗

PubMed2002

AI and SAR approaches for predicting chemical carcinogenicity: survey and status report.

A wide variety of artificial intelligence (AI) and structure-activity relationship (SAR) approaches have been applied to tackling the general problem of predicting rodent chemical carcinogenicity. Given the diversity of chemical structures and mechanisms relative to this endpoint, the shared challenge of these approaches is to accurately delineate classes of active chemicals representing distinct biological and chemical mechanism domains, and within those classes determine the structural features and properties responsible for modulating activity. In the following discussion, we present a survey of AI and SAR approaches that have been applied to the prediction of rodent carcinogenicity, and discuss these in general terms and in the context of the results of two organized prediction exercises (PTE-1 and PTE-2) sponsored by the US National Cancer Institute/National Toxicology Program. Most models participating in these exercises were successful in identifying major structural-alerting classes of active carcinogens, but failed in modeling the more subtle modifiers to activity within those classes. In addition, methods that incorporated mechanism-based reasoning or biological data along with structural information outperformed models limited to structural information exclusively. Finally, a few recent carcinogenicity-modeling efforts are presented illustrating progress in tackling some aspects of the carcinogenicity prediction problem. The first example, a QSAR model for predicting carcinogenic potency of aromatic amines, illustrates that success is possible within well-represented classes of carcinogens. From the second example, a newly developed FDA/OTR MultiCASE model for predicting the carcinogenicity of pharmaceuticals, we conclude that the definitions of biological activity and nature of chemicals in the training set are important determinants of the predictive success and specificity/sensitivity characteristics of a derived model.

Animals↗

PubMed2005

Head injuries in airbag-equipped motor vehicles with special emphasis on AIS 1 and 2 facial and loss of consciousness injuries.

OBJECTIVES: Safety of the airbag supplemental restraint system (airbag) is a well-known concern. Although many lives are saved each year through airbag use, injuries continue to occur, especially to the head. Airbag safety research has focused primarily on severe injuries, while minor and moderate injuries have been largely ignored. METHODS: In this study, 205,977 injury cases from the 1995 to 2001 National Automotive Sampling System (NASS)/ Crashworthiness Data System (CDS) were surveyed to determine the prevalence of AIS 1 and 2 facial and brain loss of consciousness (LOC) injuries and determine if these injuries are a concern. The query was focused on frontal impacts in vehicles equipped with airbags. Only occupants wearing appropriate seatbelts were included in this study so that the airbag would provide occupant protection under optimal conditions. Of the 205,977 injury cases studied, 2.4% met this criterion. RESULTS: From the data gathered, the trends seem to indicate an increase in these specific injuries, both in terms of the total number and the proportion to all injury cases. In 1995, AIS 1 and 2 head injuries accounted for 96.5% of all head injuries caused by airbags. By 2001, the percentage had risen 3.0% to 99.5%. Injuries occurring in vehicles equipped with first-generation versus second generation airbags were compared, and data seem to suggest that there is a higher rate of minor and moderate head injuries when occupants are in second-generation airbag-equipped vehicles, even when appropriate lap and shoulder belts are used. CONCLUSIONS: The short timeframe surveyed prevents drawing meaningful conclusions about statistical significance, but the graphical representations of the data in this study underscore an urgent need for further investigation based on current trends in order to understand the issue of minor and moderate head injury prevention in regard to airbags.

Abbreviated Injury Scale↗

PubMed1984

Intracellular control of axial shape in non-uniform neurites: a serial electron microscopic analysis of organelles and microtubules in AI and AII retinal amacrine neurites.

AI and AII cat retinal amacrine cells have highly varicose non-uniform, neuritic processes. Processes of both types were reconstructed via a computer system using serial electron micrographs. These reconstructions were analyzed for (a) varicosity volume, surface area, and length, (b) "neck" volume, surface area, and length, (c) number of microtubules within the varicosity, (d) number of microtubules within the "neck," and (e) volume and surface area of mitochondria and smooth endoplasmic reticulum and large smooth vesicular bodies within the processes. Correlation of these parameters revealed a linear relationship between the number of microtubules in the necks and mean neck cross-sectional area (rs = 0.780, P less than 0.001), while microtubule number within the varicosities showed no correlation with varicosity volume (rs = 0.239, P greater than 0.2). Varicosity volume did, however, correlate strongly with the summed volume of mitochondria and smooth vesicular bodies contained within the varicosity for both cell types examined. The ratio between membranous organelle volume and varicosity volume for AI amacrine processes of 1:6.97 (rs = 0.927), differed from the ratio of 1:1.80 for the AII amacrine processes (rs = 0.987). Similar relationships were observed in other nonvaricose neurites such as optic tract axons. Membranous organelles appear to contribute an additional obligatory volume to the cytosol that can be as much as seven times the organelles' direct volume. These observations suggest that both the cytoskeletal components, and the membrane organelles play a direct role in determining neurite shape.

Animals↗

PubMed1984

Isolation and sequence analysis of the human apolipoprotein CIII gene and the intergenic region between the apo AI and apo CIII genes.

We have isolated and characterized the gene for human apolipoprotein CIII, a major component of the triglyceride-rich lipoproteins. Determination of the complete DNA sequence of this gene revealed that the coding sequence is interrupted by three introns, which occur in the 5' noncoding region, in the region encoding the signal sequence and in the region coding for the mature plasma protein, respectively. We present an analysis of the structure of the apo CIII gene and compare it to the gene for apolipoprotein AI. In addition, we present the DNA sequence of the intergenic region lying between the apo AI and the apo CIII genes.

Apolipoprotein A-I↗