RESUMEN
OBJECTIVE: Progress in the management of patients with thalassemia intermedia (TI) enabled increasing rates of pregnancies among TI women worldwide. Nevertheless, information regarding TI pregnancy management and outcome is quite limited in the literature. The aim of this study was to report our experience regarding the maternal and fetal outcome of TI patients, as well as to depict the complexity of the disease and the need for multidisciplinary and personalized management as shown by the description of two interesting pregnancy cases. METHODS: We analyzed our data recorded from 60 pregnancies in 34 women over a 20-yr period. RESULTS: Forty-nine patients achieved full-term pregnancies (mean maternal age ± SD: 27.4 ± 6.5 yr) within 37 ± 3 gestation weeks. Their mean hemoglobin value was 8.33 ± 1.22 g/dL; 26.5% of patients were not transfused at all or they had been transfused only once during gestation. There were 11 abortions (18.3%). The spontaneous abortions (5/11) were related to high HbF levels. Six patients had more than two normal deliveries. Nineteen newborns (38.8%), which weighed 2-3 kg, required hospitalization to an intensive neonatal care unit for 1-3 wk. One patient presented with life-threatening complications (hemolytic anemia, thrombocytopenia, and enlargement of spleen) and another with spastic paraparesis due to extramedullary paravertebral masses. CONCLUSIONS: Although several complications can occur during a pregnancy in TI women, the careful and frequent monitoring by both hamatologists and obstetricians can lead to successful deliveries.
Asunto(s)
Complicaciones Hematológicas del Embarazo/epidemiología , Talasemia beta/epidemiología , Adulto , Transfusión Sanguínea , Femenino , Estudios de Seguimiento , Edad Gestacional , Grecia/epidemiología , Humanos , Embarazo , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/terapia , Resultado del Embarazo , Esplenectomía , Adulto Joven , Talasemia beta/diagnóstico , Talasemia beta/terapiaRESUMEN
Animal models indicate that the antimicrobial peptide hepcidin (HAMP; OMIM 606464) is probably a key regulator of iron absorption in mammals. Here we report the identification of two mutations (93delG and 166C-->T) in HAMP on 19q13 in two families with a new type of juvenile hemochromatosis.
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Péptidos Catiónicos Antimicrobianos/genética , Hemocromatosis/genética , Mutación/genética , Secuencia de Aminoácidos , Péptidos Catiónicos Antimicrobianos/química , Secuencia de Bases , Niño , Análisis Mutacional de ADN , Femenino , Hepcidinas , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
The aim of this prospective study was to evaluate the long-term efficacy and safety of hydroxyurea (HU) in patients with sickle cell disease (SCD). Thirty-four patients with sickle cell anemia (hemoglobin S [HbS]/HbS), 131 with HbS/beta(0)-thal, and 165 with HbS/beta(+)-thal participated in this trial. HU was administered to 131 patients, whereas 199 patients were conventionally treated. The median follow-up period was 8 years for HU patients and 5 years for non-HU patients. HU produced a dramatic reduction in the frequency of severe painful crises, transfusion requirements, hospital admissions, and incidence of acute chest syndrome. The probability of 10-year survival was 86% and 65% for HU and non-HU patients, respectively (P = .001), although HU patients had more severe forms of SCD. The 10-year probability of survival for HbS/HbS, HbS/beta (0)-thal, and HbS/IVSI-110 patients was 100%, 87%, and 82%, respectively, for HU patients and 10%, 54%, and 66%, for non-HU patients. The multivariate analysis showed that fetal hemoglobin values at baseline and percentage change of lactate dehydrogenase between baseline and 6 months were independently predicted for survival in the HU group. These results highlight the beneficial effect of HU, which seems to modify the natural history of SCD and raise the issue of expanding its use in all SCD patients.
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Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/mortalidad , Antidrepanocíticos/administración & dosificación , Hidroxiurea/administración & dosificación , Adulto , Anciano , Anemia de Células Falciformes/genética , Antidrepanocíticos/efectos adversos , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Hemoglobina Fetal/genética , Estudios de Seguimiento , Hemoglobina Falciforme/genética , Hospitalización/estadística & datos numéricos , Humanos , Hidroxiurea/efectos adversos , Masculino , Persona de Mediana Edad , Morbilidad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Análisis de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
At present, prevention of thalassaemia and sickle cell disease is the only realistic approach to control the birth of new patients in countries having high numbers of carriers. This is fully justified because avoiding the birth of an ever increasing number of patients may allow a more effective use of the available resources in improving the management of the patients surviving today and alleviate the already overloaded public health system from the inevitable tremendous and ever increasing cost. Moreover, prenatal diagnosis may help couples at risk to have non-thalassaemic children. Greece is one of the countries where the mean frequency of carriers is approximately 7.5 per cent (population 11 million) and has set up a nationwide programme for carrier identification in the early seventies; this is provided through a dozen of specific Units attached to the major Blood Transfusion Services of the country, on a voluntary basis and free of charge. Spread of information through mass media, the schools, and other groups has greatly contributed in creating the necessary sensitization; obstetricians and antenatal Clinics are also instrumental to this effect. Prenatal diagnosis is offered centrally (Athens) and covers satisfactorily the estimated needs (500-600 annually); the total number has already exceeded 35,000. According to information obtained from the major paediatric hospitals all over the country, the number of thalassaemia major or SCD admitted for treatment over the last ten years has been around 15 yearly (instead of an estimate of 120-130).
Asunto(s)
Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/prevención & control , Talasemia/diagnóstico , Talasemia/prevención & control , Anemia de Células Falciformes/epidemiología , Femenino , Tamización de Portadores Genéticos , Grecia/epidemiología , Humanos , Embarazo , Diagnóstico Prenatal/métodos , Salud Pública , Talasemia/epidemiologíaRESUMEN
CD177 (PRV1) expression is strongly related to polycythaemia vera (PV). Whilst studying CD177 expression in PV patients and controls, individuals with beta-thalassaemia minor were found to display an elevated expression of CD177. The study was expanded to include patients with thalassaemia intermedia, sickle cell/beta-thalassaemia and thalassaemia major. CD177 expression was increased in these thalassaemic groups and correlated with their erythropoietic activity, as assessed by the measurement of serum erythropoietin and soluble transferrin receptor levels. Within this context, elevated CD177 expression is not only a specific feature of PV but may be an indicator of increased erythropoietic activity in thalassaemia syndromes.
Asunto(s)
Eritropoyesis , Isoantígenos/biosíntesis , Glicoproteínas de Membrana/biosíntesis , Receptores de Superficie Celular/biosíntesis , Talasemia beta/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Eritropoyetina/sangre , Proteínas Ligadas a GPI , Expresión Génica , Genotipo , Humanos , Isoantígenos/genética , Janus Quinasa 2/genética , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Mutación , Policitemia Vera/sangre , Policitemia Vera/genética , ARN Mensajero/genética , Receptores de Superficie Celular/genética , Receptores de Transferrina/sangre , Talasemia beta/genética , Talasemia beta/fisiopatologíaRESUMEN
A series of cationic liposomes known as cationic phosphonolipids (CPs) were evaluated as vehicles for in vitro gene transfer in K562 erythroleukemia cells and 5637 epithelial carcinoma cells. For each CP and target cell type examined, detailed analyses were performed to determine optimal transfection conditions (lipid/ DNA (+/-) charge ratio, amount of complexed episomal DNA, liposomal and lipoplex size, complexation medium and duration of complex-cell exposure time). Lipofection conditions were determined to be both cell- and lipid-type specific. Complexation medium critically affected transfection competence. The initial size of the liposome was not always predictive of lipofection potency. The lipid chemical composition had a strong impact upon lipofection efficiency; DOPE inclusion in the liposome formulations was found to affect the levels of transgene expression in a cell-dependent way. Notably, effective transgene expression was characterized by prominent plasmid nuclear incorporation. Human A gamma- and epsilon-globin transgene nuclear incorporation and expression in 5637 cells post GLB.391-mediated lipofection lends credence to its use as a vehicle of therapeutic transgene delivery.
Asunto(s)
Fosfolípidos/química , Transfección/métodos , Cationes , Línea Celular Tumoral , Humanos , Cinética , Hibridación de Ácido Nucleico , PlásmidosAsunto(s)
Aborto Habitual/genética , Janus Quinasa 2/genética , Mutación , Adulto , Femenino , Expresión Génica , Humanos , Persona de Mediana Edad , Embarazo , Adulto JovenRESUMEN
Coexistence of Philadelphia chromosome-negative (Ph-) progenitors with the Ph+ clone in the early chronic phase of chronic myeloid leukemia (CML) has been documented in previous reports. A different evaluation of methods is needed to justify the clonality of the residual Ph- progenitors. Therefore, the X chromosome inactivation patterns in individual granulocyte-monocyte colony-forming unit (CFU-GM) colonies were studied with the clonality assay for the human androgen receptor gene. A prerequisite for this evaluation was the validation of T-lymphocytes and buccal cells as control cells representing the constitutional lyonization. The percentages of polyclonal CFU-GM cells were determined in 9 Ph+ women with CML and in 5 healthy women. Results of the clonal analysis of CFU-GM colonies were compared with those from reverse transcriptase-polymerase chain reaction analysis of single colonies for BCR/ABL transcripts. Both methods of CFU-GM cell analysis were in agreement regarding the presence of variable proportions (0%-94%) of normal cells in CML. Our results suggest that (a) T-cells and buccal cells have potential for use as controls for the clonal analysis of CML cases and (b) this method can evaluate the frequency of polyclonal/clonal CFU-GM cells in CML cases and is applicable to the analysis of myeloid clonal disorders that lack specific molecular markers.
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Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Células Progenitoras Mieloides/patología , Receptores Androgénicos/genética , Adulto , Estudios de Casos y Controles , Células Clonales/patología , Compensación de Dosificación (Genética) , Femenino , Proteínas de Fusión bcr-abl/genética , Humanos , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/patología , Métodos , Persona de Mediana Edad , ARN Mensajero/análisisRESUMEN
Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative diseases that carry intrinsically the potential for leukemic transformation. The aims of this study were (1) to detect involvement of N- and K-ras mutations in codons 12 and 13 in the pathogenesis of the chronic and blastic phases of PV and ET, (2) to study the occurrence of microsatellite instability (MSI) in chromosomes 5 and 7 during the chronic phase and blastic transformation of the disease, and (3) to examine the incidence of leukemia in patients treated with hydroxyurea (HU). Samples of PV and ET patients were analyzed with a polymerase chain reaction. No N- or K-ras mutations were detected. A positive score for MSI in chromosome 7 was found in 1 patient with PV during leukemic transformation. Three of 69 patients developed acute myelogenous leukemia, 2 with PV and 1 with ET. As of this report, the overall incidence of leukemic transformation is 5.7% (2/35 patients) in PV and 3.3% (1/30 patients) in ET patients treated with HU. These results indicate that (1) MSI is a genetic marker that can be detected, even in a small group of patients, at the blastic phase of the disease and (2) no increased leukemogenicity was noted in this group of patients treated with HU.
Asunto(s)
Cromosomas Humanos Par 5/genética , Cromosomas Humanos Par 7/genética , Hidroxiurea/efectos adversos , Leucemia/inducido químicamente , Policitemia Vera/complicaciones , Trombocitosis/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/genética , Cromosomas Humanos Par 5/fisiología , Cromosomas Humanos Par 7/fisiología , Femenino , Genes ras/genética , Genes ras/fisiología , Humanos , Hidroxiurea/uso terapéutico , Incidencia , Leucemia/etiología , Leucemia/genética , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Mutación , Policitemia Vera/tratamiento farmacológico , Policitemia Vera/genética , Trombocitosis/tratamiento farmacológico , Trombocitosis/genéticaRESUMEN
Iron overload is not uncommon in sickle cell disease (SCD) and requires regular chelation therapy in several instances. The present study evaluates the effect of deferiprone in 15 adult patients with SCD (ten beta(s)/beta(0)thalassemia and five beta(s)/beta(s)) and iron overload. Deferiprone was given at a dose of 75 mg/kg daily for 12 months. The evaluation considered pre- and post-treatment values of serum ferritin, urinary iron excretion, and T2 values of liver and heart obtained by magnetic resonance imaging (MRI). Eleven patients had a liver biopsy prior to starting therapy to evaluate iron concentration (LIC). Twelve patients completed the study with satisfactory compliance. In ten of them (83.3%) the serum ferritin levels decreased significantly at the end of the trial; in eight patients (66.6%) the reduction of serum ferritin was accompanied by a significant increase of their liver T2 values. All patients had a significant increase of urinary iron excretion in response to the drug. Ferritin levels and liver T2 values correlated with liver iron concentration; on the contrary, ferritin levels and liver T2 values failed to show any correlation with heart T2 values. Heart T2 values did not also show any correlation with left ventricular ejection fraction. Deferiprone was well tolerated and did not cause any significant adverse effects. These results suggest that deferiprone may effectively decrease the iron deposition in patients with SCD; moreover, T2 MRI proves to be a reliable and rapid, noninvasive method for assessing the liver iron load in patients with SCD.
Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Quelantes del Hierro/administración & dosificación , Sobrecarga de Hierro/tratamiento farmacológico , Piridonas/administración & dosificación , Administración Oral , Adulto , Anciano , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/metabolismo , Deferiprona , Evaluación de Medicamentos , Femenino , Ferritinas/sangre , Corazón/diagnóstico por imagen , Corazón/fisiopatología , Humanos , Hierro/orina , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/metabolismo , Hígado/diagnóstico por imagen , Hígado/metabolismo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiografía , Talasemia beta/tratamiento farmacológico , Talasemia beta/metabolismoRESUMEN
The analysis of rare chromosomal translocations in myeloproliferative disorders has highlighted the importance of aberrant tyrosine kinase signaling in the pathogenesis of these diseases. Here we have investigated samples from 679 patients and controls for the nonreceptor tyrosine kinase JAK2 V617F mutation. Of the 480 myeloproliferative disorder (MPD) samples, the proportion of positive cases per disease subtype was 30 (20%) of 152 for atypical or unclassified MPD, 2 of 134 (2%) for idiopathic hypereosinophilic syndrome, 58 of 72 (81%) for polycythemia vera, 24 of 59 (41%) essential thrombocythemia (ET), and 15 of 35 (43%) for idiopathic myelofibrosis. V617F was not identified in patients with systemic mastocytosis (n = 28), chronic or acute myeloid leukemia (n = 35), secondary erythrocytosis (n = 4), or healthy controls (n = 160). Homozygosity for V617F was seen in 43% of mutant samples and was closely correlated with chromosome 9p uniparental disomy. Homozygosity was significantly less common in ET compared with other MPD subtypes. In 53 cases analyzed, the median level of PRV1 expression was significantly higher in V617F-positive cases compared with cases without the mutation. We conclude that V617F is widespread in MPDs. Detection of this acquired mutation is likely to have a major impact on the way patients with MPD are diagnosed, as well as serving as an obvious target for signal transduction therapy.
Asunto(s)
Mutación Missense , Trastornos Mieloproliferativos/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Homocigoto , Humanos , Janus Quinasa 2 , Masculino , Repeticiones de Microsatélite , Epidemiología Molecular , Trastornos Mieloproliferativos/epidemiología , Prevalencia , Transducción de Señal/genéticaRESUMEN
The development of clinical and histopathologic manifestations of a diffuse elastic tissue defect, resembling inherited pseudoxanthoma elasticum (PXE), has been encountered with a notable frequency in patients with beta thalassemia, sickle cell disease, and sickle thalassemia. The PXE-like clinical syndrome, consisting of skin, ocular, and vascular manifestations, has a variable severity in these hemoglobinopathies and it is age-dependent, with a generally late onset, after the second decade of life. The defect is believed to be acquired rather than inherited and related to the consequences of the primary disease. The high prevalence of the findings implicates the elastic tissue injury as one of the main comorbid abnormalities encountered in beta thalassemia and the sickling syndromes. In these patients a number of complications, sometimes serious, has been recognized to be related to ocular and vascular elastic tissue defects. Because several organ systems are involved, each medical specialty should be aware of the phenomenon. This coexistence, on the other hand, introduces a novel pathogenetic aspect of PXE and an important research challenge.
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Anemia de Células Falciformes/patología , Tejido Elástico/patología , Seudoxantoma Elástico/diagnóstico , Talasemia beta/patología , Adulto , Envejecimiento , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/genética , Estrías Angioides , Diagnóstico Diferencial , Oftalmopatías/etiología , Humanos , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/genética , Seudoxantoma Elástico/patología , Piel/patología , Enfermedades Vasculares/etiología , Talasemia beta/complicaciones , Talasemia beta/genéticaRESUMEN
This paper summarizes data from a haematological, biochemical, and clinical study carried out in 73 patients of Greek origin (38 non-splenectomized children and 35 adults; 17 splenectomized) with Hereditary Spherocytosis (HS). Mean haemoglobin levels in the non-splenectomized patients were significantly lower (122 +/- 15 g/L) than those of the splenectomized group (144 +/- 15 g/L). In all patients with HS (non-splenectomized and splenectomized adults, and children) the MCHC values (355 +/- 22, 358 +/- 16 and 356 +/- 16 respectively) were significantly increased compared to a control group, while the percentage of microcytic and hyperchromic red cell subpopulations was significantly increased in the former group of adults. SDS-PAGE demonstrated that 29 patients (39.7%) had isolated spectrin deficiency, 22 patients (30.1%) had combined spectrin and ankyrin deficiency, 17 patients (23.3%) had band 3 deficiency and 1 patient had protein 4.2 deficiency. No quantitative biochemical defects were detected in 4 patients (5.5%). The biochemical findings did not correlate with the haematological and clinical phenotype of the disease.
RESUMEN
Osteoporosis in beta-thalassaemia is multifactorial; increased osteoclast function seems to play an important role in its pathogenesis. The aim of this study was to evaluate the effect of pamidronate on the osteoporosis of thalassaemia. To this effect we studied 26 patients who received this drug in doses of 30 or 60 mg i.v. once a month over 12 months. The effects were monitored by measuring bone mineral density (BMD) in association with markers of osteoclast function [soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), osteoprotegerin (OPG)] and of bone remodelling [N-telopeptide of collagen type-I (NTX), tartrate-resistant acid phosphatase isoform-5b (TRACP-5b), bone-alkaline phosphatase (bALP), and osteocalcin (OC)]. Thirty healthy individuals were also studied, as controls. NTX, TRACP-5b, bALP and OC levels were significantly higher in thalassaemic patients compared with controls; in contrast, OPG levels were significantly lower, while the levels of sRANKL varied within normal limits. Administration of pamidronate was followed by a clear decrease of NTX, TRACP-5b, OPG, and OC, and by a significant increase in the BMD of the lumbar spine, which was similar in patients of both treatment groups. These data suggest that pamidronate, at a monthly dose of 30 mg, is an effective treatment for thalassaemic osteoporosis.
Asunto(s)
Antiinflamatorios/administración & dosificación , Difosfonatos/administración & dosificación , Osteoporosis/tratamiento farmacológico , Talasemia beta/tratamiento farmacológico , Fosfatasa Ácida/sangre , Adulto , Fosfatasa Alcalina/sangre , Antiinflamatorios/uso terapéutico , Biomarcadores/sangre , Biomarcadores/orina , Transfusión Sanguínea , Densidad Ósea/efectos de los fármacos , Proteínas Portadoras/sangre , Estudios de Casos y Controles , Colágeno/orina , Colágeno Tipo I , Difosfonatos/uso terapéutico , Esquema de Medicación , Femenino , Glicoproteínas/sangre , Humanos , Isoenzimas/sangre , Vértebras Lumbares , Masculino , Glicoproteínas de Membrana/sangre , Persona de Mediana Edad , Osteocalcina/sangre , Osteoporosis/etiología , Osteoporosis/terapia , Osteoprotegerina , Pamidronato , Péptidos/orina , Ligando RANK , Receptor Activador del Factor Nuclear kappa-B , Receptores Citoplasmáticos y Nucleares/sangre , Receptores del Factor de Necrosis Tumoral , Estadísticas no Paramétricas , Fosfatasa Ácida Tartratorresistente , Talasemia beta/complicaciones , Talasemia beta/terapiaRESUMEN
Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the UGT1 A1 gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients.
Asunto(s)
Anemia de Células Falciformes/genética , Glucuronosiltransferasa/genética , Poli dA-dT/genética , Regiones Promotoras Genéticas , Talasemia/genética , Secuencia de Aminoácidos , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/complicaciones , Bilirrubina/sangre , Genotipo , Enfermedad de Gilbert/complicaciones , Enfermedad de Gilbert/genética , Grecia , Humanos , Hiperbilirrubinemia/etiología , Hiperbilirrubinemia/genética , Talasemia/sangre , Talasemia/complicacionesRESUMEN
The polymorphic sequence (AT)(X)T(Y) motif residing 0.5 kb 5' to the human -globin gene has been shown to be a binding site for a putative repressor protein, BP1, in K562 cells. The (AT)(X)T(Y) sequence is characterized by variable length and several configurations. The precise role of the (AT)(X)T(Y) repeats on the regulation of the -globin gene remains unclear. In the present study, we identified the (AT)(X)T(Y) motifs which prevail in the Greek population, established their frequency, and directly investigated their role on -globin gene expression by comparing the effects of the four identified (AT)(X)T(Y) motifs using transient expression assays. Four different configurations were found in the Greek population: the (AT)7T7 motif was the most abundant (81.8%) representing the reference sequence, the (AT)9T5 motif (16.1%), and the (AT)11T3 motif (2%), while the (AT)8T4 motif was absent from normal A chromosomes and was exclusively found on s chromosomes. To evaluate their different role on transcriptional regulation, the four motifs were subcloned upstream of the luciferase reporter gene. Two expression systems were used; MEL cells were transfected with a pGL-2 basic plasmid containing one of the four (AT)(X)T(Y) repeats, the -globin gene promoter, and the luciferase gene, while HeLa cells were transfected with a similar construct (pGL-2 enhancer) including the SV40 enhancer. After 48 h following transient transfection of the cell lines, the expression level of the reporter gene was estimated using a photoilluminometer. The transfected MEL cells exhibited a clearly reduced expression of the luciferase gene driven by the -globin promoter containing the (AT)9T5 and (AT)11T3 configurations. In contrast, HeLa cells did not exhibit any differences among the four motifs. On the basis of these results, we postulate that the (AT)9T5 and (AT)11T3 variants residing 0.5 kb 5' to the -globin gene do not represent simple polymorphisms and can affect its expression in an erythroid environment.
Asunto(s)
Región de Flanqueo 5'/genética , Globinas/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Secuencia de Bases , Regulación de la Expresión Génica , Frecuencia de los Genes , Grecia/epidemiología , Hemoglobinopatías/genética , Humanos , Plásmidos , Polimorfismo Genético , Transfección , Células Tumorales CultivadasRESUMEN
The co-existence of thalassaemia major and chronic myeloid leukaemia (CML) is a very rare event. We report a 32-year-old man with thalassaemia major whose progressively increasing leukocytosis and thrombocytosis led to the diagnosis of CML confirmed by the characteristic t(9;22)(q34;q11) chromosomal translocation and the bcr-abl (b3a2) DNA fusion. The patient was treated with hydroxyurea and anagrelide. This combination resulted in the satisfactory control of both the white blood cell and platelet counts, which has continued over the past 14 months with no major side-effects, albeit with no molecular response. The administration of hydroxyurea was also associated with a significant HbF increase.
Asunto(s)
Antidrepanocíticos/uso terapéutico , Hidroxiurea/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Inhibidores de Agregación Plaquetaria/uso terapéutico , Quinazolinas/uso terapéutico , Talasemia beta/complicaciones , Adulto , Quimioterapia Combinada , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Recuento de Leucocitos , Masculino , Recuento de Plaquetas , Inducción de Remisión , Trombocitosis/sangre , Trombocitosis/complicaciones , Trombocitosis/tratamiento farmacológico , Talasemia beta/sangre , Talasemia beta/tratamiento farmacológicoRESUMEN
OBJECTIVE: To evaluate whether arthropathy is associated with juvenile hemochromatosis and, if so, to assess the relationship between this feature and other clinical features of the disease. METHODS: Clinical, laboratory, and radiologic evidence of arthropathy was studied in 8 Greek patients with genetically proven juvenile hemochromatosis. Osteopenia and osteoporosis were assessed by bone mineral density measurement. RESULTS: Seven of the 8 patients had articular manifestations. The main affected joint was the metacarpophalangeal joint, and the arthritis was progressive independent of phlebotomy therapy. Osteopenia was observed in 2 patients, and osteoporosis in 2 patients. CONCLUSION: Arthropathy may be present in patients with juvenile hemochromatosis, with features similar to those found in patients with hemochromatosis type 1.
Asunto(s)
Enfermedades Óseas Metabólicas/etiología , Hemocromatosis/complicaciones , Osteoporosis/etiología , Adulto , Edad de Inicio , Densidad Ósea , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Femenino , Ferritinas/sangre , Hormonas Esteroides Gonadales/sangre , Humanos , Hipogonadismo/complicaciones , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , RadiografíaRESUMEN
A rare case of stomach perforation following acute aspergillosis gastritis in the course of a fatal severe aplastic anemia is reported.