Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62
Filtrar
1.
Eur J Paediatr Neurol ; 51: 140-146, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38959712

RESUMO

CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy. Ganaxolone, a neuroactive steroid, reduces the frequency of major motor seizures in children with CDD. This analysis explored the effect of ganaxolone on non-seizure outcomes. Children (2-19 years) with genetically confirmed CDD and ≥ 16 major motor seizures per month were enrolled in a double-blind randomized placebo-controlled trial. Ganaxolone or placebo was administered three times daily for 17 weeks. Behaviour was measured with the Anxiety, Depression and Mood Scale (ADAMS), daytime sleepiness with the Child Health Sleep Questionnaire, and quality of life with the Quality of Life Inventory-Disability (QI-Disability) scale. Scores were compared using ANOVA, adjusted for age, sex, number of anti-seizure mediations, baseline 28-day major motor seizure frequency, baseline developmental skills, and behaviour, sleep or quality of life scores. 101 children with CDD (39 clinical sites, 8 countries) were randomized. Median (IQR) age was 6 (3-10) years, 79.2 % were female, and 50 received ganaxolone. After 17 weeks of treatment, Manic/Hyperactive scores (mean difference 1.27, 95%CI -2.38,-0.16) and Compulsive Behaviour scores (mean difference 0.58, 95%CI -1.14,-0.01) were lower (improved) in the ganaxolone group compared with the placebo group. Daytime sleepiness scores were similar between groups. The total change in QOL score for children in the ganaxolone group was 2.6 points (95%CI -1.74,7.02) higher (improved) than in the placebo group but without statistical significance. Along with better seizure control, children who received ganaxolone had improved behavioural scores in select domains compared to placebo.


Assuntos
Qualidade de Vida , Humanos , Feminino , Masculino , Método Duplo-Cego , Criança , Pré-Escolar , Adolescente , Adulto Jovem , Resultado do Tratamento , Síndromes Epilépticas/tratamento farmacológico , Convulsões/tratamento farmacológico , Convulsões/etiologia , Pregnanolona/análogos & derivados , Espasmos Infantis
2.
Epilepsy Res ; 200: 107287, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38237219

RESUMO

PURPOSE: Validated measures capable of demonstrating meaningful interventional change in the CDKL5 deficiency disorder (CDD) are lacking. The study objective was to modify the Rett Syndrome Gross Motor Scale (RSGMS) and evaluate its psychometric properties for individuals with CDD. METHODS: Item and scoring categories of the RSGMS were modified. Caregivers registered with the International CDKL5 Clinical Research Network uploaded motor videos filmed at home to a protected server and completed a feedback questionnaire (n = 70). Rasch (n = 137), known groups (n = 109), and intra- and inter-rater reliability analyses (n = 50) were conducted. RESULTS: The age of individuals with CDD ranged from 1.5 to 34.1 years. The modified scale, Gross Motor-Complex Disability (GM-CD), comprised 17 items. There were no floor or ceiling effects and inter- and intra-rater reliability were good. Rasch analysis demonstrated that the items encompassed a large range of performance difficulty, although there was some item redundancy and some disordered categories. One item, Prone Head Position, was a poor fit. Caregiver-reported acceptability was positive. Scores differed by age and functional abilities. SUMMARY: GM-CD appears to be a suitable remotely administered measure and psychometrically sound for individuals with CDD. This study provides the foundation to propose the use of GM-CD in CDD clinical trials. Longitudinal evaluation is planned.


Assuntos
Síndromes Epilépticas , Síndrome de Rett , Espasmos Infantis , Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Psicometria , Destreza Motora , Reprodutibilidade dos Testes , Síndrome de Rett/diagnóstico , Síndrome de Rett/genética , Proteínas Serina-Treonina Quinases/genética
3.
Int J Cosmet Sci ; 39(4): 379-385, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27883196

RESUMO

OBJECTIVE: Blocking the TRPV1 receptor is an interesting approach for the treatment of sensitive skin. Here we investigated the potential of grifolin derivatives from Albatrellus ovinus to act as TRPV1 receptor blockers and their potential to serve as cosmetic active ingredients. METHODS: Binding characteristics of grifolin derivatives from Albatrellus ovinus were determined in competitive and functional in vitro assays to achieve IC50 values. The TRPV1 receptor was activated in vivo with capsaicin and noxious heat to investigate skin reddening, microcirculation, skin sensations and heat pain thresholds. RESULTS: Grifolin derivatives extracted from Albatrellus ovinus proved to inhibit the TRPV1 receptor in vitro and in vivo. Besides suppression of the TRPV1 receptor activity upon chemical stimulation with capsaicin, thermal activation was shown to be inhibited as well by application of cosmetic formulations containing 3% Albatrellus ovinus extract. The reduction of stinging and burning sensations as well as reduction of reddening and microcirculation upon irritation with capsaicin or thermal stress proved efficacy in vivo. CONCLUSION: Grifolin derivatives from Albatrellus ovinus are able to serve as fungal-derived TRPV1 receptor blockers with capability to serve as a cosmetic active ingredient on sensitive skin.


Assuntos
Basidiomycota/química , Cosméticos , Canais de Cátion TRPV/antagonistas & inibidores , Adolescente , Adulto , Animais , Células CHO , Cricetulus , Estudos Cross-Over , Método Duplo-Cego , Humanos , Pessoa de Meia-Idade , Placebos , Terpenos/farmacologia , Adulto Jovem
4.
Euro Surveill ; 20(32): 2-5, 2015 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-26290486

RESUMO

We report an imported case of louse-borne relapsing fever in a young adult Eritrean refugee who presented with fever shortly after arriving in Switzerland. Analysis of blood smears revealed spirochetes identified as Borrelia recurrentis by 16S rRNA gene sequencing. We believe that louse-borne relapsing fever may be seen more frequently in Europe as a consequence of a recent increase in refugees from East Africa travelling to Europe under poor hygienic conditions in confined spaces.


Assuntos
Borrelia/isolamento & purificação , RNA Ribossômico 16S/genética , Febre Recorrente/diagnóstico , Animais , Borrelia/genética , Ceftriaxona/administração & dosagem , DNA Bacteriano/genética , Doxiciclina/administração & dosagem , Eritreia , Humanos , Refugiados , Febre Recorrente/sangue , Febre Recorrente/tratamento farmacológico , Suíça , Viagem , Resultado do Tratamento
5.
Open Forum Infect Dis ; 2(2): ofv013, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26110162

RESUMO

This case report describes the simultaneous manifestation of acute necrotizing encephalopathy in 2 consanguineous patients after infection with influenza B based on the autosomal dominant missense mutation of the RANBP2-gene. Differential diagnosis of acute encephalopathy, clinical and radiological clues, and treatment strategies are outlined.

6.
Int Endod J ; 42(7): 639-48, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19467041

RESUMO

AIM: The aim of this Case Series was to evaluate the radiographic quality of root fillings performed 5 years previously using the noninstrumentation technology (NIT)-obturation method and to assess radiographically the outcome of these root canal treatments. METHODOLOGY: Seventeen patients requiring root canal treatment participated in this study and were re-evaluated after 5 years. After instrumentation with K-Flexofiles, Calcium-Hydroxide inter-appointment dressing, re-entry and copious irrigation with NaOCl, the teeth were root filled using the NIT. RESULTS: Immediately after obturation the root fillings were (-0.78 +/- 0.11 mm) short when taking the radiographic apex as a reference point. After 60 months these values were -0.85 +/- 0.11 mm. No statistical difference was found (P > 0.05). In the periapical region, PAI rating 1 and 2 increased from 20.1% to 75.6% after 60 months. CONCLUSIONS: * This prospective Case Series demonstrated the performance of the NIT-obturation method in vivo. * Root canals filled by the reduced-pressure method using sealer combined with gutta-percha cones showed good radiographic quality. * Periapical healing after 5 years was comparable with conventional filling techniques.


Assuntos
Obturação do Canal Radicular/métodos , Tratamento do Canal Radicular/métodos , Bismuto/uso terapêutico , Hidróxido de Cálcio/uso terapêutico , Cavidade Pulpar/diagnóstico por imagem , Combinação de Medicamentos , Resinas Epóxi/uso terapêutico , Seguimentos , Guta-Percha/uso terapêutico , Humanos , Periodontite Periapical/terapia , Tecido Periapical/diagnóstico por imagem , Estudos Prospectivos , Pulpite/terapia , Radiografia , Materiais Restauradores do Canal Radicular/uso terapêutico , Irrigantes do Canal Radicular/uso terapêutico , Preparo de Canal Radicular/instrumentação , Preparo de Canal Radicular/métodos , Prata/uso terapêutico , Hipoclorito de Sódio/uso terapêutico , Tecnologia Odontológica , Titânio/uso terapêutico , Ápice Dentário/diagnóstico por imagem , Resultado do Tratamento , Vácuo , Vibração , Cicatrização/fisiologia
7.
Cell Death Differ ; 14(2): 286-95, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16794603

RESUMO

Protein synthesis is inhibited during apoptosis. However, the translation of many mRNAs still proceeds driven by internal ribosome entry sites (IRESs). Here we show that the 5'UTR of hid and grim mRNAs promote translation of uncapped-mRNA reporters in cell-free embryonic extracts and that hid and grim mRNA 5'UTRs drive IRES-mediated translation. The translation of capped-reporters proceeds in the presence of cap competitor and in extracts where cap-dependent translation is impaired. We show that the endogenous hid and grim mRNAs are present in polysomes of heat-shocked embryos, indicating that cap recognition is not required for translation. In contrast, sickle mRNA is translated in a cap-dependent manner in all these assays. Our results show that IRES-dependent initiation may play a role in the translation of Drosophila proapoptotic genes and suggest a variety of regulatory pathways.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Biossíntese de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regiões 5' não Traduzidas/metabolismo , Animais , Apoptose , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/embriologia , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Fator de Iniciação 4E em Eucariotos/genética , Regulação da Expressão Gênica no Desenvolvimento , Resposta ao Choque Térmico , Proteínas de Homeodomínio/metabolismo , Mutação/genética , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Iniciação Traducional da Cadeia Peptídica/genética , Polirribossomos/metabolismo , Transporte Proteico , Capuzes de RNA/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica , Regulação para Cima/genética
8.
Int Endod J ; 38(2): 112-23, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15667633

RESUMO

AIM: To evaluate in a clinical case series the location of fractured instruments, how many of them could be removed and to compare these findings with the results of a similar study. METHODOLOGY: Within an 18-month period all referred endodontic cases involving fractured instruments within root canals were analysed. The protocol for removal of fractured instruments was: create straight-line access to the coronal portion of the fractured instrument, attempt to create a ditched groove around the coronal aspect of the instrument using ultrasonic files and/or to bypass it with K-Files. Subsequently, the fractured instrument was vibrated ultrasonically and flushed out of the root canal or an attempt was made to remove the instrument with the Tube-and-Hedström file-Method or similar techniques. The location of the fractured instrument and the time required for removal were recorded. Successful removal was defined as complete removal from the root canal without creating a clinically detectable perforation. RESULTS: In total, 97 consecutive cases of instrument fracture were included in the time period. In all, 84 instruments (87%) were removed successfully. There was a significant correlation between the time needed to remove fractured instruments and a decrease in success rate. Curved canals had significantly more fractured instruments than straight canals (P < 0.05). Rotary instruments fractured significantly more often in curved canals (P < 0.05) compared with other instruments. Half of all instrument fractures occurred in mesial roots of lower molars and most often when using rotating instruments. There was no statistically significant difference in the success rate with respect to the location of the fractured instrument (tooth/root type), the type of fractured instrument or the different methods of instrument removal. CONCLUSIONS: Curved canals are a higher risk for instrument fracture than straight canals. In curved canals rotary instruments (including lentulo spirals) fractured more often than other instruments. In all, 87% of the fractured instruments were removed successfully. A decrease in success rate was evident with increasing treatment time. The use of an operating microscope was a prerequisite for the techniques used to remove the fractured instruments.


Assuntos
Instrumentos Odontológicos/efeitos adversos , Cavidade Pulpar , Corpos Estranhos/terapia , Preparo de Canal Radicular/instrumentação , Distribuição de Qui-Quadrado , Instrumentos Odontológicos/estatística & dados numéricos , Falha de Restauração Dentária , Falha de Equipamento/estatística & dados numéricos , Corpos Estranhos/etiologia , Humanos , Microscopia/instrumentação , Probabilidade , Retratamento , Terapia por Ultrassom
9.
Int Endod J ; 35(4): 352-8, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12059936

RESUMO

AIM: The aim of this in vivo study was to compare the radiographic quality of root fillings performed by the NIT-obturation method versus conventional mechanical obturation. METHODOLOGY: Sixty-six patients needing root canal treatment participated in this study. The treatments were performed by three private practitioners. The root canals were instrumented with K-Flexofiles to a master apical file between sizes 25 and 60, followed by step-back flaring up to size 70. Copious irrigation was used throughout the instrumentation procedure with NaOCl (3%). The teeth were obturated either by lateral condensation, the McSpadden technique (control) or by the new non-instrumentation technology (NIT) with and without using gutta-percha points. In the NIT method, a low pressure was created within the tooth, and AH 26 sealer was sucked into the root canal system. Radiographs of the root-filled teeth were analysed and the length of the root filling, the presence of voids and the area of any other fillings determined. RESULTS: The root canal fillings of the control group (0.1 +/- 0.1 mm) and those of the NIT/gutta-percha group (0.3 +/- 0.1 mm) were both overextended when taking the apical constriction as a reference point. Root canal fillings of the NIT/gutta-percha group were statistically (P < 0.05) significantly longer than those of the NIT without gutta-percha group. The latter showed slightly underextended root canal fillings (-0.14 +/- 0.1 mm). CONCLUSIONS: The present investigation demonstrated the performance of the NIT-obturation method in vivo. Root canals filled by the reduced-pressure-method using sealer combined with gutta-percha cones exhibited equivalent radiographic quality compared to conventionally filled canals.


Assuntos
Materiais Restauradores do Canal Radicular/uso terapêutico , Obturação do Canal Radicular/métodos , Análise de Variância , Bismuto/química , Bismuto/uso terapêutico , Distribuição de Qui-Quadrado , Cavidade Pulpar/diagnóstico por imagem , Combinação de Medicamentos , Resinas Epóxi/química , Resinas Epóxi/uso terapêutico , Guta-Percha/química , Guta-Percha/uso terapêutico , Humanos , Pressão , Radiografia , Materiais Restauradores do Canal Radicular/química , Irrigantes do Canal Radicular/uso terapêutico , Obturação do Canal Radicular/instrumentação , Preparo de Canal Radicular/instrumentação , Preparo de Canal Radicular/métodos , Prata/química , Prata/uso terapêutico , Hipoclorito de Sódio/uso terapêutico , Estatísticas não Paramétricas , Propriedades de Superfície , Tecnologia Odontológica/instrumentação , Tecnologia Odontológica/métodos , Titânio/química , Titânio/uso terapêutico , Ápice Dentário/diagnóstico por imagem , Vácuo
10.
Genetics ; 158(4): 1597-614, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11514449

RESUMO

With the completion of the Drosophila genome sequence, an important next step is to extract its biological information by systematic functional analysis of genes. We have produced a high-resolution genetic map of cytological region 38 of Drosophila using 41 deficiency stocks that provide a total of 54 breakpoints within the region. Of a total of 45 independent P-element lines that mapped by in situ hybridization to the region, 14 targeted 7 complementation groups within the 38 region. Additional EMS, X-ray, and spontaneous mutations define a total of 17 complementation groups. Because these two pools partially overlap, the completed analysis revealed 21 distinct complementation groups defined by point mutations. Seven additional functions were defined by trans-heterozygous combinations of deficiencies, resulting in a total of 28 distinct functions. We further produced a developmental expression profile for the 760 kb from 38B to 38E. Of 135 transcription units predicted by GENSCAN, 22 have at least partial homology to mobile genetic elements such as transposons and retroviruses and 17 correspond to previously characterized genes. We analyzed the developmental expression pattern of the remaining genes using poly(A)(+) RNA from ovaries, early and late embryos, larvae, males, and females. We discuss the correlation between GENSCAN predictions and experimentally confirmed transcription units, the high number of male-specific transcripts, and the alignment of the genetic and physical maps in cytological region 38.


Assuntos
Mapeamento Cromossômico , Drosophila/genética , Genoma , Animais , Sequência de Bases , Northern Blotting , Southern Blotting , Bases de Dados como Assunto , Etiquetas de Sequências Expressas , Teste de Complementação Genética , Heterozigoto , Modelos Genéticos , Dados de Sequência Molecular , Mutação , Mapeamento Físico do Cromossomo , Mutação Puntual , Poli A , Software
11.
Radiother Oncol ; 60(3): 289-97, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11514009

RESUMO

BACKGROUND AND PURPOSE: Stereotactically-guided conformal radiotherapy (SCRT) allows the delivery of highly conformal dose distributions to localised brain tumours. This is of particular importance for children, whose often excellent long-term prognosis should be accompanied by low toxicity. The commercial immobilisation system in use at our hospital for adults was felt to be too heavy for children, and precluded the use of anaesthesia, which is sometimes required for paediatric patients. This paper therefore describes the design and implementation of a system for treating children with SCRT. This system needed to be well tolerated by patients, with good access for treating typical childhood malignancies. MATERIALS AND METHODS: A lightweight frame was developed for immobilisation, with a shell-based alternative for patients requiring general anaesthetic. Procedures were set up to introduce the patients to the frame system in order to maximise patient co-operation and comfort. Film measurements were made to assess the impact of the frame on transmission and surface dose. The reproducibility of the systems was assessed using electronic portal images. RESULTS: Both frame and shell systems are in clinical use. The frame weighs 0.6 kg and is well tolerated. It has a transmission of 92-96%, and fields which pass through it deliver surface doses of 58-82% of the dose at d(max), compared to 18% when no frame is present. However, the frame is constructed to maximise the availability of unobstructed beam directions. Reproducibility measurements for the frame showed a mean random error of 1.0+/-0.2mm in two dimensions (2D) and 1.4+/-0.7 mm in 3D. The mean systematic error in 3D was 2.2mm, and 90% of all overall 3D errors were less than 3.4mm. For the shell system, the mean 2D random error was 1.5+/-0.2mm. CONCLUSIONS: Two well-tolerated immobilisation devices have been developed for fractionated SCRT treatment of paediatric patients. A lightweight frame system gives a wide range of possible unobstructed beam directions, although beams that intersect the frame are not precluded, provided that output corrections are applied. A shell system allows the use of general anaesthesia. Both systems give reproducible immobilisation to complement the high-precision treatment delivery.


Assuntos
Neoplasias Encefálicas/radioterapia , Imobilização , Radioterapia Conformacional/métodos , Técnicas Estereotáxicas , Criança , Humanos , Planejamento da Radioterapia Assistida por Computador , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X
12.
EMBO J ; 20(14): 3749-59, 2001 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-11447116

RESUMO

Cyclin-dependent kinase (CDK)7-cyclin H, the CDK-activating kinase (CAK) and TFIIH-associated kinase in metazoans can be activated in vitro through T-loop phosphorylation or binding to the RING finger protein MAT1. Although the two mechanisms can operate independently, we show that in a physiological setting, MAT1 binding and T-loop phosphorylation cooperate to stabilize the CAK complex of Drosophila. CDK7 forms a stable complex with cyclin H and MAT1 in vivo only when phosphorylated on either one of two residues (Ser164 or Thr170) in its T-loop. Mutation of both phosphorylation sites causes temperature-dependent dissociation of CDK7 complexes and lethality. Furthermore, phosphorylation of Thr170 greatly stimulates the activity of the CDK7- cyclin H-MAT1 complex towards the C-terminal domain of RNA polymerase II without significantly affecting activity towards CDK2. Remarkably, the substrate-specific increase in activity caused by T-loop phosphorylation is due entirely to accelerated enzyme turnover. Thus phosphorylation on Thr170 could provide a mechanism to augment CTD phosphorylation by TFIIH-associated CDK7, and thereby regulate transcription.


Assuntos
Quinases Ciclina-Dependentes , Ciclinas/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Sequência de Aminoácidos , Animais , Biopolímeros , Ciclina H , Ciclinas/antagonistas & inibidores , Drosophila , Proteínas de Drosophila , Cinética , Dados de Sequência Molecular , Fosforilação , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Especificidade por Substrato , Quinase Ativadora de Quinase Dependente de Ciclina
13.
Genome Res ; 11(1): 67-77, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11156616

RESUMO

We performed a screen for female sterile mutations on the X chromosome of Drosophila melanogaster and identified new loci required for developmental events in oogenesis as well as new alleles of previously described genes. We present mapping and phenotypic characterization data for many of these genes and discuss their significance in understanding fundamental developmental and cell biological processes. Our screen has identified genes that are involved in cell cycle control, intracellular transport, cell migration, maintenance of cell membranes, epithelial monolayer integrity and cell survival or apoptosis. We also describe new roles for the genes dunce (dnc), brainiac (brn) and fs(1)Yb, and we identify new alleles of Sex lethal (Sxl), ovarian tumor (otu), sans filles (snf), fs(1)K10, singed (sn), and defective chorion-1 (dec-1).


Assuntos
Proteínas de Drosophila , Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Insetos/fisiologia , Proteínas de Membrana/fisiologia , Oogênese/genética , Cromossomo X/genética , Animais , Apoptose/genética , Padronização Corporal/genética , Drosophila melanogaster/fisiologia , Feminino , Genes de Insetos , Marcadores Genéticos , Masculino , Mutação
14.
Nucleic Acids Res ; 28(21): 4083-9, 2000 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11058103

RESUMO

Poly(dA.dT) sequences (T-tracts) are abundant genomic DNA elements with unusual properties in vitro and an established role in transcriptional regulation of yeast genes. In vitro T-tracts are rigid, contribute to DNA bending, affect assembly in nucleosomes and generate a characteristic pattern of CPDs (cyclobutane pyrimidine dimers) upon irradiation with UV light (UV photofootprint). In eukaryotic cells, where DNA is packaged in chromatin, the DNA structure of T-tracts is unknown. Here we have used in vivo UV photofootprinting and DNA repair by photolyase to investigate the structure and accessibility of T-tracts in yeast promoters (HIS3, URA3 and ILV1). The same characteristic photofootprints were obtained in yeast and in naked DNA, demonstrating that the unusual T-tract structure exists in living cells. Rapid repair of CPDs in the T-tracts demonstrates that these T-tracts were not folded in nucleosomes. Moreover, neither datin, a T-tract binding protein, nor Gcn5p, a histone acetyltransferase involved in nucleosome remodelling, showed an influence on the structure and accessibility of T-tracts. The data support a contribution of this unusual DNA structure to transcriptional regulation.


Assuntos
DNA Fúngico/química , DNA Fúngico/genética , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Conformação de Ácido Nucleico , Nucleossomos/fisiologia , Poli A/genética , Poli T/genética , Regiões Promotoras Genéticas/genética , Proteínas de Saccharomyces cerevisiae , Leveduras/genética , Acetiltransferases/genética , Acetiltransferases/metabolismo , Sequência de Bases , Cromossomos Fúngicos/química , Cromossomos Fúngicos/genética , Cromossomos Fúngicos/metabolismo , Cromossomos Fúngicos/efeitos da radiação , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Pegada de DNA , Reparo do DNA/genética , DNA Fúngico/metabolismo , DNA Fúngico/efeitos da radiação , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Desoxirribodipirimidina Fotoliase/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Genes Fúngicos/genética , Genoma Fúngico , Histona Acetiltransferases , Hidroliases/genética , Maleabilidade , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Raios Ultravioleta , Leveduras/enzimologia , Leveduras/efeitos da radiação
15.
Br J Radiol ; 73(872): 886-91, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11026866

RESUMO

Simulator radiographs taken as a record of breast radiotherapy planning often show ill defined breast tissue margins because exposure parameters are set to optimize visualization of the chest wall rather than the bulk of the breast. This creates difficulties when using simulator images as reference images in verification by comparing with either portal film or images from an electronic portal imaging device. Our aim was to improve breast images taken at simulation without changing exposure parameters that have been optimized for visualization of the chest wall. This has been achieved via an external filter to be used when taking radiographs with the treatment simulator. The filter is made of stainless steel coated with tin and is shaped to maintain acceptable imaging of the chest wall by covering only the section of field anterior to the chest wall. Radiographs of breast simulations using the filter have been accepted as satisfactory by both clinicians and radiographers. The filter is now in routine clinical use for breast and chest wall treatment simulation.


Assuntos
Neoplasias da Mama/radioterapia , Mamografia/instrumentação , Desenho de Equipamento , Feminino , Filtração/instrumentação , Humanos , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador , Estanho
16.
Radiother Oncol ; 57(1): 79-89, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11033192

RESUMO

BACKGROUND AND PURPOSE: To develop a method of using a multileaf collimator (MLC) to deliver intensity modulated radiotherapy (IMRT) for tangential breast fields, using an MLC to deliver a set of multiple static fields (MSFs). MATERIALS AND METHODS: An electronic portal imaging device (EPID) is used to obtain thickness maps of medial and lateral tangential breast fields. From these IMRT deliveries are designed to minimize the volume of breast above 105% of prescribed dose. The deliveries are universally-wedged beams augmented with a set of low dose shaped irradiations. Dosimetric and planning QA of this method has been compared with the standard, wedged treatment and the corresponding treatment using physical compensators. Several options for delivering the MSF treatment are presented. RESULTS: The MSF technique was found to be superior to the standard technique (P value=0.002) and comparable with the compensated technique. Both IMRT methods reduced the volume of breast above 105% dose from a mean value of 12.0% of the total breast volume to approximately 2.8% of the total breast volume. CONCLUSIONS: This MSF method may be used to reduce the high dose volume in tangential breast irradiation significantly. This may have consequences for long-term side effects, particularly cosmesis.


Assuntos
Neoplasias da Mama/radioterapia , Magnetismo , Radioterapia Conformacional/métodos , Relação Dose-Resposta à Radiação , Feminino , Humanos , Prognóstico , Tolerância a Radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Sensibilidade e Especificidade
17.
Epilepsia ; 41 Suppl 6: S174-80, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10999540

RESUMO

PURPOSE: Hilar mossy cells represent an important excitatory subpopulation of the hippocampal formation. Several studies have identified this cell type as particularly vulnerable to seizure activity in rat models of limbic epilepsy. Here we have subjected hilar mossy cell loss in the hippocampus of patients with chronic temporal lobe epilepsy (TLE) to a systematic morphological and immunohistochemical analysis. METHODS: Hippocampal specimens from 30 TLE patients were included; 21 patients presented with segmental neuronal cell loss [Ammon's horns clerosis (AHS)] and 8 with focal lesions (tumors, scars, malformations) not involving the hippocampus proper. In one additional TLE patient, no histopathological alteration could be observed. Surgical specimens from tumor patients without epilepsy (n = 2) and nonepileptic autopsy brains (n = 8) were used as controls. Hilar mossy cells in the human hippocampus were visualized using a novel polycloncal antiserum directed against the metabotropic glutamate receptor subtype mGluR7b or by intracellular Lucifer Yellow injection, confocal laser scanning microscopy, and three-dimensional morphological reconstruction. RESULTS: Compared with controls, a significant loss of mGluR7 immunoreactive mossy cells was observed in patients with AHS (p < 0.05). In contrast, TLE patients with focal lesions but structurally intact hippocampus demonstrated only a discrete, nonsignificant reduction of this neuronal subpopulation. This observation was confirmed by analysis of 62 randomly injected hilar neurons from AHS patients, in which we were unable to detect neurons with a morphology like that of hilar mossy cells. CONCLUSION: Our present data indicate significant hilar mossy cell loss in TLE patients with AHS. In contrast, hilar mossy cells appear to be less vulnerable in patients with lesion-associated TLE. Although the significance of mGluR7 immunoreactivity in mossy cells remains to be studied, loss of this cell population is compatible with alterations in hippocampal networks and regional hyperexcitability as pathogenic mechanism of AHS and TLE.


Assuntos
Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Fibras Musgosas Hipocampais/patologia , Adulto , Idoso , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Fibras Musgosas Hipocampais/ultraestrutura , Receptores de Glutamato Metabotrópico/imunologia , Receptores de Glutamato Metabotrópico/ultraestrutura , Esclerose
18.
J Cell Sci ; 113 ( Pt 12): 2119-27, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10825285

RESUMO

Bicaudal-D (Bic-D) is essential for the establishment of oocyte fate and subsequently for polarity formation within the developing Drosophila oocyte. To find out where in the germ cells Bic-D performs its various functions we made transgenic flies expressing a chimeric Bic-D::GFP fusion protein. Once Bic-D::GFP preferentially accumulates in the oocyte, it shows an initial anterior localization in germarial region 2. In the subsequent egg chamber stages 1-6 Bic-D::GFP preferentially accumulates between the oocyte nucleus and the posterior cortex in a focus that is consistently aligned with a crater-like indentation in the oocyte nucleus. After stage 6 Bic-D::GFP fluorescent signal is predominantly found between the oocyte nucleus and the dorso-anterior cortex. During the different phases several genes have been found to be required for the establishment of the new Bic-D::GFP distribution patterns. Dynein heavy chain (Dhc), spindle (spn) genes and maelstrom (mael) are required for the re-localization of the Bic-D::GFP focus from its anterior to its posterior oocyte position. Genes predicted to encode proteins that interact with RNA (egalitarian and orb) are required for the normal subcellular distribution of Bic-D::GFP in the germarium, and another potential RNA binding protein, spn-E, is required for proper transport of Bic-D::GFP from the nurse cells to the oocyte in later oogenesis stages. The results indicate that Bic-D requires the activity of mRNA binding proteins and a negative-end directed microtubule motor to localize to the appropriate cellular domains. Asymmetric subcellular accumulation of Bic-D and the polarization of the oocyte nucleus may reflect the function of this localization machinery in vectorial mRNA localization and in tethering of the oocyte nucleus. The subcellular polarity defined by the Bic-D focus and the nuclear polarity marks some of the first steps in antero-posterior and subsequently in dorso-ventral polarity formation.


Assuntos
Núcleo Celular/metabolismo , Proteínas de Drosophila , Proteínas de Insetos/metabolismo , Oócitos/metabolismo , Oócitos/ultraestrutura , Animais , Núcleo Celular/ultraestrutura , Drosophila melanogaster , Feminino , Proteínas de Fluorescência Verde , Proteínas de Insetos/genética , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
19.
Nucleic Acids Res ; 28(10): 2060-8, 2000 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-10773073

RESUMO

DNA damage formation and repair are tightly linked to protein-DNA interactions in chromatin. We have used minichromosomes in yeast as chromatin substrates in vivo to investigate how nucleotide excision repair (NER) and repair by DNA-photolyase (photoreactivation) remove pyrimidine dimers from an origin of replication ( ARS1 ). The ARS1 region is nuclease sensitive and flanked by nucleosomes on both sides. Photoreactivation was generally faster than NER at all sites. Site-specific heterogeneity of repair was observed for both pathways. This heterogeneity was different for NER and photoreactivation and it was altered in a minichromosome where ARS1 was transcribed. The results indicate distinct inter-actions of the repair systems with protein complexes bound in the ARS region (ORC, Abf1) and a predominant role of photolyase in CPD repair of an origin of replication.


Assuntos
Reparo do DNA , DNA Fúngico/genética , Desoxirribodipirimidina Fotoliase/metabolismo , Origem de Replicação , Saccharomyces cerevisiae/genética , Dano ao DNA , DNA Fúngico/efeitos da radiação , Cinética , Dímeros de Pirimidina/metabolismo , Saccharomyces cerevisiae/efeitos da radiação , Raios Ultravioleta
20.
Proteins ; 39(1): 1-8, 2000 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-10737922

RESUMO

The mammalian intracellular brain platelet-activating factor acetylhydrolase, implicated in the development of cerebral cortex, is a member of the phospholipase A2 superfamily. It is made up of a homodimer of the 45 kDa LIS1 protein (a product of the causative gene for type I lissencephaly) and a pair of homologous 26-kDa alpha-subunits which account for all the catalytic activity. LIS1 is hypothesized to regulate nuclear movement in migrating neurons through interactions with the cytoskeleton, while the alpha-subunits, whose structure is known, contain a trypsin-like triad within the framework of a unique tertiary fold. The physiological significance of the association of the two types of subunits is not known. In an effort to better understand the function of the complex we turned to genomic data mining in search of related proteins in lower eukaryotes. We found that the Drosophila melanogaster genome contains homologs of both alpha- and beta-subunits, and we cloned both genes. The alpha-subunit homolog has been overexpressed, purified and crystallized. It lacks two of the three active-site residues and, consequently, is catalytically inactive against PAF-AH (Ib) substrates. Our study shows that the beta-subunit homolog is highly conserved from Drosophila to mammals and is able to interact with the mammalian alpha-subunits but is unable to interact with the Drosophila alpha-subunit. Proteins 2000;39:1-8.


Assuntos
Encéfalo/enzimologia , Drosophila melanogaster/genética , Fosfolipases A/química , Fosfolipases A/genética , 1-Alquil-2-acetilglicerofosfocolina Esterase , Sequência de Aminoácidos , Animais , Bovinos , Córtex Cerebral/enzimologia , Clonagem Molecular , Drosophila melanogaster/enzimologia , Drosophila melanogaster/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Larva , Substâncias Macromoleculares , Mamíferos , Dados de Sequência Molecular , Fosfolipases A2 , Estrutura Secundária de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA