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Showing papers by "Sapienza University of Rome published in 1998"



Journal ArticleDOI
06 Mar 1998-Science
TL;DR: Transplantation of genetically marked bone marrow into immunodeficient mice revealed that marrow-derived cells migrate into areas of induced muscle degeneration, undergo myogenic differentiation, and participate in the regeneration of the damaged fibers.
Abstract: Growth and repair of skeletal muscle are normally mediated by the satellite cells that surround muscle fibers. In regenerating muscle, however, the number of myogenic precursors exceeds that of resident satellite cells, implying migration or recruitment of undifferentiated progenitors from other sources. Transplantation of genetically marked bone marrow into immunodeficient mice revealed that marrow-derived cells migrate into areas of induced muscle degeneration, undergo myogenic differentiation, and participate in the regeneration of the damaged fibers. Genetically modified, marrow-derived myogenic progenitors could potentially be used to target therapeutic genes to muscle tissue, providing an alternative strategy for treatment of muscular dystrophies.

2,881 citations


Journal ArticleDOI
01 Jul 1998-Nature
TL;DR: In this article, the authors showed that nanometre-sized ceramic powders can be used as solid plasticizers for polyethylene oxide (PEO) electrolytes to prevent crystallization on annealing from amorphous state above 60°C.
Abstract: Ionically conducting polymer membranes (polymer electrolytes) might enhance lithium-battery technology by replacing the liquid electrolyte currently in use and thereby enabling the fabrication of flexible, compact, laminated solid-state structures free from leaks and available in varied geometries1. Polymer electrolytes explored for these purposes are commonly complexes of a lithium salt (LiX) with a high-molecular-weight polymer such as polyethylene oxide (PEO). But PEO tends to crystallize below 60 °C, whereas fast ion transport is a characteristic of the amorphous phase. So the conductivity of PEO–LiX electrolytes reaches practically useful values (of about 10−4 S cm−1) only at temperatures of 60–80 °C. The most common approach for lowering the operational temperature has been to add liquid plasticizers, but this promotes deterioration of the electrolyte's mechanical properties and increases its reactivity towards the lithium metal anode. Here we show that nanometre-sized ceramic powders can perform as solid plasticizers for PEO, kinetically inhibiting crystallization on annealing from the amorphous state above 60 °C. We demonstrate conductivities of around 10−4 S cm−1 at 50 °C and 10−5 S cm−1 at 30 °C in a PEO–LiClO4 mixture containing powders of TiO2 and Al2O3 with particle sizes of 5.8–13 nm. Further optimization might lead to practical solid-state polymer electrolytes for lithium batteries.

2,695 citations


Journal ArticleDOI
TL;DR: JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration and is identified as a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains.
Abstract: Tight junctions are the most apical components of endothelial and epithelial intercellular cleft. In the endothelium these structures play an important role in the control of paracellular permeability to circulating cells and solutes. The only known integral membrane protein localized at sites of membrane–membrane interaction of tight junctions is occludin, which is linked inside the cells to a complex network of cytoskeletal and signaling proteins. We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins. Confocal and immunoelectron microscopy shows that JAM codistributes with tight junction components at the apical region of the intercellular cleft. A cDNA clone encoding JAM defines a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains. An mAb directed to JAM (BV11) was found to inhibit spontaneous and chemokine-induced monocyte transmigration through an endothelial cell monolayer in vitro. Systemic treatment of mice with BV11 mAb blocked monocyte infiltration upon chemokine administration in subcutaneous air pouches. Thus, JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration.

1,395 citations


Journal ArticleDOI
01 Jul 1998-Brain
TL;DR: Evidence suggests that primary dystonia results from a functional disturbance of the basal ganglia, particularly in the striatal control of the globus pallidus (and substantia nigra pars reticulata) and abnormal regulation of brainstem and spinal cord inhibitory interneuronal mechanisms.
Abstract: Co-contraction and overflow of EMG activity of inappropriate muscles are typical features of all dystonic movements whether voluntary or involuntary. Voluntary movements are slow and more variable than normal, and there is particular difficulty switching between component movements of a complex task. Reduced spinal cord and brainstem inhibition is common to many reflex studies (long-latency reflexes, cranial reflexes and reciprocal inhibition). These reflex abnormalities may contribute to the difficulties in voluntary movements but cannot be causal as they can occur outside the clinically involved territory. Clinical and neurophysiological studies have emphasized the possible role of sensory feedback in the generation of dystonic movements. Abnormalities of cortical and basal ganglia function have been described in functional imaging and neurophysiological studies of patients with dystonia and in animal models of primary dystonia. Studies of cortical function have shown reduced preparatory activity in the EEG before the onset of voluntary movements, whilst magnetic brain stimulation has revealed changes in motor cortical excitability. Functional imaging of the brain in primary dystonia has suggested reduced pallidal inhibition of the thalamus with consequent overactivity of medial and prefrontal cortical areas and underactivity of the primary motor cortex during movements. These findings are supported by preliminary neuronal recordings from the globus pallidus and the thalamus at the time of stereotaxic surgery in patients with dystonia. All this evidence suggests that primary dystonia results from a functional disturbance of the basal ganglia, particularly in the striatal control of the globus pallidus (and substantia nigra pars reticulata). This causes altered thalamic control of cortical motor planning and executive areas, and abnormal regulation of brainstem and spinal cord inhibitory interneuronal mechanisms.

789 citations


Journal ArticleDOI
TL;DR: A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset and the ability of the new scoring system to discriminate risk groups was confirmed.
Abstract: BACKGROUND: Interferon alfa is a conservative and widely used alternative to bone marrow transplantation in treatment of patients with early chronic myeloid leukemia (CML). A meta-analysis was conducted to develop a reliable prognostic scoring system for estimation of survival of patients with CML treated with interferon alfa. METHODS: Patients treated in prospective studies, including major randomized trials, were separated into learning and validation samples. Cox regression analysis and the minimum P-value approach were used to identify prognostic factors for patient survival and to discover groups in the learning sample with the greatest differences in survival. These findings were then validated by applying the new scoring system to patients in the validation sample. RESULTS: We collected data on 1573 patients who were participants in 14 studies involving 12 institutions; 1303 patients (learning sample, n = 981; validation sample, n = 322) were eligible for inclusion in this analysis, and their median survival time was 69 months (range, 1-117 months). Because two previously described prognostic scoring systems failed to discriminate risk groups satisfactorily, we developed a new scoring system that utilizes the following covariates: age, spleen size, blast count, platelet count, eosinophil count, and basophil count. Among 908 patients with complete data in the learning sample, three distinct risk groups were identified (median survival times of 98 months [n = 369; 40.6%], 65 months [n = 406; 44.7%], or 42 months [n = 133;14.6%]; two-sided logrank test, P< or =.0001). The ability of the new scoring system to discriminate these risk groups was confirmed by analysis of 285 patients with complete data in the validation sample (two-sided logrank test, P = .0002). CONCLUSIONS: A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset.

737 citations


Journal ArticleDOI
TL;DR: 1,25(OH)2D3 may negatively regulate IL-12 production by downregulation of NF-kappaB activation and binding to the p40- kappaB sequence, providing a novel interpretation to its immunosuppressive properties.
Abstract: Interleukin 12 (IL-12), produced by myelomonocytic cells, plays a pivotal role in the development of T helper 1 (Th1) cells, which are involved in the pathogenesis of chronic inflammatory autoimmune disorders. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] inhibits IL-12 production by activated macrophages and dendritic cells, thus providing a novel interpretation to its immunosuppressive properties. 1,25(OH)2D3 significantly inhibits mRNA expression for both IL-12 p35 and p40 subunits acting at the transcriptional level. The effect of 1,25(OH)2D3 on p40 promoter activation was analyzed by cotransfecting monocytic RAW264.7 cells with p40 promoter/reporter constructs and expression vectors for vitamin D3 receptor (VDR) and/or retinoid X receptor (RXRalpha). We observed transcriptional repression of the p40 gene by 1,25(OH)2D3, which required coexpression of VDR with RXR and an intact VDR DNA-binding domain. The repressive effect maps to a region in the p40 promoter containing a binding site for NF-kappaB (p40-kappaB). Deletion of the p40-kappaB site abrogates part of the inhibitory effect on the p40 promoter, confirming the functional relevance of this site. Activation of monocytic THP-1 cells in the presence of 1,25(OH)2D3 results in reduced binding to the p40-kappaB site. Thus, 1,25(OH)2D3 may negatively regulate IL-12 production by downregulation of NF-kappaB activation and binding to the p40-kappaB sequence.

656 citations


Journal ArticleDOI
TL;DR: In this paper, a simple system based on five main factors gives adequate risk assessment for counselling of patients and taking decisions, which is highly predictive for leukaemia-free survival, survival and transplant-related mortality.

619 citations


Journal ArticleDOI
TL;DR: A dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways.
Abstract: The human homologue of Drosophila Toll (hToll) is a recently cloned receptor of the interleukin 1 receptor (IL-1R) superfamily, and has been implicated in the activation of adaptive immunity. Signaling by hToll is shown to occur through sequential recruitment of the adapter molecule MyD88 and the IL-1R–associated kinase. Tumor necrosis factor receptor–activated factor 6 (TRAF6) and the nuclear factor κB (NF-κB)–inducing kinase (NIK) are both involved in subsequent steps of NF-κB activation. Conversely, a dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways.

611 citations


Journal ArticleDOI
TL;DR: Palaeo-reconstruction of the Apenninic arc suggests about 775 km of migration from the Late Oligocene to present along a transect from the Gulf of Lions to Calabria.

593 citations


Journal ArticleDOI
TL;DR: This is the first report in which deficiency of a non-collagenous ECM protein leads to a skeletal phenotype that is marked by low bone mass that becomes more obvious with age and may serve as an animal model to study the role of ECM proteins in osteoporosis.
Abstract: The resilience and strength of bone is due to the orderly mineralization of a specialized extracellular matrix (ECM) composed of type I collagen (90%) and a host of non-collagenous proteins that are, in general, also found in other tissues. Biglycan (encoded by the gene Bgn) is an ECM proteoglycan that is enriched in bone and other non-skeletal connective tissues. In vitro studies indicate that Bgn may function in connective tissue metabolism by binding to collagen fibrils and TGF-beta (refs 5,6), and may promote neuronal survival. To study the role of Bgn in vivo, we generated Bgn-deficient mice. Although apparently normal at birth, these mice display a phenotype characterized by a reduced growth rate and decreased bone mass due to the absence of Bgn. To our knowledge, this is the first report in which deficiency of a non-collagenous ECM protein leads to a skeletal phenotype that is marked by low bone mass that becomes more obvious with age. These mice may serve as an animal model to study the role of ECM proteins in osteoporosis.


Book
28 Aug 1998
TL;DR: In this article, a reduced model for hydrodynamic turbulence and coupled map lattices is proposed, and a reduction to a finite-dimensional dynamical system is presented. But the model is not suitable for high-dimensional systems.
Abstract: Introduction 1. Turbulence and dynamical systems 2. Phenomenology of turbulence 3. Reduced models for hydrodynamic turbulence 4. Turbulence and coupled map lattices 5. Turbulence in the complex Ginzburg-Landau equation 6. Predictability in high-dimensional systems 7. Dynamics of interfaces 8. Lagrangian chaos 9. Chaotic diffusion Appendix A. Hopf bifurcation Appendix B. Hamiltonian systems Appendix C. Characteristic and generalised Lyapunov exponents Appendix D. Convective instabilities Appendix E. Generalised fractal dimensions and multifractals Appendix F. Multiaffine fields Appendix G. Reduction to a finite-dimensional dynamical system Appendix H. Directed percolation.

Journal ArticleDOI
TL;DR: The data indicate that the A1555G mutation accounts for a large proportion of the Spanish families with late-onset sensorineural deafness, that this mutation has an age-dependent penetrance for deafness (enhanced by treatment with aminoglycosides), and that mtDNA backgrounds probably do not play a major role in disease expression.
Abstract: Summary Hearing loss involves both genetic and environmental factors. A mutation (A1555G) in the mtDNA has been associated with aminoglycoside-induced and nonsyndromic sensorineural deafness. The pathological significance of this mutation in Caucasoid families has not been established, and its relationship with antibiotic treatment is not well understood. We studied 70 Spanish families with sensorineural deafness (36 congenital and 34 late onset) for the mtDNA A1555G mutation. The A1555G mutation was found in 19 families with maternally transmitted deafness but not in the other 51 families or in 200 control subjects. In 12 families all the patients with the A1555G mutation who received aminoglycosides became deaf, representing 30.3% of the deaf patients in these families. None of the deaf patients from seven other families received aminoglycosides. Overall, only 17.7% of the patients with deafness and the A1555G mutation had been treated with aminoglycosides. The age at onset of deafness was lower (median age 5 years, range 1–52 years) in those treated with aminoglycosides than in those who did not receive antibiotics (median age 20 years, range 1–65 years) ( P

Journal ArticleDOI
TL;DR: Cells cultured in the presence of IL‐10 were poor stimulators of allogeneic cord blood T cells in mixed lymphocyte reaction (MLR) and presented tetanus toxin to specific T cell lines with much less efficiency than control DC.
Abstract: Human monocytes cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-13 for 7 days differentiate into cells with the morphology and function of dendritic cells (DC). We have investigated the effect of IL-10 on this differentiation pathway. In the presence of IL-10 cells did not develop DC morphology, did not express CD1a and had lower levels of MHC class II. IL-10 promoted the differentiation of large cells with the morphology, cytochemistry and membrane phenotype of macrophages, including staining for nonspecific esterase and high levels of CD14, CD16 and CD68. The effect of IL-10 was dose dependent and was best appreciated when the cytokine was added at the initiation of the culture, as addition on day 3 was less inhibitory. When added to already differentiated DC on day 6, IL-10 caused only a modest reduction of MHC class II and CD1a expression, and no acquisition of the macrophage markers CD14, CD16 and CD68. Prolonged incubation up to 5 days with IL-10 did not induce a shift of differentiated DC to macrophages. On the other hand, the macrophages obtained by culturing for 7 days with GM-CSF+IL-13+IL-10 did not shift to DC upon removal of IL-10 for up to 3 days. Thus, the effect of IL-10 on monocyte differentiation, occurs only at the precursor level and confers an irreversible phenotype. From a functional point of view, cells cultured in the presence of IL-10 were poor stimulators of allogeneic cord blood T cells in mixed lymphocyte reaction (MLR) and presented tetanus toxin (TT) to specific T cell lines with much less efficiency than control DC. In contrast, IL-10-cultured DC showed 7 times greater endocytosis of FITC-dextran. This increased endocytosis was mostly mediated via the mannose receptor, as demonstrated by blocking with unlabeled mannose. In conclusion, IL-10 inhibits DC differentiation from monocytes and, in a substantial proportion of the cells, promotes the differentiation to mature macrophages. Intriguingly, IL-10 inhibits antigen presentation while it stimulates endocytic activity.

Journal ArticleDOI
01 Jan 1998-Thyroid
TL;DR: It is demonstrated that SG-FNAB allows a more precise and adequate sampling of thyroid nodular lesions and is associated with a lower rate of false-negatives, thus improving global diagnostic accuracy in the preoperative selection of thyroid cancer.
Abstract: Fine-needle aspiration biopsy (FNAB) is an accurate, slightly invasive, and safe method for the preoperative diagnosis of thyroid nodules. Recently, ultrasound guidance has been suggested as a valuable aid to enhance FNAB diagnostic performance. In this study, we have compared diagnostic accuracy of conventional FNAB (C-FNAB) versus sonography-guided FNAB (SG-FNAB) on a large sample population of 9683 patients with thyroid nodules. Over a 15-year period, 4986 patients were investigated by C-FNAB and 4697 underwent SG-FNAB. A valid cytological diagnosis was obtained in 85.9% of C-FNAB and in 91.5% of SG-FNAB cases, allowing detection of thyroid cancer in 1.6% and 2.1% of patients, respectively. The indeterminate pattern of follicular neoplasia was observed in 238 C-FNAB (5%) and in 272 (5.4%) SG-FNAB nodules. Specimens were cytologically inadequate in 433 C-FNAB (8.7%), but only in 167 SG-FNAB cases (3.5%). A total of 535 C-FNAB and 540 SG-FNAB nodules underwent surgery. False-negative results occurred in ...

Journal ArticleDOI
TL;DR: Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage colony-stimulating factor and monoclonal antibodies against Helicobacter pylori cross-react with human tissue.

Journal ArticleDOI
TL;DR: Many manifestations of hemineglect are modulated in a similar fashion by specific sensory stimulation that also affects visuo-motor processes in normal subjects, suggesting a multifaceted organization of the internal representation of space, of spatial attention, and of their neural correlates.

Journal ArticleDOI
TL;DR: In amphibian skin secretions contain many biologically active compounds, such as biogenic amines, complex alkaloids, or peptides as mentioned in this paper, which are considered the effector molecules of innate immunity, acting as a first line of defense against bacterial infections.
Abstract: Amphibian skin secretions contain many biologically active compounds, such as biogenic amines, complex alkaloids, or peptides. Within the latter class of molecules, a large number of peptide antibiotics has been isolated and characterized from different amphibian species. Antimicrobial peptides are considered the effector molecules of innate immunity, acting as a first line of defense against bacterial infections, by perturbing the phospholipid bilayer of the target cell membrane. These gene-encoded molecules are synthesized as inactive precursors and in several cases their proparts were shown to have highly conserved structures. It has also been demonstrated that the promoter regions of inducible peptide antibiotics are often regulated by the transcriptional control machinery NF-κB/IκBα. In amphibia of Rana and Bombina genera, inhibition of transcription of the genes encoding antimicrobial peptides has been obtained by glucocorticoid treatment, which causes an increase of IκBα synthesis. Moreover, determination of the structure of a number of genes coding for antimicrobial peptides in amphibia has actually shown that their promoter regions contain recognition sites for nuclear factors. © 1999 John Wiley & Sons, Inc. Biopoly 47: 435–450, 1998

Journal ArticleDOI
TL;DR: In this article, a next-to-leading order analysis of?S = 2 processes beyond the Standard Model is presented. But the analysis is restricted to the first two generations of down-type squarks.
Abstract: We perform a Next-to-Leading order analysis of ?S = 2 processes beyond the Standard Model. Combining the recently computed NLO anomalous dimensions and the B parameters of the most general ?S = 2 effective Hamiltonian, we give an analytic formula for ?MK and ?K in terms of the Wilson coefficients at the high energy scale. This expression can be used for any extension of the Standard Model with new heavy particles. Using this result, we consider gluino-mediated contributions to ?S = 2 transitions in general SUSY models and provide an improved analysis of the constraints on off-diagonal mass terms between the first two generations of down-type squarks. Finally, we improve the constraints on R-violating couplings from ?MK and ?K.

Journal ArticleDOI
TL;DR: This analysis revealed that a major Paleolithic population expansion from the "Atlantic zone" (southwestern Europe) occurred 10,000-15,000 years ago, after the Last Glacial Maximum, with haplogroup V, an autochthonous European haplogroups most likely originated in the northern Iberian peninsula or southwestern France at about the time of the Younger Dryas.
Abstract: mtDNA sequence variation was studied in 419 individuals from nine Eurasian populations, by high-resolution RFLP analysis, and it was followed by sequencing of the control region of a subset of these mtDNAs and a detailed survey of previously published data from numerous other European populations. This analysis revealed that a major Paleolithic population expansion from the "Atlantic zone" (southwestern Europe) occurred 10,000-15,000 years ago, after the Last Glacial Maximum. As an mtDNA marker for this expansion we identified haplogroup V, an autochthonous European haplogroup, which most likely originated in the northern Iberian peninsula or southwestern France at about the time of the Younger Dryas. Its sister haplogroup, H, which is distributed throughout the entire range of Caucasoid populations and which originated in the Near East approximately 25,000-30,000 years ago, also took part in this expansion, thus rendering it by far the most frequent (40%-60%) haplogroup in western Europe. Subsequent migrations after the Younger Dryas eventually carried those "Atlantic" mtDNAs into central and northern Europe. This scenario, already implied by archaeological records, is given overwhelming support from both the distribution of the autochthonous European Y chromosome type 15, as detected by the probes 49a/f, and the synthetic maps of nuclear data.

Journal Article
TL;DR: In this paper, the authors reported on the cloning and characterization of mouse CCR8 and found that it is predominantly expressed in the thymus of the mouse and was found to be a potent chemoattractant for Th2-polarized cells.
Abstract: In this paper we report on the cloning and characterization of mouse CCR8. Like its human homologue, it is predominantly expressed in the thymus. In the periphery, murine CCR8 mRNA was found most abundantly expressed in activated Th2-polarized cells and in NK1.1+ CD4+ T cells. Human CCR8 is also preferentially expressed in human Th2-polarized cells and clones. This pattern of expression suggests that CCR8 is part of a Th2-specific gene expression program. The CCR8 ligands I-309 and its mouse homologue T cell activation gene 3 (TCA-3) are potent chemoattractants for Th2-polarized cells. Taken together, these observations strongly suggest that CCR8 plays a role in the control of Th2 responses, and may represent a potential target for treatment of allergic diseases.

Journal ArticleDOI
TL;DR: The results suggest that p73 isoforms may be differentially regulated, with four different isoforms capable of interacting among themselves and with p53 and the relative expression level of each splice variant may modulate p73 transcriptional and growth suppression activities by affecting heterodimer formation.
Abstract: p73 has been recently identified as a new structural and functional homologue of the transcription factor p53. It is expressed in either a full-length form, α, or a shorter β mRNA variant, with exon 13 spliced out. Here we report the identification and functional characterization of two new p73 splicing variants, γ (splicing out exon 11) and δ (splicing out exons 11, 12, and 13). Both γ and δ p73 variants are expressed in human peripheral blood lymphocytes, primary keratinocytes, and different tumor cell lines, including neuroblastoma, glioblastoma, melanoma, hepatoma, and leukemia. The expression pattern of the four p73 splicing variants differs in both primary cells of different lineage and established cell lines even within the same type of tumor. A two-hybrid assay was used to characterize the homodimeric and heterodimeric interactions between the p73 variants, and showed that neither p73γ nor p73δ interact with p53, whereas p73γ showed strong interactions with all p73 isoforms, and p73δ binds efficiently p73α and p73γ but only weakly p73β. At the functional level, p73γ is significantly less efficient in activating transcription of the p21Waf1/Cip1 promoter than p53 or p73β, whereas the effect of p73δ is intermediate and comparable to that of p73α. The ability of the different p73 variants to affect cell growth in p53 null osteosarcoma SAOS-2 cells correlates with their transcriptional activity on the p21Waf1/Cip1 promoter: p73β is the most efficient in inhibiting colony formation, whereas p73γ is almost ineffective. Our results suggest that p73 isoforms may be differentially regulated, with four different isoforms capable of interacting among themselves and with p53. The relative expression level of each splice variant may modulate p73 transcriptional and growth suppression activities by affecting heterodimer formation.

Journal ArticleDOI
TL;DR: The use of the PHAF offers a number of advantages with respect to the high-order ambiguity function (HAF), and removes the identifiability problem and improves noise rejection capabilities.
Abstract: Parameter estimation and performance analysis issues are studied for multicomponent polynomial-phase signals (PPSs) embedded in white Gaussian noise. Identifiability issues arising with existing approaches are described first when dealing with multicomponent PPS having the same highest order phase coefficients. This situation is encountered in applications such as synthetic aperture radar imaging or propagation of polynomial phase signals through channels affected by multipath and is thus worthy of a careful analysis. A new approach is proposed based on a transformation called product high-order ambiguity function (PHAF). The use of the PHAF offers a number of advantages with respect to the high-order ambiguity function (HAF). More specifically, it removes the identifiability problem and improves noise rejection capabilities. Performance analysis is carried out using the perturbation method and verified by simulation results.

Journal ArticleDOI
TL;DR: Procalcitonin is a promising marker for the diagnosis of early- and late-onset sepsis in neonates at high risk for this infection.
Abstract: We evaluated the reliability of serum concentrations of procalcitonin for the diagnosis of early- and late-onset sepsis in a neonatal intensive care unit (NICU) setting. Timed procalcitonin determinations were prospectively obtained during two postnatal periods: 0-48 hours of age (period 1) and 3-30 days of age (period 2). In period 1, we measured procalcitonin concentrations in 83 healthy newborns (group 0) and in 120 NICU patients (14 with culture-proven sepsis, group 1A; 14 with clinical septicemia, group 1B; 75 with no evidence of infection, group 2; and 17 with uncertain findings, group 3). After we established 95% hour-specific reference ranges for group 0, we performed multiple linear regression analyses to determine which maternal, intrapartum, and neonatal complications would affect normal procalcitonin values. Maternal diabetes was the only variable identified in group 2 patients that induced a significant deviation from procalcitonin reference ranges. Analyses of the pooled procalcitonin values obtained for group 1 patients over the 48-hour period after birth yielded a sensitivity of 92.6% and a specificity of 97.5% for procalcitonin concentrations in the detection of early-onset sepsis. In period 2, blood samples from 23 cases with systemic infections were analyzed for procalcitonin concentrations at the onset of signs of infection. The control group was formed by matching four uninfected NICU patients to each infected case. None of the procalcitonin values for the 92 controls overlapped those for the cases (sensitivity and specificity, 100%). Procalcitonin is a promising marker for the diagnosis of early- and late-onset sepsis in neonates at high risk for this infection.

Journal ArticleDOI
TL;DR: The molecular basis of these differences in the effects of As2O3 and retinoic acid may guide the clinical use of arsenic compounds and provide insights into the management of leukemias that do not respond to retinic acid.
Abstract: Background: Retinoids, which are derivatives of vitamin A, induce differentiation of acute promyelocytic leukemia (APL) cells in vitro and in patients. However, APL cells develop resistance to retinoic acid treatment. Arsenic trioxide (As2O3) can induce clinical remission in patients with APL, including those who have relapsed after retinoic acid treatment, by inducing apoptosis (programmed cell death) of the leukemia cells. In this study, we investigated the molecular mechanisms by which As2O3 induces apoptosis in retinoic acid-sensitive NB4 APL cells, in retinoic acid-resistant derivatives of these cells, and in fresh leukemia cells from patients. Methods: Apoptosis was assessed by means of DNA fragmentation analyses, TUNEL assays (i.e., deoxyuridine triphosphate labeling of DNA nicks with terminal deoxynucleotidyl transferase), and flow cytometry. Expression of the PML/RARa fusion protein in leukemia cells was assessed by means of western blotting, ligand binding, and immunohistochemistry. Northern blotting and ribonuclease protection assays were used to evaluate changes in gene expression in response to retinoic acid and As 2 O 3 treatment. Results and Conclusions: As2O3 induces apoptosis without differentiation in retinoic acid-sensitive and retinoic acidresistant APL cells at concentrations that are achievable in patients. As 2 O 3 induces loss of the PML/RARa fusion protein in NB4 cells, in retinoic-acid resistant cells derived from them, in fresh APL cells from patients, and in non-APL cells transfected to express this protein. As2O3 and retinoic acid induce different patterns of gene regulation, and they inhibit the phenotypes induced by each other. Understanding the molecular basis of these differences in the effects of As 2O3 and retinoic acid may guide the clinical use of arsenic compounds and provide insights into the management of leukemias that do not respond to retinoic acid. [J Natl Cancer Inst 1998;90:124‐33]

Journal ArticleDOI
01 Jun 1998
TL;DR: A method for query answering in AL-log based on constrained resolution, where the usual deduction procedure defined for Datalog is integrated with a method for reasoning on the structural knowledge.
Abstract: We present an integrated system for knowledge representation, called{\cal A}{\cal L} -log, based on description logics and the deductive database language Datalog. {\cal A}{\cal L}-log embodies two subsystems, called structural and relational. The former allows for the definition of structural knowledge about classes of interest (concepts) and membership relation between objects and classes. The latter allows for the definition of relational knowledge about objects described in the structural component. The interaction between the two components is obtained by allowing constraints within Datalog clauses, thus requiring the variables in the clauses to range over the set of instances of a specified concept. We propose a method for query answering in {\cal A}{\cal L}-log based on constrained resolution, where the usual deduction procedure defined for Datalog is integrated with a method for reasoning on the structural knowledge.

Journal ArticleDOI
TL;DR: In this article, a review of the Auger parameter concept and its relation to the final state relaxation energy is presented, and a simple semiquantitative model useful to rationalize the dependence of the local electronic structure on the atomic environment is presented.

Journal ArticleDOI
15 Jan 1998-Blood
TL;DR: It is suggested that collagen-induced platelet aggregation is associated with a burst of H2O2 that acts as a second messenger by stimulating the arachidonic acid metabolism and phospholipase C pathway.

Journal ArticleDOI
01 Mar 1998-Chest
TL;DR: The prevalence of right ventricular dysfunction is high in patients with end-stage pulmonary disease, but the prevalence of left ventricular Dysfunction is relatively low and appears to be related to right vents dysfunction, perhaps through ventricular interdependence.