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1.
Neurology ; 78(3): 202-9, 2012 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-22218271

RESUMO

OBJECTIVES: To describe clinical characteristics and to identify susceptibility loci for epilepsy and migraine in a Finnish family with a complex phenotype. METHODS: Participating family members were interviewed and medical files were reviewed. The seizure classification was made according to International League Against Epilepsy criteria. Migraine diagnosis was made using the validated Finnish Migraine Specific Questionnaire for Family Studies and criteria according to the current International Classification of Headache Disorders-II. DNA samples were obtained from 56 family members and nonparametric genome-wide linkage analyses were performed using 382 polymorphic microsatellite markers. The most promising loci were fine-mapped with additional microsatellite markers. RESULTS: Clinical data were obtained from 60 family members of whom 12 (20%) had idiopathic epileptic seizures. Eight of those 12 (67%) also had migraine. Altogether 33 of the 60 family members (55%) had migraine. Significant evidence of linkage was found between a locus on 14q12-q23 and migraine (p = 0.0001). Suggestive evidence of linkage in this region was also found for epilepsy with generalized tonic-clonic seizures (p = 0.0034). In addition, significant evidence of linkage was found at a locus on 12q24.2-q24.3 (p < 0.001) for migraine alone and for the combined phenotype of migraine and epilepsy. CONCLUSIONS: Our data suggest the occurrence of common susceptibility loci for epilepsy and migraine on chromosomes 14q12-q23 and 12q24.2-q24.3, implicating a shared genetic etiology for these 2 diseases.


Assuntos
Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 14/genética , Epilepsia/genética , Loci Gênicos/genética , Desequilíbrio de Ligação/genética , Transtornos de Enxaqueca/genética , Adolescente , Adulto , Criança , Feminino , Finlândia , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Adulto Jovem
2.
Lupus ; 21(1): 68-74, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22025191

RESUMO

Anti-RNA polymerase III (RNAP III) antibodies are highly specific for scleroderma (SSc) and associated with diffuse SSc and renal crisis. Coexistence of anti-RNAP III and other SSc autoantibodies is rarely documented. We report three cases with coexisting anti-RNAP III and anti-U1RNP. Autoantibodies in 3829 sera from rheumatology clinics were screened by immunoprecipitation. Anti-RNAP III-positive sera were also examined by immunofluorescence and anti-RNAP III ELISA. In total, 35 anti-RNAP III-positive sera were identified by immunoprecipitation, in which three had coexisting anti-U1RNP. All three were anti-RNAP III ELISA positive. Two had anti-RNAP I dominant (vs. RNAP III) reactivity and showed strong nucleolar staining. A case with anti-U1/U2RNP (U2RNP dominant) had systemic lupus erythematosus (SLE)-SSc overlap syndrome; however, the remaining two cases had SLE without signs of SSc. All three cases of anti-RNAP III + U1RNP fulfilled ACR SLE criteria but none in the group with anti-RNAP III alone (p = 0.0002). In contrast, only one case in the former group had sclerodermatous skin changes and Raynaud's phenomenon, vs. 92% with scleroderma in the latter (p < 0.05). Although anti-RNAP III is highly specific for SSc, cases with coexisting anti-U1RNP are not so uncommon among anti-RNAP III positives (8%, 3/35) and may be SLE without features of SSc.


Assuntos
Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Lúpus Eritematoso Sistêmico , RNA Polimerase III/imunologia , Ribonucleoproteína Nuclear Pequena U1/imunologia , Escleroderma Sistêmico/imunologia , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Escleroderma Sistêmico/sangue
3.
Pac Symp Biocomput ; : 106-17, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21121038

RESUMO

Whole exome and whole genome sequencing are likely to be potent tools in the study of common diseases and complex traits. Despite this promise, some very difficult issues in data management and statistical analysis must be squarely faced. The number of rare variants identified by sequencing is apt to be much larger than the number of common variants encountered in current association studies. The low frequencies of rare variants alone will make association testing difficult. This article extends the penalized regression framework for model selection in genome-wide association data to sequencing data with both common and rare variants. Previous research has shown that lasso penalties discourage irrelevant predictors from entering a model. The Euclidean penalties dealt with here group variants by gene or pathway. Pertinent biological information can be incorporated by calibrating penalties by weights. The current paper examines some of the tradeoffs in using pure lasso penalties, pure group penalties, and mixtures of the two types of penalty. All of the computational and statistical advantages of lasso penalized estimation are retained in this richer setting. The overall strategy is implemented in the free statistical genetics analysis software MENDEL and illustrated on both simulated and real data.


Assuntos
Estudo de Associação Genômica Ampla/estatística & dados numéricos , Sequenciamento de Nucleotídeos em Larga Escala/estatística & dados numéricos , Algoritmos , Neoplasias da Mama/genética , Biologia Computacional , Interpretação Estatística de Dados , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Modelos Logísticos , Polimorfismo de Nucleotídeo Único , Análise de Regressão , Software
4.
Genes Immun ; 11(7): 542-53, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20445563

RESUMO

The NZM2410-derived Sle1a lupus susceptibility locus induces activated autoreactive CD4(+) T cells and reduces the number and function of Foxp3(+) regulatory T cells (Tregs). In this study, we first showed that Sle1a contributes to autoimmunity by increasing antinuclear antibody production when expressed on either NZB or NZW heterozygous genomes, and by enhancing the chronic graft versus host disease response indicating an expansion of the autoreactive B-cell pool. Screening two non-overlapping recombinants, the Sle1a.1 and Sle1a.2 intervals that cover the entire Sle1a locus, revealed that both Sle1a.1 and Sle1a.2 were necessary for the full Sle1a phenotype. Sle1a.1, and to a lesser extent Sle1a.2, significantly affected CD4(+) T-cell activation as well as Treg differentiation and function. Sle1a.2 also increased the production of autoreactive B cells. As the Sle1a.1 and Sle1a.2 intervals contain only 1 and 15 known genes, respectively, this study considerably reduces the number of candidate genes responsible for the production of autoreactive T cells. These results also show that the Sle1 locus is an excellent model for the genetic architecture of lupus, in which a major obligate phenotype results from the coexpression of multiple genetic variants with individual weak effects.


Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Linfócitos T/imunologia , Animais , Autoimunidade/genética , Autoimunidade/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Feminino , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/imunologia , Lúpus Eritematoso Discoide/genética , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Vulgar/genética , Lúpus Vulgar/imunologia , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NZB , Camundongos Endogâmicos , Camundongos Knockout , Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
5.
Neurology ; 74(15): 1171-7, 2010 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-20385888

RESUMO

OBJECTIVE: To identify susceptibility loci for visual migraine aura in migraine families primarily affected with scintillating scotoma type of aura. METHODS: We included Finnish migraine families with at least 2 affected family members with scintillating scotoma as defined by the International Criteria for Headache Disorders-II. A total of 36 multigenerational families containing 351 individuals were included, 185 of whom have visual aura and 159 have scintillating scotoma. Parametric and nonparametric linkage analyses were performed with 378 microsatellite markers. The most promising linkage loci found were fine-mapped with additional microsatellite markers. RESULTS: A novel locus on chromosome 9q22-q31 for migraine aura was identified (HLOD = 4.7 at 104 cM). Fine-mapping identified a shared haplotype segment of 12 cM (9.8 Mb) on 9q21-q22 among the aura affected. Four other loci showed linkage to aura: a locus on 12p13 showed significant evidence of linkage, and suggestive evidence of linkage was detected to loci on chromosomes 5q13, 6q25, and 13q14. CONCLUSIONS: A novel visual migraine aura locus has been mapped to chromosome 9q21-q22. Interestingly, this region has previously been linked to occipitotemporal lobe epilepsy with prominent visual symptoms. Our finding further supports a shared genetic background in migraine and epilepsy and suggests that susceptibility variant(s) to visual aura for both of these traits are located in the 9q21-q22 locus.


Assuntos
Cromossomos Humanos Par 9/genética , Enxaqueca com Aura/genética , Escotoma/genética , Mapeamento Cromossômico , Finlândia , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Genótipo , Haplótipos/genética , Humanos , Exame Neurológico , Linhagem , Fatores Sexuais
6.
Int J Gynecol Cancer ; 16(5): 1749-55, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17009966

RESUMO

A decrease in vaginal length associated with treatments for gynecological malignancies, particularly pelvic radiotherapy, negatively impacts sexuality. Research into this important problem has been hampered by a lack of instrumentation to measure vaginal length. The Gynecologic Oncology Group recently evaluated the reliability of an instrument, the "vaginal sound," designed to measure vaginal length. Eighty-eight physicians and nurses attended a training session in the use of the vaginal sound that included a clinical practicum with live models. Reliability was assessed at the time of the practicum. The instrument performed well, with vaginal lengths in models without cancer in the upper range of normal as documented by Masters and Johnson. The vaginal sound also appeared to be sensitive to hypothesized changes in vaginal length. Interrater reliability was high with intraclass correlation coefficients of 0.88 among instructors and 0.76 among trainees. In conclusion, the vaginal sound is a simple, yet reproducible measure and adds methodologic rigor to studies of vaginal length.


Assuntos
Equipamentos para Diagnóstico/normas , Ginecologia/instrumentação , Vagina/anatomia & histologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
7.
Am J Hum Genet ; 79(1): 85-99, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16773568

RESUMO

The commonly used "end diagnosis" phenotype that is adopted in linkage and association studies of complex traits is likely to represent an oversimplified model of the genetic background of a disease. This is also likely to be the case for common types of migraine, for which no convincingly associated genetic variants have been reported. In headache disorders, most genetic studies have used end diagnoses of the International Headache Society (IHS) classification as phenotypes. Here, we introduce an alternative strategy; we use trait components--individual clinical symptoms of migraine--to determine affection status in genomewide linkage analyses of migraine-affected families. We identified linkage between several traits and markers on chromosome 4q24 (highest LOD score under locus heterogeneity [HLOD] 4.52), a locus we previously reported to be linked to the end diagnosis migraine with aura. The pulsation trait identified a novel locus on 17p13 (HLOD 4.65). Additionally, a trait combination phenotype (IHS full criteria) revealed a locus on 18q12 (HLOD 3.29), and the age at onset trait revealed a locus on 4q28 (HLOD 2.99). Furthermore, suggestive or nearly suggestive evidence of linkage to four additional loci was observed with the traits phonophobia (10q22) and aggravation by physical exercise (12q21, 15q14, and Xp21), and, interestingly, these loci have been linked to migraine in previous studies. Our findings suggest that the use of symptom components of migraine instead of the end diagnosis provides a useful tool in stratifying the sample for genetic studies.


Assuntos
Predisposição Genética para Doença , Transtornos de Enxaqueca/genética , Mapeamento Cromossômico , Feminino , Heterogeneidade Genética , Humanos , Escore Lod , Masculino
8.
Lupus ; 14(8): 576-82, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16175928

RESUMO

Measurement of high sensitivity C-reactive protein (hs-CRP), has been used in the assessment of disease activity in numerous rheumatic conditions including systemic lupus erythematosus (SLE). However, the utility of hs-CRP measurement in patients with lupus is uncertain. This study examined if hs-CRP can be used to assess disease activity, severity and cardiovascular risk in SLE. Serum samples from 601 visits of 213 SLE patients and 134 controls were analysed for hs-CRP by nephelometry. Detailed demographic data were obtained from all subjects and medication history and key laboratory parameters were collected. Disease activity was assessed using the SLEDAI. High sensitivity CRP was not associated with disease activity (SLEDAI), number of ACR SLE criteria or presence of any particular organ involvement. hs-CRP levels were significantly correlated with standard cardiovascular risk factors including body weight (P = 0.0002), hypertension (P = 0.001), and apolipoprotein A-I (P < 0.0001). Interestingly an inverse correlation was seen between hs-CRP levels and antimalarial use (P = 0.0018). Our results suggest that measurement of hs-CRP, though not valuable as marker of disease activity in SLE may be of some use in the assessment of cardiovascular risk. We speculate that antimalarials may help to reduce cardiovascular risk in patients with SLE.


Assuntos
Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/etiologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Apolipoproteínas/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Proteínas do Sistema Complemento/metabolismo , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Fatores de Risco , Índice de Gravidade de Doença
9.
Lupus ; 12(5): 394-9, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12765303

RESUMO

High prevalence of coeliac disease (CD) has been reported in various autoimmune disorders, buthas not been studied in the antiphospholipid syndrome (APS). We aimed to establish the prevalence of CD antibodies in a cohort of APS patients, and to examine whether CD may be responsible for some of the manifestations of APS. Fifty-seven patients (47 females, 10 males) with APS were studied for clinical manifestations and serological markers of the disease, as well as the presence of anti-endomysial antibodies using an ELISA assay (EMA-ELISA). Control subjects were 171 healthy individuals, age- and sex-matched (141 females). Eight patients with APS (14%, six females) were found to have EMA-ELISA antibodies, compared with 2/141 (1.1%) of controls (P = 0.0003). Antibodies against beta2-glycoprotein-I (beta2GPI) epitopes (GRTCPKPDDLP) were more prevalent in EMA-positive patients than in EMA-negative patients (P = 0.006). Vasculitic skin lesions were significantly more common in EMA-ELISA-positive compared with EMA-ELISA-negative patients(62.5 versus 16.3%, P = 0.01). Among the skin manifestations, superficial cutaneous necrosis (37.5 versus 2%, P = 0.007) was more prevalent in EMA-ELISA-positive than in EMA-ELISA-negative patients. EMA-ELISA antibodies are common in APS, and their presence is associated with high prevalence of antibodies recognizing certain beta2-glycoprotein epitopes, and with cutaneous manifestations of APS.


Assuntos
Síndrome Antifosfolipídica/complicações , Autoanticorpos/sangue , Doença Celíaca/complicações , Doença Celíaca/imunologia , Adulto , Síndrome Antifosfolipídica/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Glicoproteínas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Prevalência , beta 2-Glicoproteína I
10.
J Am Podiatr Med Assoc ; 91(10): 515-20, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11734607

RESUMO

This study examined the effect of customized insoles in relieving postwork discomfort in healthy individuals whose jobs require long periods of standing and walking. CompuSole insoles were worn by 122 New York City Police Department officers for up to 5 weeks for an average of 7 hours per day. The officers walked an average of 3 miles per day. Before the study, one-fifth of the police officers in this study experienced foot pain or discomfort at the end of their workday; 15% had calluses, corns, or athlete's foot; 18% had sought treatment for a foot problem in the past; and 20% had worn foot orthoses. There was a significant reduction in tiredness in the feet at the end of the day after wearing the insoles, but no improvement in back or leg discomfort. At the end of the workday, 68% had less foot discomfort and 60% were more comfortable at work when wearing the insoles.


Assuntos
Doenças do Pé/prevenção & controle , Doenças Profissionais/prevenção & controle , Sapatos , Caminhada/fisiologia , Adulto , Qualidade de Produtos para o Consumidor , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aparelhos Ortopédicos , Sensibilidade e Especificidade , Inquéritos e Questionários
11.
Hum Hered ; 52(3): 121-31, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11588394

RESUMO

OBJECTIVES: To describe, implement, and test an efficient algorithm to obtain multipoint identity-by-descent (IBD) probabilities at arbitrary positions among marker loci for general pedigrees. Unlike existing programs, our algorithm can analyze data sets with large numbers of people and markers. The algorithm has been implemented in the SimWalk2 computer package. METHODS: Using a rigorous testing regimen containing five pedigrees of various sizes with realistic marker data, we compared several widely used IBD computation programs: Allegro, Aspex, GeneHunter, MapMaker/Sibs, Mendel, Sage, SimWalk2, and Solar. RESULTS: The testing revealed a few discrepancies, particularly on consanguineous pedigrees, but overall excellent results in the deterministic multipoint packages. SimWalk2 was also found to be in good agreement with the deterministic multipoint programs, usually matching to two decimal places the kinship coefficient that ranges from 0 to 1. However, the packages based on single-point IBD estimation, while consistent with each other, often showed poor results, disagreeing with the multipoint kinship results by as much as 0.5. CONCLUSIONS: Our testing has clearly shown that multipoint IBD estimation is much better than single-point estimation. In addition, our testing has validated our algorithm for estimating IBD probabilities at arbitrary positions on general pedigrees.


Assuntos
Algoritmos , Modelos Genéticos , Software , Feminino , Genótipo , Humanos , Masculino , Meiose , Método de Monte Carlo , Linhagem
12.
Nat Genet ; 28(4): 365-70, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11479539

RESUMO

Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.


Assuntos
Cromossomos Humanos Par 11/genética , Subunidades gama da Proteína de Ligação ao GTP , Lipodistrofia/congênito , Lipodistrofia/genética , Proteínas/genética , Acantose Nigricans/complicações , Cromossomos Humanos Par 9/genética , Análise por Conglomerados , Análise Mutacional de DNA , Complicações do Diabetes , Feminino , Genes Recessivos , Ligação Genética , Marcadores Genéticos , Testes Genéticos , Haplótipos , Hepatomegalia/complicações , Proteínas Heterotriméricas de Ligação ao GTP/genética , Humanos , Hiperandrogenismo/complicações , Hipertrigliceridemia/complicações , Resistência à Insulina/genética , Líbano/epidemiologia , Lipodistrofia/complicações , Lipodistrofia/epidemiologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Noruega/epidemiologia , Especificidade de Órgãos , Linhagem , Estrutura Terciária de Proteína , Proteínas/metabolismo , Homologia de Sequência de Aminoácidos
13.
Hum Mol Genet ; 10(15): 1611-7, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11468279

RESUMO

We have earlier reported evidence for linkage to two regions on chromosome 1q32--q42 in schizophrenia families collected for two separate studies in Finland. Here we report the results of a fine mapping effort aimed at further definition of the chromosomal region of interest using a large, population-based study sample (221 families, 557 affected individuals). Most affecteds (78%) had a DSM-IV schizophrenia diagnosis and the remaining had schizophrenia spectrum disorders. We genotyped a total of 147 microsatellite markers on a wide 45 cM region of chromosome 1q. The results were analyzed separately for families originating from an internal isolate of Finland and for families from the rest of Finland, as well as for all families jointly. We used traditional two-point linkage analysis, SimWalk2 multipoint analysis and a novel gamete-competition association/linkage method. Evidence for linkage was obtained for one locus in the combined sample (Z(max) = 2.71, D1S2709) and in the nuclear families from outside the internal isolate (Z(max) = 3.21, D1S2709). In the families from the internal isolate the strongest evidence for linkage was obtained with markers located 22 cM centromeric from this marker (Z(max) = 2.30, D1S245). Multipoint analysis also indicated these loci. Some evidence for association with several markers was observed using the gamete-competition method. Interestingly, the strongest evidence for linkage in the combined study sample was obtained for marker D1S2709, which is an intragenic marker of the DISC1 gene, previously suggested as a susceptibility gene for schizophrenia. These results are consistent with the presence of susceptibility gene(s) in this chromosomal region, a result also implied in other recent family studies of schizophrenia.


Assuntos
Cromossomos Humanos Par 1 , Esquizofrenia/genética , Adulto , Alelos , Saúde da Família , Feminino , Finlândia , Ligação Genética , Genótipo , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Modelos Genéticos
14.
J Am Podiatr Med Assoc ; 91(1): 34-49, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11196330

RESUMO

The number of partial-foot amputations performed is increasing, and many recommendations have been made regarding the use of prostheses and footwear designed to prevent higher-level amputations in this population. The present study investigated the use of prostheses and shoe inserts and the types of footwear worn by partial-foot amputees in the inner city to determine whether previous recommendations are being followed as well as whether new prosthetic styles are being used. The study surveyed 110 patients (73 men and 37 women) with a mean age of 58.6 years (range, 21 to 86 years) with partial-foot amputations of all levels. The results showed that about one-half of all patients wore a shoe-insert orthosis. Although 54% wore some form of special footwear to accommodate and protect the residual foot, no patient in this study wore a shoe with a rocker-bottom sole. Only one patient with a transmetatarsal amputation used a brace and only one patient in the entire study wore a modern cosmetic foot prosthesis.


Assuntos
Amputação Cirúrgica/métodos , Amputação Cirúrgica/reabilitação , Doenças do Pé/reabilitação , Próteses e Implantes/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Pé/cirurgia , Doenças do Pé/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Pobreza , Desenho de Prótese , Ajuste de Prótese , Estudos Retrospectivos , População Urbana
15.
Thyroid ; 10(11): 945-50, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11128721

RESUMO

Interactions between malignant cells and their environment are achieved via cell-surface receptors and adhesion molecules. The extracellular matrix (ECM) and ECM-bound cytokines modulate the expression of cell-surface molecules on target malignant cells, which may lead to changes in their susceptibility to cytolysis, in their ability to present antigens, and in the induction of local immune-cell activation and patrol. Eventually, these alterations may culminate in either the destruction, or escape and proliferation, of the tumor. We studied the effects of the ECM and its components in a "naive" form or following binding of the inflammatory cytokines interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) on the surface expression of human leukocyte antigen (HLA) class-I, HLA class-II (HLA-DR), and intracellular adhesion molecule-1 (ICAM-1), on nonmalignant and malignant thyroid cells. The basal expression of HLA class-I molecules was not significantly changed either by naive ECM and its components or by ECM-bound cytokines. ECM synergized with IFNgamma and TNFalpha in inducing HLA-DR molecules on nonmalignant and malignant thyrocytes, with higher HLA-DR levels on the malignant cells. The laminin component, in particular, synergized with IFNgamma. Basal ICAM-1 expression on nonneoplastic cells was not significantly affected by the cytokines when grown in the absence of ECM, but was significantly upregulated when cells were cultured on ECM. In contrast, in malignant thyrocyte cultures, ECM significantly attenuated IFNgamma- and TNFalpha-mediated enhancement of ICAM-1 expression. We concluded that signals derived from ECM-embedded cytokines participate in the regulation of key thyroid cell surface molecules and, thus, may affect the final outcome of human thyroid malignancies.


Assuntos
Antineoplásicos/farmacologia , Antígenos HLA-DR/genética , Antígenos de Histocompatibilidade Classe I/genética , Molécula 1 de Adesão Intercelular/genética , Interferon gama/farmacologia , Neoplasias da Glândula Tireoide , Animais , Antígenos de Superfície/genética , Bovinos , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Córnea/citologia , Sinergismo Farmacológico , Matriz Extracelular/imunologia , Matriz Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Laminina/metabolismo , Glândula Tireoide/citologia , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/farmacologia
16.
J Foot Ankle Surg ; 39(5): 305-20, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11055022

RESUMO

Surgical treatment for clubfoot has been largely directed at finding the best one-stage operation for the resistant clubfoot. Eighteen patients with 27 clubfeet (average follow-up 11 years since first surgery; range, 3.5-24 years) were reviewed. More than one clubfoot operation was required in 56% of cases. Forty-six percent were corrected after one surgery; 33% required a second surgery and 14% required a third operation. One patient with particularly severe feet required a fourth operation on each foot. The mean age at the time of surgery was 1.26 years, 5.12 years, and 8 years for the first, second, and third operations, respectively. The first operation consisted of a soft-tissue release. The second and third operations consisted of more extensive soft-tissue release and various rearfoot and forefoot procedures. Radiographic values revealed an AP talocalcaneal angle of 18 degrees, AP talo-first metatarsal angle of 6 degrees, lateral talocalcaneal angle of 29.6 degrees, lateral talo-first metatarsal angle of 15 degrees, and calcaneo-first metatarsal angle of 143 degrees. At follow-up all patients had adequate function as determined by personal interview and clinical examination. We conclude that correction of resistant congenital clubfoot often requires more than one surgery, not because of a "failed first operation," but due to dynamic muscle imbalances that may not be fully recognized in infancy and early childhood. Thus, the need for a second operation should not be perceived as a failure of the first, but as part of the natural history of congenital clubfoot.


Assuntos
Pé Torto Equinovaro/cirurgia , Pé/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Pé Torto Equinovaro/complicações , Pé Torto Equinovaro/fisiopatologia , Feminino , Seguimentos , Humanos , Lactente , Estudos Longitudinais , Masculino , Reoperação , Estudos Retrospectivos
17.
Pediatr Dev Pathol ; 3(2): 126-39, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10679032

RESUMO

Our objective in this study was to identify histologically homogenous classes of childhood supratentorial neuroglial tumors. Previously, we identified five quantitative histologic factors (differing linear combinations of 17 reliably recognized histologic features in neuroglial tumors). They account for much of the histologic variance in the 703 supratentorial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the factors in cluster analyses and identified eight classes of neuroglial tumors. Each of these classes had significant differences in histology, allowing the separation of many of the conventional types of neuroglial tumors into two or more classes. For instance, fibrillary astrocytoma, pilocytic astrocytoma, subependymal giant cell astrocytoma, anaplastic astrocytoma, oligodendroglioma, and ependymoma were represented in two or more classes. Often these classes had statistically significant differences in survival distributions. For instance, the two classes of "anaplastic astrocytomas" have widely discrepant 5-year survival probabilities of 0.7 and 0.2. Use of the classes identified in this study ensures relatively homogeneous histologic subsets of tumors. We suggest that these classes will be useful for the selection of children for therapeutic clinical trials.


Assuntos
Astrocitoma/patologia , Ependimoma/patologia , Oligodendroglioma/patologia , Neoplasias Supratentoriais/patologia , Astrocitoma/classificação , Astrocitoma/mortalidade , Criança , Análise por Conglomerados , Ependimoma/classificação , Ependimoma/mortalidade , Humanos , Oligodendroglioma/classificação , Oligodendroglioma/mortalidade , Neoplasias Supratentoriais/classificação , Neoplasias Supratentoriais/mortalidade , Taxa de Sobrevida , Organização Mundial da Saúde
18.
J Pineal Res ; 28(2): 97-104, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10709971

RESUMO

The objective of this study was to determine whether daytime occupational exposure to extremely low frequency magnetic fields (MFs) suppresses nocturnal melatonin production. Sixty female volunteers were recruited. Thirty-nine worked in a garment factory, and 21 office workers served as a reference group. Exposure assessment was based on the type of sewing machine used and MF measurements around each type of machine. Eye-level MF flux density was used to classify the operators to higher (>1 microT) and lower (0.3-1 microT) exposure categories. A third group of factory workers had diverse MF exposures from other sources. The reference group had average exposure of about 0.15 microT. Urine samples were collected on Friday and Monday for three consecutive weeks. Melatonin production was assessed as urinary 6-hydroxymelatonin sulfate (6-OHMS) excretion. The ratio of Friday morning/Monday morning 6-OHMS was used to test the hypothesis that melatonin production is suppressed after 4 days of occupational MF exposure with significant recovery during the weekend. Possible chronic suppression of melatonin production was evaluated by studying exposure-related differences in the Friday values by multivariate regression analysis. The Monday/Friday ratios were close to 1.0, suggesting that there is no increase in melatonin production over the weekend. The average 6-OHMS excretion on Friday was lower among the factory workers than in the reference group, but no monotonous dose-response was observed. Multivariate regression analysis identified MF exposure, smoking, and age as significant explanatory variables associated with decreased 6-OHMS excretion.


Assuntos
Campos Eletromagnéticos/efeitos adversos , Melatonina/análogos & derivados , Exposição Ocupacional/efeitos adversos , Glândula Pineal/fisiologia , Adulto , Ritmo Circadiano , Feminino , Humanos , Melatonina/urina , Pessoa de Meia-Idade , Glândula Pineal/efeitos da radiação , Radioimunoensaio , Indústria Têxtil
19.
Foot Ankle Int ; 21(1): 45-50, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10710261

RESUMO

Macrodactyly can affect the fingers and/or toes1. Histopathologic examination will distinguish macrodactylia fibrolipomatosis or neural fibrolipoma with macrodactyly, from macrodactylia as a part of neurofibromatosis. Surgical repair is aimed at decreasing the size of the affected foot so it is as near in size and shape to the normal foot as possible. Surgical approaches have included reconstructive surgery (usually staged debulking procedures), epiphyseal plate arrest and amputation. Repeated reconstructive surgical procedures, as illustrated in this report covering patient care over a 15 year period, are usually necessary due to recurring soft tissue and boney enlargement.


Assuntos
Deformidades do Pé/cirurgia , Gigantismo/cirurgia , Dedos do Pé/anormalidades , Dedos do Pé/cirurgia , Adulto , Criança , Diagnóstico Diferencial , Feminino , Seguimentos , Pé/diagnóstico por imagem , Deformidades do Pé/etiologia , Deformidades do Pé/patologia , Gigantismo/diagnóstico por imagem , Gigantismo/etiologia , Gigantismo/patologia , Humanos , Neurofibroma/complicações , Neurofibroma/diagnóstico , Radiografia , Recidiva , Reoperação
20.
Bioelectromagnetics ; 21(1): 57-67, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10615093

RESUMO

Recently published studies indicate that having worked in occupations that involve moderate to high electromagnetic field (EMF) exposure is a risk factor for neurodegenerative diseases, including Alzheimer's disease. In these studies, the occupational groups most over-represented for EMF exposure comprised seamstresses, dressmakers, and tailors. Future epidemiologic studies designed to evaluate the possibility of a causal relationship between exposure to EMF and a neuro degenerative disease endpoint such as incidence of Alzheimer's disease, will benefit from the measurement of electromagnetic field metrics with potential biological relevance. Data collection methodology in such studies would be highly dependent upon how the metrics are defined. In this research the authors developed and demonstrated (1) protocols for collecting EMF exposure data suitable for estimating a variety of exposure metrics that may have biological relevance, and (2) analytical methods for calculation of these metrics. The authors show how exposure might be estimated under each of the three prominent EMF health-effects mechanism theories and evaluate the assertion that relative exposure ranking is dependent on which mechanism is assumed. The authors also performed AC RMS magnetic flux density measurements, confirming previously reported findings. The results indicate that seamstresses, as an occupational group, should be considered for study of the possible health effects of long-term EMF exposure.


Assuntos
Campos Eletromagnéticos , Exposição Ocupacional , Algoritmos , Vestuário , Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Feminino , Finlândia , Humanos , Microclima
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