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1.
Cytotherapy ; 12(7): 881-7, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20662612

ABSTRACT

BACKGROUND AIMS: Age-related changes that could affect the biologic features of mesenchymal stromal cells (MSC), such as a decrease in proliferation and osteoblast differentiation capacity and an increase of senescence markers and apoptosis, have been reported recently. The aim of this study was the evaluation of age-related characteristics and the correlation of age with the functional properties of MSC. METHODS: The doubling time (DT), colony-forming unit­fibroblast (CFU-F) colonies and surface antigen expression of MSC isolated from bone marrow (BM) of children (C-MSC) were compared with those from adults (A-MSC). The expression of Oct-4 and Nanog transcripts and the relative telomere length were evaluated in both groups. RESULTS: DT values were lower in C-MSC compared with A-MSC, and a higher CFU-F count was observed in children. However, the expression of Oct-4 and Nanog did not differ between C-MSC and A-MSC and was not correlated with the proliferative capacity. The telomere length was significantly higher in C-MSC compared with A-MSC. CONCLUSIONS: These data suggest that children's BM-derived MSC could be a more advantageous source of these cells for tissue engineering and cell therapy.


Subject(s)
Aging/metabolism , Cell Differentiation , Cell Proliferation , Mesenchymal Stem Cells/metabolism , Pluripotent Stem Cells/metabolism , Adult , Aging/genetics , Aging/pathology , Antigens, CD/metabolism , Biomarkers/metabolism , Bone Marrow/pathology , Cells, Cultured , Cellular Senescence , Child, Preschool , Colony-Forming Units Assay , Homeodomain Proteins/biosynthesis , Homeodomain Proteins/genetics , Humans , Immunophenotyping , Mesenchymal Stem Cells/pathology , Middle Aged , Nanog Homeobox Protein , Octamer Transcription Factor-3/biosynthesis , Octamer Transcription Factor-3/genetics , Pluripotent Stem Cells/pathology
2.
Pediatr Blood Cancer ; 52(3): 318-23, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18989891

ABSTRACT

Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children. Inherited predisposition and exposure to exogenous leukemogenic agents have been investigated as potential risk factors. Current therapy results in 5-year event-free survival exceeding 80% in children in developed countries. Predisposition to ALL and event-free outcome seems to be influenced by polymorphisms on genes involved in several metabolic pathways. The purpose of this review is to discuss the findings of different studies upon the role of gene polymorphisms in childhood ALL.


Subject(s)
Polymorphism, Genetic/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Child , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Folic Acid/metabolism , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism
3.
Tissue Eng Part B Rev ; 14(1): 53-60, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18454634

ABSTRACT

Stem cells are the self-renewing progenitors of several body tissues and are classified according to their origin and their ability to differentiate. Current research focuses on the potential uses of stem cells in medicine and how they can provide effective treatment for a range of diseases. This approach has resulted in the field of medical practice called regenerative medicine. To attain the promises of regenerative medicine, it is necessary to fully understand the biology and properties of stem cells, achieve their successful differentiation into functional tissues, overcome the barriers related to immune responses after administration, and assess any oncogenic properties that limit their use. The availability of human stem cells not only raises hope for cell replacement therapies, but also provides a system for understanding the mechanisms of embryonic development and disease progression. Nevertheless, it raises ethical concerns that need to be addressed before the use of stem cells in clinical practice.


Subject(s)
Regenerative Medicine/methods , Stem Cells/cytology , Adult Stem Cells/cytology , Animals , Bone Marrow Cells/cytology , Cell Differentiation , Cell Lineage , Cell Proliferation , Cell- and Tissue-Based Therapy/methods , Embryonic Stem Cells/cytology , Fetal Research , Humans , Immune System , Stem Cell Transplantation , Stem Cells/pathology
4.
Genet Test ; 10(3): 192-9, 2006.
Article in English | MEDLINE | ID: mdl-17020471

ABSTRACT

Familial Hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol (LDL-C) concentrations that frequently gives rise to premature coronary artery disease. The clinical expression of FH is highly variable, even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental and other genetic factors. We investigated the effect of APOCIII T1100C, FV Gln506Arg, ADRB2 Glu27Gln, SELE Ser128Arg, SELE Leu554Phe, and ENaCa Ala663Thr polymorphisms on the HDL-C variations in 84 patients with FH. For ApoCIII T1100C, subjects with the TT genotype presented higher HDL-C levels than the other genotype groups (p = 0.046). Similarly the presence of the Gln allele in ADRB2 27 Glu/Gln heterozygotes and ADRB2 27 Gln/Gln homozygotes was associated with higher HDL-C levels (p = 0.014). Among the other polymorphisms tested, none of them were associated with variations in HDL-C levels. The influence of each polymorphism on lipid concentrations was evaluated with linear regression analyses after adjustment for age and sex. Among the variables studied including total cholesterol, LDL-C, high-density lipoprotein (HDL)-C, triglycerides, apolipoprotein A (Apo-A) and B (Apo-B), and lipoprotein alpha (LP alpha), HDL-C concentration was significantly different in models applied for polymorphisms ApoCIII T1100C, FV Gln506Arg, and ADRB2 Glu27Gln (p = 0.01, p = 0.018, p = 0.04, respectively). These results suggest that HDL-C levels in FH heterozygotes may be affected by several different genetic variants.


Subject(s)
Cholesterol, HDL/blood , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/genetics , Polymorphism, Genetic , Adult , Female , Greece , Humans , Male , Middle Aged
5.
Clin Chem Lab Med ; 44(7): 799-806, 2006.
Article in English | MEDLINE | ID: mdl-16776623

ABSTRACT

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein-cholesterol (LDL-C) concentrations, which frequently gives rise to premature coronary artery disease. The clinical expression of FH is highly variable, even in patients carrying the same LDL receptor (LDLR) gene mutation. This variability may be due to environmental and other genetic factors. METHODS: We investigated paraoxonase 2 (PON 2) Ser311Cys, lipoprotein lipase (LPL) Asn291Ser, plasminogen activator inhibitor-1 (PAI-1) T11053G, beta-fibrinogen (FGB) -455 G>A and nitric oxide synthase gene (NOS) -922 A>G polymorphisms in 84 patients with FH. The effect of polymorphisms as independent factors of high lipid values was evaluated. RESULTS: The PON 2 Cys311 allele was correlated with high total cholesterol and LDL-C and apolipoprotein B levels, while LPL Asn291, PAI-1 T11053, FGB -455 G and NOS -922 A alleles were correlated with high apolipoprotein B levels. CONCLUSIONS: These results suggest that apolipoprotein B levels in FH heterozygotes may be affected by several different genetic variants.


Subject(s)
Apolipoproteins B/blood , Apolipoproteins B/genetics , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/genetics , Polymorphism, Genetic/genetics , Adult , Alleles , Female , Genotype , Greece , Humans , Lipid Metabolism , Male
6.
J Clin Lab Anal ; 20(3): 98-104, 2006.
Article in English | MEDLINE | ID: mdl-16721833

ABSTRACT

Atrial natriuretic peptide (ANP or NPPA) is the precursor protein of the form of amyloidosis called isolated atrial amyloid (IAA), which is related to the increased incidence of cardiac pathological conditions with age. Familial hypercholesterolemia (FH) patients are characterized by high concentrations of low-density lipoprotein cholesterol (LDL-C), which frequently gives rise to premature coronary artery disease (CAD). However, not all FH patients have the same clinical phenotype. The aim of the present study was to assess the relationship between ANP polymorphisms and apolipoprotein (Apo) A1 levels and CAD risk in FH patients. Transition T2238C, which leads to ANP with two additional arginines, and G664A (Val7Met) were investigated with lipid values and clinical phenotype in 83 FH patients. ApoA1 and HDL cholesterol levels were lower in GA patients compared to GG homozygotes for the G664A polymorphism. No association was found between the G664A polymorphism and CAD in our population. Moreover, ApoA1 and high-density lipoprotein cholesterol (HDL-C) levels did not differ among the different genotypes of the T2238C polymorphism, even after adjusting for age and sex. The 664A allele of the ANP polymorphism is associated with lower levels of ApoA1 and HDL-C in FH patients, but not with CAD risk. Concerning the T2238C polymorphism, no effect was found on lipid parameters or CAD incidence.


Subject(s)
Atrial Natriuretic Factor/genetics , Coronary Artery Disease/genetics , Genetic Predisposition to Disease , Hyperlipoproteinemia Type II/genetics , Polymorphism, Single Nucleotide , Adult , Atrial Natriuretic Factor/blood , Comorbidity , Coronary Artery Disease/blood , Coronary Artery Disease/epidemiology , Female , Greece/epidemiology , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/epidemiology , Lipids/blood , Male , Risk Factors , Valine/genetics
7.
Angiology ; 57(6): 729-32, 2006.
Article in English | MEDLINE | ID: mdl-17235114

ABSTRACT

A 13-year-old Greek boy with severe dyslipidemia, large tuberous xanthomas over the knees and elbows, Achilles' tendon xanthomas, and a bilateral corneal arcus was referred to the Lipid Clinic. He had a supravalvular aortic stenosis, 50% to 60% stenosis of both carotid arteries, and normal coronary arteries. Familial hypercholesterolemia was clinically diagnosed. A V408M null low-density lipoprotein receptor (LDLR) mutation was identified in homozygosity. He responded to lipid-lowering drugs by decreasing total cholesterol by 32%, low-density lipoprotein cholesterol by 33%, and triglyceride levels by 30%. Additional treatment with low-density lipoprotein-apheresis further decreased total cholesterol by 52%, low-density lipoprotein cholesterol by 55%, and triglycerides by 43%. Low-density lipoprotein cholesterol levels between apheresis sessions showed a declining pattern. A significant regression of tuberous xanthomas was noted. A suitable combination of lipid-lowering drugs is effective even in this case of homozygosity for a null LDLR mutation. Furthermore, the coadministration of statins, cholestyramine, and ezetimibe during low-density lipoprotein-apheresis tends to counterbalance the postapheresis relapse in low-density lipoprotein cholesterol levels.


Subject(s)
Hypercholesterolemia/drug therapy , Hypolipidemic Agents/therapeutic use , Mutation , Receptors, LDL/genetics , Adolescent , Anticholesteremic Agents/therapeutic use , Azetidines/therapeutic use , Blood Component Removal , Cholesterol/blood , Cholesterol, LDL/blood , Cholestyramine Resin/therapeutic use , Ezetimibe , Homozygote , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/genetics , Male , Triglycerides/blood
8.
Clin Chem Lab Med ; 43(8): 793-801, 2005.
Article in English | MEDLINE | ID: mdl-16201887

ABSTRACT

Familial hypercholesterolemia is an autosomal dominant disease defined at the molecular level mainly by the presence of mutations in the low-density lipoprotein receptor gene and is characterized by elevated low-density lipoprotein cholesterol, tendon xanthomas and increased risk of early cardiovascular disease. The type of mutation in the low-density lipoprotein receptor gene has been associated with different phenotype expression and response to statins. Several studies have been undertaken to assess the efficacy of statins and evaluate the influence of mutations on the response to treatment with statins. Not all patients respond to statin therapy with a reduction in cardiovascular disease. In this review paper, we will discuss the results available to date that correlate the low-density lipoprotein receptor genotype to the response to statins, and the interest in developing diagnostic systems which will allow identification of patients at increased risk of adverse drug reactions or patients in which a therapeutic effect is lacking.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemia Type II/drug therapy , Hyperlipoproteinemia Type II/genetics , Receptors, LDL/genetics , Genotype , Humans , Hyperlipoproteinemia Type II/blood , Lipoproteins, LDL/blood , Mutation , Phenotype
9.
Obes Res ; 12(7): 1037-41, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15292466

ABSTRACT

Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in many tissues. A polymorphism in the IL-6 gene, associated with differences in IL-6 transcription rate, has been recently described. Subjects with the -174GG genotype are prone to lipid abnormalities. We investigated the effect of the G-174C IL-6 polymorphism on health indices and lipid values of 184 Greek primary school children. The genotype distribution of the polymorphism was 37.5% for GG and 52.2% and 10.3% for GC and CC, respectively. No differences were observed between genotype distribution and gender (p = 0.37). Boys homozygous for the G allele showed higher triglyceride levels than boys carrying the C allele (86 +/- 28 vs. 74 +/- 20 mg/dL, p = 0.02) and lower mid-upper arm muscle circumference (17.46 +/- 1.86 vs. 18.91 +/- 2.53 cm, p = 0.013). In addition, girls homozygous for the G allele had higher values for suprailiac skinfolds compared with those bearing the C allele (21.28 +/- 12.56 vs. 17.09 +/- 13.36 mm, p = 0.06). These findings were confirmed by multiple linear regression analysis, after controlling for age, sex, BMI, energy and total fat intake, and weekly physical activity. From the results of the present study, we concluded that individuals homozygous for G allele on the IL-6 gene have higher values in some parameters associated with obesity.


Subject(s)
Health Status Indicators , Interleukin-6/genetics , Obesity/genetics , Polymorphism, Genetic , Schools , Students , Alleles , Anthropometry , Blood Glucose/analysis , Body Mass Index , Child , Cholesterol/blood , Diet , Exercise , Female , Greece , Homozygote , Humans , Linear Models , Male , Polymorphism, Restriction Fragment Length , Sex Characteristics , Skinfold Thickness , Triglycerides/blood
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