RESUMO
BACKGROUND: The caveolin-1 protein (structural component of membrane caveolae) plays important roles in several biological functions, such as endocytosis, cell adhesion, and cell signaling. However, this protein has been associated with mechanisms of tumorigenesis in several neoplasms. The expression patterns and roles of caveolin-1 in the oral epithelium and in embryonic and odontogenic tumor tissues are still unclear. MATERIAL AND METHODS: The expression of caveolin-1 was evaluated in samples of the normal gingival epithelium (n=7), human tooth germ (TG) (n=12), ameloblastoma (AM) (n=83), and ameloblastic carcinoma (AC) (n=9) by immunohistochemistry. Additionally, AM samples were analyzed by qRT-PCR and Western blot. RESULTS: Most TG (91.7%), AM (73.5%) and AC (100%) samples showed diverse patterns of immunohistochemical positivity for caveolin-1, while only one gingival sample was positive. The transcript levels of cav-1 were significantly upregulated by 14.9-fold in AM tissue (P = 0.0014) compared to those in normal gingival epithelial tissue, as shown by qRT-PCR. Presence of caveolin-1 protein was confirmed by Western blot analysis. The caveolin-1 immunoexpression patterns throughout the stages of TG show its importance during odontogenesis. CONCLUSIONS: The overexpression of caveolin-1 in AM and AC compared to its expression in normal gingival epithelium (adult tissue) suggests a possible role of caveolin-1 in protumoral events, but due to the similar immunoexpression observed in AM and AC, caveolin-1 may not necessarily participate in the malignant transformation process. However, future studies are needed to clarify and confirm these hypotheses.
Assuntos
Ameloblastoma , Carcinoma , Tumores Odontogênicos , Adulto , Caveolina 1 , Humanos , Germe de DenteRESUMO
Primordial odontogenic tumor (POT) is composed of variably cellular myxoid connective tissue, surrounded by cuboidal to columnar odontogenic epithelium resembling the inner epithelium of the enamel organ, which often invaginates into the underlying connective tissue. The tumor is delimited at least partially by a thin fibrous capsule. It derives from the early stages of tooth development. Syndecan-1 is a heparan sulfate proteoglycan that has a physiological role in several cellular functions, including maintenance of the epithelial architecture, cell-to-cell adhesion and interaction of cells with extracellular matrix, and with diverse growth factors, stimulating cell proliferation. Ki-67 is considered the gold standard as a cell proliferation marker. The aim of this study was to examine the expression of Syndecan-1 and Ki-67 proliferation index in POT and normal tooth germs to better understand the biological behavior of this tumor. Results showed that Syndecan-1 was more intensely expressed in subepithelial mesenchymal areas of POT, in a pattern that resembles the early stages of tooth development. The cell proliferation index (4.1%) suggests that POT is a slow growing tumor. Syndecan-1 expression in tooth germs in late cap and early bell stages was similar to POT, showing immunopositivity in subepithelial mesenchymal condensed areas. The immunohistochemical findings showed a pattern in which the population of subepithelial mesenchymal cells exhibited greater proliferative activity than the central portion of the dental papilla.
Assuntos
Antígeno Ki-67/metabolismo , Odontogênese , Tumores Odontogênicos/metabolismo , Sindecana-1/metabolismo , Germe de Dente/metabolismo , Proliferação de Células , Humanos , Mesoderma/metabolismo , Tumores Odontogênicos/fisiopatologia , Estudos Retrospectivos , Germe de Dente/fisiologiaAssuntos
Moléculas de Adesão Celular/genética , Epidermólise Bolhosa Juncional/genética , Mutação/genética , Adolescente , Adulto , Criança , Pré-Escolar , Chile/etnologia , Epidermólise Bolhosa Juncional/epidemiologia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Epidemiologia Molecular , Prevalência , Adulto Jovem , CalininaRESUMO
OBJECTIVES: To report the benefits of genetic diagnosis in patients with retinoblastoma. METHOD: Observational study. Patients with retinoblastoma and their families were included. Demographic and clinical data were recorded. Blood and tumour samples were obtained. Next generation sequencing was performed on the samples. When deletion 13 q syndrome was suspected, cytogenetics microarray was performed (Cytoscan® HD, Affymetrix, Santa Clara, CA, USA), with a high density chip of 1.9 million of non-polymorphic probes and 750 thousand SNP probes. RESULTS: Of the 7 cases were analysed 4 were male. The mean age at diagnosis was 21 months (range 5-36). Three cases had bilateral retinoblastoma, and 4 unilateral. None had family history. In all patients, blood was analysed, and a study was performed on the tissue from 2 unilateral enucleated tumours, in which 6 mutations were identified, all de novo. Just one was novel (c.164delC; case 1). One case of unilateral tumour revealed blood mosaicism, showing that his condition was inheritable, and that there is a high risk of developing retinoblastoma in the unaffected eye. The patient also has an increased risk of presenting with other primary tumours. CONCLUSION: Molecular diagnosis of RB1 in patients with retinoblastoma impacts on the decision process, costs, treatment, and prognosis of patients, as well as their families.
Assuntos
DNA de Neoplasias/genética , Neoplasias Oculares/genética , Genes do Retinoblastoma , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Ligação a Retinoblastoma/genética , Retinoblastoma/genética , Ubiquitina-Proteína Ligases/genética , Pré-Escolar , Chile , Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 13/genética , Análise Mutacional de DNA , DNA de Neoplasias/sangue , DNA de Neoplasias/isolamento & purificação , Neoplasias Oculares/sangue , Neoplasias Oculares/química , Neoplasias Oculares/diagnóstico , Feminino , Humanos , Lactente , Masculino , Mosaicismo , Mutação , Neoplasias Primárias Múltiplas/sangue , Neoplasias Primárias Múltiplas/química , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/genética , Polimorfismo de Nucleotídeo Único , Retinoblastoma/sangue , Retinoblastoma/química , Retinoblastoma/diagnóstico , Análise de Sequência de DNA/métodosRESUMO
Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 22/genética , Anormalidades Múltiplas/patologia , Criança , Pré-Escolar , Chile , Transtornos Cromossômicos/patologia , Feminino , Humanos , Masculino , SíndromeRESUMO
The tongue repositioning manoeuvre has been demonstrated to lead to a closed rest position of orofacial structures with increased contact of the velum with the tongue and a contact position of the tongue at the hard palate. Within the multifactorial etiology of snoring, the tongue repositioning manoeuvre was used as training method in conjunction with pressure indicating oral shields to reduce symptoms of snoring by stabilisation of the orofacial system. Bed partner ranking of 128 snorers treated consecutively showed a score before treatment of 8.9 on a 10 cm visual analogue scale. After treatment the score decrease to 4.2 (p<0.01). No significant BMI , age or gender specific influence of the outcome could beobserved. The data give evidence, that dynamic stabilisation of the orofacial system with oral shields in conjunction with the tongue repositioning manoevre is a valuable instrument to reduce the snoring problem.
La maniobra de reposicionamiento lingual ha demostrado tener ventaja para mantener cerrada el resto de estructuras orofaciales, con un aumento del contacto del paladar blando con la lengua y también en posición de contacto el paladar duro con la lengua. Dentro de la etiología multifactorial del ronquido, la maniobra de reposicionamiento lingual ha sido usada como método de entrenamiento, en conjunto con protectores orales que indican la presión para reducir los síntomas del ronquido y estabilizar el sistema orofacial. Un total de 128 pacientes roncadores tratados consecutivamente mostraron una puntuación antes del tratamiento de 8,9 a 10 cm en una escala visual análoga. Después del tratamiento, el puntaje disminuyó a 4,2 cm (p< 0,01). El índice de masa corporal no fue significativo, y no pudo ser observado si la edad o el género tenían influencia. Los datos evidenciaron que la estabilización dinámica del sistema orofacial, en conjunto con la maniobra de reposicionamiento lingual resulta ser una valiosa herramienta para reducir el problema del ronquido.
Assuntos
Humanos , Masculino , Adulto , Feminino , Terapia Combinada , Língua/fisiologia , Protetores Bucais , Ronco/terapia , Resultado do TratamentoRESUMO
UNLABELLED: The presence of Y chromosome fragments in patients with Turner's syndrome is known to increase the risk of gonadoblastoma and virilization. Y chromosome material is detected in up to 6% of patients with Turner's syndrome by karyotype. By DNA analysis, Y chromosome sequences have been reported in 0-60% of patients. The putative gonadoblastoma gene has been mapped to the pericentromeric region of the Y chromosome increasing the interest in studying these sequences. AIMS: 1. To determine the frequency of occult Y chromosome sequences in patients with Turner's syndrome. 2. To analyze the clinical implications of Y sequences detected by karyotype and occult Y sequences. STUDY DESIGN: Cross-sectional study of 58 patients with Turner's syndrome (30 45,X; two with structural anomalies; 26 mosaic [two of whom were 45,X/46,XY]). SRY, TSPY and DYZ3 sequences were amplified by PCR using genomic DNA from peripheral blood. RESULTS: All three Y chromosome sequences were found in one out of 56 patients whose karyotype was not suggestive of having Y chromosome material and in one patient with 45,X/46,Xr(X) karyotype. The patients with the ring chromosome and 45,X/46,XY karyotype underwent surgery and were found to have a gonadoblastoma and dysgerminoma. The four patients with Y chromosome material had non-virilized female genitalia. CONCLUSIONS: Analysis by PCR was more sensitive in detecting Y chromosome sequences than conventional karyotype. The presence of Y material was not associated with virilization. We confirmed the association of Y fragments and gonadoblastoma at an early age.
Assuntos
Cromossomos Humanos Y , Gonadoblastoma/complicações , Síndrome de Turner/complicações , Síndrome de Turner/genética , Virilismo/complicações , Adolescente , Adulto , Sequência de Bases , Proteínas de Ciclo Celular , Criança , Pré-Escolar , Chile , Estudos Transversais , Análise Citogenética/métodos , Proteínas de Ligação a DNA , Disgerminoma/complicações , Disgerminoma/diagnóstico , Disgerminoma/genética , Feminino , Gonadoblastoma/diagnóstico , Gonadoblastoma/genética , Gônadas/patologia , Gônadas/cirurgia , Gônadas/ultraestrutura , Humanos , Cariotipagem , Linfócitos/citologia , Mosaicismo , Proteínas Nucleares , Reação em Cadeia da Polimerase/métodos , Cromossomos em Anel , Aberrações dos Cromossomos Sexuais , Proteína da Região Y Determinante do Sexo , Fatores de Tempo , Fatores de Transcrição , Síndrome de Turner/diagnóstico , Virilismo/diagnósticoRESUMO
AIM: To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat. DESIGN: Double-blind, parallel, randomized, placebo-controlled, multicentre study. SUBJECTS: Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline. RESULTS: After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low. CONCLUSION: Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Lactonas/uso terapêutico , Obesidade , Adolescente , Adulto , Idoso , Antropometria , Fármacos Antiobesidade/efeitos adversos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Terapia Combinada , Diabetes Mellitus/sangue , Diabetes Mellitus/dietoterapia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/dietoterapia , Dieta Redutora , Método Duplo-Cego , Inibidores Enzimáticos/uso terapêutico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Lactonas/efeitos adversos , Lipase/antagonistas & inibidores , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Orlistate , Fatores de Risco , Redução de Peso/efeitos dos fármacosRESUMO
Genomic imprinting is a reversible phenomenon that affects the expression of genes depending on their parental origin. The best characterized human disorders resulting from an alteration of the imprinting process are Angelman and Prader-Willi syndromes. They are due to the lack of active maternal or paternal genes, respectively, from chromosome region 15q11q13. Most cases arise via interstitial deletions. We review evidence that other common cytogenetic alterations of this region, interstitial and supernumerary duplications, could be the reciprocal products of the deletions and are also affected by the imprinting phenomenon, given the predominance of maternally-derived duplications in patients ascertained due to developmental delays or autistic features.
Assuntos
Síndrome de Angelman/genética , Cromossomos Humanos Par 15/genética , Impressão Genômica/genética , Síndrome de Prader-Willi/genética , Aberrações Cromossômicas , Deleção Cromossômica , HumanosRESUMO
BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene, that codes for a chloride channel located in the apical surface of epithelial cells. The main role of this protein is the regulation of chloride transport, and secondarily, of sodium and water to the extracellular space. More than 900 gene mutations have been described, and their relative frequency in different populations depends on their ethnic origin. AIM: To report the findings of Chilean patients with cystic fibrosis, in whom the presence of 20 common mutations was analyzed. PATIENTS AND METHODS: Fifty seven patients with established diagnosis or suspicion of CF were studied. The simultaneous identification of 20 mutations and the normal delta F508 allele was done using polymerase chain reactions with a commercial assay. RESULTS: Eight mutations were found. Fifty patients fulfilled diagnostic criteria proposed by the Consensus Panel of the CF Foundation and 66% of alleles were identified in this group. delta F508 mutation was found in 45%. We did not identify mutations in any of the remaining 7 patients. CONCLUSIONS: Our results suggest that the majority of undetected mutations are associated with atypical phenotypes or that some patients in this series could have other diseases. We recommend to include mutation analysis in the evaluation of Chilean patients with CF. It is useful to establish prognosis and genetic counselling.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Mutação , Adolescente , Adulto , Criança , Pré-Escolar , Chile , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: DiGeorge anomaly, velocardiofacial syndrome and conotruncal anomaly face syndrome are part of a group of congenital malformations of the chromosome 22q11 microdeletion syndrome, since they share certain phenotypic features as well as a common genetic abnormality. The malformations include mild facial dysmorphic features, conotruncal heart defects, thymic and parathyroid hypoplasia or aplasia and cleft palate. AIM: To describe the initial clinical presentation of children with clinical and molecular diagnosis of 22q11 microdeletion. PATIENTS AND METHODS: Ten children (seven male) with the phenotypic features of 22q11 microdeletion syndrome are reported. Microdeletion was detected in peripheral lymphocytes by fluorescent in situ hybridisation (FISH) with the TUPLE-1 DNA probe. RESULTS: Two children had abnormal karyotypes, one of them had a visible deletion and another child had an unbalanced translocation inherited from his mother who had a balanced translocation between chromosomes 14 and 22. Two of the 10 patients had an anterior laryngeal web, a malformation infrequently described in this syndrome. Five patients had the diagnosis of DiGeorge anomaly, had a more serious clinical presentation and a higher early mortality. CONCLUSIONS: The high frequency of the 22q11 microdeletion syndrome, estimated at 1:5.000 newborns, and its variable presentations requires a high level of awareness for its early diagnosis and appropriate management of associated complications.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/genética , Criança , Pré-Escolar , Cromossomos Humanos Par 14/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Cariotipagem , MasculinoRESUMO
The epidemiology of whooping cough is analyzed using the disease notifications in Metropolitan Region and some rural areas from 1950 to 1990. Morbidity rate tendencies show a decreasing endemic disease interrupted by irregular increases, the last in 1985. Mortality fell from 11.9 per 100,000 in 1950 (60% of deaths in boys of less than one year old), to less than 1 per 100,000 since 1967. Since 1982, all deaths occurred in less than one year old boys. Lethality was high initially, specially in rural areas but the differences with Metropolitan area decreased since 1975. Approximately 90% of notifications are in less than one year old boys. However, there is a sustained rate elevation in boys older than 10 years old, predicting the increasing importance of the infection in young adults. The described changes antedate and are intensified by the immunization program. Their relationship to the lack of compliance with the program and the vaccine efficacy are discussed.
Assuntos
Reservatórios de Doenças , Coqueluche/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Chile/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Morbidade , População Rural , População Urbana , Vacinação , Coqueluche/mortalidade , Coqueluche/prevenção & controleRESUMO
In infants with spastic disorders and with congenital dysplasia of the hip (CDH), the microtubular content of nonmedullated and myelinated fibres of the anterior obturator nerves was studied with the electron microscope. In CDH infants, the microtubular content of nonmedullated and myelinated fibres was similar to values reported for experimental animals. In spastic patients, the microtubular content of nonmedullated fibres was similar to that found in CDH patients while the microtubular densities of 3- and 10-microns myelinated fibres were 37.5 and 16.7 microtubules/micron2, respectively, or 100% and 43% greater than corresponding values of CDH patients. We propose that the high firing rate determines the abnormally high microtubular content of myelinated axons supplying spastic muscles.