ABSTRACT
PURPOSE: Varicocele repair in non-obstructive azoospermia (NOA) was occasionally associated to ejaculated spermatozoa independently from clinical and laboratory measures. We performed a prospective study in infertile men affected by NOA and left side varicocele to find whether or not the appearance of ejaculated spermatozoa after varicocele repair is predicted by baseline measures. METHODS: Patients with NOA and grade II, or grade III left side varicocele were submitted to hormone analysis and to scrotal color Doppler ultrasound (CDU). Azoospermia was confirmed in 23 patients aged 25-47 years who were than submitted to varicocele repair through a retrograde internal spermatic vein embolization. Patients were re-evaluated after 6 months. RESULTS: Six months after varicocele repair 12 patients (52.2 %) were still azoospermic (Group 1) while 11 patients (47.8 %) reported ejaculated spermatozoa (Group 2) [sperm count: 1.3 × 10(6)/mL; 0.5 × 10(6)/mL-1.6 × 10(6)/mL (median 25th-75th centiles)]. Serum baseline FSH was lower in Group 2 compared to Group 1 (p = 0.012), while no differences between groups were revealed for all other clinical and laboratory parameters. ROC analysis indicated that baseline FSH level predicted the appearance of ejaculated spermatozoa after treatment [AUC = 0.811; 95 % Confidence Interval (CI) 0.6-0.9; p = 0.0029]. A cut-off level of FSH <10.06 mIU/mL identified 82.0 % of cases with ejaculated spermatozoa with a specificity of 81.8 % and a sensitivity of 83.3 %. CONCLUSION: Selected patients with NOA may show ejaculated spermatozoa after a non-invasive repair of a left side varicocele, therefore avoiding testicular sperm extraction. Baseline serum FSH was a valuable predictor for ejaculated spermatozoa after treatment.
Subject(s)
Azoospermia/blood , Azoospermia/surgery , Ejaculation , Embolization, Therapeutic , Follicle Stimulating Hormone/blood , Spermatozoa , Varicocele/surgery , Adult , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases. The mechanisms underlying this process are poorly understood, but probably include genetic, epigenetic alterations and changes in fetal nutrient supply. We have studied the microRNA (miRNA) expression profile in amnion from obese and control women at delivery to investigate if a specific miRNA signature is associated with obesity. The expression profile of 365 human miRNAs was evaluated with the TaqMan Array in amnion from 10 obese and 5 control (prepregnancy body mass index (BMI) >30 and <25 kg m(-2), respectively) women at delivery. Target genes and miRNA-regulated pathways were predicted by bioinformatics. Anthropometric and biochemical parameters were also measured in mothers and newborns. Seven miRNAs were expressed only in obese women (miR-422b, miR-219, miR-575, miR-523, miR-579, miR-618 and miR-659), whereas 13 miRNAs were expressed at a higher level and 12 miRNAs at a lower level in obese women than in controls. MicroRNAs significantly downregulated the neurotrophin, cancer/ErbB, mammalian target of rapamycin, insulin, adipocytokine, actin cytoskeleton and mitogen-activated protein kinase signaling pathways. In conclusion, we show that the miRNA profile is altered in amnion during obesity and hypothesize that this could affect pathways important for placental growth and function, thereby contributing to an increase in the newborn's risk of future metabolic diseases.
Subject(s)
Adiponectin/metabolism , Amnion/metabolism , Metabolic Syndrome/prevention & control , MicroRNAs/metabolism , Mothers , Obesity/complications , Adult , Computational Biology , Female , Fetal Blood/metabolism , Gene Expression Profiling , Humans , Infant Nutritional Physiological Phenomena , Infant, Newborn , Male , Obesity/blood , Pregnancy , Prenatal Exposure Delayed Effects , Signal TransductionABSTRACT
Helper-dependent adenoviral (HD-Ad) vectors have great potential for gene therapy applications; however, their administration induces acute toxicity that impairs safe clinical applications. We previously observed that PEGylation of HD-Ad vectors strongly reduces the acute response in murine and primate models. To evaluate whether PEGylated HD-Ad vectors combine reduced toxicity with the correction of pathological phenotypes, we administered an HD-Ad vector expressing the human apolipoprotein A-I (hApoA-I) to low-density lipoprotein (LDL)-receptor-deficient mice (a model for familial hypercholesterolemia) fed a high-cholesterol diet. Mice were treated with high doses of HD-Ad-expressing apo A-I or its PEGylated version. Twelve weeks later, LDL levels were lower and high-density lipoprotein (HDL) levels higher in mice treated with either of the vectors than in untreated mice. After terminal killing, the areas of atherosclerotic plaques were much smaller in the vector-treated mice than in the control animals. Moreover, the increase in pro-inflammatory cytokines was lower and consequently the toxicity profile better in mice treated with PEGylated vector than in mice treated with the unmodified vector. This finding indicates that the reduction in toxicity resulting from PEGylation of HD-Ad vectors does not impair the correction of pathological phenotypes. It also supports the clinical potential of these vectors for the correction of genetic diseases.
Subject(s)
Adenoviridae/genetics , Apolipoprotein A-I/genetics , Genetic Therapy , Genetic Vectors , Helper Viruses/genetics , Hyperlipoproteinemia Type II/genetics , Hyperlipoproteinemia Type II/therapy , Animals , Cholesterol, HDL/blood , Cholesterol, HDL/metabolism , Cholesterol, LDL/blood , Cholesterol, LDL/metabolism , Cytokines/genetics , Disease Models, Animal , Female , Gene Expression , Humans , Hyperlipoproteinemia Type II/pathology , Mice , Mice, Inbred C57BL , Plaque, Atherosclerotic/pathology , Plaque, Atherosclerotic/therapy , Polyethylene Glycols , Receptors, LDL/deficiency , Receptors, LDL/geneticsABSTRACT
BACKGROUND AND AIMS: The insulin resistance (IR) is a major metabolic impairment in severe obesity, a multifactorial disease in which the importance of the effect of single nucleotide polymorphisms (SNP) associations in different rather than individual genes was established. The aim of this study was to test the predictive value of presence/absence of polymorphisms/ variants in ß3-adrenergic receptor (ADRB3), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor γ (PPARγ), and adiponectin (ADIPOQ) genes in diagnosing the IR in obesity. SUBJECTS AND METHODS: We studied 112 (40 males, 72 females) severely obese (body mass index: 48.5±7.5 kg/m2) subjects recruited from the outpatient obesity clinic of Federico II University Hospital in Naples. Genomic DNA was extracted from peripheral leukocytes with a commercial kit. The gene polymorphisms Trp64Arg in ADRB3, -3826 A>G in UCP1, Pro12Ala in PPARγ, and c.268G>A, c.331T>C, and c.334C>T in ADIPOQ were characterized by TaqMan assay or by direct sequencing (ADIPOQ). RESULTS AND CONCLUSION: Our results demonstrate that -3826A>G UCP1 polymorphism is associated with IR in morbid obesity. Further, the lack of any polymorphisms, Trp64Arg in ADRB3 and/or -3826 A>G in UCP1 and/or Pro12Ala in PPARγ and/or c.268G>A, c.331T>C and c.334C>T in ADIPOQ, appears a useful prognostic factor (NPV=100%) toward the IR onset in these obese patients representing a further parameter for an earlier and appropriate therapy.
Subject(s)
Adiponectin/genetics , Insulin Resistance/genetics , Ion Channels/genetics , Mitochondrial Proteins/genetics , Obesity, Morbid/genetics , PPAR gamma/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Adrenergic, beta-3/genetics , Adult , Blood Glucose , Body Mass Index , DNA/genetics , Female , Humans , Insulin , Male , Polymerase Chain Reaction , Uncoupling Protein 1ABSTRACT
OBJECTIVE: The objective of the study was to look for uncoupling protein 3 (UCP3) gene variants in early-onset severe childhood obesity and to determine their effect on long-chain fatty acid oxidation and triglyceride storage. METHODS AND RESULTS: We identified four novel mutations in the UCP3 gene (V56M, A111V, V192I and Q252X) in 200 children with severe, early-onset obesity (body mass index-standard deviation score >2.5; onset: <4 years) living in Southern Italy. We evaluated the role of wild-type (wt) and mutant UCP3 proteins in palmitate oxidation and in triglyceride storage in human embryonic kidney cells (HEK293). Palmitate oxidation was â¼60% lower (P<0.05; P<0.01) and triglyceride storage was higher in HEK293 cells expressing the four UCP3 mutants than in cells expressing wt UCP3. Moreover, mutants V56M and Q252X exerted a dominant-negative effect on wt protein activity (P<0.01 and P<0.05, respectively). Telmisartan, an angiotensin II receptor antagonist used in the management of hypertension, significantly (P<0.05) increased palmitate oxidation in HEK293 cells expressing wt and mutant proteins (P<0.05; P<0.01), including the dominant-negative mutants. CONCLUSIONS: These data indicate that protein UCP3 affects long-chain fatty acid metabolism and can prevent cytosolic triglyceride storage. Our results also suggest that telmisartan, which increases fatty acid oxidation in rat skeletal muscle, also improves UCP3 wt and mutant protein activity, including the dominant-negative UCP3 mutants.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Benzimidazoles/pharmacology , Benzoates/pharmacology , HEK293 Cells/metabolism , Ion Channels/metabolism , Mitochondrial Proteins/metabolism , Muscle, Skeletal/metabolism , Obesity/metabolism , Triglycerides/metabolism , Age of Onset , Angiotensin II Type 1 Receptor Blockers/pharmacology , Child , Child, Preschool , Fatty Acids/genetics , Fatty Acids/metabolism , Female , Genetic Variation , HEK293 Cells/drug effects , Humans , Infant , Ion Channels/drug effects , Ion Channels/genetics , Italy/epidemiology , Lipid Metabolism/drug effects , Male , Mitochondrial Proteins/drug effects , Mitochondrial Proteins/genetics , Muscle, Skeletal/drug effects , Mutation/genetics , Obesity/drug therapy , Obesity/genetics , Oxidation-Reduction , Phosphorylation/drug effects , Phosphorylation/genetics , Telmisartan , Triglycerides/genetics , Uncoupling Protein 3ABSTRACT
BACKGROUND: Despite intense debate regarding whether minimally invasive techniques for total knee arthroplasty improve clinical outcomes over standard techniques, few prospective randomized trials addressing this debate are available in the literature. We therefore designed this multicenter study to assess the overall safety and effectiveness of a minimally invasive approach without the use of computer navigation in comparison with conventional knee arthroplasty. METHODS: We prospectively randomized 134 patients (101 women and thirty-three men, with an average age of 70.1 years) to undergo surgery for total knee arthroplasty with use of either minimally invasive knee instruments (sixty-six patients) or a standard approach (sixty-eight patients). The follow-up period was one year. RESULTS: On the basis of our sample size, no significant difference was detected between the groups in any of the relevant clinical areas assessed: total range of motion, Knee Society total and function scores, and visual analog scores for pain and activities of daily living. Patients who underwent minimally invasive surgery had a longer mean surgical time (by 5.6 minutes) and had less mean blood loss (by 17 mL). Radiographic measurements demonstrated reliable implant positioning in both groups. Seven patients in each group had an adverse event related to their procedure. CONCLUSIONS: On the basis of the numbers, no significant advantage to minimally invasive total knee arthroplasty over a conventional technique was observed. Greater sample sizes and a longer follow-up period are required to fully determine the long-term safety and efficacy of this minimally invasive surgical technique.
Subject(s)
Arthroplasty, Replacement, Knee/methods , Minimally Invasive Surgical Procedures/methods , Aged , Blood Loss, Surgical , Female , Follow-Up Studies , Humans , Male , Prospective StudiesABSTRACT
Male infertility is correlated with several genetic and non-genetic conditions. Microdeletions of Y chromosome are one of the most frequent genetic defects associated with male infertility. Evaluating this in infertile patients is important to assess an etiological diagnosis and possible prognosis of infertility, as well as to address clinical decision during treatment of infertility by intracytoplasmatic sperm injection, where the probability of success depends on the type and the number of deleted regions (azoospermia factor regions). To improve genetic counseling, it is useful to characterize Yq regions by a rapid and accurate method. In the current study, we evaluated the diagnostic efficiency and the time required of an in-house automated capillary electrophoresis method for Y microdeletions screening and applied it to estimate the prevalence of Y microdeletions in 100 infertile males affected by azoospermia or severe oligozoospermia (sperm count <5x10(6)/ml) and in 100 fertile male controls. In south Italian infertile men, the overall frequency of Y microdeletions was 9% (12.7% in azoospermic and 4.5% in severe oligozoospermic men). In conclusion, we think that the abovementioned procedure is suitable for the routine characterization of Y microdeletions.
Subject(s)
Azoospermia/genetics , Chromosome Deletion , Chromosomes, Human, Y , Oligospermia/genetics , Adult , Azoospermia/epidemiology , Case-Control Studies , Chromosomes, Human, Y/genetics , DNA Mutational Analysis/methods , Electrophoresis, Capillary/methods , Genetic Loci , Genetic Testing/methods , Humans , Italy/epidemiology , Karyotyping/methods , Male , Oligospermia/epidemiology , Prevalence , Seminal Plasma Proteins/genetics , Time Factors , Young AdultABSTRACT
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are well-recognized complications of obesity. This study was designed to evaluate the role of the UCP1 -3826 A>G polymorphism, adiponectin levels, leptin/adiponectin ratio (L/A), and main biochemical parameters in 102 unrelated severely obese adults [61 females and 41 males, median body mass index (BMI) = 47.8 kg/m2] with NAFLD, with (MS+) or without MS (MS-) from Southern Italy. SUBJECT AND METHODS: The UCP1 polymorphism was tested by the TaqMan method, main biochemical parameters by routinary methods, adiponectin, and leptin serum levels by enzyme-linked immunosorbent assay. MS was diagnosed according to the American Heart Association criteria, liver steatosis was detected by ultrasound. RESULTS: MS was present in 53% male and 66% female obese patients. Only total cholesterol (p=0.04 males and p=0.002 females) and L/A ratio (p=0.03 males) differed between MS+ and MS- obese patients. At multivariate analysis, severe liver steatosis was significantly associated with: UCP1 (AG+GG) genotypes [odds ratio-confidence interval (OR-CI): 4.25; 1.12-16.13], MS (OR-CI: 8.47; 1.78-40.25), low adiponectin levels (OR-CI: 0.92; 0.87-0.98), high alanine aminotransferase levels (OR-CI: 1.03; 1.00-1.06), age (ORCI: 1.08; 1.00-1.15), and male gender (OR-CI: 10.78; 1.61- 71.96). CONCLUSION: In addition to traditional factors, total cholesterol and L/A ratio appear to contribute to MS characterization in severe obesity. Furthermore, the UCP1 (AG+GG) genotypes and low adiponectin levels could predispose to a more severe liver steatosis independently of MS presence. Based on our data, polymorphic UCP1 (AG+GG) obese patients with low adiponectin levels appear to be high-risk subjects for worsening of liver steatosis, a NAFLD, possibly requiring a second-step evaluation by liver biopsy.
Subject(s)
Adiponectin/metabolism , Ion Channels/genetics , Leptin/metabolism , Mitochondrial Proteins/genetics , Obesity, Morbid/genetics , Obesity, Morbid/metabolism , Adiponectin/blood , Adolescent , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Blood Glucose/analysis , Cholesterol/blood , Fatty Liver/blood , Fatty Liver/genetics , Fatty Liver/metabolism , Female , Humans , Insulin/blood , Ion Channels/metabolism , Italy , Leptin/blood , Male , Metabolic Syndrome/blood , Metabolic Syndrome/genetics , Metabolic Syndrome/metabolism , Middle Aged , Mitochondrial Proteins/metabolism , Obesity, Morbid/blood , Polymorphism, Single Nucleotide , Statistics, Nonparametric , Triglycerides/blood , Uncoupling Protein 1 , Young Adult , gamma-Glutamyltransferase/bloodABSTRACT
BACKGROUND: Severe obesity is a major worldwide public health concern affecting 0.5-5% of the adult population. Adiponectin (Acpr30), an adipokine secreted from adipocytes, shows pleiotropic beneficial effects on obesity and related disorders. In this study, sequence analysis of Acpr30 gene (ACDC) was performed in a highly selected population of severely obese young adult patients from Southern Italy to investigate the associations between polymorphisms in the ACDC gene and the development of severe obesity concomitantly with other features of the metabolic syndrome. METHODS: The ACDC gene was analyzed by direct sequencing in the severely obese patients (n=220) and compared to healthy controls (n=116). The associations between the ACDC gene single-nucleotide polymorphisms (SNPs) and the levels of serum Acpr30 as well as the correlation with the presence of severe obesity jointly associated with other features of the metabolic syndrome were also investigated. Total serum Acpr30 concentrations were measured by the ELISA method. RESULTS: ACDC gene molecular screening revealed the presence of previously described SNPs and a new nucleotide alteration, c.355T>G, leading to a protein variant, p.L119V. Measurement of serum concentration of Acpr30 demonstrated lower levels of Acpr30 in the obese population compared to controls (30.5+/-28.3 vs. 43.9+/-35.7 microg/ml, p<0.01); in particular, significantly lower Acpr30 concentrations were observed in obese patients bearing c.-11377C>G SNP CG+GG genotypes than in those with CC genotype (22.9+/-20.5 vs. 33.1+/-29.4 microg/ml, p<0.05). CONCLUSIONS: Our results confirmed that low serum levels of Acpr30 are related to severe obesity and a difference in protein expression is associated with variants in ACDC gene promoter region.
Subject(s)
Obesity, Morbid/blood , Obesity, Morbid/genetics , Polymorphism, Single Nucleotide , Adiponectin/blood , Adiponectin/genetics , Adult , Body Mass Index , Case-Control Studies , Chi-Square Distribution , Female , Genotype , Humans , Italy/epidemiology , Male , Metabolic Syndrome/blood , Metabolic Syndrome/genetics , Mutation , Polymorphism, Single Nucleotide/genetics , Promoter Regions, GeneticABSTRACT
OBJECTIVES: Polymorphisms in the major histocompatibility complex class I chain-related gene A may influence its binding to the Natural Killer Cell Receptor G2D (NKG2D). We looked for polymorphisms in major histocompatibility complex class I chain-related gene A exon 5 and in Human Leukocyte Antigen (HLA)-DQ/DR in adult coeliac disease patients to determine whether they affected coeliac disease phenotypes. METHODS: Adult coeliac disease patients with (n=98) and without (n=93) gastrointestinal symptoms (gastrointestinal symptoms+/gastrointestinal symptoms-) and 108 control subjects from Campania (Italy) were characterized by Polymerase Chain Reaction (PCR) sequence specific oligonucleotide followed by PCR sequence specific primer assays for HLA DQ/DR, and by PCR followed by capillary electrophoresis for major histocompatibility complex class I chain-related gene A exon 5 polymorphisms. Immunoglobulin A (IgA) anti-transglutaminase antibodies were also evaluated by immunosorbent assay. RESULTS: Five different major histocompatibility complex class I chain-related gene A alleles were detected in both coeliac disease patients and control subjects. The major histocompatibility complex class I chain-related gene A 5.1 allele occurred more frequently in patients than in controls (p<0.05), and the major histocompatibility complex class I chain-related gene A 5.1/5.1 homozygous genotype increased the risk of gastrointestinal symptoms- coeliac disease (OR=2.79, 95% CI 1.15-6.79). Gastrointestinal symptoms- coeliac disease patients bearing major histocompatibility complex class I chain-related gene A 5.1/5.1 alleles showed lower anti-transglutaminase levels (18U/L) than the gastrointestinal symptoms+ coeliac disease patients (35U/L). HLA-DQ2/DQ8 genotypes did not differ between gastrointestinal symptoms+ and gastrointestinal symptoms- coeliac disease, although DQ8 tended to be more frequent in gastrointestinal symptoms- coeliac disease (11.7%) than in gastrointestinal symptoms+ coeliac disease (6%). CONCLUSIONS: Our study shows that a double dose of the major histocompatibility complex class I chain-related gene A 5.1 allele could predispose to the onset of gastrointestinal symptoms- coeliac disease. We can hypothesize that a lower level of immunological involvement in gastrointestinal symptoms- coeliac disease patients is associated with absence of gastrointestinal symptoms. This test could represent a second step in the genetic typing of high-risk subjects such as first-degree relatives of coeliac disease patients positive for the DQ2/DQ8 molecule.
Subject(s)
Celiac Disease/epidemiology , Celiac Disease/genetics , Histocompatibility Antigens Class I/genetics , Adult , Female , Genetic Predisposition to Disease , Genotype , HLA-DQ Antigens , HLA-DR Antigens , Humans , Italy/epidemiology , Male , Polymorphism, Genetic , PrevalenceABSTRACT
OBJECTIVE: To evaluate the prevalence of beta(3)-adrenergic receptor (ADRB3) Trp64Arg polymorphism and its relationship with the metabolic syndrome in severe obesity. DESIGN: Cross-sectional outpatients study. PATIENTS AND METHODS: In 265 (100 men) severely obese non-diabetic subjects and 78 (25 men) healthy volunteers, genomic DNA was isolated from peripheral leukocytes. In obese patients, plasma concentrations of leptin, lipids, glucose and insulin, the homeostasis model assessment index and blood pressure have been measured. The Trp64Arg mutation was identified with the real-time TaqMan method. RESULTS: Neither genotype distribution nor allele frequency differed between the two groups. The metabolic syndrome prevalence was 59% in obese subjects, and was higher in men than in women (65 vs 55%: P=0.03). The body mass index (BMI) was related to age tertiles (beta=0.08; P<0.001; multiple linear regression) in Trp64Arg-positive obese subjects. CONCLUSION: We confirm the high prevalence of the metabolic syndrome among severely obese subjects. ADRB3 polymorphism was significantly related to insulin resistance only in obese male subjects. Moreover, increased BMI was related to age in obese subjects with the ADRB3 polymorphism.
Subject(s)
Metabolic Syndrome/genetics , Obesity, Morbid/complications , Polymorphism, Genetic , Receptors, Adrenergic, beta-3/genetics , Adult , Age Factors , Blood Glucose/analysis , Body Mass Index , Cross-Sectional Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Insulin/blood , Italy/epidemiology , Leptin/blood , Leukocytes/metabolism , Linear Models , Lipids/blood , Male , Metabolic Syndrome/epidemiology , Mutation , Obesity, Morbid/blood , Obesity, Morbid/genetics , Sex FactorsSubject(s)
Antigens, CD1/analysis , Antigens, CD34/analysis , Leukemia-Lymphoma, Adult T-Cell/immunology , Receptors, Antigen, T-Cell, alpha-beta/analysis , T-Lymphocytes/immunology , Adolescent , Cell Line , Female , Genes, T-Cell Receptor beta , Humans , Immunophenotyping , Leukemia-Lymphoma, Adult T-Cell/genetics , Leukemia-Lymphoma, Adult T-Cell/pathologyABSTRACT
AIMS: To evaluate the complement factor H (CFH) p.402Y>H polymorphism as a risk factor in age related macular degeneration (AMD) in an Italian population. METHODS: 104 unrelated Italian AMD patients and 131 unrelated controls were screened for the CFH polymorphism p.402Y>H (c.1277 T>C), which has been associated with AMD. Retinography was obtained for patients and controls; the AMD diagnosis was confirmed by fluorescein angiograms. The c.1277 T>C polymorphism was genotyped with the TaqMan real time polymerase chain reaction single nucleotide polymorphism assay. RESULTS: The frequency of c.1277C allele was higher in AMD patients than in controls (57.2% v 39.3%; p<0.001). The odds ratio (OR; logistic regression analysis) for AMD was 3.9 (95% confidence interval (CI): 1.9 to 8.2) for CC homozygotes. The CC genotype conferred a higher risk for sporadic (OR 4.6; CI: 2.0 to 10.5) than for familial AMD (OR 2.9; CI: 1.0 to 8.4). Genotypes were not related to either age at AMD diagnosis or to AMD phenotype. However, geographic atrophy and choroidal neovascularisation were more frequent in sporadic than in familial AMD (p = 0.027). Overall, the percentage of population attributable risk for the CC genotype was 28% (95% CI:18% to 33%). CONCLUSION: The association between the p.402Y>H (c.1277T>C) polymorphism and AMD applies to the Italian population and the CC genotype is more frequent in sporadic than in familial AMD cases.
Subject(s)
Macular Degeneration/genetics , Polymorphism, Genetic , Aged , Alleles , Complement Factor H/genetics , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Risk FactorsABSTRACT
Recent results from independent studies suggest that deferiprone is more cardioprotective than deferoxamine. Patients on long-term treatment with deferiprone have a better myocardial magnetic resonance imaging pattern and less chance to develop a new cardiac disease or worsen an existing one. Most of these observations are retrospective and require confirmation from randomized controlled trials. Other new observations regard the effects of combining the two chelators. Most results indicate an additional effect on iron excretion and a significant reduction of the time required to mitigate severe iron overload and to reverse clinical heart disease. Again, these data require confirmation, as they were mostly obtained on individual cases or small groups of patients treated with a wide range of combinations of the two chelators, but the univocity of results is impressive. After many years of controversy, deferiprone is emerging as a useful oral iron chelator that enhances the chances for the patient to have optimal treatment. Well-designed and -conducted studies will help in answering the questions still open.
Subject(s)
Iron Chelating Agents/therapeutic use , Iron Overload/drug therapy , Pyridones/therapeutic use , Thalassemia/drug therapy , Agranulocytosis/chemically induced , Cardiomyopathies/etiology , Cardiomyopathies/prevention & control , Clinical Trials as Topic , Deferiprone , Deferoxamine/adverse effects , Deferoxamine/therapeutic use , Follow-Up Studies , Gastrointestinal Diseases/chemically induced , Humans , Iron/metabolism , Iron Chelating Agents/administration & dosage , Iron Chelating Agents/adverse effects , Iron Overload/complications , Iron Overload/prevention & control , Joint Diseases/chemically induced , Liver/metabolism , Liver Cirrhosis/chemically induced , Neutropenia/chemically induced , Pyridones/administration & dosage , Pyridones/adverse effects , Retrospective Studies , Thalassemia/complications , Thalassemia/therapyABSTRACT
Corallium rubrum taxonomy is based on morphologic criteria; little is known about its genome. We set up a rapid, easy method based on amplified fragment length polymorphism to characterize the genetic patterns of C. rubrum in an attempt to understand better the evolutionary relations between species from diverse geographic areas and to help define migration patterns. Applying this procedure to C. rubrum specimens from Spain and Italy, we identified 6 AFLP amplification fragments common to the 4 coral populations studied and 4 fragments that differentiated between these populations. Using this characterization we were able to plot a "genetic identity card" of this commercially harvested species, which is also a marker of pollution.
Subject(s)
Anthozoa/genetics , Demography , Phylogeny , Animals , Anthozoa/classification , Electrophoresis, Capillary , Geography , Italy , Nucleic Acid Amplification Techniques , Polymorphism, Restriction Fragment Length , SpainABSTRACT
BACKGROUND AND AIMS: The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study. METHODS: The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules. RESULTS: Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1-134), independent of the DQ at risk genotype. CONCLUSION: This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region.
Subject(s)
Celiac Disease/genetics , Diseases in Twins/genetics , Genetic Predisposition to Disease , Adolescent , Adult , DNA Fingerprinting , Female , HLA-DQ Antigens/analysis , HLA-DQ alpha-Chains , HLA-DQ beta-Chains , HLA-DR Antigens/analysis , HLA-DRB1 Chains , Histocompatibility Testing , Humans , Logistic Models , Male , Odds RatioABSTRACT
Two novel IL2-dependent cell lines, DERL-2 and DERL-7, were established from a patient with hepatosplenic gammadelta T cell lymphoma. This patient presented, at diagnosis, two discrete populations of CD56+ cells, one TCRgammadelta+, the second lacking T cell-restricted antigens. The cell lines derived displayed features corresponding to the two cellular components of the disease: DERL-2 was CD56+/CD3+/TcRgammadelta+ while DERL-7 was CD56+/CD3-/TcRgammadelta-. Along with CD56, the two cell lines shared the expression of CD7, CD2, CD158b and CD117. Karyotype analysis showed that both cell lines were near-diploid, with iso-7q and loss of one chromosome 10. In addition, DERL-2 showed 5q+ in all metaphases analyzed, while DERL-7 revealed loss of one chromosome 4. Genotypically, both cell lines shared the same STR pattern at nine loci and demonstrated an identical rearranged pattern of the T cell receptor genes beta, gamma and delta, with respect to the original tumor cells. These data indicated that both cell lines and the original neoplastic populations were T cell-derived and arose from a common ancestor. Among a large panel of cytokines tested, only SCF was able to substitute IL2 in supporting cell proliferation. Moreover, SCF and IL2 acted synergistically, dramatically enhancing cell growth. These cell lines may represent a model to further analyze the overlap area between T and NK cell malignancies, and may provide new information about the synergistic action of IL2 and SCF on normal and neoplastic T/NK cells.
Subject(s)
Lymphoma, Non-Hodgkin/immunology , Lymphoma, Non-Hodgkin/pathology , Tumor Cells, Cultured/cytology , Adult , CD3 Complex/analysis , CD56 Antigen/analysis , Cell Division/drug effects , Cytogenetic Analysis , Drug Synergism , Gene Rearrangement, beta-Chain T-Cell Antigen Receptor/genetics , Genotype , Humans , Immunophenotyping , Interleukin-2/pharmacology , Male , Receptors, Antigen, T-Cell, gamma-delta/analysis , Receptors, Antigen, T-Cell, gamma-delta/genetics , Stem Cell Factor/pharmacologyABSTRACT
BACKGROUND AND PURPOSE: Studies on cardiovascular disease have preferentially involved men because of the lower frequency of the disease in preelderly women. The aim of this analysis was to examine, with the use of a standardized ultrasound protocol, a cohort of women to differentiate early atherosclerotic lesions in different carotid segments in relation to traditional (lipoprotein abnormalities, high blood pressure, cigarette smoking) and nontraditional (oxidation markers) cardiovascular risk factors. METHODS: More than 5000 clinically healthy, middle-aged women (n=5062; age range, 30 to 69 years) living in the area of Naples in southern Italy participated in the Progetto Atena, a population-based study on the etiology of cardiovascular disease and cancer in the female population. A subsample of 310 participants underwent high-resolution B-mode ultrasound to assess intima-media thickness of common carotid artery and carotid bifurcation. RESULTS: Early atherosclerotic plaques (intima-media thickness >1.2 mm) were detected within the common carotid arteries in 37 women, in the carotid bifurcations in 77 women, and in both sites in 91 women. After age adjustment, common carotid plaques were found to be associated with higher systolic blood pressure (143 versus 138 mm Hg; P<0.05) and higher body mass index (29 versus 27 kg/m(2); P<0.01), while lesions at the carotid bifurcations were associated with higher LDL cholesterol (4.3 versus 3.8 mmol/L; P<0.01) and with smoking habit. Multivariate odds ratios for the presence of common carotid plaques were related to antibodies against oxidized LDL (odds ratio, 2.72; 95% CI, 1.46 to 5.07), and those for plaques at the bifurcation were related to lipid peroxides (odds ratio, 1.90; 95% CI, 1.04 to 3.47), and both relationships were independent of age, LDL cholesterol concentrations, body mass index, smoking habit, and systolic blood pressure. CONCLUSIONS: In a cohort of clinically healthy, middle-aged women, we found a site-specific association of traditional risk factors and oxidation markers with early atherosclerotic lesions in arterial segments differing in geometry, shear stress, extracellular matrix composition, and cell type populations.