RESUMEN
Oxidative stress (OS) is involved in several human diseases, including obesity, diabetes, atherosclerosis, carcinogenesis, as well as genetic diseases. We previously found that OS occurs in Down Syndrome as well as in Beckwith-Wiedemann Syndrome (BWS). Here we describe the clinical case of a female patient with Prader Willi Syndrome (PWS), a genomic imprinting disorder, characterized by obesity, atherosclerosis and diabetes mellitus type 2, pathologies in which a continuous and important production of free radicals takes place. We verified the presence of OS by measuring a redox biomarkers profile including total hydroperoxides (TH), non protein-bound iron (NPBI), thiols (SH), advanced oxidation protein products (AOPP) and isoprostanes (IPs). Thus we introduced in therapy an antioxidant agent, namely potassium ascorbate with ribose (PAR), in addition to GH therapy and we monitored the redox biomarkers profile for four years. A progressive decrease in OS biomarkers occurred until their normalization. In the meantime a weight loss was observed together with a steady growth in standards for age and sex.
Asunto(s)
Antioxidantes/uso terapéutico , Ácido Ascórbico/uso terapéutico , Síndrome de Prader-Willi/tratamiento farmacológico , Ribosa/uso terapéutico , Adolescente , Productos Avanzados de Oxidación de Proteínas/sangre , Quimioterapia Combinada , Femenino , Radicales Libres/sangre , Humanos , Peróxido de Hidrógeno/sangre , Hierro/sangre , Isoprostanos/sangre , Estrés Oxidativo , Potasio/uso terapéutico , Síndrome de Prader-Willi/sangre , Compuestos de Sulfhidrilo/sangre , Pérdida de PesoRESUMEN
Fibrillin-1 gene (FBN1) mutations cause Marfan syndrome (MFS), an inherited connective tissue disorder with autosomal dominant transmission. Major clinical manifestations affect cardiovascular and skeletal apparatuses and ocular and central nervous systems. We analyzed FBN1 gene in 99 patients referred to our Center for Marfan Syndrome and Related Disorders (University of Florence, Florence, Italy): 85 were affected by MFS and 14 by other fibrillinopathies type I. We identified mutations in 80 patients. Among the 77 different mutational events, 46 had not been previously reported. They are represented by 49 missense (61%), 1 silent (1%), 13 nonsense (16%), 6 donor splice site mutations (8%), 8 small deletions (10%), and 3 small duplications (4%). The majority of missense mutations were within the calcium-binding epidermal growth factor-like domains. We found preferential associations between The Cys-missense mutations and ectopia lentis and premature termination codon mutations and skeletal manifestations. In contrast to what reported in literature, the cardiovascular system is severely affected also in patients carrying mutations in exons 1-10 and 59-65. In conclusion, we were able to detect FBN1 mutations in 88% of patients with MFS and in 36% of patients with other fibrillinopathies type I, confirming that FBN1 mutations are good predictors of classic MFS.
Asunto(s)
Síndrome de Marfan/genética , Proteínas de Microfilamentos/genética , Mutación , Adolescente , Adulto , Análisis Mutacional de ADN , Femenino , Fibrilina-1 , Fibrilinas , Pruebas Genéticas , Humanos , MasculinoRESUMEN
The majority of 47, XYY males are fertile and contribute to produce chromosomally normal children. In 47, XYY carriers, most meiotic studies indicated that the extra Y chromosomes were lost in the pre-meiotic stages, but in some cases the presence of one X and the two Y chromosomes has been detected during prophase I as an X univalent plus a YY bivalent. The aim of this study was to describe sperm parameters and meiotic segregation in a case of an infertile man with a 47, XYY karyotype. Sperm morphology was evaluated for the first time by transmission electron microscopy highlighting apoptosis and necrosis as the most frequent pathologies. Meiotic segregation was explored by fluorescence in situ hybridisation technique, which makes us capable of detecting aneuploidies of sex chromosomes. The fact that the frequency of 1818XY diploidy was very high reveals an error occurring during first meiotic division. Polymerase chain reaction analysis did not show any Y microdeletion. The combination of these two techniques led us to clarify the status of the spermatogenic process, showing an altered meiotic segregation concomitant with the presence of sperm apoptosis and necrosis in a patient 47, XYY.
Asunto(s)
Infertilidad Masculina/genética , Meiosis/genética , Espermatozoides/ultraestructura , Cariotipo XYY/genética , Adulto , Apoptosis , Cromosomas Humanos Y , Humanos , Masculino , Necrosis/patología , Espermatozoides/patologíaRESUMEN
Using array comparative genome hybridisation (CGH) 41 de novo reciprocal translocations and 18 de novo complex chromosome rearrangements (CCRs) were screened. All cases had been interpreted as "balanced" by conventional cytogenetics. In all, 27 cases of reciprocal translocations were detected in patients with an abnormal phenotype, and after array CGH analysis, 11 were found to be unbalanced. Thus 40% (11 of 27) of patients with a "chromosomal phenotype" and an apparently balanced translocation were in fact unbalanced, and 18% (5 of 27) of the reciprocal translocations were instead complex rearrangements with >3 breakpoints. Fourteen fetuses with de novo, apparently balanced translocations, all but two with normal ultrasound findings, were also analysed and all were found to be normal using array CGH. Thirteen CCRs were detected in patients with abnormal phenotypes, two in women who had experienced repeated spontaneous abortions and three in fetuses. Sixteen patients were found to have unbalanced mutations, with up to 4 deletions. These results suggest that genome-wide array CGH may be advisable in all carriers of "balanced" CCRs. The parental origin of the deletions was investigated in 5 reciprocal translocations and 11 CCRs; all were found to be paternal. Using customized platforms in seven cases of CCRs, the deletion breakpoints were narrowed down to regions of a few hundred base pairs in length. No susceptibility motifs were associated with the imbalances. These results show that the phenotypic abnormalities of apparently balanced de novo CCRs are mainly due to cryptic deletions and that spermatogenesis is more prone to generate multiple chaotic chromosome imbalances and reciprocal translocations than oogenesis.
Asunto(s)
Deleción Cromosómica , Trastornos de los Cromosomas/genética , Translocación Genética , Anomalías Múltiples/genética , Aborto Habitual/genética , Adulto , Preescolar , Rotura Cromosómica , Trastornos de los Cromosomas/patología , Pintura Cromosómica , Femenino , Enfermedades Fetales/genética , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Discapacidad Intelectual/genética , Masculino , Hibridación de Ácido Nucleico , Oogénesis , Fenotipo , Diagnóstico Prenatal , EspermatogénesisRESUMEN
Pericentric inversions involving the secondary constriction (qh) region of chromosome 9 are considered to be normal variants of human karyotype. A number of investigators have suggested that chromosomal anomalies can contribute to human infertility causing spermatogenetic derangement. The present study was aimed at verifying the influence of chromosome 9 inversion on human spermatogenesis. Semen samples of 18 male carriers of chromosome 9 inversion, analysed by light microscopy, revealed that five patients were azoospermic. PCR analysis demonstrated that two of them also had Y microdeletions. The other 13 showed generally normal sperm concentrations and reduced motility. The morphological characteristics of sperm were studied by TEM and the data were elaborated by a mathematical formula. Sperm pathologies resulted more frequently in the studied group compared to controls, particularly apoptosis. Partial sequences of the A-kinase anchoring protein (Akap) 4 and 3 genes were performed in all patients, as a previous study by our group highlighted Dysplasia of Fibrous Sheath (DFS) defect in two men with inv 9 investigations. The possible effect of chromosome 9 inversion on meiotic chromosome segregation was investigated by FISH, which showed an increased incidence of diploidy. We hypothesized that this inversion could have variable effects on spermatogenesis, from azoospermia to severely altered sperm morphology, motility and meiotic segregation.
Asunto(s)
Inversión Cromosómica , Cromosomas Humanos Par 9 , Infertilidad Masculina/genética , Infertilidad Masculina/patología , Adolescente , Adulto , Humanos , Hibridación Fluorescente in Situ , Linfocitos/patología , Linfocitos/ultraestructura , Masculino , Microscopía Electrónica , Reacción en Cadena de la Polimerasa , Espermatozoides/patología , Espermatozoides/ultraestructuraRESUMEN
Epilepsy is commonly observed in patients with chromosomal aberrations. We evaluated epilepsy and electroencephalographic (EEG) features in a group of patients carrying aberrations of chromosome 18. Fourteen patients were recruited: five with an 18p deletion syndrome (18pDS); six with an 18q deletion syndrome (18qDS); two with trisomy 18p syndrome; and one with a 45,XY,t(17-18) (cen-q11.2) karyotype. Patients with 18pDS had neither epilepsy nor EEG anomalies; four patients with 18qDS had epilepsy with partial seizures occurring during infancy or early childhood. Partial seizures were also present in both patients with trisomy 18p. By contrast, mixed seizures were observed in the patient carrying a translocation between chromosomes 17 and 18. Our data and a re-evaluation of the literature suggest that epilepsy is infrequent in patients with 18pDS. Conversely, partial seizures and focal EEG anomalies may be observed in those with patients with 18qDS. Our observations suggest that the haplo-insufficiency of genes located on the long arm of chromosome 18 is more likely to be associated with epilepsy, than is haplo-insufficiency of genes located on the short arm. While further EEG/clinical investigations are needed to validate these observations, this study indicates a possible relationship between chromosome 18 genes and epilepsy.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 18/genética , Epilepsia/genética , Adolescente , Niño , Bandeo Cromosómico , Deleción Cromosómica , Cromosomas Humanos Par 17/genética , Electroencefalografía , Epilepsia/fisiopatología , Femenino , Humanos , Cariotipificación , Masculino , Literatura de Revisión como Asunto , Síndrome , Translocación Genética , TrisomíaAsunto(s)
Ataxia Cerebelosa/diagnóstico , Síndrome del Cromosoma X Frágil/diagnóstico , Paraparesia Espástica/diagnóstico , Temblor/diagnóstico , Adulto , Anciano , Encéfalo/patología , Ataxia Cerebelosa/genética , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Tamización de Portadores Genéticos , Humanos , Imagen por Resonancia Magnética , Masculino , Paraparesia Espástica/genética , Linaje , Temblor/genéticaRESUMEN
Since etiology and pathogenesis of most systemic and/or isolated vasculitides are unknown, any attempt to make a rational classification of these entities is far from being perfect. Vasculitis may be a primary disease or it may be associated with connective tissue diseases, infectious diseases, neoplasms, drug assumption, allograft rejection and so on. As secondary vasculitides constitute the majority of cases, diagnosis of primary vasculitis is made by exclusion. At the present time, the 1993 Chapel Hill Consensus Conference on Nomenclature of Primary Vasculitides provides a useful guide to clinician and pathologist for evaluating a patient with an idiopathic form of vasculitis. This classification is based on the predominant size of vessels affected and describes the main clinico-pathologic features of the various clearly defined types of systemic vasculitis. Though it suffers from omissions and contradictions, in routine practice it is of great help to distinguish diseases in this intriguing chapter of pathology.
Asunto(s)
Enfermedades Vasculares/clasificación , Enfermedades Vasculares/patología , HumanosRESUMEN
Facial hemangioma is usually isolated but its association with craniocervical arterial anomalies and structural brain malformations is well known. The acronym PHACE syndrome (posterior fossa malformation, facial hemangiomas, arterial anomalies, cardiac/aortic anomalies, and eye abnormalities) has been used to indicate that disorder in which brain anomalies are mainly represented by the Dandy-Walker malformation. We report on a 10-month-old boy affected by facial hemangioma and a complex cortical dysplasia located in the left frontal region. The lesion was characterized by a deeply infolding pachygyric cortex and a band of gray matter lining the wall of the lateral ventricle. The entire left cerebral hemisphere appeared hypoplastic. No anomalies of the posterior fossa structures or cardiac/aortic malformations were present. An overlapping clinical/pathological pattern was previously reported in another patient with facial hemangioma and cerebrovascular anomalies. These observations seem to indicate that the facial hemangiomas may be associated with disorders of the cortical development.
Asunto(s)
Anomalías Múltiples/patología , Corteza Cerebral/anomalías , Neoplasias Faciales/patología , Hemangioma/patología , Anomalías Múltiples/genética , Arterias/anomalías , Diagnóstico Diferencial , Anomalías del Ojo/patología , Cardiopatías Congénitas/patología , Humanos , Lactante , Cariotipificación , Masculino , SíndromeRESUMEN
A de novo, apparently balanced complex chromosome rearrangement (CCR) involving five chromosomes and six chromosome breakpoints was found in a child with Marfanoid habitus, kyphoscoliosis, axillary pterygium, camptodactyly, joint laxity, and mild mental retardation. Fluorescence in situ hybridization (FISH) revealed a simple translocation involving chromosomes 3 and 13, and a complex rearrangement involving chromosomes 4, 8, and 18 with four breakpoints.
Asunto(s)
Anomalías Múltiples/genética , Huesos/anomalías , Discapacidad Intelectual/patología , Translocación Genética , Anomalías Múltiples/patología , Niño , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 4/genética , Cromosomas Humanos Par 8/genética , Dedos/anomalías , Humanos , Hibridación Fluorescente in Situ , MasculinoAsunto(s)
Endocarditis Bacteriana/complicaciones , Infecciones Estafilocócicas/complicaciones , Anciano , Enfermedades de la Aorta/diagnóstico por imagen , Ecocardiografía Doppler en Color , Fístula/diagnóstico , Fístula/etiología , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/patología , Cardiopatías/diagnóstico , Cardiopatías/etiología , Humanos , MasculinoRESUMEN
Duplication of chromosome 15 (inv dup[15] chromosome) is the most common supernumerary marker chromosome in humans. Inv dup(15) chromosomes are commonly associated with mental retardation, epilepsy, behavioral problems and structural malformations. Ten patients (4 male, 6 female) were detected with inv dup(15) syndrome. At clinical follow-up three girls showed pubertal disorders: two with central precocious puberty and one with ovarian dysgenesis. As has already been found in other patients with chromosome 15p abnormalities, we believe that gynecological disorder is an important clinical finding also in patients with inv dup(15) syndrome. We report the first data of a systematic endocrinological study on inv dup(15) syndrome which suggest that endocrine investigation in these patients is both warranted and useful. Moreover, our observations confirm that a karyotype analysis in patients in whom precocious puberty is associated with mental retardation is mandatory.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 15 , Pubertad Tardía/genética , Pubertad Precoz/genética , Adolescente , Niño , Anomalías Congénitas/genética , Etinilestradiol/uso terapéutico , Femenino , Hormona Folículo Estimulante/sangre , Duplicación de Gen , Hormona Liberadora de Gonadotropina , Hormona de Crecimiento Humana/sangre , Humanos , Hidrocortisona/sangre , Hormona Luteinizante/sangre , Ovario/anomalías , Prolactina/sangre , Pubertad Tardía/tratamiento farmacológico , Pubertad Precoz/tratamiento farmacológico , Hormonas Tiroideas/sangre , Tirotropina/sangre , Hormona Liberadora de Tirotropina , Pamoato de Triptorelina/uso terapéuticoRESUMEN
CONTEXT: Several aspects of sweat gland carcinomas (incidence, classification, diagnosis, and behavior) have not been definitively clarified and need to be studied further. OBJECTIVE: The clinicopathologic findings of a large series of sweat gland carcinomas, collected during a period of 15 years, are presented. METHODS: Sixty sweat gland carcinomas (41 porocarcinomas, 3 syringomatous carcinomas, 8 ductal carcinomas, 5 adenoid cystic carcinomas, and 3 mucinous carcinomas) were analyzed histologically and immunohistochemically. RESULTS: Porocarcinomas were composed of eosinophilic and clear atypical cells arranged in solid-cystic lobular masses. These tumors were divided into 2 subgroups: horizontal porocarcinomas, showing a prominent intraepidermal component, and nodular porocarcinomas, which demonstrated predominant nodular growth. Syringomatous carcinomas presented keratinizing and nonkeratinizing cysts, dilated tubules (sometimes with a "tadpole" appearance), small neoplastic ducts, solid islands, and cellular cords. Ductal carcinomas were characterized by a prominent formation of tubules, solid islands, and cellular cords. Adenoid cystic carcinomas presented a characteristic pattern, showing basaloid monomorphous cells with moderately atypical nuclei, arranged in cribriform or solid islands and in tubular structures. Mucinous carcinomas were composed of moderately atypical cells with eosinophilic vacuolated cytoplasm, forming solid and cystic islands floating in large mucin pools. Immunohistochemically, cytokeratin was found in neoplastic cells in all cases, carcinoembryonic antigen was detected in 73% of cases, and actin-positive (myoepithelial) cells were not found. CONCLUSIONS: Although numerous studies have been published in recent years, the histologic features, histogenesis, and classification of sweat gland carcinomas still remain controversial and need to be clarified by further studies.
Asunto(s)
Adenocarcinoma/patología , Neoplasias de las Glándulas Sudoríparas/patología , Acrospiroma/química , Acrospiroma/patología , Actinas/análisis , Adenocarcinoma/química , Adenocarcinoma/clasificación , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/patología , Adenoma de las Glándulas Sudoríparas/química , Adenoma de las Glándulas Sudoríparas/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígeno Carcinoembrionario/análisis , Carcinoma Adenoide Quístico/química , Carcinoma Adenoide Quístico/patología , Niño , Femenino , Humanos , Técnicas para Inmunoenzimas , Queratinas/análisis , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias de las Glándulas Sudoríparas/química , Neoplasias de las Glándulas Sudoríparas/clasificación , Glándulas Sudoríparas/patologíaAsunto(s)
Anomalías Múltiples/genética , Elastina/genética , Anomalías Múltiples/etiología , Anomalías Múltiples/patología , ADN/química , ADN/genética , Análisis Mutacional de ADN , Trastornos del Crecimiento/patología , Humanos , Discapacidad Intelectual/patología , Polimorfismo Conformacional Retorcido-Simple , SíndromeRESUMEN
We report a case of intravenous leiomyomatosis (IVL) in a 44-year-old woman, presenting with cardiothoracic clinical manifestations. Such a rare neoplastic condition most often arises from the uterine veins. At times it may reach the right cavities of the heart and it must be considered in the differential diagnosis with a cardiac myxoma or a thrombus.
Asunto(s)
Neoplasias Cardíacas/diagnóstico , Venas Hepáticas , Leiomioma/diagnóstico , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Vasculares/diagnóstico , Vena Cava Inferior , Adulto , Femenino , Neoplasias Cardíacas/cirugía , Humanos , Leiomioma/cirugía , Invasividad Neoplásica , Neoplasias Primarias Secundarias/cirugía , Válvula Tricúspide , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía , Neoplasias Vasculares/cirugíaAsunto(s)
Neoplasias de las Glándulas Sudoríparas/patología , Acrospiroma/patología , Adenoma de las Glándulas Sudoríparas/patología , Carcinoma/patología , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoescamoso/patología , Carcinoma Mucoepidermoide/patología , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Sudoríparas/clasificación , Neoplasias de las Glándulas Sudoríparas/historia , Siringoma/patología , Terminología como AsuntoRESUMEN
AIMS: The purpose of this study was to establish whether the cell proliferation index assessed by the monoclonal antibody MIB-1 would correlate with survival in pleural malignant mesothelioma. METHODS AND RESULTS: We studied a series of seven long-term survivors with pleural malignant mesothelioma and a group of control cases with short-term survival. All cases showed MIB-1 positive cells, and labelling indices were expressed as percentage of cells with positive nuclear immunostaining by randomly counting 1000 tumour cells. A statistically significant difference was found between MIB-1 values in the long-term survival group and the control cases with short-term survival. CONCLUSIONS: Our results indicate that the differences in biological behaviour of malignant mesothelioma in long-term and short-term survivors may be explained in part by differences in tumour growth fraction and that proliferation index could represent an important prognostic parameter for this tumour.
Asunto(s)
Antígeno Ki-67/análisis , Mesotelioma/mortalidad , Neoplasias Pleurales/mortalidad , Adulto , Anciano , Recuento de Células , División Celular , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Mesotelioma/química , Mesotelioma/patología , Persona de Mediana Edad , Índice Mitótico , Neoplasias Pleurales/química , Neoplasias Pleurales/patología , Tasa de SupervivenciaRESUMEN
Central precocious puberty (PP) can be caused by chromosomal aberrations. We report three patients presenting with central PP in whom karyotype analysis demonstrated abnormal chromosomal patterns. The first patient was affected by the triple-X syndrome, commonly characterized by premature ovarian failure. The second patient, a girl with inv dup(15)(pter-->q12::q12-->pter), had a chromosomal aberration involving an imprinted region of the human genome, whose deletion is commonly associated with Prader-Willi syndrome (PWS) and hypogonadotrophic hypogonadism. The third patient was a boy carrying a rare chromosome abnormality, the duplication of chromosome 9 (q22-->qter). All patients had mental retardation, which was mild in patient 1, moderate in patient 2, and severe in case 3. They underwent treatment with luteinizing hormone releasing hormone (LHRH) analogs, which were able to stop the progression of the sexual development. We confirm that chromosomal aberrations are an important cause of central PP, and that karyotype analysis in patients with PP and mental retardation, even if mild, is necessary because chromosomal abnormalities can be present.
RESUMEN
Congenital bronchogenic cysts are usually located in the mediastinum or develop as intrapulmonary cysts. Gross examination of excised bronchogenic cysts shows them to be unilocular; histologically, these lesions are characterized by the presence of respiratory-type pseudostratified epithelium as well as small islands of cartilage and seromucinous glands. We report a case of a mediastinal bronchogenic cyst having pulmonary parenchyma within the cyst wall. The rarity of our case, the pathological and clinical features and the embryological development of bronchogenic cysts are briefly discussed.