Showing papers by "University of Florence published in 2001"

CONSENSUS: Guidelines for Diagnosis and Therapy of MEN Type 1 and Type 2

Abstract: This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT

Abstract: Background and Purpose—MRI is more sensitive than CT for detection of age-related white matter changes (ARWMC). Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI, and they differ in many aspects. This makes it difficult to compare CT and MRI studies. To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient samples, it is necessary to have a rating scale constructed for both MRI and CT. We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT. Methods—Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination (MRI or CT) performed. The patients came from 4 centers in Europe, and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale. The interrater reliability was evaluated by using κ statistics. The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas. Results—...

Improved wavelet-based watermarking through pixel-wise masking

Abstract: A watermarking algorithm operating in the wavelet domain is presented. Performance improvement with respect to existing algorithms is obtained by means of a new approach to mask the watermark according to the characteristics of the human visual system (HVS). In contrast to conventional methods operating in the wavelet domain, masking is accomplished pixel by pixel by taking into account the texture and the luminance content of all the image subbands. The watermark consists of a pseudorandom sequence which is adaptively added to the largest detail bands. As usual, the watermark is detected by computing the correlation between the watermarked coefficients and the watermarking code, and the detection threshold is chosen in such a way that the knowledge of the watermark energy used in the embedding phase is not needed, thus permitting one to adapt it to the image at hand. Experimental results and comparisons with other techniques operating in the wavelet domain prove the effectiveness of the new algorithm.

Josephson junction arrays with Bose-Einstein condensates.

Abstract: We report on the direct observation of an oscillating atomic current in a one-dimensional array of Josephson junctions realized with an atomic Bose-Einstein condensate. The array is created by a laser standing wave, with the condensates trapped in the valleys of the periodic potential and weakly coupled by the interwell barriers. The coherence of multiple tunneling between adjacent wells is continuously probed by atomic interference. The square of the small-amplitude oscillation frequency is proportional to the microscopic tunneling rate of each condensate through the barriers and provides a direct measurement of the Josephson critical current as a function of the intermediate barrier heights. Our superfluid array may allow investigation of phenomena so far inaccessible to superconducting Josephson junctions and lays a bridge between the condensate dynamics and the physics of discrete nonlinear media.

Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years.

Abstract: Objective To reassess, in a cohort of patients with early-onset multiple sclerosis, the long-term evolution of cognitive deficits, their relationship to the disease's clinical progression, and their effects on daily life. Design Ten years after our baseline assessment, we again compared the cognitive performance of patients and control subjects on a neuropsychological test battery. Clinical and demographic correlates of cognitive impairment and their effects on everyday functioning were determined by multiple linear regression analysis. Setting The research clinic of a university department of neurology. Participants Forty-five inpatients and outpatients with multiple sclerosis and 65 demographically matched healthy controls from the original sample. Main Outcome Measures Mean scores of both groups on the neuropsychological test battery in initial and 2 follow-up evaluations (about 4 and 10 years, respectively); number of cognitively impaired subjects, defined by the number of subtests failed; regression coefficients measuring the relationship between clinical variables and cognitive outcome and between mental decline and everyday functioning assessed by the Environmental and the Incapacity Status Scales. Results Previously detected cognitive defects in verbal memory, abstract reasoning, and linguistic processes were confirmed on the third testing, at which time deficits in attention/short-term spatial memory also emerged. Only 20 of 37 patients who were cognitively unimpaired on initial testing remained so by the end of the follow-up, when the proportion of subjects who were cognitively impaired reached 56%. Degree of physical disability, progressive disease course, and increasing age predicted the extent of cognitive decline. Disability level and degree of cognitive impairment were independent predictors of a patient's handicap in the workplace and in social settings. Conclusions In the course of a sufficiently long follow-up, cognitive dysfunction is likely to emerge and progress in a sizable proportion of patients. As multiple sclerosis advances, neurological and cognitive involvement tend to converge. Limitations in a patient's work and social activities are correlated with the extent of cognitive decline, independent of degree of physical disability.

Dust Formation in Primordial Type II Supernovae

Abstract: We have investigated the formation of dust in the ejecta of Type II supernovae (SNe), mostly of primordial composition, to answer the question of where are the first solid particles formed in the universe. However, we have also considered non-zero progenitor’s metallicity values up to Z = Z⊙. The calculations are based on standard nucleation theory and the scheme has been first tested on the well studied case of SN1987A, yielding results that are in agreement with the available data. We find that: i) the first dust grains are predominantly made of silicates, amorphous carbon (AC), magnetite, and corundum; ii) the largest grains are the AC ones, with sizes around 300u , whereas other grain types have smaller radii, around 10-20u The grain size distribution depends somewhat on the thermodynamics of the ejecta expansion and variations in the results by a factor � 2 might occur within reasonable estimates of the relevant parameters. Also, and for the same reason, the grain size distribution, is essentially unaffected by metallicity changes. The predictions on the amount of dust formed are very robust: for Z = 0, we find that SNe with masses in the range (12-35)M⊙ produce about 0.08M⊙ < Md < � 0.3M⊙ of dust/SN. The above range increases by roughly 3 times as the metallicity is increased to solar values. We discuss the implications and the cosmological consequences of the results.

First Results from the X-Ray and Optical Survey of the Chandra Deep Field South

Abstract: We present our first results from 120 ks of X-ray observations obtained with the Advanced CCD Imaging Spectrometer on the Chandra X-Ray Observatory. The field of the two combined exposures is 0.096 deg2 and the detection limit is to a S/N of 2 (corresponding to ~7 net counts). We reach a flux of 2 × 10-16 erg s-1 cm-2 in the 0.5-2 keV soft band and 2 × 10-15 erg s-1 cm-2 in the 2-10 keV hard band. Our combined sample has 144 soft sources and 91 hard sources, for a total of 159 sources. Fifteen sources are detected only in the hard band, and 68 only in the soft band. For the optical identification, we carried out a survey in VRI with the FORS-1 imaging spectrometer on the Antu telescope (UT-1 at VLT) complete to R ≤ 26. This data set was complemented with data from the ESO Imaging Survey (EIS) in the UBJK bands and the ESO Wide Field Imager Survey (WFI) in the B band. The positional accuracy of the X-ray detections is of the order of 1'' in the central 6'. Optical identifications are found for 90% of the sources. Optical spectra have been obtained for 12 objects. We obtain the cumulative spectra of the faint and bright X-ray sources in the sample and also the hardness ratios of individual sources. A power-law fit in the range 2-10 keV using the Galactic value of NH 8 × 1019 cm-2 yields a photon index of Γ = 1.70 ± 0.12 and 1.35 ± 0.20 (errors at 90% confidence level) for the bright and faint samples, respectively, showing a flattening of the spectrum at lower fluxes. Hardness ratio is given as a function of X-ray flux and confirms this result. The spectrum of our sources is approaching the spectrum of the X-ray background (XRB) in the hard band, which has an effective Γ = 1.4. Correlation function analysis for the angular distribution of the sources indicates that they are significantly clustered on scales as large as 100''. The scale dependence of the correlation function is a power law with index γ ~ 2, consistent with that of the galaxy distribution in the local universe. Consequently, the discrete sources detected by deep Chandra-pointed observations can be used as powerful tracers of the large-scale structure at high redshift. We discuss the log N- log S relationship and the discrete source contribution to the integrated X-ray sky flux. In the soft band, the sources detected in the field at fluxes below 10-15 erg s-1 cm-2 contribute (4.0 ± 0.3) × 10-12 erg cm-2 s-1 deg-2 to the total XRB. The flux resolved in the hard band down to the flux limit of 2 × 10-15 erg s-1 cm-2 contributes (1.05 ± 0.2) × 10-11 erg cm-2 s-1 deg-2. Once the contribution from the bright counts resolved by ASCA is included, the total resolved XRB amounts to 1.3 × 10-11 erg cm-2 s-1 deg-2, which is 60%-80% of the total measured background. This result confirms that the XRB is due to the integrated contribution of discrete sources, but shows that there is still a relevant fraction (at least 20%) of the hard XRB to be resolved at fluxes below 10-15 erg s-1 cm-2. We discuss the X-ray flux versus R magnitude relation for the identified sources. We find that 10% of the sources in our sample are not immediately identifiable at R > 26. For these sources, SX/Sopt > 15, whereas most of the ROSAT and Chandra sources have SX/Sopt < 10. We have also found a population of objects with unusually low SX/Sopt that are identified as galaxies. The R-K versus R color diagram shows that the Chandra sources continue the trend seen by ROSAT. For our 12 spectroscopically studied objects with redshifts, we observe four QSOs, five Seyfert 2 galaxies, one elliptical, and two interacting galaxies. We compare LX versus z obtained with these measurements and show that Chandra is achieving the predicted sensitivity.

Opposing cardioprotective actions and parallel hypertrophic effects of δPKC and ɛPKC

Abstract: Conflicting roles for protein kinase C (PKC) isozymes in cardiac disease have been reported. Here, deltaPKC-selective activator and inhibitor peptides were designed rationally, based on molecular modeling and structural homology analyses. Together with previously identified activator and inhibitor peptides of epsilonPKC, deltaPKC peptides were used to identify cardiac functions of these isozymes. In isolated cardiomyocytes, perfused hearts, and transgenic mice, deltaPKC and epsilonPKC had opposing actions on protection from ischemia-induced damage. Specifically, activation of epsilonPKC caused cardioprotection whereas activation of deltaPKC increased damage induced by ischemia in vitro and in vivo. In contrast, deltaPKC and epsilonPKC caused identical nonpathological cardiac hypertrophy; activation of either isozyme caused nonpathological hypertrophy of the heart. These results demonstrate that two related PKC isozymes have both parallel and opposing effects in the heart, indicating the danger in the use of therapeutics with nonselective isozyme inhibitors and activators. Moreover, reduction in cardiac damage caused by ischemia by perfusion of selective regulator peptides of PKC through the coronary arteries constitutes a major step toward developing a therapeutic agent for acute cardiac ischemia.

Quality of life in multiple sclerosis: the impact of depression, fatigue and disability

Abstract: This study deals with the assessment of quality of life and its main clinical and demographical determinants in a clinical series of 103 patients with multiple sclerosis (MS) (37 men; 66 women; mean age 44.89 years; mean disease duration 12.40 years; mean EDSS score 4.07). We used the MSQOL-54 inventory, a disease-specific instrument recently validated in an Italian population. Each patient underwent a complete clinical assessment, including that of disability status (Expanded Disability Status Scale), cognitive function (Mini Mental State Examination), depression (Hamilton Rating Scale for Depression) and fatigue (Fatigue Severity Scale). In terms of Pearson's correlations, there was a moderate inverse relationship between disability level and the MSQOL-54 physical composite score, and a moderate to strong inverse correlation between depression or fatigue severity and both the physical and mental composite scores. In a stepwise linear regression analysis, depression, fatigue and disability level were confirmed to be significant and independent predictors of quality of life. Quality of life instruments can help to provide a broader measure of the disease impact and to develop a care program tailored to the patient's needs.

A Comparison of U.S. and European University-Industry Relations in the Life Sciences

Abstract: We draw on diverse data sets to compare the institutional organization of upstream life science research across the United States and Europe. Understanding cross-national differences in the organization of innovative labor in the life sciences requires attention to the structure and evolution of biomedical networks involving public research organizations (universities, government laboratories, nonprofit research institutes, and research hospitals), science-based biotechnology firms, and multinational pharmaceutical corporations. We use network visualization methods and correspondence analyses to demonstrate that innovative research in biomedicine has its origins in regional clusters in the United States and in European nations. But the scientific and organizational composition of these regions varies in consequential ways. In the United States, public research organizations and small firms conduct R&D across multiple therapeutic areas and stages of the development process. Ties within and across these regions link small firms and diverse public institutions, contributing to the development of a robust national network. In contrast, the European story is one of regional specialization with a less diverse group of public research organizations working in a smaller number of therapeutic areas. European institutes develop local connections to small firms working on similar scientific problems, while cross-national linkages of European regional clusters typically involve large pharmaceutical corporations. We show that the roles of large and small firms differ in the United States and Europe, arguing that the greater heterogeneity of the U.S. system is based on much closer integration of basic science and clinical development.

Bose-Einstein condensation of potassium atoms by sympathetic cooling.

Abstract: We report on the Bose-Einstein condensation of potassium atoms, whereby quantum degeneracy is achieved by sympathetic cooling with evaporatively cooled rubidium. Because of the rapid thermalization of the two different atoms, the efficiency of the cooling process is high. The ability to achieve condensation by sympathetic cooling with a different species may provide a route to the production of degenerate systems with a larger choice of components.

Cytokine receptors and signaling in hepatic stellate cells.

Abstract: Following acute or chronic liver tissue damage, hepatic stellate cells (HSCs) undergo a process of activation toward a phenotype characterized by increased proliferation, motility, contractility, and synthesis of extracellular matrix components. Activation of HSCs is regulated by several soluble factors, including growth factors, cytokines, chemokines, and products of oxidative stress, as well as by extensive changes in the composition and organization of the ECM. Different groups of soluble factors may be classified according to their prevalent biological effect: (a) factors promoting HSC proliferation and/or migration (i.e., platelet-derived growth factor, basic fibroblast growth factor, insulin-like growth factor-1); (b) factors promoting fibrillar ECM accumulation, particularly transforming growth factor-beta1; (c) factors with a prevalent contractile effect on HSCs, such as endothelin-1, thrombin, angiotensin-II and vasopressin, although all these agents also may promote HSC proliferation; (d) proinflammatory cytokines and chemokines; and (e) cytokines with a prominent antiinflammatory/antifibrogenic activity, such as interleukin-10 and interferon-gamma. Additional important issues are represented by the relationship between cytokine and integrin signaling, and by the effects of oxidative stress-related molecules on cytokine signaling. In the past decade the major intracellular signaling pathways elicited by these factors in HSCs have been greatly elucidated.

Changes in DNA Methylation in Neoplasia: Pathophysiology and Therapeutic Implications

Abstract: Methylation of DNA is a biochemical modification that can influence gene expression and is involved in inactivating one of the two X chromosomes in women. Evidence that has accumulated in the past 10 years suggests that cancer cells usurp this physiologic mechanism and use it to their benefit by inactivating tumor suppressor genes and related proteins. However, the primary structure of the affected proteins remains intact; reversal of abnormalities in DNA methylation may therefore restore the tumor-suppressive function of these genes and provide a novel approach to cancer therapy. Two demethylating drugs, 5-azacytidine and 5-aza-deoxycytidine, are currently being tested in clinical trials, and several others are in preclinical development. In this article, the biological rationale for targeting aberrant methylation in cancer therapy is reviewed and completed phase I and II trials of this approach, some of which show promise for treatment of hematologic malignancies, are summarized.

Characteristics, Outcome, and Care of Stroke Associated With Atrial Fibrillation in Europe Data From a Multicenter Multinational Hospital–Based Registry (The European Community Stroke Project)

Abstract: Background and Purpose—The role of atrial fibrillation (AF) as a determinant of stroke outcome is not well established. Studies focusing on this topic relied on relatively small samples of patients, scarcely representative of the older age groups. We aimed at evaluating clinical characteristics, care, and outcome of stroke associated with AF in a large European sample. Methods—In a European Concerted Action involving 7 countries, 4462 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month survival, disability (Barthel Index), and handicap (Rankin scale). Results—AF was present in 803 patients (18.0%). AF patients, compared with those without AF, were older, were more frequently female, and more often had experienced a previous myocardial infarction; they were less often diabetics, alcohol consumers, and smokers (all P<0.001). At 3 months, 32.8% of the AF patients were dead compared with 19.9% of the non-AF patien...

Cell cycle–dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity

Abstract: Endothelial cell receptors for the angiostatic chemokines IFN-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by IFN-gamma (Mig) have not yet been identified, and the mechanisms responsible for the effects of these chemokines on angiogenesis are still unclear. IP-10 and Mig share a common functional receptor on activated T lymphocytes, named CXC chemokine receptor 3 (CXCR3). Using in situ hybridization and immunohistochemistry, we show that CXCR3 is expressed by a small percentage of microvascular endothelial cells in several human normal and pathological tissues. Primary cultures of human microvascular endothelial cells (HMVECs) likewise express CXCR3, although this expression is limited to the S/G2-M phase of their cell cycle. Both IP-10 and Mig, as well as the IFN-gamma-inducible T-cell alpha chemoattractant (I-TAC), which all share high-affinity binding for CXCR3, block HMVEC proliferation in vitro, an effect that can be inhibited by an anti-CXCR3 antibody. These data provide definitive evidence of CXCR3 expression by HMVEC and open new avenues for therapeutic interventions in all conditions in which an angiostatic effect may be beneficial.

Features of particle multiplicities and strangeness production in central heavy ion collisions between 1.7A and 158A GeV/c

Abstract: A systematic study is performed of fully integrated particle multiplicities in central Au-Au and Pb-Pb collisions at beam momenta of $1.7A \mathrm{GeV}/c, 11.6A \mathrm{GeV}/c$ (Au-Au), and $158A \mathrm{GeV}/c$ (Pb-Pb) by using a statistical-thermal model. The close similarity of the colliding systems makes it possible to study heavy ion collisions under definite initial conditions over a range of center-of-mass energies covering more than 1 order of magnitude. In order to further study the behavior of strangeness production, an updated study of Si-Au collisions at $14.6A \mathrm{GeV}$ is also presented. The data analysis has been performed with two completely independent numerical algorithms giving closely consistent results. We conclude that a thermal model description of particle multiplicities, with additional strangeness suppression, is possible for each energy. The degree of chemical equilibrium of strange particles and the relative production of strange quarks with respect to u and d quarks are higher than in ${e}^{+}{e}^{\ensuremath{-}},$ $pp,$ and $p\overline{p}$ collisions at comparable and even at lower energies. The behavior of strangeness production as a function of center-of-mass energy and colliding system is presented and discussed. The average energy per hadron in the comoving frame is close to 1 GeV per hadron despite the fact that the energy increases more than tenfold.

Effect of Metformin on Glucagon-Like Peptide 1 (GLP-1) and Leptin Levels in Obese Nondiabetic Subjects

Abstract: OBJECTIVE —To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels. RESEARCH DESIGN AND METHODS —A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects. On days 0 and 15, leptin and GLP-1(7–36)amide/(7–37) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7–36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV (DPP-IV) were also studied. RESULTS —Leptin levels were not affected by the oral glucose load, and they were not modified after metformin treatment. Metformin induced a significant ( P CONCLUSIONS —Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation.

Light emission: A temperature-tunable random laser.

Abstract: Random lasers have fascinating emission properties that lie somewhere between those of a conventional laser and a common light-bulb. We have created a random laser that can be brought above and below its threshold for laser emission by small changes in its temperature, thereby creating a light source with a temperature-tunable colour spectrum. As a single random laser can be made as small as a grain of tens of micrometres in diameter, we expect our device to find application in photonics, temperature-sensitive displays and screens, and in remote temperature sensing. Lasers are now commonplace - for example, they are used in industry and in hospitals, in bar-code scanners and compact-disc players. Conventional lasers are based on an optically active material and some sort of laser cavity that traps light for long enough for laser action to occur. A new type of laser source, known as a random laser, has been discovered that does not require a regular cavity but instead depends on a diffusive material such as a fine powder. In a random laser, light waves are trapped by multiple light scattering (that is, light diffusion), which takes over the role of the cavity in a regular laser (Fig. 1). The emission of a random-laser source has a well defined colour spectrum and can be pulsed, just like a regular laser, although its emission is in several directions because of the intrinsic randomness of the system.

A gender--dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity.

Abstract: Current literature indicates that elevated IL-6 serum levels are associated with diseases, disability and mortality in the elderly. In this paper, we studied the IL-6 promoter genetic variability at -174 C/G locus and its effect on IL-6 serum levels in a total of 700 people from 60 to 110 years of age, including 323 centenarians. We found that the proportion of homozygotes for the G allele at -174 locus decreases in centenarian males, but not in centenarian females. Moreover, we found that, only among males, homozygotes for the G allele at -174 locus have higher IL-6 serum levels in comparison with carriers of the C allele. On the whole, our data suggest that those individuals who are genetically predisposed to produce high levels of IL-6 during aging, i.e. -174 locus GG homozygous men, are disadvantaged for longevity.

Near-infrared template spectra of normal galaxies: k-corrections, galaxy models and stellar populations

Abstract: We have observed 28 local galaxies in the wavelength range between 1 and 2.4 μm in order to define template spectra of the normal galaxies along the Hubble sequence. Five galaxies per morphological type were observed in most cases, and the resulting rms spread of the normalized spectra of each class, including both intrinsic differences and observational uncertainties, is about 1 per cent in K, 2 per cent in H and 3 per cent in J. Many absorption features can be accurately measured. The target galaxies and the spectroscopic aperture (7×53 arcsec2) were chosen to be similar to those used by Kinney et al. to define template UV and optical spectra. The two data sets are matched in order to build representative spectra between 0.1 and 2.4 μm. The continuum shape of the optical spectra and the relative normalization of the near-IR ones were set to fit the average effective colours of the galaxies of the various Hubble classes. The resulting spectra are used to compute the k-corrections of the normal galaxies in the near-IR bands, and to check the predictions of various spectral synthesis models: while the shape of the continuum is generally well predicted, large discrepancies are found in the absorption lines. Among the other possible applications, here we also show how these spectra can be used to place constraints on the dominant stellar population in local galaxies. Spectra and k-corrections are publicly available and can be downloaded from the web site http://www.arcetri.astro.it/~filippo/spectra.

Social Capital and Local Development

Abstract: The concept of social capital has become more important in understanding contemporary economic development in the era of globalization. This concept, however, requires a theoretical framework that ...