Showing papers by "University of Turin published in 1999"
TL;DR: The standardized RT-PCR protocol and primer sets can now be used for molecular classification of acute leukemia at diagnosis and for MRD detection during follow-up to evaluate treatment effectiveness.
Abstract: Prospective studies on the detection of minimal residual disease (MRD) in acute leukemia patients have shown that large-scale MRD studies are feasible and that clinically relevant MRD-based risk group classification can be achieved and can now be used for designing new treatment protocols. However, multicenter international treatment protocols with MRD-based stratification of treatment need careful standardization and quality control of the MRD techniques. This was the aim of the European BIOMED-1 Concerted Action 'Investigation of minimal residual disease in acute leukemia: international standardization and clinical evaluation' with participants of 14 laboratories in eight European countries (ES, NL, PT, IT, DE, FR, SE and AT). Standardization and quality control was performed for the three main types of MRD techniques, ie flow cytometric immunophenotyping, PCR analysis of antigen receptor genes, and RT-PCR analysis of well-defined chromosomal aberrations. This study focussed on the latter MRD technique. A total of nine well-defined chromosome aberrations with fusion gene transcripts were selected: t(1;19) with E2A-PBX1, t(4;11) with MLL-AF4, t(8;21) with AML1-ETO, t(9;22) with BCR-ABL p190 and BCR-ABL p210, t(12;21) with TEL-AML1, t(15;17) with PML-RARA, inv (16) with CBFB-MYH11, and microdeletion 1p32 with SIL-TAL1. PCR primers were designed according to predefined criteria for single PCR (external primers A B) and nested PCR (internal primers C D) as well as for 'shifted' PCR with a primer upstream (E5' primer) or downstream (E3' primer) of the external A B primers. The 'shifted' E primers were designed for performing an independent PCR together with one of the internal primers for confirmation (or exclusion) of positive results. Various local RT and PCR protocols were compared and subsequently a common protocol was designed, tested and adapted, resulting in a standardized RT-PCR protocol. After initial testing (with adaptations whenever necessary) and approval by two or three laboratories, the primers were tested by all participating laboratories, using 17 cell lines and patient samples as positive controls. This testing included comparison with local protocols and primers as well as sensitivity testing via dilution experiments. The collaborative efforts resulted in standardized primer sets with a minimal target sensitivity of 10-2 for virtually all single PCR analyses, whereas the nested PCR analyses generally reached the minimal target sensitivity of 10-4. The standardized RT-PCR protocol and primer sets can now be used for molecular classification of acute leukemia at diagnosis and for MRD detection during follow-up to evaluate treatment effectiveness.
1,170 citations
TL;DR: It is concluded that plexins are receptors for multiple (and perhaps all) classes of semaphorins, either alone or in combination with neuropilins, and trigger a novel signal transduction pathway controlling cell repulsion.
1,139 citations
TL;DR: In this paper, a review of nucleosynthesis in AGB stars outlining the development of theoretical models and their relationship to observations is presented, focusing on the new high-resolution codes with high accuracy.
Abstract: ▪ Abstract We present a review of nucleosynthesis in AGB stars outlining the development of theoretical models and their relationship to observations. We focus on the new high resolution codes with...
1,125 citations
TL;DR: Recently improved information on the stellar (n, γ) cross sections of neutron magic nuclei at N = 82, and in particular of 142Nd, turn out to represent a sensitive test for models of s-process nucleosynthesis as mentioned in this paper.
Abstract: Recently improved information on the stellar (n, γ) cross sections of neutron magic nuclei at N = 82, and in particular of 142Nd, turn out to represent a sensitive test for models of s-process nucleosynthesis. While these data were found to be incompatible with the classical approach based on an exponential distribution of neutron exposures, they provide significantly better agreement between the solar abundance distribution of s nuclei and the predictions of models for low-mass asymptotic giant branch (AGB) stars. The origin of this phenomenon is identified as lying in the high neutron exposures at low neutron density obtained between thermal pulses when 13C burns radiatively in a narrow layer of a few 10-4 M☉. This effect is studied in some detail, and the influence of the currently available nuclear physics data is discussed with respect to specific further questions. In this context, particular attention is paid to a consistent description of s-process branchings in the region of the rare earth elements. It is shown that, in certain cases, the nuclear data are sufficiently accurate that the resulting abundance uncertainties can be completely attributed to stellar modeling. Thus, the s-process becomes important for testing the role of different stellar masses and metallicities as well as for constraining the assumptions used in describing the low neutron density provided by the 13C source.
898 citations
TL;DR: The findings show that cognitive factors and conditioning are balanced in different ways in placebo analgesia, and this balance is crucial for the activation of opioid or nonopioid systems.
Abstract: We investigated the mechanisms underlying the activation of endogenous opioids in placebo analgesia by using the model of human experimental ischemic arm pain. Different types of placebo analgesic responses were evoked by means of cognitive expectation cues, drug conditioning, or a combination of both. Drug conditioning was performed by means of either the opioid agonist morphine hydrochloride or the nonopioid ketorolac tromethamine. Expectation cues produced placebo responses that were completely blocked by the opioid antagonist naloxone. Expectation cues together with morphine conditioning produced placebo responses that were completely antagonized by naloxone. Morphine conditioning alone (without expectation cues) induced a naloxone-reversible placebo effect. By contrast, ketorolac conditioning together with expectation cues elicited a placebo effect that was blocked by naloxone only partially. Ketorolac conditioning alone produced placebo responses that were naloxone-insensitive. Therefore, we evoked different types of placebo responses that were either naloxone-reversible or partially naloxone-reversible or, otherwise, naloxone-insensitive, depending on the procedure used to evoke the placebo response. These findings show that cognitive factors and conditioning are balanced in different ways in placebo analgesia, and this balance is crucial for the activation of opioid or nonopioid systems. Expectation triggers endogenous opioids, whereas conditioning activates specific subsystems. In fact, if conditioning is performed with opioids, placebo analgesia is mediated via opioid receptors, if conditioning is performed with nonopioid drugs, other nonopioid mechanisms result to be involved.
811 citations
TL;DR: Cloning the chromosome 19q13 breakpoint in a patient with a reciprocal X;19 chromosome translocation identified mutations in RPS19 in 10 of 40 unrelated DBA patients, including nonsense, frameshift, splice site and missense mutations, as well as two intragenic deletions that suggest a function for R PS19 in erythropoiesis and embryogenesis.
Abstract: Diamond-Blackfan anaemia (DBA) is a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors. The disease, previously mapped to human chromosome 19q13, is frequently associated with a variety of malformations. To identify the gene involved in DBA, we cloned the chromosome 19q13 breakpoint in a patient with a reciprocal X;19 chromosome translocation. The breakpoint occurred in the gene encoding ribosomal protein S19. Furthermore, we identified mutations in RPS19 in 10 of 40 unrelated DBA patients, including nonsense, frameshift, splice site and missense mutations, as well as two intragenic deletions. These mutations are associated with clinical features that suggest a function for RPS19 in erythropoiesis and embryogenesis.
780 citations
TL;DR: In this article, the stellar (n,gamma) cross sections of neutron-magic nuclei at N = 82, and in particular of 142Nd, turned out to represent a sensitive test for models of s-process nucleosynthesis and provided significantly better agreement between the solar abundance distribution of s nuclei and the predictions of models for low mass AGB stars.
Abstract: The recently improved information on the stellar (n,gamma) cross sections of neutron-magic nuclei at N = 82, and in particular of 142Nd, turned out to represent a sensitive test for models of s-process nucleosynthesis. While these data were found to be incompatible with the classical approach based on an exponential distribution of neutron exposures, they provide significantly better agreement between the solar abundance distribution of s nuclei and the predictions of models for low mass AGB stars. Particular attention is paid to a consistent description of s-process branchings in the region of the rare earth elements. It is shown that - in certain cases - the nuclear data are sufficiently accurate that the resulting abundance uncertainties can be completely attributed to stellar modelling. Thus, the s process becomes important for testing the role of different stellar masses and metallicities as well as for constraining the assumptions for describing the low neutron density provided by the 13C source.
778 citations
TL;DR: A new role for αvβ3 integrin is indicated in the activation of an in vitro angiogenic program in endothelial cells by participating in the full activation of VEGFR‐2 triggered by VEGF‐A, which is an importantAngiogenic inducer in tumors, inflammation and tissue regeneration.
Abstract: Interaction between integrin alphavbeta3 and extracellular matrix is crucial for endothelial cells sprouting from capillaries and for angiogenesis. Furthermore, integrin-mediated outside-in signals co-operate with growth factor receptors to promote cell proliferation and motility. To determine a potential regulation of angiogenic inducer receptors by the integrin system, we investigated the interaction between alphavbeta3 integrin and tyrosine kinase vascular endothelial growth factor receptor-2 (VEGFR-2) in human endothelial cells. We report that tyrosine-phosphorylated VEGFR-2 co-immunoprecipitated with beta3 integrin subunit, but not with beta1 or beta5, from cells stimulated with VEGF-A165. VEGFR-2 phosphorylation and mitogenicity induced by VEGF-A165 were enhanced in cells plated on the alphavbeta3 ligand, vitronectin, compared with cells plated on the alpha5beta1 ligand, fibronectin or the alpha2beta1 ligand, collagen. BV4 anti-beta3 integrin mAb, which does not interfere with endothelial cell adhesion to vitronectin, reduced (i) the tyrosine phosphorylation of VEGFR-2; (ii) the activation of downstream transductor phosphoinositide 3-OH kinase; and (iii) biological effects triggered by VEGF-A165. These results indicate a new role for alphavbeta3 integrin in the activation of an in vitro angiogenic program in endothelial cells. Besides being the most important survival system for nascent vessels by regulating cell adhesion to matrix, alphavbeta3 integrin participates in the full activation of VEGFR-2 triggered by VEGF-A, which is an important angiogenic inducer in tumors, inflammation and tissue regeneration.
624 citations
595 citations
TL;DR: The distinctiveness of B-CLL B cells explains why B- CLL is different from other B-cell tumors and accounts for the development of immune deficiency and autoimmunity.
Abstract: PURPOSE: To review the recent major advances in the molecular and cell biology of B-cell chronic lymphocytic leukemia (B-CLL). METHODS: We analyzed the nature of malignant B-CLL B cells and their interactions with the microenvironment. RESULTS: B-CLL is a malignancy of a mantle zone-based subpopulation of anergic, self-reactive, activated CD5+ B cells devoted to the production of polyreactive natural autoantibodies. It is the quintessential example of a human malignancy that primarily involves defects in the induction of programmed cell death. An abnormal karyotype is observed in about 50% of patients with B-CLL. Patients with 13q14 abnormalities show heavy somatic mutation and have a benign disease. Trisomy 12 is associated with unmutated VH genes, atypical cellular morphology, and progressive disease. Extended cell survival is further shielded by a kinetic refractoriness likely promoted by abnormalities of the B-cell antigen receptor complex and favored by some cytokines that highlight a reciprocal dial...
428 citations
TL;DR: The findings indicate that in fit patients (ASA I and II), single-stage laparoscopic treatment is the better option, and preoperative ESE should be confined to poor-risk patients—i.e., those with cholangitis or severe pancreatitis.
Abstract: Background: The current management of patients with gallstone disease and ductal calculi consists of endoscopic stone extraction (ESE) followed by laparoscopic cholecystectomy (LC). Following the advent of techniques of laparoscopic ductal stone clearance, an alternative single-stage laparoscopic treatment was introduced for these patients. The European Association of Endoscopic Surgery (E.A.E.S.) set up a ductal stone trial to compare the relative efficacy and outcome of these two management options.
TL;DR: An FTIR and quadrupole mass spectroscopic study of the water-gas shift (WGS), the reverse WGS reactions, and the adsorption of the individual molecules involved has been carried out on Au/Fe2O3 and Au/TiO2 catalysts as mentioned in this paper.
TL;DR: The drying and oxidative degradation of linseed oil have been investigated through exposition of samples in form of thin films to indoor laboratory conditions, or treated at a constant temperature of 80°C, or with irradiation at wavelengths >295 mm as discussed by the authors.
TL;DR: An increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC are reported.
Abstract: PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non–small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m2 on days 1, 8, and 15 plus cisplatin 100 mg/m2 on day 2, every 28 days, or mitomycin 6 mg/m2, ifosfamide 3,000 mg/m2, and mesna on day 1 plus cisplatin 100 mg/m2 on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P = .029). The median survival time was 8.6 months in t...
TL;DR: Findings show that a spatially directed expectation of pain reduction is capable of inducing a specific effect only on the part of the body which is the target of the expectation, and suggests that a highly organized and somatotopic network of endogenous opioids links expectation, attention, and body schema.
Abstract: We induced specific expectations of analgesia on four different parts of the body to understand how endogenous opioid systems are activated by expectancies. The left hand, right hand, left foot, and right foot were simultaneously stimulated by means of a subcutaneous injection of capsaicin, which produces a painful burning sensation. Specific expectations of analgesia were induced by applying a placebo cream on one of these body parts and by telling the subjects that it was a powerful local anesthetic. In such a way, expectancy of the anesthetic effect was directed only toward the part on which the placebo cream was applied. We found that a placebo analgesic response occurred only on the treated part, whereas no variation in pain sensitivity was found on the untreated parts. If the same experiment was performed after an intravenous infusion of the opioid antagonist naloxone, this highly spatial-specific placebo response was totally abolished, indicating that it was completely mediated by endogenous opioid systems. These findings show that a spatially directed expectation of pain reduction is capable of inducing a specific effect only on the part of the body which is the target of the expectation. Most important, this specific effect is mediated by endogenous opioids, indicating that placebo-activated opioids do not act on the entire body but only on the part where expectancy is directed. This suggests that a highly organized and somatotopic network of endogenous opioids links expectation, attention, and body schema.
TL;DR: The statistics of quiescent times between successive bursts of solar flares activity, performed using 20 years of data, displays a power law distribution with exponent of 2.4.
Abstract: The statistics of quiescent times ${\ensuremath{\tau}}_{L}$ between successive bursts of solar flares activity, performed using 20 years of data, displays a power law distribution with exponent $\ensuremath{\alpha}\ensuremath{\simeq}2.4$. This is an indication of an underlying complex dynamics with long correlation times. The observed scaling behavior is in contradiction with the self-organized criticality models of solar flares which predict Poisson-like statistics. Chaotic models, including the destabilization of the laminar phases and subsequent restabilization due to nonlinear dynamics, are able to reproduce the power law for the quiescent times. A shell model of MHD turbulence correctly reproduces all the observed distributions.
TL;DR: In this paper, the V2O5-MoO3/TiO2 catalysts are considered and the presence of electronic interactions between the TiO2-supported V and Mo oxides is also apparent.
TL;DR: Findings support and extend the previous findings that CD34(+) CB stem cells could indeed be grown and expanded in vitro for an extremely long period of time and help design efficient stem cell expansion procedures for clinical use.
TL;DR: In this article, the authors reviewed all existing evidence and indications in favour of neutrino oscillations that have been obtained in the atmospheric, solar and LSND experiments and investigated possibilities to test the different neutrinos mass and mixing schemes obtained in this way.
TL;DR: In this article, the authors present a self-consistent empirical model for several plasma parameters in the extended solar corona above a polar coronal hole, derived from observations with the SOHO Ultraviolet Coronagraph Spectrometer (UVCS/SOHO) during the period between 1996 November and 1997 April.
Abstract: We present a comprehensive and self-consistent empirical model for several plasma parameters in the extended solar corona above a polar coronal hole. The model is derived from observations with the SOHO Ultraviolet Coronagraph Spectrometer (UVCS/SOHO) during the period between 1996 November and 1997 April. We compare observations of H I Lyα and O VI λλ1032, 1037 emission lines with detailed three-dimensional models of the plasma parameters and iterate for optimal consistency between measured and synthesized observable quantities. Empirical constraints are obtained for the radial and latitudinal distribution of density for electrons, H0, and O5+, as well as the outflow velocity and unresolved anisotropic most probable speeds for H0 and O5+. The electron density measured by UVCS/SOHO is consistent with previous solar minimum determinations of the white-light coronal structure; we also perform a statistical analysis of the distribution of polar plumes using a long time series. From the emission lines we find that the unexpectedly large line widths of H0 atoms and O5+ ions at most heights are the result of anisotropic velocity distributions. These distributions are not consistent with purely thermal motions or the expected motions from a combination of thermal and transverse wave velocities. Above 2 R☉, the observed transverse most probable speeds for O5+ are significantly larger than the corresponding motions for H0, and the outflow velocities of O5+ are also significantly larger than the corresponding velocities of H0. Also, the latitudinal dependence of intensity constrains the geometry of the wind velocity vectors, and superradial expansion is more consistent with observations than radial flow. We discuss the constraints and implications on various theoretical models of coronal heating and acceleration.
TL;DR: The data establish that mutations in SLC7A9 cause non-type I cystinuria, and suggest that bo,+AT is the light subunit of rBAT, and a new transcript belonging to a family of light subunits of amino acid transporters is identified.
Abstract: Cystinuria (MIM 220100) is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids. Mutations in SLC3A1, encoding rBAT, cause cystinuria type I (ref. 1), but not other types of cystinuria (ref. 2). A gene whose mutation causes non-type I cystinuria has been mapped by linkage analysis to 19q12–13.1 (refs 3,4). We have identified a new transcript, encoding a protein (bo,+AT, for bo,+ amino acid transporter) belonging to a family of light subunits of amino acid transporters, expressed in kidney, liver, small intestine and placenta, and localized its gene (SLC7A9) to the non-type I cystinuria 19q locus. Co-transfection of bo,+AT and rBAT brings the latter to the plasma membrane, and results in the uptake of L-arginine in COS cells. We have found SLC7A9 mutations in Libyan-Jews, North American, Italian and Spanish non-type I cystinuria patients. The Libyan Jewish patients are homozygous for a founder missense mutation (V170M) that abolishes bo,+AT amino-acid uptake activity when co-transfected with rBAT in COS cells. We identified four missense mutations (G105R, A182T, G195R and G295R) and two frameshift (520insT and 596delTG) mutations in other patients. Our data establish that mutations in SLC7A9 cause non-type I cystinuria, and suggest that bo,+AT is the light subunit of rBAT.
TL;DR: The superoxide radical anion O2- is both an important intermediate in heterogeneous catalytic oxidation and a useful probe for positive charges in ionic solids, such as metal oxides and zeolites as mentioned in this paper.
Abstract: The superoxide radical anion O2- is both an important intermediate in heterogeneous catalytic oxidation and a useful probe for positive charges in ionic solids, such as metal oxides and zeolites. The paper illustrates the main circumstances under which stable superoxide anions are formed at surfaces: (i) direct surface–oxygen electron transfer; (ii) photoinduced electron transfer; (iii) surface intermolecular electron transfer; (iv) decomposition of hydrogen peroxide.
TL;DR: In this paper, the chemical evolution of the Galaxy for elements from Ba to Eu, using an evolutionary model suitable for reproducing a large set of Galactic (local and nonlocal) and extragalactic constraints, has been studied.
Abstract: We follow the chemical evolution of the Galaxy for elements from Ba to Eu, using an evolutionary model suitable for reproducing a large set of Galactic (local and nonlocal) and extragalactic constraints. Input stellar yields for neutron-rich nuclei have been separated into their s-process and r-process components. The production of s-process elements in thermally pulsing asymptotic giant branch stars of low mass proceeds from the combined operation of two neutron sources: the dominant reaction 13C(α, n)16O, which releases neutrons in radiative conditions during the interpulse phase, and the reaction 22Ne(α, n)25Mg, marginally activated during thermal instabilities. The resulting s-process distribution is strongly dependent on the stellar metallicity. For the standard model discussed in this paper, there is a sharp production of the Ba-peak elements around Z Z☉/4. Concerning the r-process yields, we assume that the production of r-nuclei is a primary process occurring in stars near the lowest mass limit for Type II supernova progenitors. The r-contribution to each nucleus is computed as the difference between its solar abundance and its s-contribution, given by the Galactic chemical evolution model at the epoch of the formation of the solar system. We compare our results with spectroscopic abundances of elements from Ba to Eu at various metallicities (mainly from F and G stars), showing that the observed trends can be understood in the light of present knowledge of neutron capture nucleosynthesis. Finally, we discuss a number of emerging features that deserve further scrutiny.
TL;DR: Excellent early and late surgical results can be obtained in patients with benign valve tumors, and the prognosis for patients with a malignant valve tumor is poor.
TL;DR: In this article, a pyrex fixed-bed continuous photoreactor irradiated by a medium pressure Hg lamp was used for performing photoreactivity experiments, and the main oxidation product was benzaldehyde but benzene, benzyl alcohol and traces of benzoic acid, phenol and unidentified compounds were also detected.
Abstract: Photo-oxidation of toluene has been carried out in gas–solid regime by using polycrystalline anatase TiO2 as the catalyst. The reacting gaseous mixture was toluene, air and water in various molar ratios. A pyrex fixed-bed continuous photoreactor irradiated by a medium pressure Hg lamp was used for performing the photoreactivity experiments. The main oxidation product was benzaldehyde but benzene, benzyl alcohol and traces of benzoic acid, phenol and unidentified compounds were also detected. The molar conversion to benzaldehyde with respect to the initial amount of toluene was ca. 20% in the best experimental conditions. Benzene was produced only as a transient product during the first 3–4 h of irradiation. The dependence of feed composition and flow rate on the toluene fractional conversion was investigated. Selected experiments were performed by using N2 or CO2 instead of air. The presence of oxygen was essential for the occurrence of the photoreaction while water played an important role in order to maintain the catalyst activity. Moreover, a Fourier-transform infrared spectroscopy (FT-IR) investigation was carried out simulating the experimental conditions used during the photoreactivity experiments. The results indicated that toluene is weakly stabilised on the hydrated TiO2 particles by hydrogen-bonding with surface hydroxyl groups, and that it is photo-oxidised to benzaldehyde only in the presence of surface OH groups.
TL;DR: The establishment and characterization of two cell lines, MEC1 and MEC2, that grew spontaneously on two subsequent occasions from the peripheral blood of a patient with B-chronic lymphocytic leukemia in prolymphocytoid transformation are reported.
TL;DR: Interestingly, flow cytometric analysis of the tumour cell population revealed the existence of an aneuploid peak, which suggests that resveratrol causes apoptosis in the tumours cell population resulting in a decreased cell number.
TL;DR: The results indicate that Cu2+ and CH3Hg+ can affect, although to a different extent, glutathione metabolism in mussel tissues; common traits were a decrease in tissue glutATHione content, stimulation of GST activity and inhibition of GSH synthesis rate; on the other hand, inorganic Hg2+ (0.2 μM) did not significantly affect glutathion content and metabolism in Mussel tissues.
TL;DR: Recently, a color decomposition using structure constants was introduced for purely gluonic tree amplitudes, in a compact form involving only the linearly independent subamplitudes as discussed by the authors.
Abstract: Recently, a color decomposition using structure constants was introduced for purely gluonic tree amplitudes, in a compact form involving only the linearly independent subamplitudes. We give two proofs that this decomposition holds for an arbitrary number of gluons. We also present and prove similar decompositions at one loop, both for pure gluon amplitudes and for amplitudes with an external quark-antiquark pair.
TL;DR: An up-to-date review on this particular aspect of oxidative stress--dependent modulation of cellular functions-as well as to offer comments on the related pathophysiological implications, with special reference to human conditions of disease.
Abstract: Reactive oxygen intermediates (ROI) and other pro-oxidant agents are known to elicit, in vivo and in vitro, oxidative decomposition of omega-3 and omega-6 polyunsaturated fatty acids of membrane phospholipids (i.e, lipid peroxidation). This leads to the formation of a complex mixture of aldehydic end-products, including malonyldialdehyde (MDA), 4-hydroxy-2,3-nonenal (HNE), and other 4-hydroxy-2,3-alkenals (HAKs) of different chain length. These aldehydic molecules have been considered originally as ultimate mediators of toxic effects elicited by oxidative stress occurring in biological material. Experimental and clinical evidence coming from different laboratories now suggests that HNE and HAKs can also act as bioactive molecules in either physiological and pathological conditions. These aldehydic compounds can affect and modulate, at very low and nontoxic concentrations, several cell functions, including signal transduction, gene expression, cell proliferation, and, more generally, the response of the target cell(s). In this review article, we would like to offer an up-to-date review on this particular aspect of oxidative stress--dependent modulation of cellular functions-as well as to offer comments on the related pathophysiological implications, with special reference to human conditions of disease.