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Background When evaluating a patient for central adrenal insufficiency (CAI), there is a wide range of morning cortisol values for which no definite conclusion on hypothalamus–pituitary–adrenal (HPA) axis function can be drawn; in these cases, a stimulation test is required. Aim of this study was to develop an integrated model for CAI prediction when morning cortisol is in the grey zone, here defined as 40.0–160.0 μg/L. Methods Overall, 119 patients with history of sellar tumour which underwent insulin tolerance test (ITT) for the evaluation of HPA axis were enrolled. Supervised regression techniques were used for model development. Results An integrated predictive model was developed and internally validated, and showed a significantly better diagnostic performance than morning cortisol alone (AUC 0.811 vs 0.699, p = 0.003). A novel predictive score (CAI-score) was retrieved, on a 5.5-point scale, by considering morning cortisol (0 points if 130.1–160.0 μg/L, 1 point if 100.1–130.0 μg/L, 1.5 points if 70.1–100.0 μg/L, 2.5 points if 40.0–70.0 μg/L), other pituitary deficits (2 points if ≥ 3 deficits), and sex (1 point if male). A diagnostic algorithm integrating CAI-score and ITT was finally proposed, with an overall accuracy of 99%, and the possibility to avoid the execution of stimulation tests in 25% of patients. Conclusions This was the first study that proposed an integrated score for the prediction of CAI when morning cortisol is in the grey zone. This score might be helpful to reduce the number of patients who need a stimulation test for the assessment of HPA axis function.

Purpose The precise effects of non-steroidal anti-inflammatory drugs on the neuroendocrine hydro-electrolytic regulation are not precisely understood. The aim of this pilot study was to evaluate, in healthy subjects, the neuroendocrine response of the antidiuretic system to intravenous diclofenac infusion. Methods For this single-blinded, cross-over study, we recruited 12 healthy subjects (50% women). Test sessions were divided into three observation times (pre-test; test; 48 h post-test), which were repeated equally on two different occasions, with the administration of diclofenac (75 mg in saline solution 0.9% 100 cc) on 1 day, or placebo (saline solution 0.9% 100 cc) on another day. The night before the test the subjects were asked to collect a salivary cortisol and cortisone sample, which was repeated on the night of the procedure session. Serial urine and blood samples were collected on the test day (for osmolality, electrolytes, ACTH, cortisol, copeptin, MR-proADM, MR-proANP; the last three represent more stable and analytically reliable molecules than their respective active peptides). Moreover, the subjects were evaluated with the bioimpedance vector analysis (BIVA) before and after the test. Forty-eight hours after the end of the procedure urine sodium, urine potassium, urine osmolality, serum sodium and copeptin were revaluated together with BIVA. Results No significant changes in circulating hormone levels were observed; anyway, 48 h after diclofenac, BIVA showed a significant water retention (p p p = 0.054 cortisol; p = 0.021 cortisone). Conclusion Diclofenac resulted in an increased ECF at 48 h, but this phenomenon seems to be associated with a greater renal sensibility to the action of vasopressin rather than with an increase in its secretion. Moreover, a partial inhibitory effect on cortisol secretion can be hypothesized.

Introduction The proportion of patients with low GH response to provocative tests increases with the number of other pituitary hormone deficiencies, reason why in panhypopituitary patients GH stimulation tests may be unnecessary to diagnose GH deficiency (GHD) Purpose To re-evaluate the diagnostic cut-offs of GH response to GHRH + arginine (ARG) test related to BMI, considering the patients’ pituitary function as the gold standard for the diagnosis of GHD. Methods The GH responses to GHRH + ARG were studied in 358 patients with history of hypothalamic-pituitary disease. GHD was defined by the presence of at least 3 other pituitary deficits (n = 223), while a preserved somatotropic function was defined by the lack of other pituitary deficits and an IGF-I SDS ≥ 0 (n = 135). The cut-off with the best sensitivity (SE) and specificity (SP), was identified for each BMI category using the ROC curve analysis. To avoid over-diagnosis of GHD we subsequently searched for the cut-offs with a SP ≥ 95%. Results The best GH cut-off was 8.0 μg/l (SE 95%, SP 100%) in lean, 7.0 μg/l (SE 97.3%, SP 82.8%) in overweight, and 2.8 μg/l (SE 84.3%, SP 91.7%) in obese subjects. The cut-off with a SP ≥ 95% was 2.6 μg/l (SE 68.5%, SP 96.6%) in overweight and 1.75 μg/l (SE 70.0%, SP 97.2%) in obese subjects. Conclusions This is the first study that evaluates the diagnostic cut-offs of GH response to GHRH + ARG related to BMI using a clinical definition of GHD as gold standard. Our results suggest that with this new approach, the GHRH + ARG cut-offs should be revised to avoid GHD over-diagnosis.

Il contributo costituisce la seconda edizione, totalmente riveduta ed aggiornata, della trattazione dell'intera disciplina legale in materia di simulazione del contratto e degli atti unilaterali, unitamente ad una compiuta analisi delle ipotesi applicative esaminate alla luce della giurisprudenza più recente della Corte di Cassazione.

Purpose This study aims to compare the accuracy of mean GH profile (GHP) Methods We retrospectively enrolled 100 acromegaly patients, 68 responder, and 32 partial responder to SRLs. Controlled disease has been defined as IGF-I levels within age-related normal limits, while partial response as pathological IGF-I values despite a reduction ≥ 50%. In all patients, GHP, SGH, IGF-I, and IGFBP-3 were evaluated. Results Median GHP levels (1.2 ng/ml, IQR 0.5–2.3 ng/ml) were lower (p = 0.001) than SGH (1.9 ng/ml, IQR 1.0–3.6 ng/ml). Accuracy of GHP was 81%, whereas that of SGH was 55%, with a Kappa index of 0.520 and 0.237, respectively. In multivariable analysis GHP (p = 0.002) and IGFBP-3 (p = 0.004), but not SGH, were independently associated with normal IGF-I levels. At receiver–operator characteristic curve (ROC) analysis GHP cut-off sensitivity and specificity were 94.1% and 50.0%, respectively, while SGH sensitivity and specificity were 35.3% and 93.7%, respectively. Finally, in obese patients the GH cut-off level (both as SGH and GHP) associated to good disease control was significantly different with respect to not obese ones. Conclusions GHP associates with IGF-I (and therefore with appropriate control of disease) with higher accuracy than SGH. When GH evaluation is needed, the measurement of mean GHP should be preferred and use of BMI-related cut-offs is suggested.

In patients with suspected acromegaly, evaluation of IGF-I is recommended as first-line test, while the assessment of GH-nadir during oral glucose tolerance test (OGTT) is advised as confirmatory test. The procedure of this test generally involves GH measurement every 30 min (30') from baseline to +120' or +180'. However, the optimal timing of samplings for the distinction between patients with or without active acromegaly is still a matter of debate.Sixty-seven healthy subjects and 46 acromegalic patients who achieved documented and persistent long-term cure were enrolled. A greedy algorithm was used to identify the minimal subset of time-points that sufficed to correctly detect GH suppression.The sampling at 90' was the one in which a GH level 1 μg/L was most frequently achieved (i.e., in 91.3% of cured acromegalic patients and in 91.0% of healthy subjects). Considering the whole cohort, the best combination of 2 time-points was +90' and +150' and achieved 95.6% accuracy; the best combination of 3 time-points was +60', +90' and +150' and achieved 99.1% accuracy. The minimal subset of GH determinations that demonstrated perfect accuracy (100%) needed the inclusion of 4 time-points, namely +60', +90', +120' and +150'.A subset of 4 time-points (60' - 90' - 120' - 150') was identified as the most relevant to detect GH suppression at OGTT, with a perfect classification of 100% of subjects. This supports the possibility to restrict the blood samplings to these time-points when assessing disease cure, with possible advantages in terms of saving time and lowering costs.

Simflowny is an open platform which automatically generates parallel code of scientific dynamical models for different simulation frameworks. Here we present major upgrades on this software to support an extended set of families of models, in particular: i) a new generic family for partial differential equations, which can include spatial derivatives of any order, ii) a new family for agent based models to study complex phenomena --either on a spatial domain or on a graph--. Additionally we introduce a flexible graphical user interface (GUI) to accommodate these and future families of equations. This paper describes the new GUI architecture and summarizes the formal representation and implementation of these new families, providing several validation results., 26 pages, 21 figures

Motivating employees is a way to make them give their best to the organization for the achievement of organizational goals. But choosing the strategy for motivation may differ from time to time and organization to organization because it is a psychological sensation and it is depending on the preference of employees. The study attempted to identify the intrinsic and extrinsic factors affecting the work motivation of BSBA Graduates working in different institutions here in the CarCanMadCarLan area. With a view to collect primary data, and adopted a questionnaire from the Republic of Macedonia (Employee Satisfaction Survey, 2009) was provided to 40 respondents. The study identified 11 broad categories of motivation factors such as (1) management, (2) employee competence, (3) training opportunities in the organization, (4) premises and technical working conditions, (5) remuneration, (6) relationships between employees, (7) workload, (8) influence, (9) responsibility, (10) trust and finally (11) image of the organization. The study found that intrinsic factors have a significantly higher impact on the employee’s motivation than extrinsic factors. Finally, the study concluded that the BSBA employees working in different institutions are adequately motivated. On the basis of these findings, implications of the finding for future study were stated.

Hydrocarbons are the main components of diesel oil and are toxic for the majority of plants. A few plant species, known as phytoremediators, are tolerant of hydrocarbons and can survive the stressful conditions of soils contaminated with diesel oil. Canavalia ensiformis, a plant species that is well distributed throughout the tropics, possesses advantageous features for a potential resistance to soil contamination, such as fast growth and a deep root system. Thus, the aim of the present study was to evaluate the tolerance of C. ensiformis when it was exposed to soil contaminated with diesel oil. Seedlings were subjected to two treatments: contaminated soil (CS) (95 ml/kg of diesel oil) and non-contaminated soil (NCS) for a period of 30 days; its growth, morphology, anatomy, and physiology were analyzed. Despite the high level of toxicity, some individuals were able to survive in CS. These plants had root apical meristems with high levels of mitosis and were able to issue new roots with more developed aerenchyma tissue. Because the surviving plants presented no marks of cellular damage on the organs formed (root and leaves) during the experiment, the species capacity of growth on CS was confirmed. Although, long-term field experiments, applying different contaminant concentrations, should be considered to infer about the species resistance and use as phytoremediator.

A espinheira-santa (Maytenus muelleri - Celastraceae) é a planta medicinal nativa do Sul do Brasil, cujas folhas são tradicionalmente utilizadas pela medicina popular para o tratamento de úlceras e outros problemas gástricos. Existem poucos trabalhos publicados sobre a produção de mudas e técnicas de propagação vegetativa da espécie. A propagação de espinheira-santa por estaquia poderia ser um método eficiente para obtenção de material homogêneo, com características genéticas desejáveis, produzido a partir de plantas matrizes selecionadas. O presente trabalho teve por objetivo estudar os efeitos da aplicação de ácido indol butírico (AIB), em solução e em pó, no enraizamento de estacas de espinheira-santa coletadas nas quatro estações do ano (abril/2005 a janeiro/2006), bem como averiguar, por meio de análises anatômicas e histoquímicas das estacas, a presença de possíveis impedimentos à iniciação do enraizamento adventício. Estacas provenientes de ramos de plantas matrizes de seis anos cultivadas da Estação Experimental do Canguiri, Pinhais, PR, foram coletadas e tratadas com AIB (0, 1500, 3000 mg L-1 ou mg kg-1), em solução alcoólica (50% v/v) e em talco. Aos 365 dias foram avaliadas as porcentagens de estacas enraizadas e mortas, número e comprimento médio de raízes formadas por estaca. Análises anatômicas e histoquímicas com lugol e cloreto férrico foram realizadas. A estação mais promissora para o enraizamento foi o verão/2006 com 62,50% para o tratamento controle, devido à menor lignficação dos ramos no período de intenso crescimento vegetativo. O número médio de raízes formadas por estaca foi de 6,94 (solução) e o comprimento médio de raízes formadas/estaca chegou a 4,82 cm nesta mesma estação. As concentrações de AIB aplicadas não foram eficientes na indução radicial, independentemente do modo de aplicação. Foi detectada a presença de uma camada quase contínua de fibras e braquiesclereídes, a qual constitui barreira anatômica à indução radicial. Os testes histoquímicos revelaram a presença de amido e de compostos fenólicos nas estacas, em todas as estações do ano. A dificuldade ou demora no enraizamento não pode ser justificada pela falta de reservas de amido nos tecidos das estacas, mas pode ser justificada pela presença de compostos fenólicos, possivelmente do grupo dos monofenóis, que causam a degradação do AIA, interferindo negativamente na indução do enraizamento."Espinheira-santa" (Maytenus muelleri - Celastraceae) is a medicinal plant native to Southern Brazil, the leaves of which are traditionally used in popular medicine for the treatment of stomach ulcers and other gastric problems. There are few published studies about seedling production and vegetative propagation techniques for this species. The propagation of "espinheira-santa" by cuttings could be an efficient method to obtain homogeneous material, with desirable genetic characteristics, produced from selected mother plants. This paper aimed to study the effects of indolebutyric acid (IBA) application, in solution and in powder, on the rooting of "espinheira-santa" cuttings, collected in four seasons (April/2005 to January/2006), as well as to investigate, by means of cutting anatomical and histochemical analyses, the presence of possible impediments to adventitious rooting initiation. Cuttings from branches of six-year mother plants grown at "Estação Experimental do Canguiri", Pinhais, Paraná State, Brazil, were collected and treated with IBA (0, 1500, 3000 mg L-1 or mg kg-1) in alcoholic solution (50% v/v) and in powder. After 365 days, the percentages of rooted and dead cuttings, the number and mean length of roots/cutting were evaluated. Anatomical and histochemical analyses were performed with lugol and ferric chloride. The most promising season for rooting was Summer/2006, with 62.50% of rooting for the control treatment, due to the lesser lignification degree of branches in intense vegetative growth period. The mean number of roots/cutting was 6.94 (solution) and the mean length of roots/cutting was 4.82 cm in that same season. The applied IBA concentrations were not efficient in inducing root growth, regardless of the application method. An almost continuous layer of fibers and stone cells was detected, constituting an anatomical barrier for rooting induction. The histochemical tests revealed the presence of starch and phenolic compounds in cuttings, in all seasons. The difficulty or delay in rooting cannot be justified by the absence of starch reserve in the cutting tissues but by the presence of phenolic compounds, possibly of the group of monophenols, which cause IAA degradation, negatively affecting rooting induction.

Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus highly prevalent in the cattle population that has been isolated from the milk and the serum of healthy infected cows. Several studies reported the sensitivity and the permissiveness of some human cells to BoHV-4 infection. Moreover, our recent study demonstrated that some human cells sensitive but not permissive to BoHV-4 support a persistent infection protecting them from tumor necrosis factor- α –induced apoptosis. Together, these observations suggested that BoHV-4 could represent a danger for public health. To evaluate the risk of human infection by BoHV-4 through milk or serum derivatives, we investigated the resistance of BoHV-4 to the mildest thermal treatments usually applied to these products. The results demonstrated that milk pasteurization and thermal decomplementation of serum abolish BoHV-4 infectivity by inactivation of its property to enter permissive cells. Consequently, our results demonstrate that these treatments drastically reduce the risk of human infection by BoHV-4 through treated milk or serum derivatives.

A set of energy-momentum constraint-preserving boundary conditions is proposed for the first-order Z4 case. The stability of a simple numerical implementation is tested in the linear regime (robust stability test), both with the standard corner and vertex treatment and with a modified finite-differences stencil for boundary points which avoids corners and vertices even in cartesian-like grids. Moreover, the proposed boundary conditions are tested in a strong field scenario, the Gowdy waves metric, showing the expected rate of convergence. The accumulated amount of energy-momentum constraint violations is similar or even smaller than the one generated by either periodic or reflection conditions, which are exact in the Gowdy waves case. As a side theoretical result, a new symmetrizer is explicitly given, which extends the parametric domain of symmetric hyperbolicity for the Z4 formalism. The application of these results to first-order BSSN-like formalisms is also considered., Revised version, with conclusive numerical evidence. 23 pages, 12 figures

Nas sementes de leguminosas é comum a ocorrência de dormência devido à dureza do tegumento. Sementes de bordão-de-velho (Samanea saman (Jacq.) Merr.), angico-de-bezerro (Piptadenia moniliformis Benth.), pau-ferro (Caesalpinia ferrea Mart. ex. Tul.) e sabiá (Mimosa caesalpiniifolia Benth.) foram submetidas aos seguintes tratamentos: escarificação com lixa, água a 80ºC por 1,0; 2,5 e 5,0min; água à temperatura ambiente (12; 24 e 48h); ácido sulfúrico concentrado (1; 5 e 10min) e álcool etílico (5; 10 e 25min), visando a quebra da dormência. De sabiá foram testados os artículos e as sementes nuas. Usou-se o delineamento inteiramente ao acaso, com quatro repetições (50 sementes/repetição). Os tratamentos com ácido sulfúrico resultaram em maiores percentuais de germinação para bordão-de-velho (98,5-99,0%) e para pau-ferro (76,5-89,0%). Para angico-de-bezerro, destacaram-se água a 80ºC durante 1,0 ou 2,5min, e ácido durante 10min (82,5; 74,0 e 87,0% de germinação, respectivamente). Maiores percentagens de germinação foram obtidas nas sementes nuas de sabiá do que nos artículos, destacando-se, com germinação de 73,0 a 93,5%, os tratamentos com água a 80ºC, com ácido 5 e 10min, e com álcool etílico por 5min. Considerando-se o custo e os riscos na utilização do ácido sulfúrico, é preferível, para quebrar a dormência das sementes estudadas, a utilização dos tratamentos com água a 80ºC, ainda que seja necessário aumento na densidade de semeadura.In legume seeds dormancy imposed by the hard seed coat is common. Seeds of four legumes, Samanea saman (Jacq.) Merr., Piptadenia moniliformis Benth., Caesalpinia ferrea Mart. ex. Tul., and Mimosa caesalpiniifolia Benth. were scarified with sand paper; hot water (80ºC) for 1, 2.5 and 5.0 min; water at room temperature for 12, 24 and 48h; concentrated sulphuric acid for 1, 5 and 10 min; and in ethilic alcohol for 5, 10 and 25 min, to break seed coat dormancy. In M. caesalpiniifolia the treatments were applied to both articule and naked seeds. A completely randomized experimental design with four replications (50 seeds/ replication) was used. The treatments with sulfuric acid were the most effective on S. saman (98.5-99.0% germination) and C. ferrea (76.5-89%). For P. moniliformis, germination was best achieved after the application of hot water (1 or 2.5 min) and sulphuric acid during 10 min (82.5, 74 and 87% germination, respectively). For M. caesalpiniifolia, the results with naked seeds were better than with articules, the hot water, sulphuric acid (5 and 10min), and ethilic alcohol (5min) treatments being especially effective, with germination ranging from 73% to 93.5%. Due to the costs and risks when using sulphuric acid, it would be recommended the use of hot water treatments, even if some increase in sowing density becomes necessary.

We had previously shown that a genetically engineered Ig expressing an immunodominant CD4+ T epitope corresponding to the 110-120 amino acids of influenza virus hemagglutinin (HA), activated T cells more efficiently than the synthetic peptide. Taking advantage of a T cell hybridoma specific for HA 110-120 and transfected with a reporter gene under the IL-2 promoter, we studied the kinetics of generation and persistence on surface MHC-II of the HA 110-120 peptide derived from various carriers. Our results show that the generation rate of immunogenic MHC II-peptide complex is dependent on the nature of the carrier. Abs specific for HA 110-120 peptide or for other epitopes on HA affect through various mechanisms the presentation of HA 110-120 peptide to T cells. The persistence of immunogenic MHC II-peptide complex on the surface of APC is not dependent on the nature of the carrier and correlates with the half-life of class II molecules, suggesting an irreversible binding of peptides to MHC-II molecules in 2PK3 murine B lymphoma cells.

The necessary and sufficient conditions for a three‐dimensional Lorentzian metric to admit a group Gr of isometries acting on s‐dimensional orbits are given. These conditions are expressed in terms of the eigenvalues and eigenvectors of the Ricci tensor. As a by‐product, the set of (abstract) groups that can act isometrically and maximally on such metrics is obtained.

The prevalence of anti-lentiviruses antibodies of small ruminants was investigated in goat herds in the city of Teresina, PI, Brazil. A seroepidemiological survey was conducted involving 480 animals, apparently healthy, belonging to six rural properties. The diagnostic test was the agar gel immunodiffusion (AGID), using antigens produced from cellular cultures infected with caprine arthritis encephalitis virus (CAEV Cork). Prevalences by gender and age were estimated considering sampling fractions for each farm. A general prevalence of 4.2%, was observerved, being 4.2% for females and 3.6% for males. Prevalences were higher among older goats. Regarding the breed standard, 23.5% were of the Anglo Nubian, 5.9% of the Boer, 35.3% Anglo Nubian x Boer crossbred, and 35.3% of undefined breed. It is concluded that small ruminant lentiviruses are endemic among goat herds of Teresina.

The construction of numerical solutions of Einstein's General Relativity equations is formulated as an initial-value problem. The space-plus-time (3 + 1) decomposition of the spacetime metric tensor is used to discuss the structure of the field equations. The resulting evolution system is shown to depend in a crucial way on the coordinate gauge. The mandatory use of singularity avoiding coordinate conditions (like maximal slicing or similar gauges) is explained. A brief historical review of Numerical Relativity is included, showing the enormous effort in constructing codes based in these gauges, which lead to non-hyperbolic evolution systems, using "ad hoc" numerical techniques. A new family of first order hyperbolic evolution systems for the vacuum Einstein field equations in the harmonic slicing gauge is presented. This family depends on a symmetric 3 × 3 array of parameters which can be used to scale the dynamical variables in future numerical applications.

Serum samples from 147 patients with different systemic autoimmune diseases (SLE, Sjögren's syndrome, and progressive systemic sclerosis) were tested for anti-Fc gamma R activity using mouse rFc gamma RII in an ELISA. High reactivity compared to normal individuals was found for patients with all three diseases. The anti-Fc gamma R antibody was purified from several serum samples by affinity chromatography on a Sepharose column coupled with denatured, murine rFc gamma RII. Both IgM and IgG antibodies were found. To analyze the specificity of the affinity-purified autoantibody, cells (human neutrophils, IFN-gamma-stimulated neutrophils, monocytes, and the THP-1 monocytic cell line) that express different combinations of Fc gamma R (CD64, CD32, CD16) were stained with the affinity purified Ig. Ig directed against all three types of Fc gamma R were found. The results may reflect on the role of Fc gamma R-specific antibodies in the pathology of autoimmune diseases.

The epitope corresponding to amino acid residues 147-161 of the nucleoprotein (NP) of influenza A virus is recognized by CTL in association with H-2Kd class I Ag. Herein, we engineered an Ig molecule carrying this CTL epitope by replacing the diversity gene segment of the H chain V region of an anti-arsonate antibody with an oligonucleotide that encodes the CTL epitope. The chimeric H chain gene was expressed either alone or together with the parental L chain in the nonsecreting BALB/c myeloma B cell line, SP2/0. The Ig produced by cells transfected with both the chimeric H chain and parental L chains genes expressed the NP epitope but lost the original arsonate binding activity. In addition, SP2/0 cells expressing the chimeric H chain either alone or together with the parental L chain were lysed by class I restricted NP-epitope specific CTL. By contrast, SP2/0 cells pulsed with soluble chimeric Ig molecules were not lysed by the specific CTL. These observations indicate that: 1) this particular CTL epitope can be expressed on Ig molecules without altering the H and L chain pairing; 2) this CTL epitope can be generated from this chimeric Ig in which it is surrounded by flanking regions distinct from those of the viral NP; and 3) the generation of this CTL epitope from the Ig molecule requires the endogenous pathway as do viral proteins.

Irrotational dust metrics are considered by requiring the hypersurfaces orthogonal to the matter wordlines to be of constant curvature. The resulting line elements are either contained in the well‐known Szekeres dust solutions or they are homogeneous metrics of Bianchi class I or V.

A numerical code is presented which uses modern shock capturing methods to evolve spherically symmetric perfect fluid space-times. Harmonic slicing is used to ensure singularity avoidance, which is crucial in strong field situations. Some tests are presented, including an application to the stellar collapse problem.

The BALB/c myeloma protein ABPC48 binds beta(2-6)-linked fructosans and expresses genes derived from the VHX24 and V kappa 10 gene families. We have selected 30 hybridomas expressing the VHX24 gene family derived from mitogen-stimulated spleen cells of naive BALB/c mice and mice injected at birth with the syngeneic monoclonal anti-ABPC48Id, IDA10. The majority of mAb with kappa L chains uses V kappa 1. Antibodies reacting with IDA10 use both V kappa 10 and V kappa 1. Most of these VHX24+ mAb reacted with one or more members of a limited panel of predominantly polysaccharide Ag that have been previously observed to interact with antibodies expressing the VHX24 gene family. Nucleotide sequencing of selected VH and V kappa genes shows a very low frequency of somatic mutation. The effect of neonatal anti-Id injection on VHX24-V kappa pairing and Id expression is discussed.

The results presented in this paper explore the molecular basis for expression of the A48 regulatory Id (RI). A48 RI+ mAb derived from idiotypically manipulated mice molecularly resembled the A48 and UPC 10 prototypes of this system by utilizing a VHX24-Vk10 combination. Id expression by these antibodies was not restricted by a particular D region sequence, JH, or JK segment, but quantitative differences in Id expression were associated with utilization of different members of the VK10 germ-line gene families. The VL sequences of these A48 RI+ mAb has identified amino acid residues lying in four different idiotope-determining regions which may contribute to the structural correlate of this Id. A comparative sequence analysis of the VH regions of these VHX24 utilizing A48 RI+ mAb with several A48 RI+ mAb utilizing VHJ558 or VH7183 VH genes as well as a hybrid transfectoma antibody derived from two A48 RI-, VHJ558 utilizing hybridomas, all suggested that four nonconsecutive positions which lie outside the idiotope-determining regions may contribute structural elements toward expression of this Id. The VH and VL regions of the A48RI+, VHX24-Vk 10+ mAb showed low to moderate levels of somatic mutation which showed different patterns of distribution between the complementary determining region (CDR) and framework regions in the H and L chains. Although the VK sequences contained 50% of the replacement mutations in the CDR, with a replacement/silent mutation ratio of 10, the CDR of the VH sequences contained only 31% of the replacement mutations with a replacement/silent mutation ratio of 0.69.

A complete analog front-end, with the exclusion of the frequency synthesizer, for FM broadcasting occupies 2.8 mm 2 active area in a standard 0.35 μm CMOS technology. The use of current driven passive mixer and switch capacitor polyphase filter gives +100 dBμV IIP3, 52 dB adjacent channel selectivity and +39 dB image rejection without trimming or tuning. The output noise is 390 nV//√Hz, with a conversion gain of about 39 dB. This front-end consumes only 5 mA from a 2.4 V supply © 2006 IEEE.

A class of dynamical shift conditions is shown to lead to a pseudohyperbolic evolution system, both in the Z4 and in the BSSN numerical relativity formalisms. This is done by using a plane-wave analysis which can be viewed as an extension of the standard Fourier analysis for this kind of systems. The proposed class generalizes the harmonic shift condition, where light speed is the only nontrivial characteristic speed, and it is contained into the multiparameter family of minimal distortion shift conditions recently proposed by Lindblom and Scheel. The relationship with the analogous ``dynamical freezing'' shift conditions used in black hole simulations is discussed.

While vaccines are effective in adults, they are less successful in newborns and infants. Neonatal unresponsiveness to vaccines could be owing to immaturity of lymphocytes and/or to inhibition by maternal antibodies. Unresponsiveness of newborn to vaccines can be overcame by genetic immunization. In the present study we investigated the effect of maternal antibodies on the anti-influenza virus protective response in progeny born to dams immunized with plasmid containing the hemagglutinin gene or UV-inactivated virus. The effect of maternal antibodies was studied in plasmid immunized F1 mice born to BALB/c dams, previously immunized with virus or plasmid and crossed with C57BL/6 males, as well as in offspring born to BALB/c dams immunized with plasmid and then immunized with UV-inactivated WSN virus. We have found that the inhibition period of the anti-HA antibody response in offspring born to dams immunized with DNA is shorter than that of offspring born to dams immunized with virus. Furthermore, there is a persistent inhibitory effect on B cells from offspring born to dams immunized with virus or injected with antiviral monoclonal antibodies (MoAb), after the decline of maternal antibody titers. The analysis of the haemagglutinin-specific clonotype reactivity pattern of offspring born to dams immunized with inactivated influenza virus or with a plasmid showed that clonotypes producing antibodies specific for the immunizing virus strain were predominant in offspring born to dams immunized with DNA compared to those born to dams immunized with virus. Maternal antibodies do not affect cell-mediated immunity. These findings might be used to design efficient vaccination schedules for newborns and infants.

Serum autoantibodies to fibrillin 1, the major component of microfibrils in the extracellular matrix, recently have been reported to occur in the tight skin mouse and in patients with systemic sclerosis, but not in patients with other connective tissue diseases. This study was undertaken to determine whether antifibrillin 1 antibodies could be detected in patients with localized forms of scleroderma.Sera from 50 patients with localized scleroderma (27 with linear scleroderma and 23 with morphea) and 51 normal controls were tested for IgG and IgM antifibrillin 1 autoantibodies, using a radioimmunoassay (RIA) and a human recombinant fibrillin 1 protein (rFbn-1).Both in patients with linear scleroderma and in those with morphea, mean levels of IgM and IgG binding to rFbn-1 were significantly higher than in controls. Eight patients with linear scleroderma (30%) and 6 patients with morphea (26%) had IgG autoantibodies to fibrillin 1 (rFbn-1) by RIA, compared with 3 controls (6%) (P = 0.006 and P = 0.022, respectively). No correlations between antifibrillin 1 antibodies and active skin disease or antinuclear antibody positivity were found.Autoantibodies to fibrillin 1 occur in patients with both forms of localized scleroderma (linear scleroderma and morphea). The clinical and pathogenetic significance of this autoimmune response remains to be determined.

Nas sementes de leguminosas é comum a ocorrência de dormência devido à dureza do tegumento. Sementes de bordão-de-velho (Samanea saman (Jacq.) Merr.), angico-de-bezerro (Piptadenia moniliformis Benth.), pau-ferro (Caesalpinia ferrea Mart. ex. Tul.) e sabiá (Mimosa caesalpiniifolia Benth.) foram submetidas aos seguintes tratamentos: escarificação com lixa, água a 80ºC por 1,0; 2,5 e 5,0min; água à temperatura ambiente (12; 24 e 48h); ácido sulfúrico concentrado (1; 5 e 10min) e álcool etílico (5; 10 e 25min), visando a quebra da dormência. De sabiá foram testados os artículos e as sementes nuas. Usou-se o delineamento inteiramente ao acaso, com quatro repetições (50 sementes/repetição). Os tratamentos com ácido sulfúrico resultaram em maiores percentuais de germinação para bordão-de-velho (98,5-99,0%) e para pau-ferro (76,5-89,0%). Para angico-de-bezerro, destacaram-se água a 80ºC durante 1,0 ou 2,5min, e ácido durante 10min (82,5; 74,0 e 87,0% de germinação, respectivamente). Maiores percentagens de germinação foram obtidas nas sementes nuas de sabiá do que nos artículos, destacando-se, com germinação de 73,0 a 93,5%, os tratamentos com água a 80ºC, com ácido 5 e 10min, e com álcool etílico por 5min. Considerando-se o custo e os riscos na utilização do ácido sulfúrico, é preferível, para quebrar a dormência das sementes estudadas, a utilização dos tratamentos com água a 80ºC, ainda que seja necessário aumento na densidade de semeadura. In legume seeds dormancy imposed by the hard seed coat is common. Seeds of four legumes, Samanea saman (Jacq.) Merr., Piptadenia moniliformis Benth., Caesalpinia ferrea Mart. ex. Tul., and Mimosa caesalpiniifolia Benth. were scarified with sand paper; hot water (80ºC) for 1, 2.5 and 5.0 min; water at room temperature for 12, 24 and 48h; concentrated sulphuric acid for 1, 5 and 10 min; and in ethilic alcohol for 5, 10 and 25 min, to break seed coat dormancy. In M. caesalpiniifolia the treatments were applied to both articule and naked seeds. A completely randomized experimental design with four replications (50 seeds/ replication) was used. The treatments with sulfuric acid were the most effective on S. saman (98.5-99.0% germination) and C. ferrea (76.5-89%). For P. moniliformis, germination was best achieved after the application of hot water (1 or 2.5 min) and sulphuric acid during 10 min (82.5, 74 and 87% germination, respectively). For M. caesalpiniifolia, the results with naked seeds were better than with articules, the hot water, sulphuric acid (5 and 10min), and ethilic alcohol (5min) treatments being especially effective, with germination ranging from 73% to 93.5%. Due to the costs and risks when using sulphuric acid, it would be recommended the use of hot water treatments, even if some increase in sowing density becomes necessary.

The ministerial decrees of 15/4/94 and 14/12/94 defined the new payment schedules for hospital services during ordinary and day hospitalization; the hospital discharge form (SDO) is the main source of this information. The services are defined by the classification of ROD ("raggruppamenti omogenei di diagnosi"), adapted from the American DRG ("Diagnosis related groups"), which have substituted the traditional system of payment by production factor. On the basis of the DRG identified and the length of hospital stay, the Region pays the hospital the cost of hospitalization. The main diagnosis at discharge, secondary diagnosis, complications and diagnostic/therapeutic procedures all contribute to the determination of 489 DRG. Groups of pathologies are reclassified into 25 MDC ("Major Diagnostic Categories"). The 11th MDC includes the uronephrological DRG (302-333). The nephrological sector has been penalized by the inadequate value given to related procedures and diagnostic limitations. In order to guarantee efficacious diagnostic and therapeutic procedures, without impoverishing the nephrological budget and reducing the management autonomy of the divisions and autonomous services with hospitalization, it is necessary to introduce quality controls and corrective measures to the procedures that maintain the value of diagnosis and comply with financial considerations.

We had previously shown that a genetically engineered Ig expressing an immunodominant CD4+ T epitope corresponding to the 110-120 amino acids of influenza virus hemagglutinin (HA), activated T cells more efficiently than the synthetic peptide. Taking advantage of a T cell hybridoma specific for HA 110-120 and transfected with a reporter gene under the IL-2 promoter, we studied the kinetics of generation and persistence on surface MHC-II of the HA 110-120 peptide derived from various carriers. Our results show that the generation rate of immunogenic MHC II-peptide complex is dependent on the nature of the carrier. Abs specific for HA 110-120 peptide or for other epitopes on HA affect through various mechanisms the presentation of HA 110-120 peptide to T cells. The persistence of immunogenic MHC II-peptide complex on the surface of APC is not dependent on the nature of the carrier and correlates with the half-life of class II molecules, suggesting an irreversible binding of peptides to MHC-II molecules in 2PK3 murine B lymphoma cells.

The possible role of silicone in the pathogenesis of a scleroderma-like syndrome is still unresolved. It has been proposed that silicone escaping from breast implants potentiates the progression of the disease. To clarify whether silicone enhances development of fibrotic skin lesions and autoantibodies, we tested its effect on tight skin (TSK/+) mice. TSK/+ mice spontaneously develop skin fibrosis and characteristic autoantibodies which resemble human scleroderma. The results of the present study indicate that silicone administration does not enhance development of skin fibrosis nor synthesis of autoantibodies to RNA polymerase and topoisomerase in TSK/+ mice.

The possible role of silicone in the pathogenesis of a scleroderma-like syndrome is still unresolved. It has been proposed that silicone escaping from breast implants potentiates the progression of the disease. To clarify whether silicone enhances development of fibrotic skin lesions and autoantibodies, we tested its effect on tight skin (TSK/+) mice. TSK/+ mice spontaneously develop skin fibrosis and characteristic autoantibodies which resemble human scleroderma. The results of the present study indicate that silicone administration does not enhance development of skin fibrosis nor synthesis of autoantibodies to RNA polymerase and topoisomerase in TSK/+ mice.

The authors present a case of idiopathic pulmonary fibrosis with an unusual onset in the form of acute interstitial pneumonia. On being admitted to hospital the 53-year-old woman presented an altered breathing pattern which initially required oxygen therapy using Venturi's oxygen mask followed by sedation and mechanical ventilation with appropriate FiO2 to guarantee adequate pO2 and arterial saturation. For diagnostic purposes bronchiolar and alveolar lavage was immediately performed together with transbronchial biopsy during the course of fibrobronchoscopy. The results of these tests revealed a syndrome of interstitial pneumonia and widespread alveolar lesion with an enhanced lymphocyte population. Antibac-terial and immunosuppressive therapy (6-methylprednisolone and cyclophosphamide) commenced on the basis of these tests caused a temporary improvement in blood-gas parameters and parenchymal thickening. But in spite of treatment the patient's cardiocirculatory and respiratory conditions deteriorated, causing death. This case report raises a number of different questions regarding both diagnosis and treatment. With regard to diagnosis it is worth underlining the absence of hyaline membrane, pathognomonic of widespread alveolar lesions, in biopsies removed while the patient was still alive. With regard to treatment, in addition to specific antibiotic and immunosuppressive therapy, the authors consider that surfactants might be of some help given that widespread alveolar damage can be attributed to pulmonary fibrosis.

The advent of genetic engineering has allowed for the expression and production of recombinant proteins carrying short immunogenic epitopes of foreign antigens. These antigenized molecules represent valuable tools to investigate the molecular basis of antigen fragmentation, generation and presentation of peptide to lymphocytes, the induction of epitope specific immunity and potentially the development of a new generation of vaccines. Recently, we expressed viral epitopes on immunoglobulin molecules by replacing the D segment of a variable region of the heavy chain (VH) gene with a B cell epitope from the V3-loop of HIV-1 envelope protein, as well as a cytotoxic T lymphocyte (CTL) and a T helper epitope from influenza virus nucleoprotein and hemagglutinin, respectively. The T cell peptides generated from the immunoglobulin molecules produced by cells transfected with chimeric V genes, activated specific T cells as they do when generated from viral proteins. Possible practical applications for the development of prophylactic and immunotherapeutic reagents are envisioned for immunoglobulin molecules bearing foreign epitopes.

Serum samples from 147 patients with different systemic autoimmune diseases (SLE, Sjögren's syndrome, and progressive systemic sclerosis) were tested for anti-Fc gamma R activity using mouse rFc gamma RII in an ELISA. High reactivity compared to normal individuals was found for patients with all three diseases. The anti-Fc gamma R antibody was purified from several serum samples by affinity chromatography on a Sepharose column coupled with denatured, murine rFc gamma RII. Both IgM and IgG antibodies were found. To analyze the specificity of the affinity-purified autoantibody, cells (human neutrophils, IFN-gamma-stimulated neutrophils, monocytes, and the THP-1 monocytic cell line) that express different combinations of Fc gamma R (CD64, CD32, CD16) were stained with the affinity purified Ig. Ig directed against all three types of Fc gamma R were found. The results may reflect on the role of Fc gamma R-specific antibodies in the pathology of autoimmune diseases.

The epitope corresponding to amino acid residues 147-161 of the nucleoprotein (NP) of influenza A virus is recognized by CTL in association with H-2Kd class I Ag. Herein, we engineered an Ig molecule carrying this CTL epitope by replacing the diversity gene segment of the H chain V region of an anti-arsonate antibody with an oligonucleotide that encodes the CTL epitope. The chimeric H chain gene was expressed either alone or together with the parental L chain in the nonsecreting BALB/c myeloma B cell line, SP2/0. The Ig produced by cells transfected with both the chimeric H chain and parental L chains genes expressed the NP epitope but lost the original arsonate binding activity. In addition, SP2/0 cells expressing the chimeric H chain either alone or together with the parental L chain were lysed by class I restricted NP-epitope specific CTL. By contrast, SP2/0 cells pulsed with soluble chimeric Ig molecules were not lysed by the specific CTL. These observations indicate that: 1) this particular CTL epitope can be expressed on Ig molecules without altering the H and L chain pairing; 2) this CTL epitope can be generated from this chimeric Ig in which it is surrounded by flanking regions distinct from those of the viral NP; and 3) the generation of this CTL epitope from the Ig molecule requires the endogenous pathway as do viral proteins.

The BALB/c myeloma protein ABPC48 binds beta(2-6)-linked fructosans and expresses genes derived from the VHX24 and V kappa 10 gene families. We have selected 30 hybridomas expressing the VHX24 gene family derived from mitogen-stimulated spleen cells of naive BALB/c mice and mice injected at birth with the syngeneic monoclonal anti-ABPC48Id, IDA10. The majority of mAb with kappa L chains uses V kappa 1. Antibodies reacting with IDA10 use both V kappa 10 and V kappa 1. Most of these VHX24+ mAb reacted with one or more members of a limited panel of predominantly polysaccharide Ag that have been previously observed to interact with antibodies expressing the VHX24 gene family. Nucleotide sequencing of selected VH and V kappa genes shows a very low frequency of somatic mutation. The effect of neonatal anti-Id injection on VHX24-V kappa pairing and Id expression is discussed.

The results presented in this paper explore the molecular basis for expression of the A48 regulatory Id (RI). A48 RI+ mAb derived from idiotypically manipulated mice molecularly resembled the A48 and UPC 10 prototypes of this system by utilizing a VHX24-Vk10 combination. Id expression by these antibodies was not restricted by a particular D region sequence, JH, or JK segment, but quantitative differences in Id expression were associated with utilization of different members of the VK10 germ-line gene families. The VL sequences of these A48 RI+ mAb has identified amino acid residues lying in four different idiotope-determining regions which may contribute to the structural correlate of this Id. A comparative sequence analysis of the VH regions of these VHX24 utilizing A48 RI+ mAb with several A48 RI+ mAb utilizing VHJ558 or VH7183 VH genes as well as a hybrid transfectoma antibody derived from two A48 RI-, VHJ558 utilizing hybridomas, all suggested that four nonconsecutive positions which lie outside the idiotope-determining regions may contribute structural elements toward expression of this Id. The VH and VL regions of the A48RI+, VHX24-Vk 10+ mAb showed low to moderate levels of somatic mutation which showed different patterns of distribution between the complementary determining region (CDR) and framework regions in the H and L chains. Although the VK sequences contained 50% of the replacement mutations in the CDR, with a replacement/silent mutation ratio of 10, the CDR of the VH sequences contained only 31% of the replacement mutations with a replacement/silent mutation ratio of 0.69.