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1.
Genet Med ; 23(11): 2087-2095, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34262154

RESUMO

PURPOSE: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. METHODS: From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. RESULTS: LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56-4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6-5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case-control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). CONCLUSION: This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.


Assuntos
Ataxia Telangiectasia , Melanoma , Proteínas Mutadas de Ataxia Telangiectasia/genética , Austrália , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Melanoma/genética
2.
Acta Neurol Scand ; 122(2): 124-31, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19814753

RESUMO

OBJECTIVES: Explore the genetic and clinical incidence of von Hippel-Lindau disease in patients presenting with isolated central nervous system hemangioblastomas. RESULTS: We report a 3.2% (1/31) and 25% (8/32) incidence of genetic and clinical VHL, respectively. One patient tested positive for a VHL mutation that has not previously been reported. This genotype phenotypically predicts VHL type 2B. We had seven patients with renal cysts. In a total follow-up of 33 person years, none of these cysts progressed to renal cell carcinoma. CONCLUSION: von Hippel-Lindau disease anchored in germline mutations of the VHL gene is rare in the Norwegian population as opposed to clinical VHL disease, which appears to be relatively common in patients with apparently sporadic hemangioblastomas. There exists insufficient data regarding the natural history of patients with renal cysts, which makes it difficult to include or disregard these lesions as an entity of VHL disease.


Assuntos
Neoplasias do Sistema Nervoso Central/genética , Hemangioblastoma/genética , Doença de von Hippel-Lindau/genética , Adulto , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/epidemiologia , Estudos Transversais , Análise Mutacional de DNA , Feminino , Triagem de Portadores Genéticos , Testes Genéticos , Mutação em Linhagem Germinativa , Hemangioblastoma/diagnóstico , Hemangioblastoma/epidemiologia , Humanos , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/epidemiologia , Doenças Renais Císticas/genética , Masculino , Pessoa de Meia-Idade , Noruega , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/epidemiologia
3.
Histopathology ; 53(5): 578-87, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18983467

RESUMO

AIMS: To investigate the relationship between phenotype and genotype in oligodendroglial tumours and evaluate whether 1p/19q status can be reliably predicted from histological findings. METHODS AND RESULTS: Three neuropathologists reviewed the association between 10 histological variables, location and genetic losses at 1p, 19q and 17p13 in 63 oligodendroglial tumours (cohort 1). Based on these findings, a multiple logistic regression model for prediction of 1p/19q status was constructed. The ability of this model to predict 1p/19q status was tested on cohort 2, comprising 20 oligodendroglial tumours. Loss of heterozygosity at 1p, 19q and 17p13 was analysed using polymerase chain reaction. Combined 1p/19q loss and losses at 17p13 were mutually exclusive (P < 0.001). The variable H1a (more or <50% of cells with round, uniform nuclei and perinuclear halos) demonstrated the strongest association with 1p/19q status (odds ratio 11.9, 95% confidence interval 3.6, 39.6, P < 0.001). Calcifications, absence of gemistocytic cells and a non-temporal/non-insular location were also associated. The correct 1p/19q status was predicted in 80% of cases in cohort 2. CONCLUSIONS: There is a strong association between phenotype and genotype in oligodendroglial tumours. However, even when all significant variables are accounted for, perfect prediction (100%) of 1p/19q status cannot be obtained.


Assuntos
Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 1/genética , Perda de Heterozigosidade/genética , Oligodendroglioma/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/patologia , Oligodendroglioma/patologia , Fenótipo
4.
J Mol Med (Berl) ; 83(5): 406-10, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15759101

RESUMO

Many patients with tyrosinaemia type 1 have a mosaic pattern of fumarylacetoacetase (FAH) immunopositive or immunonegative nodules in liver tissue. This phenomenon has been explained by a spontaneous reversion of the mutation in one allele to a normal genotype, but only a few nodules have been examined. We now report on a Norwegian patient, compound heterozygous for the mutations IVS12g(+5)-->a and G(1009-->)A, with liver mosaicism, but with an immunopositive nodule in which both primary mutations were intact. In the immunopositive hepatocytes of this nodule, genetic analyses showed a new mutation, C(1061-->)A, 6 bp upstream of the primary mutation IVS12g(+5)-->a in the FAH gene. The splicing defect caused by the primary mutation is most likely suppressed by the new mutation due to improvement of the splicing site. In the same liver we demonstrate another nodule of regenerating immunopositive tissue due to reversion of one of the primary mutations to a normal genotype. Together with the original cells this makes a triple mosaicism of hepatocytes with one, two or three point mutations in the FAH gene.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Fígado/enzimologia , Mutação Puntual , Splicing de RNA , Tirosinemias/genética , Alelos , Substituição de Aminoácidos , Clonagem Molecular , Códon , Análise Mutacional de DNA , Éxons , Humanos , Hidrolases/deficiência , Imuno-Histoquímica , Fígado/metabolismo , Fígado/cirurgia , Mosaicismo , Noruega , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Serina/metabolismo , Tirosinemias/metabolismo
5.
Eur J Clin Nutr ; 59(4): 597-602, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15741988

RESUMO

BACKGROUND: Enhanced cyclooxygenase-2 (COX-2) expression is associated with carcinogenesis, ischemia, angiogenesis, inflammation, and neurodegeneration. The preventing effect of aspirin and nonsteroidal anti-inflammatory drugs is partly due to inhibition of the COX-2 enzyme. Fruit and vegetables (FVs) contain numerous compounds that may decrease disease risk by several different mechanisms, for example through the inhibition of COX-2 activity. OBJECTIVE: We tested the hypothesis that an increased intake of FVs would modulate the COX-2 expression in peripheral blood cells. DESIGN: A strictly controlled dietary crossover study (n = 39). After 1 week run-in period with no FVs in the diet, one group was given two portions of FVs (2 FV), while another group was given five portions (5 FV) daily for 14 days. Following a 2 weeks washout period and 1 week run-in, the regimens were switched between the groups. Gene expression analysis of COX-2 mRNA in blood samples was performed by quantitative real-time-PCR. RESULTS: No significant treatment effect of diet intervention was found in the crossover analyses (P = 0.74). However, the individual variation in response may seem large. CONCLUSIONS: These data does not contradict the recommendations for an increased intake of FVs. Further studies on expression directly and indirectly, through analysis of factors regulating and being regulated by COX-2, should be carried out. A first step would be to evaluate the correspondence between COX-2 mRNA expression and products of the COX pathway, like prostaglandins. Naturally occurring polymorphisms of COX-2 promoters and coding regions might contribute to functional variations and response to different diets. SPONSORSHIP: Norwegian Research Council, National Nutrition Council, Throne Holst Foundation for Nutrition Research, Freia Chokoladefabriks Medisinske Fond and the Norwegian Cancer Society.


Assuntos
Células Sanguíneas/fisiologia , Frutas , Expressão Gênica/fisiologia , Prostaglandina-Endoperóxido Sintases/sangue , Prostaglandina-Endoperóxido Sintases/genética , Verduras , Adulto , Estudos Cross-Over , Ciclo-Oxigenase 2 , Feminino , Humanos , Masculino , Proteínas de Membrana , Noruega , RNA Mensageiro/sangue , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Estudantes
6.
Tidsskr Nor Laegeforen ; 121(1): 64-8, 2001 Jan 10.
Artigo em Norueguês | MEDLINE | ID: mdl-12013617

RESUMO

BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder caused by germline mutations in the APC gene. FAP is characterised by a variable, but normally large number of colorectal adenomas and variations in extracolonic manifestations. These variations are associated with specific mutations of the APC gene. MATERIAL AND METHODS: Representatives from 70 Norwegian families are under molecular investigation. Analyses have so far been concentrated on the part of the APC gene associated with classic FAP. RESULTS: Germline mutations causing FAP have been identified in 36 of the 70 families examined. All mutations identified are confined to the first half of the gene and correlate to classic FAP. INTERPRETATION: Because of the mutation heterogeneity in FAP, the size of the APC gene and variations in phenotype, it is a laborious task to identify the causative mutations. Better approaches to the analysis of the whole APC have now been established and will result in a higher degree of mutation detection independent of phenotype. Family history and phenotype-genotype correlations are still important guidelines for efficient molecular genetic analysis of the APC gene. Genetic surveillance, personal and socio-economic benefits from presymptomatic and predictive testing of members of FAP families are discussed.


Assuntos
Polipose Adenomatosa do Colo/genética , Genes APC , Predisposição Genética para Doença , Cromossomos Humanos Par 5 , Feminino , Aconselhamento Genético , Técnicas Genéticas , Testes Genéticos , Genótipo , Mutação em Linhagem Germinativa , Humanos , Masculino , Noruega , Linhagem , Fenótipo
7.
Cancer Res ; 59(5): 1160-3, 1999 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10070978

RESUMO

The tumor suppressor protein p53 is aberrantly localized to the cytoplasm of neuroblastoma cells, compromising the suppressor function of this protein. Such tumors are experimentally induced in transgenic mice expressing the large tumor (T) antigen of polyomaviruses. The oncogenic mechanisms of T antigen include complex formation with, and inactivation of, the tumor suppressor protein p53. Samples from 18 human neuroblastomas and five normal human adrenal glands were examined. BK virus DNA was detected in all neuroblastomas and none of five normal adrenal glands by PCR. Using DNA in situ hybridization, polyomaviral DNA was found in the tumor cells of 17 of 18 neuroblastomas, but in none of five adrenal medullas. Expression of the large T antigen was detected in the tumor cells of 16 of 18 neuroblastomas, but in none of the five adrenal medullas. By double immunostaining BK virus T antigen and p53 was colocalized to the cytoplasm of the tumor cells. Immunoprecipitation revealed binding between the two proteins. The presence and expression of BK virus in neuroblastomas, but not in normal adrenal medulla, and colocalization and binding to p53, suggest that this virus may play a contributory role in the development of this neoplasm.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/virologia , Glândulas Suprarrenais/virologia , Vírus BK/isolamento & purificação , Neuroblastoma/patologia , Neuroblastoma/virologia , Neoplasias das Glândulas Suprarrenais/genética , Glândulas Suprarrenais/citologia , Glândulas Suprarrenais/patologia , Animais , Antígenos Virais de Tumores/análise , Antígenos Virais de Tumores/genética , Criança , Genes APC , Genes p53 , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/virologia , Camundongos , Camundongos Transgênicos , Neuroblastoma/genética , Reação em Cadeia da Polimerase , Tumor de Wilms/genética , Tumor de Wilms/patologia , Tumor de Wilms/virologia
8.
J Nurs Adm ; 25(6): 29-32, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7776004

RESUMO

As home healthcare becomes increasingly "high-tech," home health administrators struggle to provide nursing students with traditional community health nursing experiences. The gap between education and service widens as university faculty turn to other community health agencies, including academic nursing centers, for clinical placements. Strategies that administrators and faculty can use to modify current clinical experiences in ways that expand agency services while meeting the educational goals are presented.


Assuntos
Enfermagem em Saúde Comunitária/educação , Agências de Assistência Domiciliar/organização & administração , Cuidados de Enfermagem , Competência Clínica , Bacharelado em Enfermagem , Humanos , Medicare , Mentores , Registros de Enfermagem , Estudantes de Enfermagem , Estados Unidos
9.
Am J Community Psychol ; 20(6): 753-74, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1302448

RESUMO

Used meta-analysis to analyze 66 studies that evaluated the relationship between social support available to the mother and maternal behaviors and attitudes. Investigators sampled relatively homogeneous populations of white, middle-class, married mothers of young children without physical or mental disabilities. A variety of instruments were used to assess key study variables. Significant correlations existed between both emotional and material support and maternal behaviors. Implications of these findings for funding of family support programs and for professionals working with mothers are discussed.


Assuntos
Atitude , Comportamento Materno , Relações Mãe-Filho , Apoio Social , Criança , Transtornos do Comportamento Infantil/psicologia , Pré-Escolar , Pessoas com Deficiência/psicologia , Feminino , Retardo do Crescimento Fetal/psicologia , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco
10.
Nurse Educ ; 17(3): 21-3, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1518571

RESUMO

Nursing faculty across the country are developing nurse-managed centers to provide students with community health experiences. Although students deliver much of the care provided within nursing centers, the literature offers little data on the quality of student-rendered care. This study evaluated client satisfaction with care received from student nurses. Results have direct implications for faculty supervising students in community health nursing agencies.


Assuntos
Ambulatório Hospitalar/organização & administração , Satisfação do Paciente , Estudantes de Enfermagem , Competência Clínica , Humanos , Pesquisa em Avaliação de Enfermagem , Qualidade da Assistência à Saúde
11.
Tidsskr Nor Laegeforen ; 109(7-8): 832-5, 1989 Mar 10.
Artigo em Norueguês | MEDLINE | ID: mdl-2539657

RESUMO

A Norwegian polyposis family (PP29) including ten affected cases over five generations is reported with clinical case histories. In the first three generations one patient died in her thirties of "tuberculosis" and the other five affected patients died of gastrointestinal cancer. Of 12 at risk in the 4th generation, three had polyposis and underwent prophylactic colectomies, six were normal at regular follow-up rectoscopies till 35-40 years of age and three avoided examination. One of four at risk persons in the 5th generation had polyposis and underwent colectomi with ileoanal anastomosis. DNA-typing using D5S71 (p11c11) showed segregation which confirmed linkage and almost ruled out the possibility of any of the three non-controlled at risk persons being polyposis gene carriers. Another family (PP11) illustrates how typing, using the probe D5S71, may allow early and prenatal diagnosis.


Assuntos
Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/prevenção & controle , Adulto , Idoso , DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Linhagem , Diagnóstico Pré-Natal
12.
J Gen Microbiol ; 134(6): 1737-46, 1988 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3065456

RESUMO

An analysis of the bet genes governing the osmoregulatory choline-glycine betaine pathway of Escherichia coli was performed. A 9 kb BamHI fragment, located 30 to 39 kb counterclockwise of the EcoRI site of lacZ, coded for all known Bet activities. The following genes were identified: the betA gene for the choline dehydrogenase, the betB gene for the betaine aldehyde dehydrogenase, and the betT gene or operon for the high-affinity choline transport. The betB and the betT genes were named in this paper, and the clockwise gene order was shown to be betA,B,T. Subcloning gave plasmids which expressed each of the three Bet activities separately. The cloned bet genes remained osmotically regulated, indicating the existence of several osmotically regulated promoters in the bet region. Salmonella typhimurium, which carried the bet region of E. coli in the broad-host-range vector pRK293 expressed the three Bet activities and displayed increased osmotic tolerance in the presence of choline.


Assuntos
Betaína/metabolismo , Colina/metabolismo , Escherichia coli/genética , Genes Bacterianos , Mapeamento Cromossômico , Cromossomos Bacterianos , Clonagem Molecular , Escherichia coli/metabolismo , Regulação da Expressão Gênica , Oxirredutases/metabolismo , Salmonella typhimurium/genética , Equilíbrio Hidroeletrolítico
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