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1.
Br Dent J ; 225(4): 357-362, 2018 08 24.
Article in English | MEDLINE | ID: mdl-30117496

ABSTRACT

If dental professionals want to improve the oral health of their patients, they need to address what makes them sick: the social determinants of health. In this article, we propose a model of 'social dentistry' that shows how dentists could tackle these fundamental causes of oral disease. Socially engaged dentists conduct actions at three levels. At the individual level, they provide patient-centred care and, when necessary, liaise with local resources to better address what makes their patients sick. At the community level, they adapt their practice to the needs of the most vulnerable groups and advocate for healthier local policies. At the societal level, they are engaged in upstream actions addressing the social determinants of health.


Subject(s)
Dentistry , Stomatognathic Diseases/prevention & control , Dentistry/methods , Humans , Models, Theoretical , Professional Role , Social Determinants of Health
2.
JDR Clin Trans Res ; 3(1): 109-110, 2018 01.
Article in English | MEDLINE | ID: mdl-30938650

ABSTRACT

Knowledge Transfer Statement: We are calling researchers, educators, and dental professionals to be at the forefront of actions addressing social determinants of health. We indeed argue that 1) it is the dentists' and other oral health care professionals' role to tackle social determinants of health and 2) as researchers and educators, we need to help clinicians in this endeavor and lead the development of a "social dentistry" movement.


Subject(s)
Dentistry , Social Determinants of Health , Social Justice , Social Medicine , Humans , Professional Role , United States
3.
Eur Arch Paediatr Dent ; 18(6): 385-391, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29086891

ABSTRACT

AIM: The aim of this national survey was to record the use of nitrous oxide and the perceptions of French dental practitioners to this form of sedation. The use of nitrous oxide sedation (NOS) has been authorised in private dental practice in France since December 2009 but, to date, no study implementing both quantitative and qualitative methods has explored such use. METHODS: The data were collected using a Google Forms questionnaire. A mixed methodology was used for data analysis: a quantitative approach to explore the use of conscious sedation and a qualitative thematic approach (using Nvivo software) to determine the practitioner's perception of it. RESULTS: Responses were collected from 225 practitioners (19% of the target population of 1185). Most of the responders were trained in NOS use in private dental clinics. Seventy-three percent of those who trained privately actually used NOS, compared to 53% of those trained at university (p-value = 0.0052). Above all, NOS was used for children requiring restorative dentistry. The average price of the sedation was 50 Euros and it lasted, on average, for 37 min. The qualitative and thematic analysis revealed the financial and technical difficulties of implementing NOS in private practice. However, it also showed the benefits and pleasure associated with NOS use. CONCLUSION: This statistical survey of French dental practitioners offers an insight of the current state of the use of conscious sedation with nitrous oxide in private general dental practice in France. It also includes the first report of dental practitioners' perceptions of NOS use and may lead to a better understanding of the reasons why sedation is sometimes not used in private practice.


Subject(s)
Anesthesia, Dental/statistics & numerical data , Anesthetics, Inhalation , Nitrous Oxide , Practice Patterns, Dentists'/statistics & numerical data , Private Practice , Anesthetics, Inhalation/economics , France , Humans , Nitrous Oxide/economics , Surveys and Questionnaires
4.
Br Dent J ; 223(6): 419-424, 2017 Sep 22.
Article in English | MEDLINE | ID: mdl-28937118

ABSTRACT

Patient- or person-centred care is the current paradigm in the health profession yet there is still no clear understanding of what it means or how it could be implemented in dentistry. Building on a previously proposed person-centred model in clinical dentistry, in this article a person-centred dental clinical approach is presented. The approach consists of three guiding principles - humility, hospitality and mindfulness - that influence the different processes of the dental clinical encounter: connecting, examining, sharing, and intervening. The presented approach provides a rich opportunity for dentists to fine tune their own clinical approach in order to keep up with the upcoming expectations of their patients.


Subject(s)
Dental Care , Patient-Centered Care , Dentists , Humans , Self Care
5.
JDR Clin Trans Res ; 1(1): 97-98, 2016 Apr.
Article in English | MEDLINE | ID: mdl-30931689

ABSTRACT

KNOWLEDGE TRANSFER STATEMENT:: This fictional narrative can be used by dental education professionals when teaching about the patient-dentist relationship. In particular, this narrative may be useful in patient-centered programs in dental education.

6.
Diabetes Metab ; 34(5): 497-506, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18948050

ABSTRACT

AIM: There is growing evidence that periodontal disease may favour the incidence or aggravation of diabetes and its complications. To investigate the issue, we conducted a meta-analysis of the effect of periodontal therapy on glycaemic control in diabetic patients. METHODS: A literature search was carried out using seven databases (Medline, EMBASE, LILACS, The Cochrane Library, Pascal, IADR Abstracts and Current Contents), with no language restrictions. We followed the QUOROM-recommended standards for improving the quality of reporting meta-analyses of interventional studies. RESULTS: Twenty-five studies, involving 976 subjects altogether, were included in the present systematic review. Of these, nine studies, involving a total of 485 patients, were controlled trials and were included in the meta-analysis. The standardized mean difference in HbA(1c) with the treatment of periodontal disease was 0.46 (95% CI: 0.11, 0.82). These findings suggest that periodontal treatment could lead to a significant 0.79% (95% CI: 0.19, 1.40) reduction in HbA(1c) level. CONCLUSION: The present meta-analysis represents the best information available to date that addresses this issue, and suggests that periodontal treatment could improve glycaemic control. Nevertheless, these results need to be viewed with caution because of a lack of robustness, and deficiencies in the design of some of the studies included. A randomized controlled trial with sufficient statistical power would help to confirm the results of this meta-analysis.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus/blood , Periodontics , Clinical Trials as Topic , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Female , Humans , Male
7.
J Radiol ; 88(9 Pt 1): 1133-43, 2007 Sep.
Article in French | MEDLINE | ID: mdl-17878875

ABSTRACT

PURPOSE: To describe, with an ethical perspective, the information shared between patients, referring physicians, radiologists and technologists related to an imaging procedure to better understand the patients experiences based on the type of patient-provider relationship. METHODS: Cognitive diagrams were created to identify the different actors, their respective role, and the exchanges of information that will affect these roles at the time of examination. Then, the content of the shared information was studied relative to romanesque literature and semi-directed interviews with patients and imaging professionals. RESULTS: Ethical dysfunctions were observed. These are most frequently reported in the literature. But they were also observed in the field. In-depth evaluation are needed to obtain a better assessment of the current situation. CONCLUSION: Ethical concepts related to imaging studies are widely accepted. However, adhering to such concepts may not always be sufficient to ensure successful implementation. To achieve this objective, specific training based on accurate understanding of patients experiences will probably be required.


Subject(s)
Diagnostic Imaging/ethics , Ethics, Medical , Disclosure , Humans , Models, Theoretical , Physician-Patient Relations/ethics , Physicians/ethics , Prescriptions , Professional-Patient Relations/ethics , Radiology/ethics , Referral and Consultation/ethics , Technology, Radiologic/ethics
8.
J Microsc ; 215(Pt 2): 139-48, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15315500

ABSTRACT

This paper presents the first application of high-resolution X-ray synchrotron tomography to the imaging of large microvascular networks in biological tissue samples. This technique offers the opportunity of analysing the full three-dimensional vascular network from the micrometre to the millimetre scale. This paper presents the specific sample preparation method and the X-ray imaging procedure. Either barium or iron was injected as contrast agent in the vascular network. The impact of the composition and concentration of the injected solution on the X-ray synchrotron tomography images has been studied. Two imaging modes, attenuation and phase contrast, are compared. Synchrotron high-resolution computed tomography offers new prospects in the three-dimensional imaging of in situ biological vascular networks.


Subject(s)
Blood Vessels/ultrastructure , Microcirculation/ultrastructure , Animals , Capillaries/ultrastructure , Cerebrovascular Circulation , Humans , Image Processing, Computer-Assisted , Rats , Sensitivity and Specificity , Synchrotrons , Tomography, X-Ray/methods
9.
J Appl Toxicol ; 21(6): 449-60, 2001.
Article in English | MEDLINE | ID: mdl-11746191

ABSTRACT

Diethylene glycol monohexyl ether (DEGHE; CAS no. 112-59-4), an industrial chemical, was investigated for the potential to produce genotoxic effects using three in vitro and two in vivo tests. No mutagenic activity occurred in either the absence or presence of metabolic activation with a Salmonella typhimurium reverse assay using strains TA98, TA100, TA1535, TA1537 and TA1538. In a Chinese hamster ovary (CHO) forward gene mutation test (HGPRT locus) there was an increase in the mutation frequencies, which were relatively small compared with the solvent control values, somewhat inconsistent between duplicate cultures and occurred particularly in the presence of metabolic activation. Linear regression analysis indicated a marginally significant trend for dosage versus mutation frequency, suggesting that DEGHE was weakly positive in this test. A sister chromatid exchange test in CHO cells showed no significant dosage-related effects in the presence or absence of metabolic activation. A peripheral blood micronucleus test in mice by dosing with an intraperitoneal injection of DEGHE did not show any potential for DEGHE to increase the incidence of micronucleated polychromatophilic erythrocytes. In a first femoral bone marrow chromosome aberration test in the rat by peroral dosing, DEGHE did not cause any increase in aberrations for 12-h and 24-h samples with males and females or with females at 48-h sampling. However, with males at 48 h the two lowest doses showed an increased number of aberrations, but not at the high doses. A repeat study in males with a larger number of doses and 24-h and 48-h samples did not replicate this finding. It is concluded that DEGHE may have limited weak mutagenic activity in vitro but is devoid of clastogenic potential.


Subject(s)
Chromosome Aberrations/chemically induced , Ethylene Glycols/toxicity , Sister Chromatid Exchange/drug effects , Administration, Oral , Animals , Bone Marrow Cells , CHO Cells , Cricetinae , DNA Mutational Analysis , Dose-Response Relationship, Drug , Female , Femur/cytology , Male , Mice , Micronucleus Tests , Mutagenicity Tests , Rats , Regression Analysis , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Sex Factors
10.
Carcinogenesis ; 21(9): 1661-9, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10964097

ABSTRACT

The purposes of the present study were: (i) to investigate the potential use of several biomarkers as quantitative indicators of the in vivo conversion of ethylene (ET) to ethylene oxide (EO); (ii) to produce molecular dosimetry data that might improve assessment of human risk from exogenous ET exposures. Groups (n = 7/group) of male F344 rats and B6C3F1 mice were exposed by inhalation to 0 and 3000 p. p.m. ET for 1, 2 or 4 weeks (6 h/day, 5 days/week) or to 0, 40, 1000 and 3000 p.p.m. ET for 4 weeks. N:-(2-hydroxyethyl)valine (HEV), N:7-(2-hydroxyethyl) guanine (N7-HEG) and HPRT: mutant frequencies were assessed as potential biomarkers for determining the molecular dose of EO resulting from exogenous ET exposures of rats and mice, compared with background biomarker values. N7-HEG was quantified by gas chromatography coupled with high resolution mass spectrometry (GC-HRMS), HEV was determined by Edman degradation and GC-HRMS and HPRT: mutant frequencies were measured by the T cell cloning assay. N7-HEG accumulated in DNA with repeated exposure of rodents to 3000 p.p.m. ET, reaching steady-state concentrations around 1 week of exposure in most tissues evaluated (brain, liver, lung and spleen). The dose-response curves for N7-HEG and HEV were supralinear in exposed rats and mice, indicating that metabolic activation of ET was saturated at exposures >/=1000 p.p.m. ET. Exposures of mice and rats to 200 p.p.m. EO for 4 weeks (as positive treatment controls) led to significant increases in HPRT: mutant frequencies over background in splenic T cells from exposed rats and mice, however, no significant mutagenic response was observed in the HPRT: gene of ET-exposed animals. Comparisons between the biomarker data for both unexposed and ET-exposed animals, the dose-response curves for the same biomarkers in EO-exposed rats and mice and the results of the rodent carcinogenicity studies of ET and EO suggest that too little EO arises from exogenous ET exposure to produce a significant mutagenic response or a carcinogenic response under standard bioassay conditions.


Subject(s)
Ethylene Oxide/metabolism , Ethylene Oxide/toxicity , Ethylenes/pharmacokinetics , Ethylenes/toxicity , Guanine/analogs & derivatives , Valine/analogs & derivatives , Animals , Biomarkers/analysis , Biotransformation , Carcinogens/pharmacokinetics , Carcinogens/toxicity , DNA/drug effects , DNA/metabolism , DNA Damage , Dose-Response Relationship, Drug , Ethylene Oxide/pharmacokinetics , Guanine/biosynthesis , Hemoglobins/metabolism , Hypoxanthine Phosphoribosyltransferase/genetics , Inhalation Exposure , Male , Mice , Mice, Inbred Strains , Mutation , Rats , Rats, Inbred F344 , T-Lymphocytes/enzymology , Valine/biosynthesis
11.
Environ Mol Mutagen ; 36(1): 13-21, 2000.
Article in English | MEDLINE | ID: mdl-10918355

ABSTRACT

Octamethylcyclotetrasiloxane (OMCTS; CAS No. 556-67-2) was evaluated in a genetic toxicity battery. In preincubation tests with Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538, no mutagenicity was detected (maximum dose = 5 mg/plate) with or without S9 in two independent trials. Treatment of cultured Chinese hamster ovary (CHO) cells was limited by cytotoxicity at OMCTS concentrations greater than 0.003 mg/mL without S9 and 0.03 mg/mL with S9. CHO cells treated with up to 0.003 mg/mL without S9 and 0.03 mg/mL with S9 showed no significant dose-related increases in chromosomal aberration frequencies. No significant dose-related increases in sister chromatid exchanges (SCEs) occurred in OMCTS-treated CHO cells (maximum OMCTS concentration = 0.003 mg/mL without S9; 0.03 mg/mL with S9). Therefore, OMCTS was concluded to be negative in the SCE assay. In a screen for in vivo clastogenic potential, Sprague-Dawley rats received 700 ppm OMCTS by whole-body vapor inhalation 6 hr daily for 5 days. A negative control group received filtered air on the same schedule. A positive control group was exposed to filtered air on the same schedule and received cyclophosphamide 24 hr before termination. The OMCTS-treated animals were terminated 6 and 24 hr after the final exposure. Positive and negative control animals were terminated 24 hr after the last exposure. No significant, treatment-related increases in chromosomal aberrations were detected. The results of these studies indicate that OMCTS does not possess significant in vitro genotoxic potential. No adverse genetic findings were seen in the in vivo screen for chromosome aberrations.


Subject(s)
Adjuvants, Immunologic/toxicity , Mutagenicity Tests/methods , Siloxanes/toxicity , Animals , Bone Marrow/drug effects , CHO Cells/drug effects , Chromosome Aberrations , Cricetinae , Female , Male , Rats , Rats, Sprague-Dawley , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Sister Chromatid Exchange
12.
J Biomech ; 33(4): 395-405, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10768388

ABSTRACT

A mathematical model of blood flow through the circle of Willis was developed, within a linear framework. Comprehensive analytical solutions, including a remarkably small number of parameters, were derived in the cases of obstructive lesions of extracranial carotid arteries. The influence of these lesions and the role of anterior and posterior communicating arteries on the blood pressure at the entry of the cerebral territories were quantified and analyzed emphasizing that the responses of the system of Willis to obstructive carotid lesions are extremely varied, depending on the communicating artery anatomy. Comparison with numerical results obtained by using a non-linear model showed no physiologically significant differences. Such a model might be an essential tool for an accurate assessment of the cerebral hemodynamics in carotid diseases.


Subject(s)
Carotid Stenosis/physiopathology , Cerebrovascular Circulation , Circle of Willis/physiopathology , Models, Cardiovascular , Carotid Artery, Internal , Hemodynamics/physiology , Humans
13.
J Biomech Eng ; 122(6): 661-6, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11192389

ABSTRACT

Maximal wall shear stress (MWSS) in the convergent part of a stenosis is calculated by the interactive boundary-layer theory. A dimensional analysis of the problem shows that MWSS depends only on a few measurable parameters. A simple relationship between MWSS and these parameters is obtained, validated, and used to calculate the magnitude of MWSS in a carotid stenosis, as a function of the patency of the circle of Willis and the stenotic pattern. This demonstrates the huge effect of collateral pathways. Elevated MWSS are observed even in moderate stenoses, provided they are associated with a contralateral occlusion, a large anterior, and narrow posterior communicating arteries, suggesting a potential risk of embolus release in this configuration.


Subject(s)
Carotid Artery, Internal/physiopathology , Carotid Stenosis/physiopathology , Circle of Willis/physiopathology , Models, Cardiovascular , Circle of Willis/pathology , Humans , Regression Analysis , Stress, Mechanical , Vascular Patency
14.
Genomics ; 62(3): 519-24, 1999 Dec 15.
Article in English | MEDLINE | ID: mdl-10644451

ABSTRACT

The cornea contains, as a major element, a transparent stroma produced and maintained by keratocytes (fibroblasts). Through molecular biology studies using cultured human corneal fibroblasts, a cDNA that was shown to be novel was isolated and sequenced. This novel gene product, named SH3-domain binding protein 4 (SH3BP4), contains a 5.6-kb message that is present in normal human corneal fibroblasts and all tissues examined, with higher levels in pancreas, placenta, heart, and kidney. SH3BP4 was localized by FISH analysis to human chromosome 2q37.1-q37.2 near the telomere. The deduced sequence for SH3BP4 was found to contain a 963-amino-acid open reading frame that has homology to a 479-amino-acid protein in GenBank called EH-binding protein. Although the entire sequence of EH-binding protein aligns with SH3BP4, the alignment is not complete or contiguous. Therefore, SH3BP4 has an additional 73 amino acids at the N-terminus and an additional 411 amino acids near the C-terminus that are not present in EH-binding protein. Consensus sequence domains identified in SH3BP4 include a SH3 domain, three N-P-F motifs, a P-X-X-P motif noted for binding to SH3 domains, a bipartite nuclear targeting signal, and a tyrosine phosphorylation site. SH3BP4 homologies and consensus sequence sites indicate that it may be involved in a newly identified cascade of proteins involved in endocytosis, intracellular sorting, and the cell cycle.


Subject(s)
Adaptor Proteins, Signal Transducing , Carrier Proteins/genetics , Cornea/cytology , DNA, Complementary/genetics , Fibroblasts/metabolism , Amino Acid Motifs/genetics , Amino Acid Sequence , Base Sequence , Chromosomes, Human, Pair 2/genetics , Cloning, Molecular , Fibroblasts/cytology , Humans , In Situ Hybridization, Fluorescence , Molecular Sequence Data , Physical Chromosome Mapping , Sequence Homology, Amino Acid , src Homology Domains/genetics
15.
Invest Ophthalmol Vis Sci ; 39(7): 1266-72, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9620089

ABSTRACT

PURPOSE: The authors have developed monoclonal antibodies (mAbs) to characterize the sequential biochemical changes in corneal epithelial cells after they differentiate from stem cells, located in the limbus, and migrate centripetally to follow the pathway of terminal differentiation. The purpose of this study was to identify a protein (recognized by mAb HE1/11F) with increased expression associated with the transition of the limbal epithelium to corneal epithelium. METHODS: The distribution and identification of the protein(s) were performed using an indirect immunohistochemical staining technique and a western blot analysis, respectively. A rabbit corneal epithelial cDNA library, constructed in the Uni-Zap XR vector, was screened with mAb HE1/11F to select cDNA clones expressing polypeptide(s) recognized by this mAb. Additional overlapping cDNA clones were obtained from a primer extension cDNA library to determine the sequence of the complete open reading frame encoding the protein recognized by mAb HE1/11F. RESULTS: Rabbit corneal epithelium exhibited strong immunostaining with mAb HE1/11F, however, the limbal epithelial cells stained weakly. HE1/11F recognized 160-kDa (HEBM1) and 100-kDa (HEBM2) polypeptides in the corneal epithelial extracts. The amino acid sequence of the protein deduced from the nucleotide sequence of the cDNA exhibited a close homology to that of a RhoA (Ras-related small GTPase)-associated serine-threonine kinase (ROCK-I or Rho-associated coiled-coil kinase). A 160-kDa RhoA-binding polypeptide with a molecular mass similar to that of HEBM1 and ROCK-I was detected in the corneal epithelial extracts. These findings strongly suggested that HEBM1 was rabbit ROCK-I. The identity of HEBM1 was further confirmed from the reactivity of mAb HE1/11F with ROCK-I immunoprecipitated from rabbit corneal epithelial extracts using anti-ROCK-I antibodies. CONCLUSIONS: The increased expression of a protein identified as ROCK-I from cDNA analyses is associated with rabbit corneal epithelial differentiation and transition from the limbal to corneal surface. Therefore, a RhoA signaling pathway is likely to be associated with corneal epithelial differentiation (maturation). A close homology among the cDNA sequences of rabbit, mouse, rat, and human ROCK-I indicates that this RhoA-associated kinase is a well-conserved protein.


Subject(s)
Epithelium, Corneal/enzymology , Limbus Corneae/enzymology , Protein Serine-Threonine Kinases/metabolism , Amino Acid Sequence , Animals , Antibodies, Monoclonal , Blotting, Western , Cell Differentiation , Electrophoresis, Polyacrylamide Gel , Fluorescent Antibody Technique, Indirect , Humans , Immunoenzyme Techniques , Intracellular Signaling Peptides and Proteins , Mice , Molecular Sequence Data , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/immunology , Rabbits , Rats , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Stem Cells/enzymology , rho-Associated Kinases
16.
Biochim Biophys Acta ; 1397(2): 119-25, 1998 Apr 29.
Article in English | MEDLINE | ID: mdl-9565663

ABSTRACT

Three overlapping genomic clones to chick lumican were isolated and then characterized using restriction enzyme analyses, Southern blot analyses with cDNA probes, and by DNA sequencing. The results showed chick lumican gene to consist of 3 exons with a 2.9-kb first intron and a 4.2-kb second intron. Transcription initiation sites, identified by S1 nuclease experiments using genomic fragments containing exon 1 and by primer extension analysis of RNA, indicated the first exon to be 303 b. Two TATA sequences were 31 and 49 bases upstream of the first exon. The first exon contained all 5' untranslated sequence. The second exon was 896 b and contains 20 b of untranslated sequence, and codes for the start methionine to the end of the 10th leucine rich repeat. The third exon is 880 b and codes for the remainder of the core protein, and 724 b of untranslated 3' sequence. A 1-kb genomic fragment containing a portion of exon 1 and upstream sequence in a luciferase reporter sector showed specific promotor activity in the forward, but not the reverse direction when transfected into corneal fibroblasts. These results show the chick lumican gene to consist of three exons, and that regulatory elements are present within 1 kb upstream of the first exon.


Subject(s)
Chondroitin Sulfate Proteoglycans/genetics , Exons , Keratan Sulfate/genetics , Animals , Base Sequence , Chickens/genetics , Cloning, Molecular , Cornea/metabolism , Lumican , Molecular Sequence Data , Restriction Mapping , Sequence Analysis
17.
J Biol Chem ; 273(16): 9615-21, 1998 Apr 17.
Article in English | MEDLINE | ID: mdl-9545293

ABSTRACT

Corneal proteoglycans have chondroitin/dermatan and keratan sulfate (KS) chains and belong to the leucine-rich proteoglycan gene family. Corneal KS is N-linked to Asn of an NX(S/T) site through a complex oligosaccharide linkage region. Only some sites receive KS, whereas others remain in a high mannose form. To determine whether the attachment of KS was biased toward specific sites, we isolated trypsin-digested KS-containing fragments of chick corneal proteoglycans and sequenced the peptides. Results showed that all of the peptides sequenced aligned to the deduced amino acid sequence of either chick lumican or chick keratocan at the first, third, and fourth potential N-linked sites. Sites 1 and 4 in lumican and keratocan are in a homologous location. By analogy with the structure of ribonuclease inhibitor (a Leu-rich repeat containing protein), the KS chains would extend outward on the outer face of a horseshoe-like structure. The amino acid sequences surrounding the potential N-linked sites were also compared. Sites receiving KS tend to have a higher occurrence of aromatic residues, in particular Phe, located within 3 amino acids of NX(S/T). These conserved Phe residues may have a role in the conversion of high mannose N-linked oligosaccharides to polylactosamine and/or keratan sulfate.


Subject(s)
Chondroitin Sulfate Proteoglycans/chemistry , Chondroitin Sulfate Proteoglycans/metabolism , Cornea/metabolism , Keratan Sulfate/chemistry , Keratan Sulfate/metabolism , Oligosaccharides/chemistry , Proteoglycans/chemistry , Proteoglycans/metabolism , Amino Acid Sequence , Animals , Base Sequence , Cattle , Chickens , Chondroitin Sulfate Proteoglycans/genetics , Cloning, Organism , DNA, Complementary , Glycosylation , Keratan Sulfate/genetics , Lumican , Models, Molecular , Molecular Sequence Data , Multigene Family , Polymerase Chain Reaction , Protein Structure, Secondary , Proteoglycans/genetics , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid
18.
J Appl Toxicol ; 18(2): 129-42, 1998.
Article in English | MEDLINE | ID: mdl-9570696

ABSTRACT

5-Vinyl-2-norbornene (VNB: CAS no. 3048-64-4), an industrial chemical that produces hyaline droplet nephropathy in the male rat with associated alpha2u-globulin increases, was investigated in vitro and in vivo for its genotoxic potential. A Salmonella typhimurium reverse mutation assay (strains TA98, 100, 1535, 1537, 1538) was negative both without (dose range 0.003-0.3 mg per plate) and with (0.003-0.3 mg per plate) metabolic activation. A forward gene mutation test in Chinese Hamster Ovary (CHO) cells (HGPRT locus) did not show any significant concentration-related increases in mutation frequencies in the absence (0.01-0.1 mg ml[-1]) or presence (0.005-0.1 mg ml[-1]) of metabolic activation. In a sister chromatid exchange (SCE) test, VNB did not produce statistically significant or dose-related increases in the incidence of SCEs in the absence (0.02-0.06 mg ml[-1]) or presence (0.005-0.03 mg ml[-1]) of metabolic activation. A bone marrow chromosome aberration test was conducted in groups of 10 male and 10 female Sprague-Dawley rats exposed for 6 hr/day for 5 consecutive days to mean (+/- SD) VNB vapor concentrations of 0 (air control), 48.1 +/- 1.29, 146 +/- 9.2, or 336 +/- 8.5 ppm. Marrow was collected 6 and 24 hr after the final exposure. No statistically significant or dose-related increases in chromosomal aberrations occurred in the VNB-exposed animals. 5-Vinyl-2-norbornene did not show any potential for genotoxic activity with this in vitro-in vivo battery of tests.


Subject(s)
CHO Cells/drug effects , Mutation/drug effects , Norbornanes/toxicity , Salmonella typhimurium/drug effects , Sister Chromatid Exchange/drug effects , Animals , Chromosome Aberrations , Cricetinae , Dose-Response Relationship, Drug , In Vitro Techniques , Male , Mutagenicity Tests , Rats , Salmonella typhimurium/genetics
20.
J Appl Toxicol ; 17 Suppl 1: S31-6, 1997 May.
Article in English | MEDLINE | ID: mdl-9179725

ABSTRACT

Methyl tertiary-butyl ether (MTBE) is one of the highest production volume chemicals in the USA. Previous results from in vitro genetic toxicity studies suggested that it was not mutagenic. However, chronic exposure at high levels resulted in liver tumors in female mice and kidney tumors in male rats. The current program assessed in vivo genotoxicity and also explored the possibility that a mutagenic mechanism was involved in the carcinogenic process. The specific tests used included the Drosophila sex-linked-recessive-lethal test, the rat bone marrow cytogenetics test, the mouse bone marrow micronucleus test and the in vivo-in vitro hepatocyte unscheduled DNA synthesis test in the mouse. All tests produced negative results, indicating that the potential for in vivo mutagenic activity was low. These data also suggest that the tumorigenic activity was probably the result of a non-genotoxic process.


Subject(s)
Air Pollutants/toxicity , Carcinogens/toxicity , Methyl Ethers/toxicity , Animals , Bone Marrow/drug effects , DNA/biosynthesis , Dose-Response Relationship, Drug , Drosophila melanogaster , Female , Liver/drug effects , Male , Mice , Micronucleus Tests , Mutagenicity Tests , Rats , Rats, Inbred F344
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