RESUMO
BACKGROUND: Although several instruments have been developed to identify patients with an at-risk mental state (ARMS) for psychosis and first episode of psychosis (FEP), up to now there were no instruments for a detailed assessment of risk factors and indicators of emerging psychosis and the temporal development of psychiatric symptoms over the whole life span in these patients. We therefore developed the Basle Interview for Psychosis (BIP). The aim of this study is to describe the development of the BIP and to report about its psychometric properties. METHODS: The BIP is a comprehensive semi-structured interview that was developed for the Basel early detection of psychoses (FePsy) study. Its items were derived from the most important risk factors and indicators of psychosis described in the literature and from several existing instruments. It contains the following six sections: 1) social and physical development and family, 2) signs and symptoms, 3) vulnerability, 4) help-seeking behavior, 5) illness insight, 6) evaluation of the interview. To estimate the inter-rater reliabilities of the items of sections 2 and 3, 20 interviews were conducted and rated by 8 well-trained raters. The factorial structure of the BIP section "signs and symptoms" was explored in a sample of 120 ARMS and 77 FEP patients. On the basis of the discovered factorial structure, we created new subscales and assessed their reliabilities and validities. RESULTS: Of the 153 studied items of sections 2 and 3, 150 (98â%) were rated with sufficiently high agreement (inter-rater reliability >â0.4). The items of section "signs and symptoms" could be grouped into 5 subscales with predominantly good to very good internal consistencies, homogeneities, and discriminant and convergent validities. Predictive validities could be demonstrated for the subscales "Positive Psychotic Symptoms", "Disturbance of Thinking" and the total score. DISCUSSION: The BIP is the first interview for comprehensively assessing risk factors and indicators of emerging psychosis and the temporal development of psychiatric symptoms over the whole life span, which has been validated in ARMS and FEP patients. We could show that the BIP has excellent psychometric properties.
Assuntos
Entrevista Psicológica/métodos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Adulto , Família , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Aceitação pelo Paciente de Cuidados de Saúde , Psicometria , Reprodutibilidade dos Testes , AutoimagemRESUMO
Air pollution has become a major concern in industrial or highly populated areas. Although legislation has been enacted to limit pollution levels, air quality monitoring still needs to be carried out by stations which are located at fixed points unable to provide the spatial evolution of pollutants. This research, focused on the city of Gijón (Asturias), includes a Computational Fluid Dynamics model capable of simulating the dispersion of pollutants in a large urban environment (12x18 km[Formula: see text]). Different wind conditions were simulated with two sources of emission. The results show the influence of the terrain on the dispersion of pollutants in open spaces whilst simultaneously scrutinizing the origin of diffuse industrial pollution circulating over the city of Gijon. The simulation allows us to set limits in the areas with higher levels of contamination or to analyse the variations of particle concentration in height. Therefore, this research defines and validates a methodology to generate numerical models which grant us the opportunity to observe the spatial evolution of pollutants in large areas. This result endorses further use in other lines of research, such as the evaluation of corrective measures to improve air quality in highly polluted environments.
RESUMO
Air pollution, representing one of the major environmental crises affecting us all, is responsible for half a million deaths each year in Europe. This research shows a numerical model based on Computational Fluid Dynamics (CFD) and a methodology for its validation allowing to know the evolution of particles in open urban environments. In this case, the model represents an area of Gijón (Asturias), specifically chosen as it serves to highlight a location at which the daily limit values of PM10 set by the regulations are most frequently exceeded. A numerical model has been developed at a scale of 1:10,000 to simulate the dispersion of pollutants, including particulate emissions. A physical model at the same scale was built using 3D printing. This model was tested in a wind tunnel and analysed in the four main wind directions. To carry out the tests, a particle generation system was designed and manufactured, and the necessary infrastructure was built to take measurements using an optical particle meter. Results show that the numerical model meets the expected objectives and is capable of predicting the behaviour of particle dispersion in the air. The numerical model produces results in the same order of magnitude as the physical model, although there is a tendency to underestimate the maximum values with respect to the measured ones.
RESUMO
A simple, accurate, sensitive, and precise reversed-phase (RP) high-performance liquid chromatographic (HPLC) method with fluorescence detection allowing the sensitive and specific quantitation of the newer fluoroquinolones levofloxacin and moxifloxacin is described. Moxifloxacin is used as the internal standard for the determination of levofloxacin and vice versa. A single-step liquid-liquid extraction from human plasma is sufficient for both quinolones. The method is linear from 0.1 to 15 microg/mL and 0.2 to 7 microg/mL for levofloxacin and moxifloxacin, respectively, covering the clinically relevant plasma concentration range. The limits of quantitation are 0.05 microg/mL (levofloxacin) and 0.2 microg/mL (moxifloxacin). The method is successfully applied to plasma drug level monitoring in a volunteer receiving single therapeutic doses of levofloxacin or moxifloxacin at two different occasions.
Assuntos
Antibacterianos/sangue , Compostos Aza/sangue , Cromatografia Líquida de Alta Pressão/métodos , Levofloxacino , Ofloxacino/sangue , Quinolinas/sangue , Espectrometria de Fluorescência/métodos , Fluoroquinolonas , Moxifloxacina , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Adenovirus-induced liver necrosis is rare. Because the era of AIDS (acquired immunodeficiency syndrome) this entity was seen predominantly in infants suffering from inborn immunodeficiency syndromes or from iatrogenic immunosuppression because of bone marrow or liver transplantation. Here, we report a case of a 30-year-old woman with AIDS who developed fever and rapidly progressing liver failure. A frozen section from a needle biopsy of the liver allowed a quick diagnosis of viral liver necrosis. The light-microscopic and electron microscopic aspects were typical of adenovirus infection and should be known to the surgical pathologist. The diagnosis was confirmed by immunohistochemistry and DNA hybridization analysis.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Infecções por Adenoviridae/complicações , Fígado/patologia , Adenoviridae/ultraestrutura , Infecções por Adenoviridae/patologia , Adulto , Biópsia por Agulha , Evolução Fatal , Feminino , Humanos , Fígado/ultraestrutura , Fígado/virologia , Microscopia Eletrônica , NecroseRESUMO
Ultraviolet absorbance spectroscopy and differential scanning calorimetry were employed to study the heat-induced helix-to-coil transition of the oligoribonucleotide rA7U7. The analysis of concentration-dependent ultraviolet 'melting' profiles was used to derive the van't Hoff transition enthalpy delta HUVvH (-458 kJ/mol cooperative unit). From the DSC data we calculated the calorimetric transition enthalpy delta Hcal (-412.6 kJ/mol duplex) as well as delta HcalvH (-447.9 kJ/mol cooperative unit). For the size of the cooperative unit we obtained lambda approximately 1. In contrast to this result, by means of statistical numerical deconvolution we show that intermediate states are significantly populated; at the maximum the fraction of these states reaches 25.4% of the total population. Therefore, this DSC-deconvolution technique offers a more appropriate way to register amounts of populated intermediate states which are not sufficient to obtain a value of lambda which is essentially lower than unity.
Assuntos
Conformação de Ácido Nucleico , Oligorribonucleotídeos , Varredura Diferencial de Calorimetria , Matemática , Oligorribonucleotídeos/síntese química , Espectrofotometria Ultravioleta , TermodinâmicaRESUMO
Heat induced helix-to-coil transitions are studied in the form of ultraviolet-hypochromicity profiles by absorbance spectroscopy, and delta Cp-curves by differential scanning calorimetry of self-complementary ribonucleotides. The results are analyzed and compared. Van 't Hoff transition enthalpies derived by UV-experiments incorporating concentration variations are found to differ from six-parameter and two-parameter Marquardt-fits on the melting profiles. A measure for the maximum number of nucleotides in intermediate states is obtained from a statistical deconvolution. It yields a range from 12.5% for the shortest nucleotide up to 31.5% for r(UA)7. Model independent calorimetric data are reported. A limit for intra-molecular loop-formation preference is reached by rG(UA)6C within this sequence.
Assuntos
Adenina/química , Sequências Hélice-Alça-Hélice , Oligorribonucleotídeos/química , Uridina/química , Varredura Diferencial de Calorimetria , Modelos Químicos , Conformação de Ácido Nucleico , TermodinâmicaRESUMO
An interaction of dipalmitoylphosphatidylcholine (PC) and phosphatidylserine (PS) with manganous ions has been investigated by measuring the effect of bound manganese upon the longitudinal relaxation rate, 1/T1, of the solvent water protons and evaluating the enhancement factor epsilon b. The observed enhancement values were used to determine the number of interacting sites per polar head group, n, and the values of association constants, KA, of manganese to PC and PS. Changes in epsilon b correlate with structural changes at the interacting site. By increasing the temperature one can see an abrupt decrease in epsilon b within the temperature interval from 40 to 50 degrees C indicating the thermal phase transition of PC as established by calorimetry, fluorescence and high-resolution NMR measurements. That an enhancement of 1/T1 of the solvent-water protons occurs at all is explained by assuming a restricted rotation of the Mn2+-aquo complex in the bound state. In addition we suppose that the rotation of the Mn2+-aquo complex is the mechanism which dominates the relaxation of the water protons in teh bulk solvent when phospholipids are present.
Assuntos
Manganês , Fosfatidilcolinas , Fosfatidiletanolaminas , Fosfatidilserinas , Sítios de Ligação , Espectroscopia de Ressonância de Spin Eletrônica , Cinética , Matemática , Conformação Molecular , Temperatura , TermodinâmicaRESUMO
1H-, 13C- and 31P-NMR spectra of egg-yolk phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidic acid (PA) and cosonicated mixtures of these phospholipids were obtained from ultrasonicated dispersions containing Pr3+, Eu3+, Gd3+ and Mn2+ ions. The differences in chemical shift values, deltaN, between the "inner" and "outer" resonance signals for the different nuclei of the polar head group of egg-yolk phosphatidyl choline provide information about the average distances of the paramagnetic ion within the polar groups of the phospholipid molecules. In the Pr(2H2O)3+n/egg-yolk phosphatidylcholine system the ions are nearest to the phosphate and -CH2CH2 group, respectively but relatively far from the N(CH3)3 group of the polar head group of the lipid. The integral analysis of the 1H-NMR spectra obtained from dispersions containing Pr3+ and Mn2+ ions enables us to calculate the number of the polar groups in both sides of the egg-yolk phosphatidylcholine bilayer, the size of lipid vesicle and to give some features of the arrangement of the phospholipid molecules in cosonicated egg-yolk phosphatidylcholine/phosphatidylserine vesicles. At p2H 8.3 in PC/PS mixtures an extreme asymmetry is observed with PS preferentially in the outer side of the membrane. This side contains approximately three times more PS than PC molecules. Some comments are made concerning the quantitative integral analysis of proton-noise decoupled 31P-NMR spectra as obtained from similar phospholipid mixtures by Michaelson et al. and Berden et al.
Assuntos
Ácidos Fosfatídicos , Fosfatidilcolinas , Fosfatidiletanolaminas , Fosfatidilserinas , Fosfolipídeos , Sítios de Ligação , Isótopos de Carbono , Gema de Ovo , Európio , Feminino , Gadolínio , Espectroscopia de Ressonância Magnética , Conformação Molecular , Isótopos de Fósforo , PraseodímioRESUMO
The heat effects involved in thermal unfolding of five tRNAs with different primary structures have been determined by direct differential scanning microcalorimetry. The overall molar values of the transition enthalpy (delta Ht) are 1150 kJ/mol for tRNA Lys2 (yeast), 1250 kJ/mol for tRNA Phe (yeast), 1350 kJ/mol for tRNA Val (yeast), 1490 kJ/mol for tRNA Val (E. coli) and 1630 kJ/mol for tRNA Tyr (E. coli). The tRNAs differ in their melting behaviour as can be shown by a comparison of the calorimetric curves. The calorimetrically measured delta Ht values are about 350 kJ/mol higher than the transition enthalpy values for the cloverleaf arrangement, which were estimated using the known parameters for G.C and A.U base pairs.
Assuntos
Conformação de Ácido Nucleico , RNA de Transferência , Sequência de Bases , Varredura Diferencial de Calorimetria , Escherichia coli , Desnaturação de Ácido Nucleico , Saccharomyces cerevisiaeRESUMO
When guanine and uracil form hydrogen bonds in the pairing scheme first proposed by Crick one would expect that poly(A,G) will form an unperturbed double helix with poly U at room temperature in a dilute electrolyte solution (0.1 M NaCl). We have demonstrated by Raman- and IR-spectroscopy that the secondary structure of poly(A.G) . poly U is very similar to the structure of poly A . poly U; only the thermal stability of the double helix seems slightly lower than the stability of poly A . poly U, whereas the average helix length is unaffected by the dispersed G . U base pairs. From our input ratio of guanine and adenine we estimate that about every fourth base pair is a wobble pair.
RESUMO
AIM: The protein kinase B (PKB)/Akt is known to stimulate the cellular uptake of glucose and amino acids. The kinase is expressed in proximal renal tubules. The present study explored the influence of Akt/PKB on renal tubular phosphate transport. METHODS: The renal phosphate transporter NaPi-IIa was expressed in Xenopus oocytes with or without PKB/Akt and Na(+) phosphate cotransport determined using dual electrode voltage clamp. Renal phosphate excretion was determined in Akt2/PKBbeta knockout mice (akt2(-/-)) and corresponding wild-type mice (akt2(+/+)). Transporter protein abundance was determined using Western blotting and phosphate transport by (32)P uptake into brush border membrane vesicles. RESULTS: The phosphate-induced current in NaPi-IIa-expressing Xenopus oocytes was significantly increased by the coexpression of Akt/PKB. Phosphate excretion [micromol per 24 h per g BW] was higher by 91% in akt2(-/-) than in akt2(+/+) mice. The phosphaturia of akt2(-/-) mice occurred despite normal transport activity and expression of the renal phosphate transporters NaPi-IIa, NaPi-IIc and Pit2 in the brush border membrane, a significantly decreased plasma PTH concentration (by 46%) and a significantly enhanced plasma 1,25-dihydroxyvitamin D(3) concentration (by 46%). Moreover, fractional renal Ca(2+) excretion was significantly enhanced (by 53%) and bone density significantly reduced (by 11%) in akt2(-/-) mice. CONCLUSIONS: Akt2/PKBbeta plays a role in the acute regulation of renal phosphate transport and thus contributes to the maintenance of phosphate balance and adequate mineralization of bone.
Assuntos
Túbulos Renais/enzimologia , Fosfatos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/metabolismo , Animais , Transporte Biológico , Biomarcadores/sangue , Biomarcadores/urina , Western Blotting , Calcificação Fisiológica , Calcitriol/sangue , Feminino , Homeostase , Hipofosfatemia Familiar/enzimologia , Hipofosfatemia Familiar/genética , Masculino , Potenciais da Membrana , Camundongos , Camundongos Knockout , Microvilosidades/enzimologia , Hormônio Paratireóideo/sangue , Técnicas de Patch-Clamp , Proteínas Proto-Oncogênicas c-akt/deficiência , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Sódio/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/genética , XenopusRESUMO
The thermal denaturation of a series of oligoribonucleotides of the form rAxUy (x = 5 or 7 and y = 3-11) has been characterized by means of IR spectroscopy, UV spectroscopy, and DSC. IR spectra proved the occurrence of double- and triple-helical regions at various contents of uracil residues in the nucleotide. From DSC measurements transition enthalpies, entropies, and free enthalpies were derived. The effect of fraying in terminal base pairs of symmetrical nucleotides (x = y) was quantified. Thermodynamic excess parameters due to dangling ends (5'A and 3'U), terminal AU base pairs, and UAU base triplets were obtained by comparing DSC results from different nucleotides. Empirical values for contributions of base stacking and pairing to the stability of terminal AU base pairs have been estimated: for nucleotides under study with a high degree of fraying at the ends of the helix the major stabilization effect comes from base stacking. The size of the cooperative unit lambda in most nucleotides under study is larger than 1; i.e., in these cases intermolecular cooperation takes place. Through deconvolution of DSC data maximum populations of intermediate states FI,max were obtained. On the basis of these results all nucleotides under study were proved to melt in multistate manner. FI,max increases with the number of base pairs, decreases through dangling ends, and shows approximately constant values for triple-helical aggregates of the series rA5Uy as well as rA7Uy.
Assuntos
Oligorribonucleotídeos , RNA de Cadeia Dupla , Códon , Modelos Químicos , Conformação de Ácido Nucleico , Espectrofotometria Infravermelho , TermodinâmicaRESUMO
The spectral parameters of amino acid residue side chain and peptide bond absorptions in the region 1800-1440 cm-1 have been obtained by using an inverse matrix method applied to the infrared spectra of 42 amino acids, dipeptides, and higher peptides in aqueous solution. In addition the pH-dependent extinction coefficients of the amino acid and peptide COO-/NH3+ end groups were derived. It is shown that the secondary structure prediction accuracy of proteins by multivariate data analysis methods increases slightly, if the side chain absorbances of the residues asparagine, glutamine, aspartic acid, glutamic acid, arginine, tyrosine, and lysine are subtracted from the amide I and amide II region.
Assuntos
Proteínas/química , Amidas/química , Aminoácidos/química , Concentração de Íons de Hidrogênio , Peptídeos/química , Estrutura Secundária de Proteína , Espectrofotometria InfravermelhoRESUMO
Infrared Spectroscopy was used to determine the numbers of base pairs for yeast 5S RNA and 5.8S RNA. The spectra were recorded at 20 degrees C and 50 degrees C, where tertiary interactions are assumed to be of less importance. It may be concluded that the structure of both RNAs is highly ordered and that there are large contributions of tertiary interactions. The results are compared with data derived from structural models that were proposed in the literature as well as with data previously published for prokaryotic 5S RNAs.
Assuntos
RNA Fúngico , Saccharomyces cerevisiae/análise , Composição de Bases , Modelos Estruturais , Conformação de Ácido Nucleico , Espectrofotometria Infravermelho , TemperaturaRESUMO
AIMS: Ossifying fibromyxoid tumour is a rare lesion that generally occurs in the soft tissues of proximal limbs/girdle, or head and neck. Histologically, it usually consists of bland, mitotically inactive, S100+ cells in a fibromyxoid matrix with a characteristic peripheral ossification. However, we present two cases that deviated from this pattern. MATERIAL AND METHODS: One tumour, which was removed from the axilla of a 55-year-old female, was unusual in its large size (120 mm in diameter) and in its restriction of bone formation to its central zones. The other tumour, which occurred in a 62-year-old female, was remarkable in its acral location on the hand and high mitotic activity (four mitoses per high-power field). These features caused concern and follow-up of the patients was recommended. So far there have been no recurrences (25 and 18 months after surgery, respectively). An additional previously undescribed feature was the presence of fibronexus-like structures by electron microscopy in the second case. However, a myofibroblastic phenotype was not supported by the immunohistochemical findings. CONCLUSION: Though a distinct entity, ossifying fibromyxoid tumour may exhibit a wider clinicopathological spectrum than generally recognized.
Assuntos
Fibroma/patologia , Ossificação Heterotópica/patologia , Neoplasias de Tecidos Moles/patologia , Biomarcadores Tumorais/metabolismo , Feminino , Fibroma/metabolismo , Fibroma/cirurgia , Humanos , Imuno-Histoquímica , Filamentos Intermediários/ultraestrutura , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Ossificação Heterotópica/metabolismo , Ossificação Heterotópica/cirurgia , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/cirurgia , Resultado do TratamentoRESUMO
The gamma delta TCR is expressed on 1 to 5% of CD3+ human peripheral blood T lymphocytes. The majority of peripheral blood gamma delta T cells expresses V gamma 9 paired with V delta 2; this subset strongly responds to certain microbial ligands. Other gamma delta T cell subsets with unknown Ag specificity expressing different V gamma elements are present in peripheral blood and lymphoid tissue. We describe a new anti-human V gamma mAb termed 23D12 with unusual specificity. As revealed by analysis of a large number of T cell clones and transfectants expressing molecularly well-defined gamma delta TCR, mAb 23D12 recognized several, but not all, members of the human V gamma 1 family, specifically V gamma 2, V gamma 3, and V gamma 4 but not V gamma 5 or V gamma 8. In combination with available mAb against V gamma 4, mAb 23D12 was used to identify V gamma 2- or V gamma 3-bearing cells. On average, 23D12+ cells accounted for 18% of peripheral blood gamma delta T cells and 56% of postnatal gamma delta thymocytes. In combination with anti-V gamma 9 mAb, mAb 23D12 23D12 identified gamma delta cells expressing V elements other than V gamma 2, V gamma 3, V gamma 4, or V gamma 9. Such cells are detectable in peripheral blood and postnatal thymus. Using mAb 23D12, we also confirmed the appearance of two distinct TCR gamma-chains on the surface of some gamma delta T cells.