RESUMO
The genetic diversity and population structure of Salvia lachnostachys Benth were assessed. Inter Simple Sequence Repeat (ISSR) molecular markers were used to investigate the restricted distribution of S. lachnostachys in Parana State, Brazil. Leaves of 73 individuals representing three populations were collected. DNA was extracted and submitted to PCR-ISSR amplification with nine tested primers. Genetic diversity parameters were evaluated. Our analysis indicated 95.6% polymorphic loci (stress value 0.02) with a 0.79 average Simpson's index. The Nei-Li distance dendrogram and principal component analysis largely recovered the geographical origin of each sample. Four major clusters were recognized representing each collected population. Nei's gene diversity and Shannon's information index were 0.25 and 0.40 respectively. As is typical for outcrossing herbs, the majority of genetic variation occurred at the population level (81.76%). A high gene flow (Nm = 2.48) was observed with a correspondingly low fixation index. These values were generally similar to previous studies on congeneric species. The results of principal coordinate analysis (PCA) and of arithmetic average (UPGMA) were consistent and all three populations appear distinct as in STRUCTURE analysis. In addition, this analysis indicated a majority intrapopulation genetic variation. Despite the human pressure on natural populations our study found high levels of genetic diversity for S. lachnostachys. This was the first molecular assessment for this endemic species with medicinal proprieties and the results can guide for subsequent bioprospection, breeding programs or conservation actions.
Assuntos
DNA de Plantas/análise , Variação Genética , Repetições de Microssatélites , Salvia/genética , Brasil , Conservação dos Recursos Naturais/métodos , Fluxo Gênico , Genética Populacional , Filogenia , Melhoramento Vegetal/métodos , Folhas de Planta/genética , Análise de Componente Principal , Salvia/fisiologiaRESUMO
Postsynaptic density-95 (PSD-95/SAP-90) is a palmitoylated peripheral membrane protein that scaffolds ion channels at excitatory synapses. To elucidate mechanisms for postsynaptic ion channel clustering, we analyzed the cellular trafficking of PSD-95. We find that PSD-95 transiently associates with a perinuclear membranous compartment and traffics with vesiculotubular structures, which migrate in a microtubule-dependent manner. Trafficking of PSD-95 with these vesiculotubular structures requires dual palmitoylation, which is specified by five consecutive hydrophobic residues at the NH(2) terminus. Mutations that disrupt dual palmitoylation of PSD-95 block both ion channel clustering by PSD-95 and its synaptic targeting. Replacing the palmitoylated NH(2) terminus of PSD-95 with alternative palmitoylation motifs at either the NH(2) or COOH termini restores ion channel clustering also induces postsynaptic targeting, respectively. In brain, we find that PSD-95 occurs not only at PSDs but also in association with intracellular smooth tubular structures in dendrites and spines. These data imply that PSD-95 is an itinerant vesicular protein; initial targeting of PSD-95 to an intracellular membrane compartment may participate in postsynaptic ion channel clustering by PSD-95.
Assuntos
Proteínas do Tecido Nervoso/metabolismo , Ácidos Palmíticos/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/metabolismo , Animais , Transporte Biológico , Brefeldina A/farmacologia , Linhagem Celular , Núcleo Celular/metabolismo , Polaridade Celular , Córtex Cerebral/citologia , Sequência Consenso , Proteína 4 Homóloga a Disks-Large , Cães , Células Epiteliais/metabolismo , Proteínas de Fluorescência Verde , Guanilato Quinases , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Canal de Potássio Kv1.4 , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Proteínas de Membrana , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Nocodazol/farmacologia , Núcleosídeo-Fosfato Quinase/metabolismo , Ratos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Associadas SAP90-PSD95 , SinapsesRESUMO
PSD-95 is a neuronal PDZ protein that associates with receptors and cytoskeletal elements at synapses, but whose function is uncertain. We found that overexpression of PSD-95 in hippocampal neurons can drive maturation of glutamatergic synapses. PSD-95 expression enhanced postsynaptic clustering and activity of glutamate receptors. Postsynaptic expression of PSD-95 also enhanced maturation of the presynaptic terminal. These effects required synaptic clustering of PSD-95 but did not rely on its guanylate kinase domain. PSD-95 expression also increased the number and size of dendritic spines. These results demonstrate that PSD-95 can orchestrate synaptic development and are suggestive of roles for PSD-95 in synapse stabilization and plasticity.
Assuntos
Interneurônios/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Células Piramidais/fisiologia , Receptores de Glutamato/metabolismo , Sinapses/fisiologia , Animais , Células Cultivadas , Dendritos/ultraestrutura , Proteína 4 Homóloga a Disks-Large , Potenciais Pós-Sinápticos Excitadores , Hipocampo/citologia , Interneurônios/citologia , Interneurônios/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Técnicas de Patch-Clamp , Terminações Pré-Sinápticas/fisiologia , Estrutura Terciária de Proteína , Células Piramidais/citologia , Células Piramidais/metabolismo , Ratos , Agregação de Receptores , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Proteínas Associadas SAP90-PSD95 , Sinapses/metabolismo , Transmissão Sináptica , Vesículas Sinápticas/fisiologia , TransfecçãoRESUMO
In the present contribution, the properties of dipropylene glycol isobornyl ether (Pribelance) are discussed, especially in the context of microemulsion and emulsion formulations. Pribelance is a new low-toxic anti-foaming hydrotrope with excellent co-surfactant properties that has some similarities with long-chain alcohols, but in contrast to them, it is liquid at room temperature. In combination with another, more hydrophilic co-surfactant, it allows significant amounts of oil to be solubilized in water. Possible applications such as in cosmetics, as an anti-foaming agent or as additive to cooling lubricants are discussed. Further potential applications are plasticizers, fermentation systems, agrochemicals and waste-water treatments.
Assuntos
Canfanos/química , Propilenoglicóis/química , Tensoativos/química , Animais , Canfanos/toxicidade , Propilenoglicóis/toxicidade , Coelhos , Ratos , Solubilidade , Tensoativos/toxicidade , TemperaturaRESUMO
A new species of the genus Euricrium is described-Euricrium edwardsi sp. n.-from the State of Paraná, southern Brazil. Additional material of E. varians is identified and illustrated, expanding the known distribution of the species. E. unimacula (Lane), n.com. is redescribed based on the female holotype and illustrated, and formally transferred to Euricrium. A key for the Neotropical species of Euricrium is presented and comments are made on the known diversity of the genus.
Assuntos
Dípteros , Distribuição Animal , Animais , Brasil , FemininoRESUMO
The objective of this work was to develop an image reconstruction algorithm for 2D dosimetry using Al2O3:C and Al2O3:C,Mg optically stimulated luminescence (OSL) films imaged using a laser scanning system. The algorithm takes into account parameters associated with detector properties and the readout system. Pieces of Al2O3:C films (~8 mm × 8 mm × 125 µm) were irradiated and used to simulate dose distributions with extreme dose gradients (zero and non-zero dose regions). The OSLD film pieces were scanned using a custom-built laser-scanning OSL reader and the data obtained were used to develop and demonstrate a dose reconstruction algorithm. The algorithm includes corrections for: (a) galvo hysteresis, (b) photomultiplier tube (PMT) linearity, (c) phosphorescence, (d) 'pixel bleeding' caused by the 35 ms luminescence lifetime of F-centers in Al2O3, (e) geometrical distortion inherent to Galvo scanning system, and (f) position dependence of the light collection efficiency. The algorithm was also applied to 6.0 cm × 6.0 cm × 125 µm or 10.0 cm × 10.0 cm × 125 µm Al2O3:C and Al2O3:C,Mg films exposed to megavoltage x-rays (6 MV) and 12C beams (430 MeV u-1). The results obtained using pieces of irradiated films show the ability of the image reconstruction algorithm to correct for pixel bleeding even in the presence of extremely sharp dose gradients. Corrections for geometric distortion and position dependence of light collection efficiency were shown to minimize characteristic limitations of this system design. We also exemplify the application of the algorithm to more clinically relevant 6 MV x-ray beam and a 12C pencil beam, demonstrating the potential for small field dosimetry. The image reconstruction algorithm described here provides the foundation for laser-scanned OSL applied to 2D dosimetry.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Magnésio/química , Dosimetria por Luminescência Estimulada Opticamente/métodos , Algoritmos , Óxido de Alumínio/química , Carbono/química , Lasers , Dosimetria por Luminescência Estimulada Opticamente/instrumentaçãoRESUMO
This work evaluates the dosimetric properties of newly developed optically stimulated luminescence (OSL) films, fabricated with either Al2O3:C or Al2O3:C,Mg, using a prototype laser scanning reader, a developed image reconstruction algorithm, and a 6 MV therapeutic photon beam. Packages containing OSL films (Al2O3:C and Al2O3:C,Mg) and a radiochromic film (Gafchromic EBT3) were irradiated using a 6 MV photon beam using different doses, field sizes, with and without wedge filter. Dependence on film orientation of the OSL system was also tested. Diode-array (MapCHECK) and ionization chamber measurements were performed for comparison. The OSLD film doses agreed with the MapCHECK and ionization chamber data within the experimental uncertainties (<2% at 1.5 Gy). The system background and minimum detectable dose (MDD) were <0.5 mGy, and the dose response was approximately linear from the MDD up to a few grays (the linearity correction was <10% up to ~2-4 Gy), with no saturation up to 30 Gy. The dose profiles agreed with those obtained using EBT3 films (analyzed using the triple channel method) in the high dose regions of the images. In the low dose regions, the dose profiles from the OSLD films were more reproducible than those from the EBT3 films. We also demonstrated that the OSL film data are independent on scan orientation and field size over the investigated range. The results demonstrate the potential of OSLD films for 2D dosimetry, particularly for the characterization of small fields, due to their wide dynamic range, linear response, resolution and dosimetric properties. The negligible background and potential simple calibration make these OSLD films suitable for remote audits. The characterization presented here may motivate further commercial development of a 2D dosimetry system based on the OSL from Al2O3:C or Al2O3:C,Mg.
Assuntos
Algoritmos , Óxido de Alumínio/química , Dosimetria Fotográfica/instrumentação , Medições Luminescentes/instrumentação , Óptica e Fotônica , Calibragem , Relação Dose-Resposta à Radiação , Dosimetria Fotográfica/métodosRESUMO
Ewing's Sarcoma (ES), the second most frequent bone tumor in childhood and adolescence, and the probably closely related peripheral primitive neuroectodermal tumor (pPNET) share a unique cytogenetic translocation between chromosomes 11 and 22. Both of them expose high amounts of a glycoprotein on their cell surface, which can be specifically detected by the mAb HBA-71. The cDNA coding for the HBA-71 antigen was isolated by screening a cDNA expression library constructed from a pPNET-derived cell line. Nucleotide sequencing revealed the HBA-71 antigen to be the product of the pseudoautosomal gene MIC2 previously identified by the mAb 12E7 in haematopoietic cells. This antigen is a glycoprotein with a molecular weight of about 29,000 and is expressed in low amounts in most human cell lines and probably normal tissues and tumors with only a few exceptions. In T-cells the antigen is involved in cell adhesion processes. In ES- and pPNET-derived cell lines MIC2 expression is significantly enhanced. No gross changes in posttranslational modification could be observed. The high expression results in easy and specific detection of the antigen in immunocytochemical analysis of paraffin embedded tissue sections making HBA-71 a useful tool in tumor diagnosis.
Assuntos
Antígenos CD , Antígenos de Neoplasias/genética , Moléculas de Adesão Celular/genética , Glicoproteínas de Membrana/metabolismo , Sarcoma de Ewing/genética , Antígeno 12E7 , Anticorpos Monoclonais/imunologia , Western Blotting , DNA/genética , Epitopos , Expressão Gênica , Humanos , Glicoproteínas de Membrana/genética , Peso Molecular , RNA Mensageiro/genética , RNA Neoplásico/genéticaRESUMO
Rab3A and rab3C are GTP-binding proteins of synaptic vesicles that regulate vesicle exocytosis. Rabphilin is a candidate rab3 effector at the synapse because it binds to rab3s in a GTP-dependent manner, it is co-localized with rab3s on synaptic vesicles, and it dissociates with rab3s from the vesicles during exocytosis. Rabphilin contains two C(2) domains, which could function as Ca(2+) sensors in exocytosis and is phosphorylated as a function of stimulation. However, it is unknown what essential function, if any, rabphilin performs. One controversial question regards the respective roles of rab3s and rabphilin in localizing each other to synaptic vesicles: although rabphilin is mislocalized in rab3A knock-out mice, purified synaptic vesicles were shown to require rabphilin for binding of rab3A but not rab3A for binding of rabphilin. To test whether rabphilin is involved in localizing rab3s to synaptic vesicles and to explore the functions of rabphilin in regulating exocytosis, we have now analyzed knock-out mice for rabphilin. Mice that lack rabphilin are viable and fertile without obvious physiological impairments. In rabphilin-deficient mice, rab3A is targeted to synaptic vesicles normally, whereas in rab3A-deficient mice, rabphilin transport to synapses is impaired. These results show that rabphilin binds to vesicles via rab3s, consistent with an effector function of rabphilin for a synaptic rab3-signal. Surprisingly, however, no abnormalities in synaptic transmission or plasticity were observed in rabphilin-deficient mice; synaptic properties that are impaired in rab3A knock-out mice were unchanged in rabphilin knock-out mice. Our data thus demonstrate that rabphilin is endowed with the properties of a rab3 effector but is not essential for the regulatory functions of rab3 in synaptic transmission.
Assuntos
Encéfalo/fisiologia , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Neurotransmissores/metabolismo , Vesículas Sinápticas/fisiologia , Proteínas rab de Ligação ao GTP , Proteínas Adaptadoras de Transdução de Sinal , Animais , Córtex Cerebral/fisiologia , Clonagem Molecular , Primers do DNA , Exocitose , Proteínas de Ligação ao GTP/deficiência , Proteínas de Ligação ao GTP/genética , Camundongos , Camundongos Knockout , Modelos Neurológicos , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Plasticidade Neuronal , Reação em Cadeia da Polimerase , Mapeamento por Restrição , Frações Subcelulares/fisiologia , Sinapses/fisiologia , Proteínas de Transporte Vesicular , Proteínas rab3 de Ligação ao GTP , Rabfilina-3ARESUMO
BACKGROUND: The high incidence of aortic disease in subjects with congenital aortic valve malformations suggests a causative relationship between these 2 conditions. The histological observation in aortic dilatation/aneurysm/dissection is Erdheim cystic medial necrosis (CMN), a noninflammatory loss of smooth muscle cells (SMCs), fragmentation of elastic fibers, and mucoid degeneration. METHODS AND RESULTS: To examine whether apoptosis is 1 of the mechanisms underlying CMN and aortic medial layer SMC loss, ascending aortic wall specimens from 32 patients were collected at cardiothoracic surgery and examined by histochemical staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling. From echocardiography results, 4 groups of patients were identified: bicuspid valve carriers with (bi/dil) or without (bi/0) aortic dilatation and tricuspid valve carriers with (tri/dil) or without (tri/0) aortic dilatation. Massive focal apoptosis was observed in the medial layers of bi/dil (mean apoptotic index [mAI], 8.1+/-6.0) and tri/dil (mAI, 8.1+/-8.3) compared with tri/0 (mAI, 0.9+/-1.2; P=0.0079 and P=0.037). In bi/0 (mAI, 9.1+/-5.7) compared with tri/0 (mAI, 0.9+/-1.2), rates of medial SMC apoptosis were increased (P=0.0025). Bi/dil (mean age, 40. 6+/-15.7 years) were significantly younger than tri/dil (mean age, 56.4+/-12.8 years) undergoing the same operation (P=0.0123). CONCLUSIONS: Premature medial layer SMC apoptosis could be part of a genetic program underlying aortic disease in patients with aortic valve malformations.
Assuntos
Aorta Torácica/anormalidades , Aorta Torácica/patologia , Valva Aórtica/anormalidades , Cardiopatias Congênitas/complicações , Adolescente , Adulto , Idoso , Aorta Torácica/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Apoptose , Ecocardiografia , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/patologia , NecroseRESUMO
To obtain biodegradable polymers with variable surface properties for tissue culture applications, poly(ethylene glycol) blocks were attached to poly(lactic acid) blocks in a variety of combinations. The resulting poly(D,L-lactic acid)-poly(ethylene glycol)-monomethyl ether (Me.PEG-PLA) diblock copolymers were subject to comprehensive investigations concerning their bulk microstructure and surface properties to evaluate their suitability for drug delivery applications as well as for the manufacture of scaffolds in tissue engineering. Results obtained from 1H-NMR, gel permeation chromatography, wide angle X-ray diffraction and modulated differential scanning calorimetry revealed that the polymer bulk microstructure contains poly(ethylene glycol)-monomethyl ether (Me.PEG) domains segregated from poly(D,L-lactic acid) (PLA) domains varying with the composition of the diblock copolymers. Analysis of the surface of polymer films with atomic force microscopy and X-ray photoelectron spectroscopy indicated that there is a variable amount of Me.PEG chains present on the polymer surface, depending on the polymer composition. It could be shown that the presence of Me.PEG chains in the polymer surface had a suppressive effect on the adsorption of two model peptides (salmon calcitonin and human atrial natriuretic peptide). The possibility to modify polymer bulk microstructure as well as surface properties by variation of the copolymer composition is a prerequisite for their efficient use in the fields of drug delivery and tissue engineering.
Assuntos
Materiais Biocompatíveis , Ácido Láctico/química , Polietilenoglicóis/química , Biodegradação Ambiental , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Propriedades de SuperfícieRESUMO
Rac2, a member of the Rho family of GTPases, is highly expressed in myeloid cells and is a regulator of the NADPH-oxidase complex. A murine genomic clone was isolated that contains the 5' end and putative promoter region of the Rac2 gene. Ribonuclease protection experiments detected 13 transcription initiation sites scattered 50 to 130 bp upstream of the translation initiation site. Transient transfection studies revealed that -7 kb to +31 bp (relative to the strongest transcription initiation site) of the Rac2 gene 5'-flanking region exhibited strong promoter activity in both RAW 264.7 macrophage cells that express the endogenous Rac2 gene and NIH-3T3 fibroblast cells that do not express the endogenous gene. Truncated Rac2 promoter fragments containing as little as the -74 to +31 bp sequence produced full transcriptional activity. However, a -57 to +31 promoter fragment directed significantly less transcription, and a -39 to +31 promoter fragment was transcriptionally inactive. In vitro binding assays revealed sequence-specific and widely expressed DNA-binding activities that interacted within the -74 to -58 Rac2 promoter cis element. Oligonucleotide competition and antibody disruption studies indicated that these complexes contained the transcription factors Spl and Sp3. Specific ablation of the Sp1/Sp3 binding site significantly decreased Rac2 promoter activity in both RAW 264.7 and NIH-3T3 cells. Additional cis elements may be required to restrict Rac2 promoter activity to hematopoietic cells expressing the endogenous gene.
Assuntos
GTP Fosfo-Hidrolases/genética , Proteínas de Ligação ao GTP/genética , Regiões Promotoras Genéticas , Células 3T3 , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular , DNA/genética , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação ao GTP/fisiologia , Expressão Gênica , Regulação da Expressão Gênica , Genes Reporter/genética , Células HeLa , Humanos , Células Jurkat , Células K562 , Luciferases/genética , Camundongos , Dados de Sequência Molecular , Ligação Proteica , Proteínas Recombinantes de Fusão/genética , Transcrição Gênica , Transfecção , Proteínas rac de Ligação ao GTPRESUMO
Allelotypes (TP53, AFM051xd10 and alu-i1) in normal DNA and in DNA from paraffin-embedded tumours of a patient with a p53 germ-line mutation were compared in order to demonstrate LOH. Microdissection was applied in order to overcome difficulties with the interpretation of LOH data from a pelvic recurrence of a primary malignant histiocytoma. Furthermore, a rapid and simple boiling method was developed in order to reduce the loss of DNA usually occurring during traditional methods for DNA extraction. The conclusion drawn is that it is of utmost importance to use highly enriched fractions of tumour cells when performing LOH-studies. It is also shown that a rapid and simple boiling procedure is sufficient to release enough DNA of microdissection-enriched tumour cells for microsatellite analysis by PCR to detect allelic imbalance.
Assuntos
Alelos , DNA de Neoplasias/análise , Deleção de Genes , Histiocitoma Fibroso Benigno/genética , Sequência de Bases , DNA/análise , DNA/genética , DNA de Neoplasias/genética , Dissecação , Éxons , Genes p53 , Heterozigoto , Histiocitoma Fibroso Benigno/química , Histiocitoma Fibroso Benigno/patologia , Humanos , Linfócitos/química , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Inclusão em Parafina , Polimorfismo Genético , Valores de ReferênciaRESUMO
Meta-tetrahydroxyphenylchlorin (mTHPC) exhibits significant cytotoxicity against a variety of human cells in culture in combination with light, but also in dark reaction. The ovarian cancer cell line SK-OV3 was incubated with various concentrations of mTHPC and in comparison with Taxol and Cisplatin: then the effect on cell growth was determined. mTHPC exhibited an IC50 of 0.9 muM after 24 hours incubation (IC50 of 1.25 after 2 hours), whereas Cisplatin and Taxol, which, have been used as first line agents for the treatment of ovarian carcinomas, inhibited cell proliferation with an IC50 concentration of 4.6 muM and 78 nM after 24 hours incubation, respectively. Incubation of SK-OV3 cells with mTHPC for 5 days resulted in cytostatic cytotoxicity at a concentration of 0.5 muM. The photodynamic effect of mTHPC depends/among other parameters/on the concentration of the dye present. In combination with light (approximately 15 J/cm2) a linear relationship between the dose of mTHPC and the amount of necrotic cells was observable. Higher concentrations of mTHPC caused necrosis of the ovarian tumor cells. The intracellular concentration of mTHPC showed a linear increase up to 28.6 nM (incubation concentration). In summary, these studies demonstrated that mTHPC exhibits potent antiproliferative activity by inducing necrosis after application of light. MTHPC might be a promising agent with cytostatic and photodynamic properties for the treatment of metastasing ovarian carcinomas. A sensitive PCR method was not able to show the induction of apoptosis in the SK-OV3 ovarian cell line. Using propidium staining, it could be proved that the cell death was caused by necrosis and not through apoptosis after irradiation with light.
Assuntos
Antineoplásicos/farmacologia , Mesoporfirinas/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Fotoquimioterapia , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Feminino , Humanos , Mesoporfirinas/farmacocinética , Necrose , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Células Tumorais CultivadasRESUMO
Myotonic dystrophy (DM) is the most common adult muscular dystrophy and follows an autosomal dominant pattern of inheritance. Up to now, the clinical diagnosis of DM was based on symptoms presented such as encephalopathy, facies myopathica, paresthesia, atrophy, myotonia, mental retardation, cataract, diabetes, cardiac conduction defects and electromyography. Since 1991 the specific molecular defect in DM is known and a respective diagnosis is possible. The mutation responsible for DM is the expansion of an unstable trinucleotide repeat, (CTG)n, in the 3'-untranslated region of the myotonin protein kinase gene. It is now generally accepted that the CTG repeat length correlates with the clinical category and the age at onset of the disease; therefore genetic tests are essential in monitoring and management of DM-patients and their family members. Based on the average incidence in Europe about 1000 affected individuals can be expected in Austria, a high percentage of whom is, however, not recognized as carries of the DM-mutation. After having established a genetic diagnosis in Austria allowing the detection of this mutation in DM-patients and their relatives, improvement of the diagnostic procedure should be possible.
Assuntos
Distrofia Miotônica/genética , Adulto , Áustria/epidemiologia , Aberrações Cromossômicas , Transtornos Cromossômicos , DNA , Humanos , Biologia Molecular , Distrofia Miotônica/enzimologia , Distrofia Miotônica/epidemiologia , Linhagem , Proteínas Quinases/metabolismo , Repetições de TrinucleotídeosRESUMO
In the mammalian hippocampus, neurogenesis persists into adulthood, and increased generation of newborn neurons could be of clinical benefit following concussive head injuries. Post-traumatic neurogenesis has been well documented using "open" traumatic brain injury (TBI) models in rodents; however, human TBI most commonly involves closed head injury. Here we used a closed head injury (CHI) model to examine post-traumatic hippocampal neurogenesis in mice. All mice were subjected to the same CHI protocol, and a gross-motor based injury severity score was used to characterize neurologic impairment 1h after the injury. When analyzed 2weeks later, post-traumatic neurogenesis was significantly increased only in mice with a high degree of transient neurologic impairment immediately after injury. This increase was associated with an early increase in c-fos activity, and subsequent reactive astrocytosis and microglial activation in the dentate gyrus. Our results demonstrate that the initial degree of neurologic impairment after closed head injury predicts the induction of secondary physiologic and pathophysiologic processes, and that animals with severe neurologic impairment early after injury manifest an increase in post-traumatic neurogenesis in the absence of gross anatomic pathology.
Assuntos
Giro Denteado/fisiopatologia , Regulação da Expressão Gênica/fisiologia , Traumatismos Cranianos Fechados/complicações , Traumatismos Cranianos Fechados/patologia , Doenças do Sistema Nervoso/etiologia , Neurogênese/fisiologia , Animais , Bromodesoxiuridina/metabolismo , Giro Denteado/patologia , Modelos Animais de Doenças , Proteínas do Domínio Duplacortina , Feminino , Galectina 3/metabolismo , Regulação da Expressão Gênica/genética , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/metabolismo , Neuropeptídeos/metabolismo , Pró-Opiomelanocortina/genética , Proteínas Proto-Oncogênicas c-fos/metabolismoRESUMO
PURPOSE: To benchmark the quality of Monte Carlo simulation results with the commissioning data for a Varian TrueBeam accelerator. METHODS: IAEA phase space files of a 6MV TrueBeam accelerator provided by Varian were implemented using GEANT4 Monte Carlo code. The present application consisted of upper and lower jaws and a cubic water phantom of 0.125 cubic meters in volume. Both radial and transverse dose profiles (in 5 different depths) and a central axis percentage depth dose (PDD) curve were recorded in the phantom. Field sizes of as small as 4×4 cm2 and as large as 30×30 cm2 were simulated with 2.0E9 incident particles each. The results were then compared with our commissioning data performed in a Wellhoffer Blue Phantom with a 0.13cc ion-chamber and a 0.8×0.8mm diode. RESULTS: The GEANT4 simulated PDD curve compared favorably within â¼2% against the measured ion-chamber PDD for all field sizes and against the measured diode PDD for all fields less then 20×20cm2 . The simulated in-plane and cross-plane profiles compared well within 2 mm at the 50% level against the measured profiles for all field sizes. CONCLUSIONS: These results demonstrate the feasibility of utilizing Monte-Carlo simulated beam data in the commissioning of a linear accelerator. The increasing speed and capability of the desktop computer will Result in the adoption of Monte- Carlo techniques for dosimetric calculations.
RESUMO
PURPOSE: This study aims to evaluate treatment plans generated by Step- and-Shoot (SS), Sliding Window (SW) and Volumetric Modulated Arc Therapy (VMAT) in order to assess the differences in dose volume histograms of planning target volume (PTV) and organs at risk (OAR), conformity indices, radiobiological evaluations, and plan quality for prostate cancer cases. METHODS: Six prostate cancer patients treated in our center were selected for this retrospective study. Treatment plans were generated with Eclipse version 8.9 using 10 MV photon beams. For VMAT, Varian Rapid Arc with 1 or 2 arcs, and for SS and SW IMRT, 7-9 fields were used. Each plan had three PTVs with prescription doses of 81, 59.4, and 45 Gy to prostate, to prostate and lymph nodes, and to pelvis, respectively. Doses to PTV and OAR and the conformal indices (COIN) were compared among three techniques. The equivalent uniform dose (EUD), tumor control probability (TCP) and normal tissue complication probability (NTCP) was also calculated and compared. RESULTS: The mean doses to the PTV prostate on average were 83 Gy and the percent differences of mean dose among all techniques were below 0.28. For bladder and rectum, the percent differences of mean dose among all techniques were below 2.2. The COIN did not favour any particular delivery method over the other. The TCP was higher with SS and SW for four patients and higher with VMAT for two patients. The NTCP for the rectum was the lowest with VMAT in all patients except one. CONCLUSIONS: Preliminary data shows similar target coverage in general. We will extend our study to include 15 patients to compare different approaches with statistics. We will attempt to define characteristics predictive of the superior delivery technique.