RESUMO
Phosphine metal-organic frameworks (P-MOFs) are crystalline porous coordination polymers that contain phosphorus functional groups within their pores. We present the use of X-ray absorption spectroscopy (XAS) at the P K-edge to determine the phosphine to phosphine oxide ratio in two P-MOFs with MIL-101 topology. The phosphorus oxidation state is of particular interest as it strongly influences the coordination affinity of these materials for transition metals. This method can determine the oxidation state of phosphorus even when the material contains paramagnetic nuclei, differently from NMR spectroscopy. We observed that phosphine in LSK-15 accounts for 72 ± 4% of the total phosphorus groups and that LSK-12 contains only phosphine oxide.
Assuntos
Compostos Organometálicos/química , Fosfinas/química , Espectroscopia por Absorção de Raios X , Espectroscopia de Ressonância Magnética , Óxidos/química , Fósforo/química , Polímeros/química , Porosidade , Difração de Raios XRESUMO
BACKGROUND: Falling is the leading cause of accidental death after 65. Fall prevention programs are effective, but they involve few seniors. This article reviewed the literature on facilitators and barriers to participate in such programs. METHODS: A literature review was conducted to identify documents in English, German and French published between 1990 and May 2012. Medline database, PsychInfo, Psychological and behavioral sciences and Francis were systematically searched, as were the bibliographies and some journals of public health, gerontology and social sciences. Of 462 documents found, 19 were selected and analyzed. RESULTS: Of the 19 articles selected, 12 were on qualitative studies and 7 on literature reviews. Among the barriers to participation in falls prevention programs, documents highlighted the perception of fall as an inevitable event, the inadequate timing of prevention intervention and material difficulties. Conversely, being referred to prevention intervention by a professional, being convinced by the social benefits of interventions and the adequacy of interventions to the needs of beneficiaries were factors facilitating the participation and compliance of the elderly. CONCLUSION: This literature review identified three major issues to consider when implementing sustainable and acceptable fall prevention programs: choice of the referring agent, and social representations of falling.
Assuntos
Acidentes por Quedas/prevenção & controle , Acessibilidade aos Serviços de Saúde , Idoso , HumanosRESUMO
This communication reports the first observation of the formation of HOË produced under two different High energy ion beams, (18)O(8+) and (36)Ar(18+) having Linear Energy Transfers (LET) of 65 and 350 eV nm(-1) respectively, at temperatures up to 411 K. Both scavenging with various concentrations of SCN(-) and heavy-ion pulse radiolysis methods are used with an original temperature and pressure regulated optical cell. Deconvolution of kinetics is used to analyze the evolution of HOË track segment yields as a function of time and temperature. It takes care of involving the ionic strength effect and Arrhenius expression in the rate constants correction. The results show a fast decay of HOË yields in the 10(-10)-10(-8) s range which denotes an efficient reactivity of this species in the track structure of the ion beam. This effect is enhanced with the lowest LET of O(8+). Increasing the temperature also accelerates the decays for both ions. These observations are discussed in terms of temperature activation of reactions and the track structure exhibiting the formation of HOË in a "low LET" penumbra around the ionization tracks. HOË track segment yields at 100 ns, of 0.4 × 10(-7) and 0.6 × 10(-7) mol J(-1), respectively for 350 and 65 eV nm(-1), are not affected by temperature.
RESUMO
Solutions containing 8 and 32 wt% myoglobin are studied by means of infrared spectroscopy, as a function of temperature (290 K and lower temperatures), in the mid- and far-infrared spectral range. Moreover, ultrafast time-resolved infrared measurements are performed at ambient temperature in the O-D stretching region. The results evidence that the vibrational properties of water remain the same in these myoglobin solutions (anharmonicity, vibrational relaxation lifetime ) and in neat water. However, the collective properties of the water molecules are significantly affected by the presence of the protein: the orientational time increases, the solid-liquid transition is affected in the most concentrated solution and the dynamical transition of the protein is observed, from the point of view of water, even in the least concentrated solution, proving that the water and myoglobin dynamics are coupled.
Assuntos
Mioglobina/química , Água/química , Espectroscopia de Infravermelho com Transformada de Fourier , TemperaturaRESUMO
Sulfur K-edge X-ray absorption spectroscopy (XAS) has been used to distinguish between aqueous and solid sulfates and to investigate changes in their speciation. Data have been collected for tetrahedrally coordinated S in K2SO4 and KHSO4 solids and aqueous solutions. With a first qualitative analysis of the X-ray absorption near-edge structure (XANES) spectra, it has been observed that those for solids are much more structured and distinguishable from those of aqueous solutions. The protonation state has a strong effect on the white line of sulfates and has been assigned to the different charge delocalization in the samples, the effect of the solvating water molecules and multiple scattering effects. In the extended X-ray absorption fine structure (EXAFS) spectra, the backscattering from the first O shell dominated the EXAFS fine structure function, χ(k), but the nonlinear multiple scattering contributions occurring in the first coordination shell are significant and must be considered in the EXAFS analysis. The intensity of these contributions strongly depend on the symmetry of the system. For a distorted tetrahedron, the intensity of the multiple scattering contributions is less than that found in a regular tetrahedron. The FEFF code has been used to model the contributions of the multiple-scattering processes. The observed experimental evidence in the XAS data can be used to distinguish between sulfates in solids and liquids. This is applicable to many chemical, geochemical, and biological systems.
RESUMO
The infrared spectra of water confined in well controlled pore glasses were recorded as a function of the pore size ranging from 8 to 320 nm and in the 30-4000 cm(-1) spectral range using the ATR technique. The experiments prove that even in the large pores, the water network is significantly perturbed. The energy of the connectivity (or hindered translation) band (around 150 cm(-1)) is found to increase when the pore size decreases, indicating that confinement increases the H-bonding between neighbouring water molecules. Moreover, a drastic decrease of the FWHM of the connectivity band was observed upon confinement. This can be related to some ordering induced by the rigid walls of the pores. Furthermore, the partial filling of pores causes a significant modification to the water network, resembling heating of the trapped liquid and suggesting a role played by the water/air interface.
Assuntos
Nanoestruturas/química , Água/química , Tamanho da Partícula , Porosidade , Espectrofotometria Infravermelho , Propriedades de SuperfícieRESUMO
Background: Venous thromboembolism (vte) in malignancy is associated with poor outcomes. We conducted a retrospective review of vte in patients with endometrial cancer to characterize the vte incidence, identify factors that contribute to vte risk, and compare survival outcomes in patients with and without vte. Methods: A retrospective chart review identified 422 eligible patients who underwent surgery for endometrial cancer (1 January 2014 to 31 July 2016). The primary outcome was vte. Binary logistic regression identified risk factors for vte; significant risk factors were included in a multivariate analysis. Kaplan-Meier estimates are reported, and log rank tests were used to compare the Kaplan-Meier curves. Risk-adjusted estimates for overall survival based on vte were determined using a multivariate Cox proportional hazards model. Results: The incidence of vte was 6.16% overall and 0.7% within 60 days postoperatively. Non-endometrioid histology, stages 3 and 4 disease, laparotomy, and age (p < 0.1) were identified as factors associated with vte and were included in a multivariate analysis. The overall death rate in patients with vte was 42% (9% without vte): hazard ratio, 5.63; 95% confidence interval, 2.86 to 11.08; p < 0.0001. Adjusting for age, stage of disease, and histology, risk of death remained significant for patients with a vte: hazard ratio, 2.20; 95% confidence interval, 1.09 to 4.42; p = 0.0271. Conclusions: A method to identify patients with endometrial cancer who are at high risk for vte is important, given the implications of vte for patient outcomes and the frequency of endometrial cancer diagnoses. Factors identified in our study might assist in the recognition of such patients.
Assuntos
Neoplasias do Endométrio/complicações , Tromboembolia Venosa/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Hesperetin is a natural compound known for its cholesterol-lowering effect and a wide range of pharmacological activities. OBJECTIVES: Investigating the potential anticancer activities of Hesperetin in malignant hematolymphoid cell lines HuT78 and MJ, derived from patients with Cutaneous T-Cell Lymphomas (CTCL). METHODS: The cytotoxic effect of Hesperetin on two different CTCL cell lines, HuT78 and MJ, was assessed by MTS-based colorimetric assay. Apoptosis, cell cycle, ROS (Reactive Oxygen Species) and molecular analysis were performed using flow-cytometry and immunoblotting. RESULTS: Hesperetin-treated CTCL cells were arrested at the sub-G1 phase of cell cycle with the concomitant decrease in the expression of the cell cycle regulator protein cyclin B. In addition, the study found that the cellular treatment with Hesperetin caused an induction of apoptosis, which was independent of ROS generation. Hesperetin caused a significant decrease in the expression level of anti-apoptotic protein Bcl-xL and an increase in cleaved caspase-3 and PARP proteins in CTCL cells. Furthermore, Hesperetin treatment in CTCL cells down-regulated the expression of Notch1 and phosphorylation of STAT3 (Tyr705) and inhibited NFκBp65. CONCLUSION: This study highlights the anticancer properties of Hesperetin. Which induces apoptosis in CTCL cells via STAT3/Notch1/NFκB mediated signaling pathway, suggesting that further development of this novel class of flavonoid may contribute to new drug discovery for certain hematolymphoid malignancies.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Citrus/química , Hesperidina/farmacologia , NF-kappa B/antagonistas & inibidores , Receptor Notch1/antagonistas & inibidores , Fator de Transcrição STAT3/antagonistas & inibidores , Antineoplásicos Fitogênicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Hesperidina/química , Humanos , Estrutura Molecular , NF-kappa B/metabolismo , Receptor Notch1/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
We used small-angle neutron scattering to study the effects of the high hydrostatic pressure on the structure of beta-lactoglobulin. Experiments were carried out at pH 7 on the dimeric form of the protein in a pressure range going from 50 MPa to 300 MPa. These measurements allow the protein size and the interactions between macromolecules to be studied during the application of pressure. Increasing pressure up to 150 MPa leads to a swollen state of the protein that gives rise to an increase of the radius of gyration by about 7%. Within this pressure range, we also show that the interaction between macromolecules weakens although it remains repulsive. The measurements show an aggregation process occurring above 150 MPa. From the spectra analysis, it appears that the aggregation occurs mainly by association of the dimeric units.
Assuntos
Lactoglobulinas/química , Animais , Bovinos , Dimerização , Concentração de Íons de Hidrogênio , Pressão Hidrostática , Difração de Nêutrons , Dobramento de Proteína , Espalhamento de RadiaçãoRESUMO
The KAI1 gene, located on human chromosome 11p11.2, suppresses tumor metastasis when expressed in certain cancer cells. To evaluate whether dysregulation of KAI1 occurs during the progression of human prostatic cancer, protein expression, mutation, and allelic loss of KAI1 were analyzed using a tissue bank of 98 primary cancers and 32 metastases. By immunohistochemical staining, high levels of KAI1 protein are detected in the epithelial but not stromal compartment of normal prostatic and benign prostatic hyperplasia tissue. In epithelial cells, KAI1 protein is expressed on the plasma membrane. KAI1 protein expression is downregulated in more than 70% of the 49 primary prostatic cancers from untreated patients. In 10 such untreated patients, down-regulation of KAI1 protein occurred in all of the lymph node metastases examined. In 15 patients with metastatic disease who had failed androgen ablation therapy, more than 90% of the primary prostatic cancers had downregulation, with 60% having no KAI1 protein expression. Primers derived from the sequences flanking each exon of KAI1 were used to analyze KAI1 mutation and allelic loss by the method of PLR-single-strand conformational polymorphism. Using this method, no point mutation or allelic loss was detected in metastases from 10 patients. No allelic loss was detected in an additional 34 primary and 12 lymph node metastases via microsatellite analysis using the marker D11S1344, which is located in the region of KAI1. These results demonstrate that KAI1 protein expression is consistently down-regulated during the progression of human prostatic cancer and that this down-regulation does not commonly involve either mutation or allelic loss of the KAI1 gene.
Assuntos
Antígenos CD , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Glicoproteínas de Membrana , Metástase Neoplásica/genética , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas , Alelos , Cromossomos Humanos Par 11/genética , Análise Mutacional de DNA , DNA de Neoplasias/genética , Epitélio/metabolismo , Humanos , Hibridização In Situ , Proteína Kangai-1 , Metástase Linfática/genética , Masculino , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Próstata/metabolismo , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologiaRESUMO
A newly developed method of comparative genomic hybridization (CGH) employing quantitative statistical comparisons was applied to DNA from two different types of advanced prostate cancer tissue. Multiple CGH analyses were obtained for each chromosome in each tumor, and the results of point-by-point comparison of the mean tumor:normal color ratio to a control normal:normal color ratio in each of 1247 evenly distributed data channels constituting the entire human genome were interpreted as loss, gain, or no change in copy number in the tumor genome. Group I tissue was obtained from prostate cancer metastases from 20 patients, 19 of whom had received no prior prostate cancer treatment. This DNA also was analyzed by Southern and microsatellite allelotyping at 53 different loci on 20 different chromosome arms. CGH results agreed with allelotyping results at 92% of the informative loci studied. These samples, which contained highly enriched tumor DNA, showed the highest rates of alteration yet reported in several chromosomal regions known to be altered frequently in prostate cancer: 8q gain (85%), 8p loss (80%), 13q loss (75%), 16q loss (55%), 17p loss (50%), and 10q loss (50%). Group II tissue was obtained predominately from primary or recurrent tumor from 11 patients who had been treated with long-term androgen-deprivation therapy and developed androgen-independent metastatic disease. Quantitative CGH analysis on DNA from these tissues showed chromosomal alterations that were very similar to those found in group I, suggesting that untreated metastatic tumors contain the bulk of chromosomal alterations necessary for recurrence to occur during androgen deprivation. In the entire data set, a number of previously undetected regions of frequent loss or gain were identified, including losses of chromosomes 2q (42%), 5q (39%), 6q (39%), and 15q (39%) and gains of chromosomes 11p (52%), 1q (52%), 3q (52%), and 2p (45%). Chi-squared analysis showed a significantly higher frequency of gain of the 4q25-q28 region in tumors from African-American patients, indicating a possible oncogene whose activation may play a role in the higher rate of progression seen in this ethnic group. Additional study of these frequently altered regions may provide insight into the mechanism of prostate cancer progression and lead to important tools for tumor-specific prognosis and therapy.
Assuntos
Alelos , Androgênios , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Aberrações Cromossômicas , DNA de Neoplasias/genética , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/secundário , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Southern Blotting , DNA de Neoplasias/análise , Genoma Humano , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , Neoplasias da Próstata/patologia , Reprodutibilidade dos TestesRESUMO
To clarify the processes of hemeproteins reduction, three classes of these proteins (ferric, ferrous and desFe) were reduced by hydrated electrons generated by pulse radiolysis. Spectral and kinetic investigations were made on alpha hemoglobin chain and myoglobin. Human alpha chain has been chosen to avoid all ferric contaminations and horse ferric myoglobin to eliminate all ferrous protein fractions. We have successively studied the influences of: the iron presence, its oxidation state (II and III), the protein charge and the iron-ligand nature (H2O, OH-, N3- and CN-). For alpha human hemoglobin chain without metallic ion or with ferrous iron, the reduction rates are the same: 1.1 +/- 0.2.10(10) M-1.s-1. In the case of horse ferric myoglobin, the reduction rates depend principally on the protein charge (from pH 6.3 to pH 9.5, the reduction rate of Mb(FeIII)N3- decreases from 2.5 +/- 0.5.10(10) M-1.s-1 to 1.2 +/- 0.2.10(10) M-1.s-1) and are also modulated by the equilibrium constant of the hemeprotein-ligand association (1.2 +/- 0.2.10(10) M-1.s-1 for Mb(FeIII)N3- and 0.8 +/- 0.2.10(10) M-1.s-1 for Mb(FeIII)CN-, at pH 9.8).
Assuntos
Elétrons , Compostos Férricos , Compostos Ferrosos , Hemeproteínas , Fenômenos Químicos , Físico-Química , Globinas , Concentração de Íons de Hidrogênio , Cinética , Metamioglobina/análogos & derivados , Mioglobina , Oxirredução , Radiólise de Impulso , EspectrofotometriaRESUMO
Bacteriophage T4 lysozyme is a basic molecule with an isoelectric point above 9.0, and an excess of nine positive charges at neutral pH. It might be expected that it would be energetically costly to bring these out-of-balance charges from the extended, unfolded, form of the protein into the compact folded state. To determine the contribution of such long-range electrostatic interactions to the stability of the protein, five positively charged surface residues, Lys16, Arg119, Lys135, Lys147 and Arg154, were individually replaced with glutamic acid. Eight selected double, triple and quadruple mutants were also constructed so as to sequentially reduce the out-of-balance formal charge on the molecule from +9 to +1 units. Each of the five single variant proteins was crystallized and high-resolution X-ray analysis confirmed that each mutant structure was, in general, very similar to the wild-type. In the case of R154E, however, the Arg154 to Glu replacement caused a rearrangement in which Asp127 replaced Glu128 as the capping residue of a nearby alpha-helix. The thermal stabilities of all 13 variant proteins were found to be fairly similar, ranging from 0.5 kcal/mol more stable than wild-type to 1.7 kcal/mol less stable than wild-type. In the case of the five single charge-change variants, for which the structures were determined, the changes in stability can be rationalized in terms of changes in local interactions at the site of the replacement. There is no evidence that the reduction in the out-of-balance charge on the molecule increases the stability of the folded relative to the unfolded form, either at pH 2.8 or at pH 5.3. This indicates that long-range electrostatic interactions between the substituted amino acid residues and other charged groups on the surface of the molecule are weak or non-existent. Furthermore, the relative stabilities of the multiple charge replacement mutant proteins were found to be almost exactly equal to the sums of the relative stabilities of the constituent single mutant proteins. This also clearly indicates that the electrostatic interactions between the replaced charges are negligibly small. The activities of the charge-change mutant lysozymes, as measured by the rate of hydrolysis of cell wall suspensions, are essentially equal to that of the wild-type lysozyme, but on a lysoplate assay the mutant enzymes appear to have higher activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Muramidase/química , Fagos T/enzimologia , Arginina/química , Eletroquímica , Estabilidade Enzimática , Ligação de Hidrogênio , Lisina/química , Modelos Moleculares , Muramidase/genética , Muramidase/metabolismo , Mutagênese Sítio-Dirigida , Fagos T/genética , Temperatura , Difração de Raios XRESUMO
OBJECTIVES: To evaluate the perinatal results of infants born between 23 and 25.6 weeks of gestation. METHODS: Medical charts of all women giving birth prematurely (23-25.6 w) from January 2005 to December 2011 were retrospectively reviewed. Cases of malformed infants or deliveries elsewhere were excluded. RESULTS: 198 infants were included. Chorioamnionitis occurred in 86 (43.4%) of the whole group: 26 (86.7%) in the 23-week; 35 (53.8%) in the 24-week and 25 (24.3%) in the 25-week groups. Foetal maturation with antenatal corticosteroids was complete in 119 cases (60.1%): 4 (13.3%) in the 23-week; 35 (53.8%) in the 24-week and 80 (77.7%) in the 25-week groups. Foetal death at birth occurred in 22 cases (11%) and 61 newborns (30.8%) died in the neonatal period. Of the 106 survivors with 2 years complete follow-up, 45 infants (42.4%) did not present sequelae; 16 infants (15.1%) had severe sequelae. A 66.6% (4) of infants born at 23 weeks of gestation did not present sequelae compared with a 32.3% (11) at 24 weeks and 45.4% (30) at 25 weeks. CONCLUSIONS: The chorioamnionitis rate was higher when gestational age was lower. The foetal maturation rate was higher when gestational age was higher. A low severe sequelae rate was observed in the whole series, particularly in the 23-week group where the rate was lower than expected; however, these results could have been influenced by the small size of the 23-week group.
Assuntos
Corticosteroides/uso terapêutico , Maturidade dos Órgãos Fetais/efeitos dos fármacos , Idade Gestacional , Lactente Extremamente Prematuro , Resultado da Gravidez , Corticosteroides/administração & dosagem , Adulto , Peso ao Nascer , Corioamnionite/epidemiologia , Feminino , Morte Fetal , Seguimentos , Humanos , Recém-Nascido , Terapia Intensiva Neonatal/estatística & dados numéricos , Pulmão/embriologia , Morte Perinatal , Gravidez , Estudos RetrospectivosRESUMO
The strong variation of ligand-binding properties with pH for carp hemoglobin is not reflected in the electronic distribution of the heme-iron. Thus, we can suppose that hemoglobin affinity is directly controlled by the protein and by some particular changes of the iron atom.
Assuntos
Hemoglobinas , Regulação Alostérica , Animais , Carpas , Concentração de Íons de Hidrogênio , Ferro , Ligantes , Análise Espectral/métodos , Raios XRESUMO
Spin states equilibrium of hemoglobin-iron varies with external conditions: pH, allosteric effectors, temperature. The small electronic reorganization of the iron caused by the spin state changes has been detected by X-ray absorption near edge structure (XANES) spectroscopy at room temperature. The iron K-edge region which is sensitive to spin state is located in 7110-7130 eV. Here are presented the 100% high spin and 100% low spin XANES spectra of carp azido ferric hemoglobin.
Assuntos
Metemoglobina/análogos & derivados , Animais , Carpas , Espectrometria por Raios XRESUMO
Prostate intraepithelial neoplasia (PIN) is a purported prostate cancer precursor lesion and a candidate biomarker for efficacy assessment in prostate cancer chemoprevention trials. Loss of expression of the pi-class glutathione S-transferase enzyme GSTP1, which is associated with the hypermethylation of deoxycytidine residues in the 5'-regulatory CG island region of the GSTP1 gene, is a near-universal finding in human prostate cancer. GSTP1 expression was assessed by immunohistochemistry in 60 high-grade PIN samples adjacent to and distant from prostate adenocarcinoma. Whereas abundant enzyme polypeptide expression was evident in all normal prostatic tissues, all samples of high-grade PIN and adenocarcinoma were completely devoid of GSTP1. DNA from 10 high-grade PIN lesions was analyzed for GSTP1 CG island methylation changes using a PCR technique targeting a polymorphic (ATAAA)n repeat sequence in the promoter region of the GSTP1 gene. Somatic GSTP1 CG island methylation changes were detected in DNA from 7 of the 10 PIN lesions. Allele discrimination was possible for 5 of the 10 DNA samples: 2 of the 5 samples exhibited DNA methylation changes at both alleles; whereas 3 samples displayed no DNA methylation changes at either allele. GSTP1 CG island methylation changes were present in each of the five homozygous samples. Hypermethylation of the 5'-regulatory region of the GSTP1 gene may serve as an important molecular genetic biomarker for both prostate cancer and PIN. The finding of frequent GSTP1 methylation changes in PIN and prostate cancer supports a role for PIN lesions as a prostate cancer precursor and may provide insight to the molecular pathogenesis of prostate cancer.
Assuntos
Adenocarcinoma/enzimologia , Biomarcadores Tumorais/genética , Glutationa Transferase/genética , Neoplasia Prostática Intraepitelial/enzimologia , Neoplasias da Próstata/enzimologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Metilação de DNA , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Reação em Cadeia da Polimerase , Neoplasia Prostática Intraepitelial/genética , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologiaRESUMO
Astrocytomas and oligodendrogliomas are two brain tumors that follow different clinical courses. Although many of these tumors can be identified based on standard histopathological criteria, a significant percentage present notable problems in diagnosis. To identify markers that might prove useful in distinguishing glioma subtypes, we prepared and analyzed cDNA libraries for differential expression of genes in an astrocytoma (grade II), an oligodendroglioma (grade II), and a meningioma (benign). The tumor libraries were compared by sequencing randomly selected clones and tabulating the expression frequency of each gene. In addition to identifying several genes previously reported or expected to be differentially expressed among these tumors, several potential new brain tumor markers were identified and confirmed by Northern blot analysis of a panel of brain tumors. A surprising result of this analysis was the observation that several larger-sized transcripts for various genes were predominantly expressed in the oligodendroglioma tumors, when compared to the other brain tumors or in non-tumor gray matter. These findings are consistent with different pre-mRNA splicing patterns observed between oligodendrogliomas and astrocytomas. In support of this hypothesis, our screen revealed significantly higher levels of two hnRNP A1 transcripts in oligodendrogliomas. hnRNP A1 is a component of the spliceosome whose expression levels affect splice site selection in vivo. The preferential expression of larger-sized transcripts for several genes in oligodendrogliomas may be useful for distinguishing astrocytic and oligodendroglial gliomas.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Glioma/classificação , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B , Oligodendroglioma/genética , Técnica de Subtração , Astrocitoma/genética , Northern Blotting , DNA Complementar/genética , Biblioteca Gênica , Glioma/genética , Ribonucleoproteína Nuclear Heterogênea A1 , Ribonucleoproteínas Nucleares Heterogêneas , Humanos , Peso Molecular , Splicing de RNA/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Ribonucleoproteínas/genética , Análise de Sequência de DNA , Spliceossomos/metabolismoRESUMO
13Carbon monoxide (CO), when bound to hemoglobin, yields (13)C NMR resonances (CO-Fe resonances). 100% CO liganded tetrameric hemoglobin ((13)C-labelled CO) was prepared for (13)C-NMR observation. The information about exchange kinetics between the four subunits (2alpha and 2B), were derived by changing the temperature (in the range 275-313K) and the observation frequency (4.7T, 9.4T and 18.8T). The first results confirmed previous observations of slow exchange between free and bound (2alpha and 2B together) CO. Besides, the exchange between alpha and B subunits were found slow at the NMR timescale, even under 313K and 4.7T conditions. Furthermore, intermediate temperatures (283-303K) allowed the observation of broad unresolved lines at 9.4T, corresponding both to CSA contribution and exchange linebroadening. Finally, low temperatures (less than 277K, at 9.4T) provided four relatively broad - but clearly distinguishable lines - indicating that a slow exchange rate was reached between four Fe-CO geometries on the subunits. This also indicated that two main Fe-CO orientations were different, even between similar chains (alpha1-alpha2 and B1-B2).
Assuntos
Carboxihemoglobina/química , Isótopos de Carbono , Humanos , Ressonância Magnética Nuclear Biomolecular/métodos , Temperatura , TermodinâmicaRESUMO
OBJECTIVE: The aim of this study was to investigate the perception, knowledge, opinions and beliefs about AD in the French population to improve care for patients with Alzheimer's disease. DESIGN: A cross-sectional telephone survey in 2008. SETTING: French "Alzheimer Plan 2008-2012". PARTICIPANTS: 2013 respondents, representative of the French population. MEASUREMENTS: The respondents answered a questionnaire in which they were presented with a series of attitudinal statements about health in general and AD. RESULTS: Main results are summarized as followed: (a) Respondents think that AD can be devastating for a family (93%). This devastating feeling prevails in the population >75 years old and in people who know patient with AD. (b) General population has a reasonable knowledge about AD, but is still unable to recognize early stages: 95% of respondents considered that difficulties to manage administrative papers and find their way back home suggest early AD. (c) 91% of the population would like to know the diagnosis if they had AD. (d) 38% of the population know or have known at least one patient within their social circle. People think that the care of AD's patient can be better but they trust in the French government to improve it. CONCLUSION: General representation of AD is changing in a positive way and, even though AD is perceived as a calamity, people are confident that solutions will be found in the future.