RESUMO
We report the cloning and characterization of the human eukaryotic protein translation initiation factor EIF2C1 gene. The human EIF2C1 gene consists of 19 exons and 18 introns that span a region of almost 50 kb. It is located on the short arm of chromosome 1 in the region 1p34-p35. This genomic region is frequently lost in human cancers such as Wilms tumors, neuroblastoma, and carcinomas of the breast, liver, and colon. The human EIF2C1 gene is ubiquitously expressed at low to medium levels. Differential polyadenylation and splicing result in a complex transcriptional pattern. The cDNA sequence is 7478 bp long and contains an extremely large 3' untranslated region of 4799 bp with multiple, short repeated segments composed of mono-, tri-, or quattronucleotides interspersed throughout. The human EIF2C1 gene belongs to a multigene family in human. It is highly conserved during evolution, sharing about 90% identity with rabbit eIF2C and 70% identity with plant AGO1 at the amino acid level. These facts suggest that human EIF2C1 might play an important physiological role.
Assuntos
Cromossomos Humanos Par 1 , Fatores de Iniciação em Eucariotos , Fatores de Iniciação de Peptídeos/genética , Adulto , Sequência de Aminoácidos , Proteínas Argonautas , Sequência de Bases , Northern Blotting , Bandeamento Cromossômico , Mapeamento Cromossômico , Clonagem Molecular , Sequência Conservada , Feminino , Feto/metabolismo , Humanos , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Fatores de Iniciação de Peptídeos/metabolismo , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Transcrição GênicaRESUMO
Activation of beta-catenin-mediated transcription is the nuclear end point of organ-specific Wnt signaling. In the developing kidney, Wnt-4, a secreted glycoprotein, acts as an autoinducer of the mesenchymal to epithelial transition that underlies normal nephron development. Dysregulation of this epithelial transformation process may lead to Wilms' tumors (WTs). In this study, we investigated the potential role of the beta-catenin proto-oncogene, a candidate downstream target molecule of Wnt-4 signaling, in the development of WTs. In 6 of 40 tumors (15%), mutation analysis revealed heterozygous missense mutations or small deletions that result in the loss of important regulatory phosphorylation sites within the beta-catenin protein. These findings indicate that activating beta-catenin mutations may play a significant role in the development of WTs and establish a direct link between Wilms' tumorigenesis and the Wnt signal transduction pathway governing normal kidney development.
Assuntos
Proteínas do Citoesqueleto/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Mutação , Proteínas Proto-Oncogênicas/genética , Transativadores , Tumor de Wilms/genética , Genes Supressores de Tumor , Genes do Tumor de Wilms , Humanos , Neoplasias Renais/patologia , Proto-Oncogene Mas , Transdução de Sinais/genética , Tumor de Wilms/patologia , Proteínas Wnt , Proteína Wnt4 , beta CateninaRESUMO
BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are at increased risk for diarrhea and enteric infections. We studied (1) the epidemiology of enteric pathogens associated with diarrhea, (2) the diagnostic yield of stool examination and endoscopic evaluation, (3) risks to develop diarrhea, and (4) the impact of diarrhea on patients' survival. METHODS: A total of 1933 participants in the Swiss HIV Cohort Study were prospectively followed up for a median of 25.5 months. A total of 560 diarrheal episodes were evaluated by standardized stool examination. Endoscopic evaluation was performed in 25% of patients with chronic diarrhea. RESULTS: The incidence of diarrhea was 14.2 per 100 person-years (95% confidence interval, 13.0-15.4). Among patients with CD4 cell counts below 0.05 x 10(9)/L, the probability to develop diarrhea within 1, 2, and 3 years was 48.5%, 74.3%, and 95.6%, respectively. The risk to develop diarrhea was increased among patients with severe immunodeficiency, homosexual men, and patients taking antiretroviral therapy. Pneumocystis carinii chemoprophylaxis did not reduce the risk of diarrhea. Diarrhea was an independent negative predictor of survival. Enteric pathogens were detected in 16.5% of 212 acute diarrheal episodes and in 46% of 348 chronic diarrheal episodes. The sensitivity of histological and stool examination was similar except for the diagnosis of intestinal cytomegalovirus infection and leishmaniasis, which required invasive evaluation. CONCLUSIONS: Intestinal infections were diagnosed in less than 50% of chronic diarrheal episodes. The prevalence of enteric pathogens tended to decrease during the observation period, possibly because of improved antiretroviral therapy. Endoscopic evaluation did not improve the diagnostic yield compared with stool examination except for the diagnosis of cytomegalovirus enteritis and leishmaniasis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Diarreia/microbiologia , Enterite/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diarreia/parasitologia , Diarreia/virologia , Endoscopia Gastrointestinal , Enterite/complicações , Enterite/diagnóstico , Enterite/parasitologia , Enterite/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Fatores de RiscoRESUMO
Progressive multifocal leucoencephalopathy is caused by infection with JC virus. The disease affects patients with immunodeficiencies, hematologic diseases, and patients treated with radiotherapy. The disease is characterised by foci of demyelinisation with atypical astrocytes and oligodendrocytes. Oligodendrocytes contain typical intranuclear inclusions. Progressive multifocal leucoencephalopathy and its verification is presented in three cases. Two patients died of progression of a malignant neoplasm and the leucoencephalopathy was a complication of the malignancy. The third case was a biopsy specimen taken from the brain of a patient who received a renal transplant. The material of all patients was analysed by light and electron microscopy, and in situ hybridisation with a probe specific for JC virus. In situ hybridisation proved to be the most specific and a simple method to demonstrate the infection in all cases. It is useful in instances in which the histologically detectable lesion is not characteristic, and in cells in which the conventional histologic methods fail to reveal the intranuclear inclusions of JC virus.
Assuntos
Encéfalo/patologia , Encéfalo/virologia , Leucoencefalopatia Multifocal Progressiva/patologia , Idoso , Humanos , Hibridização In Situ , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/classificação , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/virologia , MasculinoRESUMO
BACKGROUND: Intestinal neuronal dysplasia (IND) of the colonic submucous plexus is considered to be a congenital malformation of the enteric nervous system causing symptoms resembling those of Hirschsprung's disease. In contrast with the established diagnosis of aganglionosis using enzyme histochemistry, controversy exists over the diagnostic criteria of IND on rectal biopsies previously defined by a consensus report and the causal relation between morphological findings and clinical symptoms. AIMS: The interobserver variability was prospectively investigated with respect to final diagnoses and several histological features in rectal biopsy specimens from children suspected of having colonic motility disturbances. METHODS: 377 biopsy specimens from 108 children aged 4 days to 15 years were independently coded without knowledge of clinical symptoms by three experienced pathologists for 20 histological features, and a final diagnosis was given for every case. Interobserver variation for the different items and the final diagnosis were analysed using Cohen's kappa statistic. Clinical data at biopsy and outcome after 12 months were related to morphological findings. RESULTS: The three pathologists agreed completely with respect to the diagnosis Hirschsprung's disease (kappa = 1), but in only 14% of the children without aganglionosis. In 15 (17%) of the 87 children without aganglionosis, at least one pathologist judged the case as normal, while another diagnosed IND. kappa values were close to the zero value expected by chance for the diagnoses normal and IND. Young age was related to the presence of several morphological features-for example, acetylcholine esterase staining and presence of giant ganglia. Children with chronic constipation diagnosed as having IND, given no other specific diagnosis by any of the pathologists, were significantly younger (median 8.8 months) and had a higher cure rate after one year (60%) than constipated patients considered by all observers to have no histological abnormalities (median 6.1 years, cure rate 23%). CONCLUSIONS: In contrast with Hirschsprung's disease, there is a high interobserver variation with regard to the different morphological features and final diagnosis of IND, based on the criteria and conditions of the previous consensus report. The high frequency of histological "abnormalities" in young infants suggests that some of the features may represent a normal variant of postnatal development rather than a pathological process. Investigations using more refined and morphometric methods in rectal specimens from infants and children without bowel disease are needed to define the normal range of morphological appearance at different ages. These preliminary data indicate that, with current knowledge, rectal biopsy for diagnostic purposes should only be performed in constipated children for diagnosis of Hirschsprung's disease.
Assuntos
Colo/anormalidades , Colo/inervação , Sistema Nervoso Entérico/anormalidades , Doença de Hirschsprung/patologia , Reto/patologia , Adolescente , Criança , Pré-Escolar , Constipação Intestinal/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Variações Dependentes do Observador , Prognóstico , Estudos ProspectivosRESUMO
The normal function of the p53 tumor suppressor protein can be perturbed by non-mutational mechanisms. The E6 protein encoded by high risk strains of human papilloma virus (HPV) targets the p53 protein resulting in enhanced degradation via the ubiquitin pathway. We have used nested PCR for detecting the presence of HPV DNA in 58 primary head and neck tumors and 15 metastatic lymph nodes, which had been prescreened for p53 mutations in exons 5 to 8. HPV DNA sequences were detected in 12 tumors (20.6%) and 4 metastatic lymph nodes (21%). HPV type 16 DNA was predominantly found in tumors (n = 11) and lymph nodes (n = 4), one tumor was positive for HPV type 18 sequences. Five of 12 HPV-positive tumors (41%) carried a p53 mutation. Of 46 HPV-negative tumors, 16 (34.8%) carried a p53 mutation. Thus, HPV positivity and p53 mutations were not mutually exclusive in head-and-neck cancer. Three of 6 normal tissues adjacent to the tumor were positive for HPV type 16, while no viral DNA was found in the corresponding tumors. Thus, the presence of HPV type 16 DNA did not directly confer a growth advantage on the population of emerging tumor cells. Instead, these tumors lack normal p53 function due to mutation.
Assuntos
DNA Viral/análise , Genes p53 , Neoplasias de Cabeça e Pescoço/virologia , Mutação , Papillomaviridae/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , Metástase Linfática , Reação em Cadeia da PolimeraseRESUMO
Wilms' tumor is rare in adults. Its histology, grading and staging are identical to those in children. Investigators agree on a combined modality approach in the treatment of adult Wilms' tumor (AWT), but differ on how aggressive it should be. Some advocate adopting the current pediatric protocols which take into account tumor stage and grade. Others recommend using advanced disease regimens for all stages and grades. We report on an 18 year-old male with stage IV favorable histology Wilms' tumor. The patient underwent radical nephrectomy and received postoperative radiotherapy with intensive four-drug chemotherapy. He had one relapse after 12 months which was successfully treated with chemotherapy and radiotherapy. He remains in remission without relapses 36 months after the initial diagnosis. The genetics of Wilms' tumor has been well studied in children but is practically unknown in adults; karyotype and molecular genetic studies in this case were normal.
Assuntos
Neoplasias Renais/patologia , Neoplasias Pulmonares/secundário , Tumor de Wilms/secundário , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Terapia Combinada , Genes do Tumor de Wilms/genética , Humanos , Técnicas Imunoenzimáticas , Cariotipagem , Neoplasias Renais/química , Neoplasias Renais/genética , Neoplasias Renais/terapia , Neoplasias Pulmonares/terapia , Masculino , Estadiamento de Neoplasias , Nefrectomia , Tomografia Computadorizada por Raios X , Tumor de Wilms/química , Tumor de Wilms/genética , Tumor de Wilms/terapiaRESUMO
The nemaline myopathies are muscle disorders of variable severity and age of onset, with characteristic nemaline bodies in the sarcoplasm. Genes for dominant (NEM1) and recessive (NEM2A) nemaline myopathy have been localised to chromosomes one and two, respectively. A missense mutation in the alpha-tropomyosin gene (TPM3) has been associated with NEM1 in one family. Probands from 76 other nemaline myopathy families have now been screened for TPM3 mutations. One proband, who was not noted to have any weakness neonatally, but who died at 21 months of age, was shown to be homozygous for a single strand conformation polymorphism (SSCP) in skeletal-muscle-specific exon 1 of TPM3. Sequencing revealed homozygosity for a nonsense mutation at codon 31 (CAG to TAG). The patient should have no functioning alpha-tropomyosin slow protein. The nemaline bodies in this patient were exclusively in type one fibres, consistent with the expression of TPM3 only in type one fibres.
Assuntos
Homozigoto , Mutação/genética , Miopatias da Nemalina/genética , Miopatias da Nemalina/fisiopatologia , Tropomiosina/genética , Evolução Fatal , Testes Genéticos , Variação Genética , Humanos , Lactente , Masculino , Músculo Esquelético/patologia , Mutação de Sentido Incorreto/genética , Miopatias da Nemalina/patologiaRESUMO
Applications of fluorescence in situ hybridization (FISH) for translocation studies and biological dosimetry would benefit substantially from reliable and efficient automatic detection of metaphase chromosomes labeled with fluorescent dyes. We replicated and evaluated a fluorescence metaphase finder previously developed at the Medical Research Council (MRC), Human Genetics Unit (Scotland) and at Lawrence Berkeley Laboratory (LBL; California). The MRC/LBL system seemed to detect nearly all of the metaphases on the test slides, but it presented an unacceptable number of false positives (about five false positives per one true positive). Furthermore, we determined that the system actually overcalled true detections by counting certain metaphase spreads twice (duplicates). Through modifications of the MRC/LBL system, we developed the Lawrence Livermore National Laboratory (LLNL) system, which minimizes the detection of duplicates, incorporates new detection features, uses a binary decision tree (BDT) for classification, and provides functionalities to improve scanning accuracy and improve the post-detection review. To test the new system, DAPI-stained preparations of metaphase chromosomes from blood lymphocytes of four unrelated donors were placed on slides in drops ranging from 7 mm to 20 mm in diameter. Drops contained between 5 and 200 scorable metaphases each. The LLNL system achieved approximately 90% detection of non-duplicated metaphases as verified by an expert cytogeneticist, with typically less than one false positive per every one true positive detected.
Assuntos
Cromossomos Humanos , Hibridização in Situ Fluorescente/métodos , Automação , Células Cultivadas , Estudos de Avaliação como Assunto , Corantes Fluorescentes , Humanos , Metáfase , Sensibilidade e EspecificidadeAssuntos
Coristoma , Proteínas de Ligação a DNA/genética , Neoplasias Renais/patologia , Músculos , Fatores de Transcrição/genética , Tumor de Wilms/patologia , Diferenciação Celular , Proteínas de Ligação a DNA/fisiologia , Expressão Gênica , Genes do Tumor de Wilms , Humanos , Neoplasias Renais/genética , Neoplasias Renais/fisiopatologia , Proteína MyoD/biossíntese , Miogenina/biossíntese , Cadeias Pesadas de Miosina/biossíntese , Polimorfismo Conformacional de Fita Simples , Fatores de Transcrição/fisiologia , Proteínas WT1 , Tumor de Wilms/genética , Tumor de Wilms/fisiopatologiaRESUMO
A 9-month-old boy with a primary cystic lymphangioma of the right kidney is reported. The clinical and radiological features favored a malignant tumor. Histology revealed the lesion to be a lymphangioma; the diagnosis was confirmed by immunohistochemistry and chemical analysis of the intracystic fluid. Lymphangiomas of the kidney are rare in adults; they are even rarer in infants and children. Nevertheless, renal lymphangiomas should be considered in the differential diagnosis of multicystic, unilateral renal masses, independent of the age of the patient.
Assuntos
Neoplasias Renais/patologia , Linfangioma Cístico/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Lactente , Neoplasias Renais/química , Neoplasias Renais/diagnóstico por imagem , Linfangioma Cístico/química , Linfangioma Cístico/diagnóstico por imagem , Masculino , UltrassonografiaRESUMO
UNLABELLED: The Schwartz-Jampel syndrome (SJS; chondrodystrophic myotonia; McK 255,800) is a recessively inherited condition defined by myotonia, short stature, and bone dysplasia. Genetic linkage between SJS and chromosomal region 1q36-34 has been observed in several families, but the gene has not yet been identified. We studied the clinical and radiological features in 81 patients from the literature and 5 own patients trying to identify distinct subgroups. In addition, we tested genetic linkage to the SJS locus on chromosome 1 in one family with two affected sibs. We found that a group of patients have mild skeletal changes which may be secondary consequences of myotonia, while another group of patients appear to have primary bone dysplasia with myotonia. Within this latter group, there are differences in age of manifestation, clinical course and pattern of bone changes. We tentatively isolate three different types of SJS: type 1A, usually recognized in childhood, with moderate bone dysplasia, corresponding to the original descriptions of Schwartz, Jampel and Aberfeld; type 1B, similar to type 1A but recognizable at birth, with more pronounced bone dysplasia resembling Kniest dysplasia; and type 2, manifest at birth, with increased mortality and bone dysplasia resembling Pyle disease. Genetic analysis of the family with two sibs affected by SJS type 2 showed evidence against linkage to chromosome 1p36-34. CONCLUSIONS: SJS is clinically and radiologically heterogeneous. The causes of heterogeneity are not known yet but are likely to include both different mutations at the SJS locus on chromosome 1 and the presence of a second SJS locus. A tentative clinico-radiological classification can be useful for the characterization of patients and the development of genotype-phenotype correlations.
Assuntos
Cromossomos Humanos Par 1 , Ligação Genética/genética , Osteocondrodisplasias/genética , Adolescente , Osso e Ossos/patologia , Criança , Pré-Escolar , Mapeamento Cromossômico , Feminino , Seguimentos , Triagem de Portadores Genéticos , Humanos , Lactente , Recém-Nascido , Masculino , Osteocondrodisplasias/classificação , Osteocondrodisplasias/diagnóstico , Linhagem , FenótipoRESUMO
Background: Soft tissue tumors often present a major diagnostic challenge for the pathologist. The correct diagnosis has important prognostic and therapeutic consequences. In recent years significant progress has been made in identifying characteristic chromosomal abnormalities associated with certain solid tumors. More than 85% of tumors in the Ewing's sarcoma (ES) family contain a specific t(11;22) (q24;q12) translocation. Methods and Results: We present six patients with a soft tissue tumor of which only four were diagnosed primarily as belonging to the ES family. All cases were further examined by the following methods: immunohistochemistry with MIC2, cytogenetics, nested reverse transcription-polymerase chain reaction of the t(11;22), using fresh-frozen or formalin-fixed, paraffin-embedded archival material. Conclusions: This method clearly allowed the diagnosis of a tumor of the ES family in all six cases.
RESUMO
Minimally invasive treatments for benign prostatic hyperplasia (BPH) are currently very controversial. Nd:YAG laser transurethral thermocoagulation of the prostate is the technique most frequently used. The objective of this study was to assess the correlation between the morphological effects observed and the changes visible on magnetic resonance imaging during this type or treatment in the human prostate, in order to evaluate the tissue effects obtained according to the power and the interaction time applied. In 10 patients requiring radical prostatectomy for urological cancer, visual laser ablation of the prostate (VLAP) was performed during the 10 days preceding the radical operation (range: 1 to 9 days). The entire gland was submitted to pathological examination in order to correlate the histological result with contrast magnetic resonance imaging performed in 6 patients, using a standard transrectal coil, 12 to 24 hours before complete resection of the prostate. The morphological examination showed zones of periurethral necrosis of variable volume, accompanied by extensive peripheral haemorrhage, containing vessels with a partially obliterated lumen. Contrast magnetic resonance imaging (T1) showed that laser-induced lesions had a low density appearance and were perfectly demarcated with peripheral heterogeneous and hyperdense zones. In contrast with the experimental investigations performed to date, we demonstrated a clearly delayed tissue effect. Our experience demonstrates that a period of several hours between laser treatment and removal of the operative specimen is not sufficient to evaluate the extent of laser-induced lesions. High resolution magnetic resonance imaging with a standard transrectal coil, sometimes combined with a multiple coil, is very valuable to assess the effects of laser.
Assuntos
Fotocoagulação a Laser , Imageamento por Ressonância Magnética , Hiperplasia Prostática/cirurgia , Idoso , Silicatos de Alumínio , Meios de Contraste , Hemorragia/diagnóstico , Hemorragia/patologia , Humanos , Fotocoagulação a Laser/métodos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Necrose , Neodímio , Próstata/patologia , Prostatectomia , Hiperplasia Prostática/patologia , Fatores de Tempo , Uretra/patologia , ÍtrioRESUMO
BACKGROUND: Early detection of pathophysiological factors associated with permanent and severe brain damage in preterm infants requiring intensive care is a major issue in neonatal neurology. The aim of this study was to investigate if an abnormal CO2 reactivity of cerebral blood flow in high risk very low birth weight infants is associated with severe brain injury demonstrated at autopsy or by neurodevelopment examination at 18 months. METHODS: The CO2 reactivity of cerebral blood flow (xenon-133) was measured in 18 mechanically ventilated, severely ill, very low birthweight infants (gestational age 26-32 weeks, birthweight: 630-1360 g) during the first 36 hours of life. Cerebral outcome was assessed on autopsy findings (n = 8) or at the age of 18 months using Bayley developmental scales (n = 10). RESULTS: Eight infants with normal development at 18 months (within mean +/- 2.5 SD of reference group) and two infants with normal cerebral autopsy findings had a median CO2 reactivity of 24.4%/kPa CO2 (interquartile range 14.7-41.2). Two infants with abnormal development (> 2.5 SD below mean) and six infants with hypoxic-ischaemic encephalopathy at autopsy has a median CO2 reactivity of 3.4%/kPa CO2 (interquartile range 8.0-11.7). CONCLUSION: In mechanically ventilated very low birthweight infants low CO2 reactivity of cerebral blood flow (below 10%/kPa CO2) during the first 36 hours of life was associated with poor neurodevelopmental outcome or hypoxic-ischaemic encephalopathy at autopsy. Loss of CO2 reactivity may play a role in the pathogenesis of hypoxic ischaemic encephalopathy. It is a candidate for predicting early severe brain damage in preterm infants requiring intensive care and for controlling the effect of early interventions.
Assuntos
Dano Encefálico Crônico/diagnóstico , Encéfalo/irrigação sanguínea , Dióxido de Carbono , Doenças do Prematuro/diagnóstico , Recém-Nascido de muito Baixo Peso , Respiração Artificial , Resistência Vascular/fisiologia , Encéfalo/patologia , Dano Encefálico Crônico/patologia , Dano Encefálico Crônico/fisiopatologia , Dióxido de Carbono/fisiologia , Feminino , Seguimentos , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/fisiopatologia , Lactente , Recém-Nascido , Doenças do Prematuro/patologia , Doenças do Prematuro/fisiopatologia , Masculino , Fluxo Sanguíneo Regional/fisiologiaRESUMO
In this article, we address the issue of persistence of chromosome exchanges following acute in vitro exposure of rat peripheral blood to 137Cs. Irradiation occurred 24 hr after culture initiation, and metaphase chromosomes were prepared 2, 3, 4, and 5 days later. Chromosomes 1, 2, and 4 were painted in unique colors and scored for structural aberrations. Dicentric chromosomes and acentric fragments diminished rapidly with time, as expected. Translocations exhibited greater persistence, but still showed a reduction in frequency, reaching a plateau of approximately 65 and 55% of their initial values, 4 days after exposure to 1 and 2 Gy, respectively. An exponentially declining model was fit to the combined dicentric, acentric fragment, and translocation frequencies, which showed that all three aberration types declined at equivalent rates. The frequencies of dicentrics and fragments declined to a plateau of zero, while translocations reached a plateau at frequencies significantly greater than zero. The decline in translocations with time is inconsistent with prevailing theoretical expectations, but is consistent with a model where some translocations are fully stable (persistent) and some are unstable (not persistent) through cell division. These results may have implications for radiation biodosimetry in humans.
Assuntos
Radioisótopos de Césio/efeitos adversos , Hibridização in Situ Fluorescente , Linfócitos/efeitos da radiação , Translocação Genética , Animais , Células Cultivadas , Raios gama/efeitos adversos , Masculino , Índice Mitótico , Probabilidade , Ratos , Ratos Wistar , Fatores de TempoRESUMO
UNLABELLED: We report two brothers with renal dysplasia and congenital hepatic fibrosis. One patient died shortly after birth of lung hypoplasia. The second developed end-stage renal failure at 14 months. The hepatic fibrosis progressed to cirrhosis and hepatic failure. Pancreatic function was normal, but increased echogenicity was seen on ultrasound. At age 3 years and 9 months a successful combined liver-kidney transplantation was performed. The features of our patients are compatible with the "renal-hepatic-pancreatic dysplasia" syndrome. CONCLUSION: Renal-hepatic-pancreatic dysplasia is an autosomal recessive disorder with variable expression. Combined liver-kidney transplantation offers a new therapeutic option.
Assuntos
Anormalidades Múltiplas , Rim/anormalidades , Cirrose Hepática/congênito , Pâncreas/anormalidades , Humanos , Recém-Nascido , Rim/patologia , Rim/cirurgia , Falência Renal Crônica/etiologia , Transplante de Rim , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Transplante de Fígado , Masculino , Rim Policístico Autossômico Recessivo , SíndromeRESUMO
A seven-month-old, female domestic shorthair cat was presented to the Veterinary Teaching Hospital, University of Zurich, with abnormal facial features, retarded growth and progressive hindlimb paresis. On physical examination the cat had a flat, broad face with hypertelorism, frontal bossing, small ears and thickened upper and lower eyelids. The corneas of both eyes were clear and the pupils were dilated. The skin was generally thickened, most prominently on the dorsal aspect of the neck. Radiography of the entire skeleton revealed a severely deformed spinal column, bilateral hip luxation with hip dysplasia, an abnormally shaped skull and generalised decreased bone opacity. The clinical features and radiographic changes were suggestive of mucopolysaccharidosis. The toluidine blue spot test on a urine sample, however, was negative for glycosaminoglycans. Further biochemical investigations revealed a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase, EC 2.7.8.17) in peripheral leukocytes and an elevation of many lysosomal enzymes in the serum of the cat which is diagnostic for mucolipidosis type II. Histology and electron microscopy of different tissues are briefly summarised. The findings of this cat, the first reported case of mucolipidosis type II are compared with other similar storage diseases described in the cat.
Assuntos
Doenças do Gato/diagnóstico , Mucolipidoses/veterinária , Animais , Axônios/ultraestrutura , Osso e Ossos/anormalidades , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/ultraestrutura , Cartilagem/ultraestrutura , Doenças do Gato/metabolismo , Doenças do Gato/patologia , Gatos , Tecido Conjuntivo/ultraestrutura , Feminino , Leucócitos/enzimologia , Leucócitos/ultraestrutura , Microscopia Eletrônica/veterinária , Mucolipidoses/diagnóstico , Mucolipidoses/patologia , Mucopolissacaridose I/diagnóstico , Mucopolissacaridose I/metabolismo , Mucopolissacaridose I/veterinária , Mucopolissacaridose VI/diagnóstico , Mucopolissacaridose VI/metabolismo , Mucopolissacaridose VI/veterinária , Mucopolissacaridose VII/diagnóstico , Mucopolissacaridose VII/metabolismo , Mucopolissacaridose VII/veterinária , Radiografia , Pele/ultraestruturaRESUMO
The primary food mutagens found in cooked meat are the heterocyclic aromatic amines, including 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). High dose, acute exposures of MeIQx produce hepatic tumours in some mouse and rat strains. By assaying chromosome damage it may be possible to correlate aberrations with exposure to a mutagen. Whole chromosome painting by fluorescence in situ hybridization allows the rapid screening of metaphase chromosomes for rearrangements. This technique was applied to female mice (C57BL/6) chronically fed 100-400 ppms MeIQx for up to 6 months. Two tissues, blood and bone marrow, were screened with multicolour whole chromosome painting probes (1,2,3 and 8). The mice showed no outward signs of toxicity at any dose and very few chromosome aberrations were observed. A slight but significant increase in sister chromatid exchanges (SCE) was seen at 400 ppm in blood at 6 months. When MeIQx was removed from the diet for 1 month there was an apparent decline in SCEs only for animals previously given the 400 ppm diet.
Assuntos
Medula Óssea/efeitos dos fármacos , Carcinógenos/toxicidade , Aberrações Cromossômicas , Mutagênicos/toxicidade , Quinoxalinas/toxicidade , Animais , Medula Óssea/patologia , Células da Medula Óssea , Aberrações Cromossômicas/genética , Meios de Cultura , Feminino , Fêmur , Fluoresceína-5-Isotiocianato/química , Manipulação de Alimentos , Hibridização in Situ Fluorescente , Linfócitos/efeitos dos fármacos , Linfócitos/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Testes para Micronúcleos , Quinoxalinas/sangue , Troca de Cromátide Irmã/genéticaRESUMO
Tumors of the Ewing's sarcoma family often present a major diagnostic challenge for the pathologist. In recent years, significant progress has been made in identifying characteristic chromosomal rearrangements associated with certain solid tumors. More than 85% of Ewing's sarcoma and related tumors present a specific t(11;22) (q24;q12) balanced translocation, which generates a fusion transcript of the EWS gene and the FLI-1 gene. The cloning of the t(11;22)(q24;q12) breakpoint has raised the possibility of using a reverse transcription-polymerase chain reaction (RT-PCR) based assay as a diagnostic tool. We report an improvement of the established method, which currently depends on fresh or snap-frozen tissue, so that it is possible to use formalin-fixed, paraffin-embedded tissue as a source of RNA. The described nested RT-PCR assay enables the pathologist to investigate retrospectively archival tumor samples or to confirm the diagnosis in cases where no fresh or frozen material is available.