RESUMEN
We tracked temporal changes in protist diversity at the Long Term Ecological Research (LTER) station MareChiara in the Gulf of Naples (Mediterranean Sea) on eight dates in 2011 using a metabarcoding approach. Illumina analysis of the V4 and V9 fragments of the 18S rDNA produced 869 522 and 1 410 071 sequences resulting in 6517 and 6519 OTUs, respectively. Marked compositional variations were recorded across the year, with less than 2% of OTUs shared among all samples and similar patterns for the two marker tags. Alveolata, Stramenopiles and Rhizaria were the most represented groups. A comparison with light microscopy data indicated an over-representation of Dinophyta in the sequence dataset, whereas Bacillariophyta showed comparable taxonomic patterns between sequence and light microscopy data. Shannon diversity values were stable from February to September, increasing thereafter with a peak in December. Community variance was mainly explained by seasonality (as temperature), trophic status (as chlorophyll a), and influence of coastal waters (as salinity). Overall, the background knowledge of the system provided a sound context for the result interpretation, showing that LTER sites provide an ideal setting for high-throughput sequencing (HTS) metabarcoding characterisation of protist assemblages and their relationships with environmental variations.
Asunto(s)
Alveolados/clasificación , Biodiversidad , Plancton/clasificación , Rhizaria/clasificación , Estramenopilos/clasificación , Alveolados/genética , Alveolados/aislamiento & purificación , Clorofila/metabolismo , Clorofila A , Ecología , Mar Mediterráneo , Filogenia , Plancton/genética , Plancton/aislamiento & purificación , Plancton/metabolismo , Rhizaria/genética , Rhizaria/aislamiento & purificación , Estramenopilos/genéticaRESUMEN
Ostreopsis cf. ovata is a benthic dinoflagellate that produces palytoxin-like compounds that adversely affect both marine vertebrates and invertebrates and are reported to be responsible for human intoxication in aerosol form. In this work, a histopathological analysis accompanied by quantitative evaluation of tissue injury in mussels (Mytilus galloprovincialis) exposed to O. cf. ovata cells under natural and experimental conditions, provided baseline data on the health status of the mussels in terms of defensive and regressive pathological changes. We recorded a total of 15 health parameters in the digestive system, muscle, kidney and gills in mussels exposed to O. cf. ovata both in the laboratory and at sea. Animals exposed to different concentrations of O. cf. ovata cells (300, 500 and 1000cellsml(-)(1)) for 48h showed activation of the inflammatory response, which increased with the cell concentration, mainly characterized by haemocyte aggregates actively enclosing the algae, while mussel mortality was also recorded in some cases. Moreover the use of image analysis for the evaluation of digestive tubule damage revealed a pronounced increase in the lumen in terms of its area, perimeter and circularity, with a shift in a high percentage of tubules from an adsorbing profile to an atrophic profile. Animals collected from the natural environment during a summer bloom of O. cf. ovata in the Gulf of Naples (Italy) showed comparable lesions in terms of types and severity. This is the first quantitative study assessing damage to the digestive epithelia in terms of lumen modifications in mussels exposed to O. cf. ovata. The presented methodology provides a new technique for automating the evaluation of epithelial tubule modifications. Our results highlight the importance of monitoring the presence of O. cf. ovata in this area, taking into account the effects on the residing marine species.
Asunto(s)
Mytilus/parasitología , Mariscos/parasitología , Animales , Dinoflagelados , Técnicas Histológicas , Procesamiento de Imagen Asistido por Computador , ItaliaRESUMEN
The serum- and glucocorticoid-regulated kinase (Sgk1) is essential for hormonal regulation of epithelial sodium channel-mediated sodium transport and is involved in the transduction of growth factor-dependent cell survival and proliferation signals. Growing evidence now points to Sgk1 as a key element in the development and/or progression of human cancer. To gain insight into the mechanisms through which Sgk1 regulates cell proliferation, we adopted a proteomic approach to identify up- or downregulated proteins after Sgk1-specific RNA silencing. Among several proteins, the abundance of which was found to be up- or downregulated upon Sgk1 silencing, we focused our attention of RAN-binding protein 1 (RANBP1), a major effector of the GTPase RAN. We report that Sgk1-dependent regulation of RANBP1 has functional consequences on both mitotic microtubule activity and taxol sensitivity of cancer cells.
Asunto(s)
Carcinoma/genética , Carcinoma/metabolismo , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Resistencia a Antineoplásicos/genética , Proteínas Inmediatas-Precoces/metabolismo , Proteínas Nucleares/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Transcripción Genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Paclitaxel/farmacología , Fosforilación , Proteómica , Interferencia de ARN , Factor de Transcripción Sp1/metabolismoRESUMEN
Posttransplant lymphoproliferative disorder (PTLD) is a major complication of solid-organ transplantation. With human immunodeficiency virus infection (an analogous immunosuppressive state), elevated kappa and lambda immunoglobulin free light chains (FLCs) in peripheral blood are associated with increased risk of lymphoma. To assess the role of B-cell dysfunction in PTLD, we measured circulating FLCs among Canadian transplant recipients, including 29 individuals with PTLD and 57 matched transplant recipients who were PTLD-free. Compared with controls, PTLD cases had higher kappa FLCs (median 1.53 vs. 1.07 times upper limit of normal) and lambda FLCs (1.03 vs. 0.68). Using samples obtained on average 3.5 months before PTLD diagnosis, cases were more likely to have polyclonal FLC elevations (i.e. elevated kappa and/or lambda with normal kappa/lambda ratio: odds ratio [OR] 4.2, 95%CI 1.1-15) or monoclonal elevations (elevated kappa and/or lambda with abnormal ratio: OR 3.0, 95%CI 0.5-18). Strong FLC-PTLD associations were also observed at diagnosis/selection. Among recipients with Epstein-Barr virus (EBV) DNA measured in blood, EBV DNAemia was associated with FLC abnormalities (ORs 6.2 and 3.2 for monoclonal and polyclonal elevations). FLC elevations are common in transplant recipients and associated with heightened PTLD risk. FLCs likely reflect B-cell dysfunction, perhaps related to EBV-driven lymphoproliferation.
Asunto(s)
Anticuerpos Antivirales/sangre , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Trastornos Linfoproliferativos/etiología , Trasplante de Órganos/efectos adversos , Adolescente , Adulto , Linfocitos B/inmunología , Linfocitos B/virología , Estudios de Casos y Controles , Niño , Preescolar , ADN Viral/genética , Femenino , Herpesviridae/genética , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/virología , Humanos , Huésped Inmunocomprometido , Lactante , Trastornos Linfoproliferativos/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Adulto JovenRESUMEN
The t(4;14) translocation in multiple myeloma (MM) simultaneously dysregulates two apparent oncogenes: fibroblast growth factor receptor 3 (FGFR3) controlled by the 3' immunoglobulin heavy chain enhancer on der(14) and MMSET controlled by the intronic Emu enhancer on der(4). Although all MM tumors and cell lines with a t(4;14) translocation have dysregulated MMSET, about 25% do not express FGFR3. Therefore, the function of dysregulated wild-type (WT) FGFR3 in the pathogenesis of MM remains unclear. We developed a murine transgenic (TG) model in which WT FGFR3 is overexpressed in B lymphoid cells. Although high levels of FGFR3 resulted in lymphoid hyperplasia in about one-third of older mice, no increase in tumorigenesis was observed. However, double TG FGFR3/Myc mice develop mature B lymphoma tumors that occur with a higher penetrance and shorter latency than in single TG Myc mice (P=0.006). We conclude that expression of high levels of WT FGFR3 can be oncogenic and cooperate with MYC to generate B lymphoid tumors. This suggests that dysregulated FGFR3 expression is likely to be essential at least for the early stages of pathogenesis of MM tumors that have a t(4;14) translocation.
Asunto(s)
Linfoma de Células B/etiología , Mieloma Múltiple/etiología , Proteínas Proto-Oncogénicas c-myc/fisiología , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/fisiología , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Southern Blotting , Western Blotting , Femenino , Perfilación de la Expresión Génica , Genes de Inmunoglobulinas , Humanos , Técnicas para Inmunoenzimas , Inmunofenotipificación , Inmunoprecipitación , Linfoma de Células B/patología , Masculino , Ratones , Ratones Transgénicos , Mieloma Múltiple/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Newborn gene therapy, because it can prevent the damage caused by the onset of a disease, deserves specific attention. To evaluate gene transfer in tissues of newborn mice, we used a human immunodeficiency virus (HIV)-2 based lentiviral vector pseudotyped with vesicular stomatitis virus G glycoprotein expressing the green fluorescent protein reporter gene under the control of the cytomegalovirus promoter. We found that very low doses of HIV-2 could infect and be expressed in newborn mice. Under these conditions, the virus was preferentially expressed in the liver and hepatocytes were the predominant target. The treatment was not toxic, the infected liver cells proliferated and the transduced gene was stably expressed. Adult mice could be infected by HIV-2, but the vector was detected in the liver only utilizing the sensitive method of polymerase chain reaction coupled with Southern blot. Direct comparison between newborn and adult recipients demonstrated a much greater efficiency of liver transduction in the newborn mouse. These results indicate that the combination of early intervention and low multiplicity of infection may be a strategy for preferentially and efficiently targeting newborn liver for gene therapy applications.
Asunto(s)
Animales Recién Nacidos , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , VIH-2/genética , Hepatocitos/metabolismo , Transducción Genética/métodos , Adenoviridae/genética , Animales , Southern Blotting , Proliferación Celular , Femenino , Expresión Génica , Proteínas Fluorescentes Verdes/análisis , Proteínas Fluorescentes Verdes/genética , Hepatocitos/citología , Hígado/metabolismo , Pulmón/metabolismo , Ratones , Ratones Endogámicos , Microscopía Fluorescente , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Bazo/metabolismoRESUMEN
Monitoring gene therapy of glycogen storage disease type 1a in a mouse model was achieved using [(18)F]FDG and a dedicated animal scanner. The G6Pase knockout (KO) mice were compared to the same mice after infusion with a recombinant adenovirus containing the murine G6Pase gene (Ad-mG6Pase). Serial images of the same mouse before and after therapy were obtained and compared with wild-type (WT) mice of the same strain to determine the uptake and retention of [(18)F]FDG in the liver. Image data were acquired from heart, blood pool and liver for twenty minutes after injection of [(18)F]FDG. The retention of [(18)F]FDG was lower for the WT mice compared to the KO mice. The mice treated with adenovirus-mediated gene therapy had retention similar to that found in age-matched WT mice. These studies show that FDG can be used to monitor the G6Pase concentration in liver of WT mice as compared to G6Pase KO mice. In these mice, gene therapy returned the liver function to that found in age matched WT controls as measured by the FDG kinetics in the liver compared to that found in age matched wild type controls.
Asunto(s)
Fluorodesoxiglucosa F18/metabolismo , Terapia Genética , Glucosa-6-Fosfatasa/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/diagnóstico por imagen , Enfermedad del Almacenamiento de Glucógeno Tipo I/terapia , Tomografía Computarizada de Emisión , Animales , Modelos Animales de Enfermedad , Glucosa/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/metabolismo , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Radiofármacos/metabolismoRESUMEN
Glycogen storage disease type 1a (GSD-1a), characterized by hypoglycemia, liver and kidney enlargement, growth retardation, hyperlipidemia, and hyperuricemia, is caused by a deficiency in glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis. To evaluate the feasibility of gene replacement therapy for GSD-1a, we have infused adenoviral vector containing the murine G6Pase gene (Ad-mG6Pase) into G6Pase-deficient (G6Pase(-/-)) mice that manifest symptoms characteristic of human GSD-1a. Whereas <15% of G6Pase(-/-) mice under glucose therapy survived weaning, a 100% survival rate was achieved when G6Pase(-/-) mice were infused with Ad-mG6Pase, 90% of which lived to 3 months of age. Hepatic G6Pase activity in Ad-mG6Pase-infused mice was restored to 19% of that in G6Pase(+/+) mice at 7-14 days post-infusion; the activity persisted for at least 70 days. Ad-mG6Pase infusion also greatly improved growth of G6Pase(-/-) mice and normalized plasma glucose, cholesterol, triglyceride, and uric acid profiles. Furthermore, liver and kidney enlargement was less pronounced with near-normal levels of glycogen depositions in both organs. Our data demonstrate that a single administration of a recombinant adenoviral vector can alleviate the pathological manifestations of GSD-1a in mice, suggesting that this disorder in humans can potentially be corrected by gene therapy.
Asunto(s)
Terapia Genética , Glucosa-6-Fosfatasa/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/terapia , Hígado/metabolismo , Adenoviridae , Animales , Modelos Animales de Enfermedad , Vectores Genéticos , Glucosa-6-Fosfatasa/metabolismo , Glucosa-6-Fosfato/metabolismo , Humanos , Ratones , Ratones Noqueados , Microsomas Hepáticos/metabolismoRESUMEN
The response of the forearm vasculature to acetylcholine (7.5, 15, and 30 microg/min, each for 5 minutes) and sodium nitroprusside (0.8, 1.6, and 3.2 microg/min, each for 5 minutes) was evaluated in 32 never-treated hypertensive outpatients (17 men and 15 women, aged 43+/-7 years) and in 24 normotensive control subjects (14 men and 10 women, aged 42+/-6 years). Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. In both hypertensive and normotensive groups, a deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene was determined by polymerase chain reaction. The response to acetylcholine was significantly reduced in hypertensive patients versus control subjects: at the highest dose (30 microg/min), forearm blood flow was 13.9+/-6.3 mL x 100 mL tissue(-1) x min(-1) in hypertensives versus 27.1+/-9.7 mL x 100 mL tissue(-1) x min(-1) in the controls (P<.001); similarly, vascular resistance was 10.6+/-5.6 U in hypertensive patients and 4.9+/-1.9 U in normotensive subjects. In the hypertensive group, the patients with DD genotype showed significantly less endothelium-dependent vasodilation compared with ID+II genotypes (at the highest dose of acetylcholine, forearm blood flow was 12.1+/-4.2 versus 17.0+/-4.1 mL x 100 mL tissue(-1) x min(-1)) (P<.005). The vasodilator effect of sodium nitroprusside infusions was not statistically different in DD and ID+II hypertensive patients. In conclusion, our data suggest that ACE polymorphism affects endothelium-dependent vasodilation in hypertensive patients and confirm that hypertensive patients had a blunted response to the endothelium-dependent agent acetylcholine.
Asunto(s)
Endotelio Vascular/fisiología , Hipertensión/genética , Peptidil-Dipeptidasa A/genética , Vasodilatación/fisiología , Adulto , Análisis de Varianza , Presión Sanguínea , Femenino , Genotipo , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo GenéticoRESUMEN
OBJECTIVES: This study sought to evaluate the possible association of polymorphism of the angiotensin-converting enzyme (ACE) gene with blood pressure and left ventricular mass index (LVMI). BACKGROUND: The renin-angiotensin system seems to be involved in the pathogenesis of essential hypertension. Moreover, recent epidemiologic observations demonstrate that many subjects with left ventricular hypertrophy have normal blood pressure levels, suggesting that factors other than hemodynamic overload may contribute to the hypertrophy. METHODS: The study included 140 untreated hypertensive outpatients who underwent ambulatory blood pressure monitoring, echocardiographic evaluation and analysis for insertion (I)/ deletion (D) polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Blood pressure was measured at 24 h, and LVMI was calculated by the Devereux formula, in each patient. RESULTS: Left ventricular mass index values (mean +/- SD) were 137 +/- 28 g/m2 in patients with the DD genotype, 125 +/- 27 g/m2 in those with the ID genotype and 115 +/- 27 g/m2 in those with II genotype. The frequencies of the DD, ID and II genotypes were 45.71% (n = 64), 46.42% (n = 65) and 7.85% (n = 11), respectively, and were in Hardy-Weinberg equilibrium. The strongest association between left ventricular mass and DD genotype in our cohort appeared to be an independent cardiovascular risk factor (DD vs. ID: odds ratio [OR] 2.497, 95% confidence interval [CI] interval 1.158 to 5.412, p < 0.05; DD vs. II: OR 6.577, 95% CI 1.169 to 28.580, p < 0.02). CONCLUSIONS: Our data show that the LVMI was significantly enhanced in patients with the DD genotype.
Asunto(s)
Eliminación de Gen , Hipertensión/genética , Hipertrofia Ventricular Izquierda/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Adulto , Anciano , Ecocardiografía , Femenino , Genotipo , Humanos , Italia , Masculino , Persona de Mediana EdadRESUMEN
The present work describes the distribution of HCV genotypes in Calabria. The data presented suggest that, in the sample of population investigated, genotype 1b is the most prevalent followed by the 2b and the 2a.. In addition it is important to note that in Calabria the prevalence of genotype 1b is strikingly high in respect to the other Italian pullulation. An Association between HCV type 1b and the more severe clinical course of the liver disease has been reported. Although the data presented indicate that in Calabria most of the subjects enrolled in the study are infected by a virulent HCV strain, no association has been found with more severe clinical manifestations.
Asunto(s)
Hepacivirus/genética , Hepatitis C/epidemiología , Hepatitis Crónica/epidemiología , ARN Viral/química , Adulto , Factores de Edad , Anciano , Femenino , Hepacivirus/aislamiento & purificación , Hepatitis C/virología , Hepatitis Crónica/virología , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de RiesgoRESUMEN
The ACE gene has recently been shown to be associated with myocardial infarction, especially in subjects considered at low risk for coronary heart disease (CHD) according to common classification criteria. The possible relationship between deletion polymorphism in this gene and CHD risk factors, as well as asymptomatic extracoronary atherosclerosis, has been investigated in the present study. One hundred and seventy-four subjects, enrolled in a cardiovascular disease prevention study, underwent clinical and biochemical examination and ACE-I/D polymorphism determination. Subjects > 45 years of age (n = 107) also received echo-Doppler examination of the carotid arteries. Based on the results of ACE-I/D polymorphism, subjects were divided into three groups: homozygous for deletion (D/D), homozygous for insertion (I/I) and heterozygous (I/D). The prevalence of CHD risk factors as well as of extracoronary atherosclerosis was similar in the three genotype groups. Similarly, there was no association between the presence of atherosclerotic lesions and genotype in subjects at low and high CHD risk. Ten subjects with diabetes mellitus had ACE-D/D genotype. Among these subjects seven had hypertension. Eight subjects with diabetes mellitus had ACE-I/D genotype and only one of these was hypertensive. None of the ACE-I/I subjects was diabetic. ACE-I/D polymorphism seems to play a role in the development of hypertension, at least in diabetic subjects. Its determination may help to identify and monitor diabetic subjects prone to hypertension.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Hipertensión/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Adulto , Secuencia de Bases , Marcadores Genéticos , Humanos , Hipertensión/etiología , Masculino , Persona de Mediana Edad , Datos de Secuencia MolecularRESUMEN
The frequency and distribution of angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism, and its association with other known risk factors for coronary atherosclerosis, has been studied, in a normal south Italian population. Subjects homozygous for deletion showed elevated fasting blood glucose levels when compared with subjects homozygous for insertion. The difference was consistent with an increased number of type 2 diabetics among the former group of subjects.
Asunto(s)
Glucemia/genética , Eliminación de Gen , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Enfermedad de la Arteria Coronaria/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
A multicentric retrospective study on leukemic ophthalmopathy (LO) is reported. It includes 21 patients, 16 males and 5 females, with acute leukemia (AL) observed in 10 SIOP centers. LO developed in three patients at the time of diagnosis of AL; five patients were in first complete remission (three off therapy); four patients were in second or third remission; and nine were in combined relapse. Most frequent symptoms were blurred vision, photophobia, and ocular pain. Two patients with acute nonlymphoblastic leukemia died before treatment; another underwent bone marrow transplantation; one patient with B-cell acute lymphoblastic leukemia (B-ALL) treated with chemotherapy and radiotherapy died 4 months after LO; the remaining 17 children were treated according to different schedules with (10) or without (7) radiotherapy on the affected eye. Twelve patients achieved ocular remission and four of these had a second ocular relapse. Complete remission after LO treatment lasting for more than 3, 7, 24, 29 months was observed in four patients. The authors conclude that cure is possible in patients who had LO in first complete remission treated with chemotherapy and radiotherapy at high dose on the affected eye.
Asunto(s)
Ojo/patología , Infiltración Leucémica/terapia , Enfermedad Aguda , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The present study was designed to investigate on possible association between SstI polymorphism in the ApoAI-CIII-AIV gene cluster, classical coronary heart disease risk factors and extracoronary atherosclerosis. One hundred and twenty six male subjects were enrolled and underwent echo-Doppler examination of carotid and femoral arteries, coronary heart disease risk factors assessment and SstI genotyping. The frequency of the rare SsI allele was 12.1% and 6.7% in subjects with or without extracoronary lesions respectively and was not associated with differences in the distribution of coronary heart disease risk factors. Forty subjects had hypertension, 34 homozygous for the frequent allele and 6 with presence of the rare allele. Among these, 10 subjects (29%) and 5 subjects (83%), respectively, had extracoronary atherosclerosis. Furthermore, subjects homozygous for the rare allele exhibited lipid abnormalities and a family history positive for hypertension and/or hyperlipidemia. These findings suggest a possible role for the ApoAI-CIII-AIV gene complex in both lipid metabolism and blood pressure regulation and could be of help to identify, within hypertensives, those subjects prone to extracoronary atherosclerosis.
Asunto(s)
Apolipoproteína A-I/genética , Apolipoproteínas A/genética , Apolipoproteínas C/genética , Arteriosclerosis/epidemiología , Arteriosclerosis/genética , Hipertensión/genética , Polimorfismo de Longitud del Fragmento de Restricción , Alelos , Apolipoproteína C-III , Secuencia de Bases , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/genética , Cartilla de ADN , Desoxirribonucleasas de Localización Especificada Tipo II , Femenino , Humanos , Hipertensión/fisiopatología , Italia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Familia de Multigenes , Reacción en Cadena de la Polimerasa , Factores de RiesgoRESUMEN
We analysed the allelic and genotypic frequencies of three restriction fragment length polymorphisms in the region of chromosome 11 encoding apolipoprotein AI and CIII genes in a free-living population from South Italy (Calabria). These markers are located at -2500 and -78 bp from the transcription start site of apolipoprotein AI gene (XmnI and MspI, respectively), and in the 3' untranslated region of apolipoprotein CIII gene (SstI). XmnI and SstI label rare alleles (X2 and S2 indicate the presence of the site), whereas the absence of the MspI site (because of a G to A transition) marks the rare allele, M2. Pairwise linkage disequilibrium analysis was determined. Two significant non-random associations were found: a positive disequilibrium between ApoA1/XmnI and ApoA1/MspI markers (P < 0.0001), and a negative disequilibrium between ApoA1/XmnI and ApoC3/SstI markers (P < 0.05). Statistical analysis showed a significant difference in the S2-M2 haplotype frequency between the group of subjects with serum cholesterol levels in the highest decile (P < 0.005) and the group with serum cholesterol levels below the highest decile. The allelic frequency for each locus showed no significant difference between the two groups for all other metabolic parameters, included total cholesterol serum levels. These haplotypes are a more precise measure of genetic variations in the apolipoprotein cluster and their use should allow the mapping of mutations responsible for high serum cholesterol levels.
Asunto(s)
Apolipoproteínas/genética , Cromosomas Humanos Par 11 , Desequilibrio de Ligamiento , Polimorfismo de Longitud del Fragmento de Restricción , Adulto , Anciano , Alelos , Apolipoproteína A-I/genética , Apolipoproteína C-III , Apolipoproteínas C/genética , Secuencia de Bases , Southern Blotting , Distribución de Chi-Cuadrado , ADN/análisis , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Haplotipos , Humanos , Hipercolesterolemia/genética , Lípidos/sangre , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Familia de Multigenes , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
A multicentric retrospective study on leukemic ophthalmopathy (LO) is reported, including 38 patients (21 males, 17 females) with acute leukemia (AL) observed from 1976 to 1985. LO developed in four patients at the time of diagnosis of AL; ten were in first complete remission (eight off therapy), 12 in second remission, and 12 in combined relapse. The children were treated according to different schedules of systemic and intrathecal chemotherapy with or without radiotherapy (RT) of the affected eye. Ocular remission occurred in 32 of 38 patients, but with subsequent ocular relapse in six of the 32. Complete remission after LO treatment lasting for more than 24, 30, 40, and 78 months was observed in four of the ten children with isolated LO in first AL marrow remission. The authors concluded that systemic and intrathecal chemotherapy probably is associated with RT (at least 30 Gy to the affected eye). Aggressive treatment is justified because children with isolated ocular relapse can still be cured.