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1.
J Nutr Health Aging ; 26(1): 37-45, 2022.
Article in English | MEDLINE | ID: mdl-35067701

ABSTRACT

OBJECTIVES: The co-occurrence of multiple medical or psycho-social conditions (geriatric syndromes (GS) and age-related diseases) is a growing concern in older people. Given the diversity of these conditions and their complex interactions, our aim was to determine whether they could be structured into synthetic dimensions in order to facilitate the management of multimorbidity. DESIGN: The underlying structure of 10 GSs and 8 age-related diseases was identified using a multiple correspondence analysis (MCA), and confronted to subjective and objective health outcomes. SETTING: community residents from Bordeaux City (France) older than 75 years in 2010. PARTICIPANTS: 630 adults aged 75+ years who lived in Bordeaux and participated in the 10-year follow-up of the Three-City study. MEASUREMENTS: GSs included physical frailty, cognitive impairment and dementia, dependency, depressive symptoms, polymedication, thinness, falls, sensory deficit, social isolation, incontinence. Age-related diseases were cancer, cardiac diseases, peripheral vascular diseases, diabetes, hypertension, pulmonary diseases, osteoporosis, other chronic diseases. Association of the MCA-derived independent dimensions was assessed with 10-year visit subjective health and well-being, and with incident death and entry into institution during the remaining cohort follow-up. RESULTS: Most of the participants (82%) had at least two age-related syndromes or diseases. The MCA structured the 18 conditions into three major dimensions: Degradation (D) driven by GS, Vascular (V), and Psychosocial (P) representing 68.7%, 7.4%, and 5.7% of the total variance, respectively. Dimension D was a strong predictor of future death and institutionalization. Dimensions D and P were strongly associated with current well-being. CONCLUSIONS: This work confirmed that multimorbidity is very common among older adults, and demonstrated the essential role of GS as manifestations of aging, even more than age-related diseases.


Subject(s)
Frailty , Geriatric Assessment , Accidental Falls , Aged , Aging , Geriatric Assessment/methods , Humans , Syndrome
2.
Mol Ecol ; 25(10): 2195-209, 2016 May.
Article in English | MEDLINE | ID: mdl-26989881

ABSTRACT

Understanding the distribution of genetic diversity in the light of past demographic events linked with climatic shifts will help to forecast evolutionary trajectories of ecosystems within the current context of climate change. In this study, mitochondrial sequences and microsatellite loci were analysed using traditional population genetic approaches together with Bayesian dating and the more recent approximate Bayesian computation scenario testing. The genetic structure and demographic history of a commercial fish, the black scorpionfish, Scorpaena porcus, was investigated throughout the Mediterranean and Black Seas. The results suggest that the species recently underwent population expansions, in both seas, likely concomitant with the warming period following the Last Glacial Maximum, 20 000 years ago. A weak contemporaneous genetic differentiation was identified between the Black Sea and the Mediterranean Sea. However, the genetic diversity was similar for populations of the two seas, suggesting a high number of colonizers entered the Black Sea during the interglacial period and/or the presence of a refugial population in the Black Sea during the glacial period. Finally, within seas, an east/west genetic differentiation in the Adriatic seems to prevail, whereas the Black Sea does not show any structured spatial genetic pattern of its population. Overall, these results suggest that the Black Sea is not that isolated from the Mediterranean, and both seas revealed similar evolutionary patterns related to climate change and changes in sea level.


Subject(s)
Genetic Variation , Genetics, Population , Perciformes/genetics , Animals , Bayes Theorem , Black Sea , Climate Change , Cluster Analysis , DNA, Mitochondrial/genetics , Evolution, Molecular , Mediterranean Sea , Microsatellite Repeats , Sequence Analysis, DNA
3.
J Nutr Health Aging ; 19(4): 468-73, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25809812

ABSTRACT

OBJECTIVES: To investigate the concordance between walking (WS) and psychomotor speed (PS), correlates of both tasks, and their capacity to predict mortality in the elderly. DESIGN, SETTING AND PARTICIPANTS: Seven-year cohort study of 1,365 community-dwelling subjects aged 65-95 years, participating in the Bordeaux sample of the Three City Study, a French prospective cohort designed to evaluate the risk of cognitive decline attributable to vascular risk factors. MEASUREMENTS: Participants completed a battery of cognitive assessments including time to complete Trail Making Test A used as a PS measure, and a measure of WS. Socio-demographic determinants, co-morbidities, functional and cognitive evaluation, and incident mortality were taken into account. RESULTS: Mean age was 75.7 (SD ± 5.4) years. WS and TMT-A speed have very low concordance (kappa coefficient=.05). The correlates of each measure were different: mostly clinical co-morbidities for WS, and mostly cognition and function for TMT-A speed. However, TMT-A speed and WS are both independent predictors of death after seven years of follow-up. CONCLUSION: WS and TMT-A speed could be considered as two different dimensions of age-related slowness, but both performances were associated with higher risk of mortality.


Subject(s)
Cognition Disorders/epidemiology , Mortality , Psychomotor Performance/physiology , Walking/physiology , Acceleration , Aged , Aged, 80 and over , Cognition/physiology , Cognition Disorders/mortality , Comorbidity , Female , France/epidemiology , Humans , Male , Prospective Studies , Residence Characteristics , Risk Factors , Time Factors , Trail Making Test
4.
J Nutr Health Aging ; 18(10): 876-82, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25470802

ABSTRACT

OBJECTIVE: To investigate the association of the change in practice of leisure and social activities with dementia risk taking into account the evolution of cognitive performances. DESIGN, SETTING, AND PARTICIPANTS: From the PAQUID prospective cohort re-examined every 2 years until the 20-year follow-up since 1988, 1461 subjects were seen at 10th year of follow-up. Engagement in 10 leisure and social activities was collected at baseline and at the 10-year follow-up visit for 805 subjects. Four categories of change in activity engagement were considered: subjects who remained active; remained inactive; became inactive and became active. Adjustment on confounders (age, gender, educational level, diabetes, stroke and depression) and rate of evolution of cognitive performances was made with the multivariate Cox proportional hazards model. MAIN OUTCOME MEASURES: Time to incident cases of dementia occurring between the 10th and the 20th year of follow-up. RESULTS: A total of 258 incident dementia cases were documented. The risk of dementia was lower for subjects remaining or becoming active (cumulative risk of dementia: 30%) compared to those remaining or becoming inactive (52% and 42%, respectively) (p<0.0001). Multivariate adjustment including rate of cognitive decline during the first decade of FU did not change these relationships. CONCLUSION: This prospective cohort study suggests a significant association between change in leisure and social activities during old age and risk of dementia.


Subject(s)
Dementia/psychology , Leisure Activities , Social Behavior , Aged , Aged, 80 and over , Cognition Disorders/complications , Cognition Disorders/psychology , Dementia/complications , Female , Follow-Up Studies , Humans , Leisure Activities/psychology , Male , Proportional Hazards Models , Prospective Studies , Risk
5.
Diabetes Res Clin Pract ; 101(2): 226-35, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23831112

ABSTRACT

AIM: Diabetes is known to impair health-related quality of life (HrQol). Our aim was to analyse a comprehensive set of potential determinants of HrQol in a large sample of patients with diabetes. METHODS: This study is based on the ENTRED 2007 study, a representative sample of adults (18 years and older) with diabetes. Data were extracted from postal self-reported questionnaires (from patients and medical practitioners) and from reimbursements from the National health insurance data system. HrQol was assessed with the MOS SF-12 for mental (MCS) and physical (PCS) component summaries. Multivariate linear regression models were used to analyse the variables associated with HrQol. RESULTS: SF-12 MCS and PCS were available in 2832 patients with T2DM, with a mean age 64 years (1715 males, 56%). Lower income, severe hypoglycaemic episodes, hospitalisation ≥24 h, instrumental daily living (IADL) restriction, low satisfaction for social support and an HbA1c within the 8.1-10.0% range were associated with lower MCS rating, whereas an older age and male gender were associated with higher MCS. Older age, female sex, higher BMI, lower income, insulin treatment, macrovascular complications, severe hypoglycaemic episodes, hospitalisation ≥24 h, and IADL restriction were associated with lower PCS values whereas having no need for social support was associated with higher PCS values. DISCUSSION: HrQol associated factors are multiple but mainly linked with socio-demographic factors, diabetes complications and satisfaction for social support. A patient centred approach should be tested to prevent impairment of HrQol and thus to decrease the burden of diabetes. Assessment of social support should be included.


Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Aged , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Male , Middle Aged , Quality of Life , Social Support , Surveys and Questionnaires
6.
J Appl Microbiol ; 115(3): 897-907, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23701119

ABSTRACT

AIMS: The aim of this study was to identify the origin of faecal pollution impacting the Elorn estuary (Brittany, France) by applying microbial source tracking (MST) markers in both oysters and estuarine waters. METHODS AND RESULTS: The MST markers used were as follows: (i) human-, ruminant- and pig-associated Bacteroidales markers by real-time PCR and (ii) human genogroup II and animal genogroup I of F-specific RNA bacteriophages (FRNAPH) by culture/genotyping and by direct real-time reverse-transcriptase PCR. The higher occurrence of the human genogroup II of F-specific RNA bacteriophages using a culture/genotyping method, and human-associated Bacteroidales marker by real-time PCR, allowed the identification of human faecal contamination as the predominant source of contamination in oysters (total of 18 oyster batches tested) and waters (total of 24 water samples tested). The importance of using the intravalvular liquids instead of digestive tissues, when applying host-associated Bacteroidales markers in oysters, was also revealed. CONCLUSIONS: This study has shown that the application of a MST toolbox of diverse bacterial and viral methods can provide multiple lines of evidence to identify the predominant source of faecal contamination in shellfish from an estuarine environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Application of this MST toolbox is a useful approach to understand the origin of faecal contamination in shellfish harvesting areas in an estuarine setting.


Subject(s)
Bacteroidetes/isolation & purification , Feces/microbiology , Ostreidae/microbiology , RNA Phages/isolation & purification , Seawater/microbiology , Water Pollutants/analysis , Animals , Bacteroidetes/genetics , Escherichia coli/isolation & purification , Estuaries , Feces/virology , France , Genetic Markers , Genotype , Ostreidae/virology , RNA Phages/genetics , Real-Time Polymerase Chain Reaction , Rivers/microbiology , Shellfish/microbiology , Shellfish/virology
7.
Neuroepidemiology ; 41(1): 20-8, 2013.
Article in English | MEDLINE | ID: mdl-23548733

ABSTRACT

BACKGROUND/AIMS: This study was designed to develop a practical risk score for predicting 5-year survival after the diagnosis of dementia. METHODS: Using the Paquid Study (prospective, population-based, long-term cohort study), we created a prognosis score with incident cases of dementia and validated it in another prospective, population-based, long-term cohort study, the Three City Study. - RESULTS: Among the 3,777 subjects enrolled in the Paquid Study, 454 incident cases of dementia were included in this study. After a 5-year follow-up period, 319 (70.3%) were deceased. The score was constructed from three independent prognostic variables (gender, age at diagnosis and number of ADL restricted). The discriminant ability of the score was good with a c index of 0.754. Sensitivity was 64.7% and specificity 76.3%. In the validation cohort, the discriminant ability of the prognostic score with c statistics was 0.700. Sensitivity was 26.3% and specificity 95.4%. CONCLUSIONS: The prognostic factors selected in the predictive model are easily assessable, so this simple score could provide helpful information for the management of dementia, particularly to identify patients with duration of the disease greater than 5 years.


Subject(s)
Dementia/epidemiology , Activities of Daily Living , Aged , Dementia/diagnosis , Dementia/mortality , Female , Humans , Incidence , Male , Prognosis , Prospective Studies , Risk Factors , Sensitivity and Specificity , Survival Rate
8.
Dement Geriatr Cogn Disord ; 35(5-6): 313-24, 2013.
Article in English | MEDLINE | ID: mdl-23594926

ABSTRACT

There is agreement that elderly people complain about word finding difficulties, particularly proper names. However, few studies have focused on the prevalence of this complaint in the general population, nor is it clearly known whether it is predictive of dementia. The aim of this study was to fill this gap using the PAQUID cohort. 1,838 people aged 65 or more completed questionnaires and neuropsychological evaluation regularly during 13 years. Results show that the complaint about proper name retrieval concerns 64% of people aged above 65 years, and the complaint about common names 30%. The complaint was not associated with enhanced risk of dementia, whereas short naming tests were. Only a marginal relation was found between these naming tests and word retrieval complaint. This study emphasizes the importance of proper name retrieval complaint in the general population and suggests that elderly subjects can be reassured in the absence of other symptoms.


Subject(s)
Dementia/psychology , Memory Disorders/psychology , Aged , Aged, 80 and over , Cognition/physiology , Cohort Studies , Disease Progression , Female , Humans , Male , Mental Recall , Neuropsychological Tests , Predictive Value of Tests , Prevalence , Psychomotor Performance
9.
Neurology ; 76(6): 518-25, 2011 Feb 08.
Article in English | MEDLINE | ID: mdl-21288982

ABSTRACT

OBJECTIVE: To examine associations between metabolic syndrome (MetS) and its individual components with risk of cognitive decline on specific cognitive functions. METHODS: Participants were 4,323 women and 2,764 men aged 65 and over enrolled in the longitudinal Three-City Study. Cognitive decline, defined as being in the worst quintile of the distribution of the difference between baseline score and either 2- or 4-year follow-up, was assessed by the Mini-Mental State Examination (MMSE, global cognitive function), the Isaacs Set Test (IST, verbal fluency), and the Benton Visual Retention Test (BVRT, visual working memory). MetS was defined by National Cholesterol Education Program-Adult Treatment Panel III criteria (at least 3 of 5 cardio-metabolic abnormalities: hypertension, high waist circumference, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, hyperglycemia). Proportional hazards models were adjusted for age, gender, educational level, center, baseline cognitive score, APOE4 genotype, and other potential confounders. RESULTS: MetS at baseline was associated with an increased risk of cognitive decline on MMSE (hazard ratio [HR] = 1.22 [1.08-1.37]; p = 0.001) and BVRT (HR = 1.13 [1.01-1.26]; p = 0.03) but not on IST (HR = 1.11 [0.95-1.29]; p = 0.18). Among MetS components, hypertriglyceridemia and low HDL cholesterol were significantly associated with higher decline on MMSE; diabetes, but not elevated fasting glycemia, was significantly associated with higher decline on BVRT and IST. CONCLUSIONS: MetS as a whole and several of its components had a negative impact on global cognitive decline and specific cognitive functions in older persons.


Subject(s)
Cognition Disorders/epidemiology , Cognition Disorders/psychology , Metabolic Syndrome/epidemiology , Metabolic Syndrome/psychology , Aged , Cognition Disorders/etiology , Cohort Studies , Female , Follow-Up Studies , France/epidemiology , Humans , Longitudinal Studies , Male , Metabolic Syndrome/complications , Neuropsychological Tests , Prospective Studies , Risk Factors
10.
J Nutr Health Aging ; 14(10): 854-61, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21125205

ABSTRACT

BACKGROUND: Worldwide, degenerative eye diseases (age-related maculopathy (ARM), cataract, glaucoma) are the main causes of visual impairment and blindness, which contribute to disability in the elderly. Mainly three types of nutritional factors are investigated for their potential protection against eye ageing: antioxidants; lutein and zeaxanthin (carotenoids which accumulate specifically in the eye); omega 3 polyunsaturated fatty acids. Few epidemiological studies have been conducted in this field, particularly in Europe. OBJECTIVE: The Alienor (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) Study aims at assessing the associations of eye diseases with nutritional factors, determined from plasma measurements and estimation of dietary intakes. DESIGN, SETTING AND PARTICIPANTS: Subjects were recruited in Bordeaux (France) from the ongoing population-based 3C study. In 2006-2008, 963 subjects from the 3C Study, aged 73 years or more, had an eye examination and will have follow-up eye examinations every 2 years. MEASUREMENTS: Vascular, genetic and nutritional factors were assessed at baseline (1999-2001) and follow-up examinations of the 3C Study. Eye diseases were classified according to international classifications. RESULTS: Nutritional status and vascular disease and risk factors were similar between participants and non participants, except for a slight difference in plasma triglycerides and HDL-cholesterol. As expected, the prevalence of eye diseases was high: early and late ARM (28.4 % and 5.6 %, respectively), open-angle glaucoma and treated ocular hypertension (4.8 % and 10.0 %, respectively), cataract extraction (45.2 %), retinopathy (8.4 %), retinal vein occlusion (1.1 %), epiretinal membrane (3.9 %), current use of artificial tears (17.3 %). CONCLUSIONS: This study confirms the high prevalence of eye diseases in the elderly. Its main strength is the combination of nutritional, vascular and genetic information, collected over a 7 year period of time before the first eye examination. It may help design future interventional studies, which might be common with other age-related disorders, because of common nutritional factors.


Subject(s)
Aging , Diet , Eye Diseases/epidemiology , Health Surveys , Nutritional Status , Research Design , Aged , Aged, 80 and over , Diagnostic Techniques, Ophthalmological , Eye Diseases/metabolism , Eye Diseases/physiopathology , Female , France/epidemiology , Humans , Longitudinal Studies , Male , Prevalence , Risk Factors , Sex Factors
11.
Rev Neurol (Paris) ; 166(6-7): 594-605, 2010.
Article in French | MEDLINE | ID: mdl-20236672

ABSTRACT

INTRODUCTION: Verbal fluency tasks are frequently used in neuropsychological examinations. The aim of this study was to produce norms for a normal elderly population in semantic (colors, animals, fruits, city names) and letter fluency (letters "L" and "P") tasks performed in 60 seconds. METHODS: These data were collected as part of the PAQUID cohort, a French population-based study on aging conducted in Gironde and Dordogne. RESULTS: The sub-sample analyzed included 1730 non-institutionalized and non-demented subjects. Norms were calculated according to age (70-74 years, 75-79 years, >or=80 years), sex and educational level (no diploma, primary degree, secondary degree and higher). For each task, the number of correct words produced and repetition errors were analyzed. CONCLUSION: The contribution of this work is to provide clinicians with normative scores for semantic and letter fluency tasks helpful for interpreting the performances of elderly patients consulting for cognitive disorders.


Subject(s)
Aged/psychology , Speech Disorders/diagnosis , Aged, 80 and over , Aging/psychology , Blindness/psychology , Cohort Studies , Dementia/psychology , Female , France , Hearing Disorders/psychology , Humans , Male , Prospective Studies , Reference Values
12.
Exp Eye Res ; 90(3): 461-4, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20036236

ABSTRACT

This study sought to determine the distribution of opticin, an extracellular matrix small leucine-rich repeat protein secreted by the non-pigmented ciliary body epithelium (CBE), in pathological eye tissues including posterior hyaloid membranes (PHM) and epiretinal membranes (ERM) from subjects with proliferative diabetic retinopathy (PDR), central retinal vein occlusion (CRVO) and proliferative vitreoretinopathy (PVR). Eight enucleated eyes and eleven surgically excised PHMs/ERMs from patients with PDR, CRVO or PVR were analysed by immunohistochemistry for the presence and distribution of opticin, vitreous (delineated by a type II collagen antibody) and blood vessels (using CD31 and CD34 antibodies as endothelial markers). Opticin was present at the basal surface of the non-pigmented CBE and, in a patchy distribution, within CBE cells in all 8 enucleated globes. It also co-localised with the type II collagen of vitreous, where present, in these eyes. Opticin was present in 16 of the 19 PHMs/ERMs, where it was arranged in layers (10 membranes), diffusely (4 membranes) or in foci (2 membranes). Where in a layered pattern, opticin co-localised with vitreous type II collagen incorporated into the membrane, whereas the other two patterns did not co-localise with type II collagen labelling. We concluded that even in advanced proliferative retinal disease, the CBE continues to express and secrete opticin. Opticin was co-distributed with vitreous type II collagen and was also present in the pre-retinal membranes of proliferative retinopathies, where it could play a role in their development.


Subject(s)
Diabetic Retinopathy/metabolism , Epiretinal Membrane/metabolism , Extracellular Matrix Proteins/metabolism , Proteoglycans/metabolism , Retinal Vein Occlusion/metabolism , Vitreoretinopathy, Proliferative/metabolism , Adult , Aged , Aged, 80 and over , Antigens, CD34/metabolism , Blood Vessels/metabolism , Ciliary Body/metabolism , Collagen Type II/metabolism , Epithelium/metabolism , Female , Humans , Immunoenzyme Techniques , Male , Middle Aged , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Vitreous Body/metabolism
13.
Eye (Lond) ; 22(10): 1214-22, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18309340

ABSTRACT

This review will focus on the molecular organisation of the adult vitreous and how it undergoes ageing changes throughout life that result in vitreous liquefaction and a predisposition towards posterior vitreous detachment and retinal break formation. At birth, the vitreous humour is in a gel state due to the presence of a network of fine collagen fibrils. With ageing, these collagen fibrils progressively aggregate due to a loss of type IX collagen from their surfaces. The aggregation of collagen fibrils may cause vitreous liquefaction which, when combined with an age-related weakening of postbasal vitreoretinal adhesion, predisposes to posterior vitreous detachment. Throughout postnatal life, the posterior border of the vitreous base migrates posteriorly from the ora serrata into the peripheral retina. This is due to new collagen synthesis by the peripheral retina. This new collagen intertwines with pre-existing cortical vitreous collagen to create new adhesions and thereby extends the vitreous base posteriorly. If irregularities in the posterior border of the vitreous base arise from this process, there is a predisposition towards retinal break formation during posterior vitreous detachment and subsequent rhegmatogenous retinal detachment.


Subject(s)
Aging/physiology , Basement Membrane/chemistry , Extracellular Matrix/chemistry , Retina/chemistry , Vitreous Body/chemistry , Basement Membrane/metabolism , Chondroitin Sulfate Proteoglycans/chemistry , Collagen/biosynthesis , Collagen/chemistry , Extracellular Matrix/metabolism , Extracellular Matrix Proteins/chemistry , Fibrillins , Heparan Sulfate Proteoglycans/chemistry , Humans , Hyaluronic Acid/chemistry , Microfilament Proteins/chemistry , Proteoglycans/chemistry , Retina/physiology , Retinal Detachment/etiology , Vitreous Body/anatomy & histology , Vitreous Body/physiology , Vitreous Detachment/metabolism
14.
Eye (Lond) ; 16(4): 454-60, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12101453

ABSTRACT

Recently, several groups have published new information regarding the origins and structure of the vitreous humour, and the inner limiting lamina (ILL) of the retina. This short article provides an overview of this new information. It is proposed that vitreous proteins are derived from several different cell types with the posterior half of the non-pigmented ciliary epithelium being prominent in the expression of several connective tissue macromolecules. In addition, some basement membrane macromolecules are also expressed by the ciliary body and may subsequently be assembled on the surface of the Müller cells to form the ILL. New data suggest that the posterior half of the non-pigmented ciliary epithelium has substantial secretory activity and is likely to play a pivotal role in eye development.


Subject(s)
Ciliary Body/physiology , Eye Proteins/biosynthesis , Vitreous Body/metabolism , Basement Membrane/metabolism , Collagen/biosynthesis , Epithelium/metabolism , Humans
15.
Invest Ophthalmol Vis Sci ; 42(10): 2202-10, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11527931

ABSTRACT

PURPOSE: To determine the structure, location, and tissue-specific expression of the mouse opticin gene (Optc) and to compare expression in the eye with that of Prelp, collagen II, and collagen IX. METHODS: Expressed sequence tags (ESTs) to mouse opticin were identified and the full-length sequence obtained after PCR reactions using a 15-day-postconception (dpc) whole-mouse embryo cDNA library. The mouse chromosomal localization of Optc was determined by radiation hybrid mapping and its genomic structure determined using an Optc-containing BAC clone. Tissue-specific expression of opticin, PRELP, collagen II, and collagen IX mRNAs was investigated by in situ hybridization and by dot blot hybridization for opticin. RESULTS: The Optc gene was localized to mouse chromosome 1 at 74.3 cM and consisted of seven exons spanning 10 kb. The Optc gene was less than 4 kb from the Prelp gene. In situ hybridization localized opticin mRNA exclusively to the presumptive ciliary body during development and to the nonpigmented ciliary epithelium of the adult mouse eye. Expression of Prelp was also detected in the nonpigmented ciliary epithelium of the adult eye. However, expression of collagen types II and IX was detected largely in the developing mouse eye, with type IX expression confined primarily to the presumptive ciliary body. CONCLUSIONS: The Optc, Prelp, and fibromodulin (Fmod) genes form a cluster on mouse chromosome 1. Opticin may represent a marker for ciliary body differentiation. Continued expression of opticin in the adult mouse eye suggests functions other than that of putative regulator of vitreous collagen fibrillogenesis.


Subject(s)
Chromosome Mapping , Chromosomes/genetics , Ciliary Body/metabolism , Extracellular Matrix Proteins/genetics , Eye Proteins/genetics , Proteoglycans/genetics , Amino Acid Sequence , Animals , Base Sequence , Ciliary Body/embryology , Collagen/genetics , Collagen/metabolism , Expressed Sequence Tags , Extracellular Matrix Proteins/metabolism , Eye Proteins/metabolism , Gene Expression , Glycoproteins/genetics , Glycoproteins/metabolism , Humans , In Situ Hybridization , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Polymerase Chain Reaction , Proteoglycans/metabolism , RNA, Messenger/metabolism , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid
16.
J Biol Chem ; 275(3): 2123-9, 2000 Jan 21.
Article in English | MEDLINE | ID: mdl-10636917

ABSTRACT

A prominent 45-kDa component was identified by protein staining following SDS-polyacrylamide gel electrophoresis of a 4 M guanidine hydrochloride extract from bovine vitreous collagen fibrils. Peptide sequences obtained from this component were used as a basis for the cloning (from human retinal cDNA) and sequencing of a novel member of the leucine-rich repeat extracellular matrix protein family that we have named opticin. Opticin mRNA was found by reverse transcription polymerase chain reaction in ligament and skin as well as in retina. An open reading frame containing 332 amino acids was identified, the first 19 amino acids representing a signal peptide. The deduced amino acid sequence of the mature protein encodes a 35-kDa protein with a calculated isoelectric point of 5.4. The central domain of this protein consists of six B-type leucine-rich repeats. This domain is flanked by cysteine clusters including a C-terminal two-cysteine cluster containing an additional leucine-rich repeat. The N-terminal region contains a cluster of potential O-glycosylation sites, and analysis of bovine vitreous opticin demonstrated the presence of sialylated O-linked oligosaccharides substituting the core protein. Opticin shows highest protein sequence identity to epiphycan (42%) and osteoglycin (35%) and belongs to Class III of the leucine-rich repeat extracellular matrix protein family.


Subject(s)
Extracellular Matrix Proteins/chemistry , Extracellular Matrix Proteins/genetics , Extracellular Matrix/chemistry , Vitreous Body/chemistry , Amino Acid Sequence , Animals , Base Sequence , Blotting, Northern , Cattle , Collagen/metabolism , Electrophoresis, Polyacrylamide Gel , Extracellular Matrix Proteins/isolation & purification , Glycoproteins/chemistry , Humans , Intercellular Signaling Peptides and Proteins , Leucine/chemistry , Male , Molecular Sequence Data , Multigene Family , Peptides/metabolism , Phylogeny , Proteoglycans/chemistry , Retina/chemistry , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Amino Acid , Small Leucine-Rich Proteoglycans , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tissue Distribution
17.
Diabet Med ; 14(1): 29-34, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9017350

ABSTRACT

This study evaluates polymorphonuclear neutrophil (PMN) cell performance in 61 diabetic patients free of infection (40 Type 1, 21 Type 2), using tests that explore all the functional steps of PMN: (1) adherence: expression of adhesion molecules, CD 11a, CD 11b, CD 11c; nylon fiber adherence test; (2) chemotaxis under agarose towards the bacterial oligopeptide FMLP and complement fractions, used as attracting agents; (3) phagocytosis of opsonized latex microbeads; (4) bactericidal activity: chemiluminescence assessment of the oxidative killing potential before and after stimulation by opsonized zymosan and PMA; nitroblue tetrazolium reduction test. Results were analysed according to potentially influential factors: metabolic control (HbA1C, glycaemia), age of patient, type of diabetes, disease duration, and existence of vascular complications. PMN chemotaxis was significantly lower in patients than in healthy controls (p < 0.001) and associated with spontaneous adherence and increased expression of adhesion molecules (CD 11b, CD 11c). The increased response to chemiluminescence reflects spontaneous activation of PMN cells and increased free radical production; after stimulation, response was lower than in controls. The type of diabetes, the age of patients, HbA1C level and disease duration did not affect the responses. Chemotaxis and chemiluminescence were further reduced in patients with vascular complications and hyperglycaemia. We conclude that all steps of PMN functioning are altered in diabetic patients, which may increase the risk of vascular complications and infectious episodes.


Subject(s)
Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Neutrophil Activation/physiology , Neutrophils/physiology , Adult , Cell Adhesion/physiology , Chemotaxis, Leukocyte/physiology , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Female , Humans , Male , Middle Aged , Neutrophils/cytology , Phagocytosis/physiology
18.
Bioorg Med Chem ; 3(10): 1357-68, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8564402

ABSTRACT

Six novel docetaxel analogues that possess a N-(7-nitrobenz-2-oxa-1,3-diazo-4-yl)amido-6-caproyl chain in position 7 or 3' (11 and 16a), a N-(7-nitrobenz-2-oxa-1,3-diazo-4-yl)amido-3-propanoyl group at 3' (16b) and a 5'-biotinyl amido-6-caproyl chain in position 7, 10 or 3', respectively, have been synthesized. These compounds exhibit activity against microtubule disassembly similar to that of docetaxel but show discrepant activities on living cells. Although addition of microtubules to 11, 16a and b enhance their fluorescence, no shift of the emission maxima was observed. The fluorescent docetaxel derivatives show a specific labeling of microtubules in living cells, demonstrating that the microtubule cytoskeleton constitutes their main subcellular localization.


Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Paclitaxel/analogs & derivatives , Taxoids , Animals , Antineoplastic Agents, Phytogenic/chemistry , Avidin/chemistry , Biotin/chemistry , Brain Chemistry , Cattle , Cells, Cultured , Docetaxel , Fluorescent Dyes/chemical synthesis , Macropodidae , Magnetic Resonance Spectroscopy , Microtubules/drug effects , Microtubules/metabolism , Paclitaxel/chemical synthesis , Paclitaxel/chemistry , Tubulin/metabolism
19.
J Mal Vasc ; 20(2): 107-12, 1995.
Article in French | MEDLINE | ID: mdl-7650435

ABSTRACT

UNLABELLED: Vascular complications in diabetic patients is a complex, probably multifactorial phenomena involving cellular phagocytosis. The aim of this study was to evaluate polymorphonuclear performance in 61 infection free diabetic patients based on tests of the different cell functions: 1) adhesion:adhesion molecule expression CD11a, CD11b, CD11c; adhesion test on nylon fibers. 2) chemotaxis:chemotaxis under aragose to FMLP (bacteria oligopeptide) and complement fractions. 3) Phagocytosis:latex beads. 4) Bacteriocidal power:chemoluminescence photometric oxidative potential before and after stimulation with opsonized zymosan and PMA; reduction of tetrazolium nitroblue. RESULTS were analyzed according to type of diabetes, glucose control, duration of the disease, history of infection and presence of vascular complications. RESULTS: compared with a group of 30 controls, the diabetic patients had a significant impaired polynuclear chemotaxis function (p < 0.001) with both spontaneous adhesion and increased expression of adhesion molecules (CD 11b, CD 11c). The chemoluminescence test was increased at the baseline level due to spontaneous polynuclear adhesion and increased production of free radicals. This response decreased after stimulation compared with controls. The type of diabetes, Hb A1c level and history of infection did not appear to have an effect. Inversely, changes in chemotaxis and chemoluminescence were greater in patients with vascular complications. In summary, all the functions of polynuclear neutrophils tested were altered in diabetic patients and could favor vascular complications and infections episodes.


Subject(s)
Diabetes Mellitus/blood , Diabetic Angiopathies/blood , Neutrophils/physiology , Adult , Aged , Antigens, CD/blood , Basal Metabolism , Blood Bactericidal Activity , Case-Control Studies , Chemotaxis, Leukocyte , Evaluation Studies as Topic , Humans , Luminescent Measurements , Middle Aged , Phagocytosis , Stimulation, Chemical
20.
J Clin Periodontol ; 21(3): 177-83, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8157770

ABSTRACT

The polymorphonuclear neutrophil (PMN) appears to be an important cell in the protection of the host from pathogenic periodontal microorganisms and, despite some reports to the contrary, it is generally assumed that early-onset forms of periodontal disease (including both juvenile and rapidly progressing periodontitis) are associated with a defect in PMN chemotactic behaviour. The purpose of the present study was to examine the peripheral PMN chemotactic behaviour, using the under agarose method, in 4 groups, namely healthy periodontium group (n = 7), gingivitis group (n = 8), early-onset periodontitis group (n = 17) and adult periodontitis group (n = 8). PMN from early-onset periodontitis patients showed normal random and chemotactic locomotory behaviour when compared with those of PMN from subjects of the other groups. No statistically significant difference could be found among the 4 studied groups, with regard to spontaneous and oriented migration.


Subject(s)
Aggressive Periodontitis/immunology , Chemotaxis, Leukocyte , Neutrophils/immunology , Periodontitis/immunology , Adult , Age of Onset , Analysis of Variance , Electrophoresis, Agar Gel/methods , Female , Gingivitis/immunology , Humans , Male
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