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Showing papers by "University of Siena published in 1998"


Journal ArticleDOI
TL;DR: The Mediterranean basin has been studied in great detail over the past 20 years because of the anomalous natural presence of mercury, and marine animals of this basin have higher mercury body burdens than the same species in the Atlantic.

729 citations


Journal ArticleDOI
TL;DR: A large repertoire of functional antibodies with similar properties was produced by appending short variable complementarity-determining region 3 (CDR3) onto the two antibody germ line segments most frequently found in human antibodies by concentrating sequence diversity in regions of the antibody structure that are centrally located in the antigen binding site.

588 citations


Book
15 Nov 1998
TL;DR: Patterns and Meanings consists of case studies which make use of corpora and concordance technology and focuses on information that usually cannot be found in dictionaries, grammars, language textbooks or other resources but which the study of corpus data makes available.
Abstract: Patterns and Meanings consists of case studies which make use of corpora and concordance technology. Each case study elaborates a problem area, makes reference to both the descriptive and applied literature thus far, and then suggests ways of exploiting corpus data to shed light on the problem. Language phenomena investigated include word sense, phraseology and syntax, metaphor and creative use, text reference, idiom, and translation. Emphasis is given to information that usually cannot be found in dictionaries, grammars, language textbooks or other resources, but which the study of corpus data makes available. This work is particularly important not only for its language description insights, but also for pedagogical application. Further useful suggestions are included on setting up a medium-sized corpus on a personal computer.

407 citations


Journal ArticleDOI
TL;DR: In this paper, a systemic analysis of the relationships among components of a system's web, the flows of energy and other resources converging to produce the output (biomass, biodiversity, assets, industrial products) can be evaluated on a common basis, i.e. the content of solar equivalent energy.

366 citations


Journal Article
TL;DR: It is shown that a proportion of diffuse gastric cancer families of European origin have germ-line E-cadherin mutations; however, these mutations are absent in intestinal gastriccancer families.
Abstract: E-cadherin germ-line mutations have recently been described as a molecular basis for early-onset familial gastric cancer in Maori kindred. We screened 18 gastric cancer families of European origin for germ-line mutations to determine the proportion in which E-cadherin mutations occur and the clinical characteristics of the affected families. Truncating mutations were identified in three kindred with familial diffuse gastric cancer. In these families, the age of onset of gastric cancer was variable, the penetrance was incomplete, and one kindred contained individuals with cancers at other sites. Here, we show that a proportion of diffuse gastric cancer families of European origin have germ-line E-cadherin mutations; however, these mutations are absent in intestinal gastric cancer families.

325 citations


Journal ArticleDOI
TL;DR: It is shown that bacteria induce de novo synthesis of both major histocompatability complex (MHC) class I and II molecules in a mouse dendritic cell culture system and are shown to be a potentially useful mean for the correct delivery of exogenous antigens to be presented efficiently on MHC class I molecules.
Abstract: Here, we show that bacteria induce de novo synthesis of both major histocompatability complex (MHC) class I and II molecules in a mouse dendritic cell culture system. The neo-biosynthesis of MHC class I molecules is delayed as compared with that of MHC class II. Furthermore, bacteria stabilize MHC class I molecules by a 3-fold increase of their half-life. This has important consequences for the capacity of dendritic cells to present bacterial antigens in the draining lymph nodes. In addition, a model antigen, ovalbumin, expressed on the surface of recombinant Streptococcus gordonii is processed and presented on MHC class I molecules. This presentation is 10(6) times more efficient than that of soluble OVA protein. This exogenous pathway of MHC class I presentation is transporter associated with antigen processing (TAP)-dependent, indicating that there is a transport from phagolysosome to cytosol in dendritic cells. Thus, bacteria are shown to be a potentially useful mean for the correct delivery of exogenous antigens to be presented efficiently on MHC class I molecules.

275 citations


Journal ArticleDOI
TL;DR: It is demonstrated that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.
Abstract: Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. TheCTGF gene promotor contains a trans...

255 citations


Journal ArticleDOI
TL;DR: In this article, the inverse relationship between female participation and fertility appears to have broken down on a cross-country basis in the Western industrialized nations and Mediterranean Europe contributed to this breakdown with its combination of record low fertility and low participation.
Abstract: In this paper the authors address two related questions: first, why does the inverse relationship between female participation and fertility appear to have broken down on a cross-country basis in the Western industrialized nations and, second, why has Mediterranean Europe contributed to this breakdown with its combination of record low fertility and low participation? They re-examine the cross-country fertility--participation nexus from a long-term perspective and verify that there are no longer reasons to expect a systematic inverse relationship to hold for developed countries. The authors argue further that differences in participation and fertility reflect differences in the 'economics of the family' across countries. In Mediterranean countries, the combination of low fertility and low participation is favored by a family-centered welfare system, a family-biased production system and a family-oriented value system. And, contrary to widespread expectations, a very cohesive family has encouraged very low fertility. Copyright 1998 by Oxford University Press.

215 citations


Journal ArticleDOI
TL;DR: The introduction of another variable, the ER genotype, in the analysis of VDR genetic determination of BMD, may represent a useful model in the identification of patients at risk of developing a multigenic disorder like osteoporosis.
Abstract: Bone mass and bone turnover are under genetic control. Restriction fragment length polymorphisms (RFLPs) at the vitamin D receptor (VDR) gene locus have been recently correlated to bone mineral density (BMD) and rate of bone loss. However, agreement on this relationship is not universal. The existence of ethnical and environmental differences between populations, a health-based selection bias in several previous studies, and the involvement of other genes could explain these discordant findings. In this study, we examined the relationship of VDR and estrogen receptor (ER) gene RFLPs with lumbar spine and upper femur BMD in 426 Italian postmenopausal women, 57.7 +/- 0.4 yr old (144 normal, 106 osteopenic, and 176 osteoporotic). VDR gene RFLPs for ApaI, Bsm I, and TaqI restriction endonucleases and ER RFLPs for PvuII and XbaI restriction endonucleases were assessed by Southern blotting analysis and were indicated, respectively, as A-a, B-b, T-t, P-p, and X-x (uppercase letters signifying the absence and lowercase letters the presence of the restriction site). After correcting for potential confounding factors (age, height, weight, age since menopause, osteophytosis, and facet joint osteoarthritis), a statistically significant VDR genotype effect on lumbar BMD (P = 0.01, analysis of covariance), but not on femoral BMD, was detected, with subjects in AABBtt genotype showing a 13% lower BMD than those with aabbTT genotype (P < 0.05, Tukey's test). Moreover, a statistically significant prevalence of AABBtt genotype in osteoporotics, and of AabbTT and aabbTT genotypes in nonosteoporotics, were detected. Conversely, there was no significant relationship of ER genotype to either lumbar or femoral BMD, even though a trend for higher BMD values in women with the ER PP genotype (with respect to those with ER pp genotype) was detected. When mean lumbar BMD was calculated for women grouped by ER and VDR genotype, we observed a significant difference between those within the 2 opposite associations AABBtt-PPXX and aabbTT-ppxx (0.71 +/- 0.05 vs. 0.97 +/- 0.03 g/cm2, P < 0.05 Tukey's test). These results are consistent with a segregation of the VDR AABBtt genotype with a higher risk of developing osteoporosis, in the Italian female population. The introduction of another variable, the ER genotype, in the analysis of VDR genetic determination of BMD, may represent a useful model in the identification of patients at risk of developing a multigenic disorder like osteoporosis.

212 citations


Journal ArticleDOI
TL;DR: The mutation analysis revealed a high preponderance of mutations involving or creating cysteine residues, pointing to sites important for the tertiary folding and/or protein function, and highlights several amino acids which may be involved in XLRS1-specific protein-protein interactions.
Abstract: X-linked retinoschisis (XLRS) is the most common cause of juvenile macular degeneration in males, resulting in vision loss early in life The gene involved in XLRS was identified recently It encodes a protein with a disoidin domain, suggested to be involved in cell-cell interactions We have screened the gene for mutations in 234 familial and sporadic retinoschisis cases and identified 82 different mutations in 214 (91%) Thirty one mutations were found more than once, ie 2-10 times, with the exception of the 214G→A mutation which was found in 34 apparently unrelated cases The origin of the patients, the linkage data and the site of the mutations (mainly CG dinucleotides) indicate that most recurrent mutations had independent origins and thus suggest the existence of a significant new mutation rate in XLRS1 The mutations identified cover the entire spectrum, from small intra-genic deletions (7%), to nonsense (6%), missense (75%), small frameshifting insertions/deletions (6%) and splice site mutations (6%) Since, regardless of the mutation type, no females with a typical RS phenotype were identified, RS seems to be caused by loss-of-function mutations only Mutations occurred non-randomly, with hotspots at several CG dinudeotides and a C6 stretch Exons 1-3 contained few, mainly translation-truncating mutations, arguing against an important functional role for this segment of the protein Exons 4-6, encoding the discoidin domain, contained most, mainly missense mutations An alignment of 32 discoidin domain proteins was constructed to reveal the consensus sequence and to deduce the functional importance of the missense mutations identified The mutation analysis revealed a high preponderance of mutations involving or creating cysteine residues, pointing to sites important for the tertiary folding and/or protein function, and highlights several amino acids which may be involved in XLRS1-specific protein-protein interactions Despite the enormous mutation heterogeneity, patients have relatively uniform clinical manifestations although with great intra-familial variation in age at onset and progression

185 citations


Journal ArticleDOI
TL;DR: The dynamic observations that are allowed by these noninvasive measures of pathology have demonstrated direct correlations between axonal changes and disability, making a compelling case for increased emphasis on finding treatments of MS that may limit damage to CNS axons or salvage injured axons.
Abstract: Recent magnetic resonance imaging (MRI) and magnetic resonance spectroscopic (MRS) techniques have focused the attention of the multiple sclerosis (MS) research community on reanalysis of classic pathological approaches that have suggested significant axonal injury in this demyelinating disease. There now is abundant evidence from animal work that substantial "innocent bystander" damage to axons can occur with central nervous system (CNS) inflammation. Given the close interactions between axons and glia, it is no surprise that glial damage leads to secondary axonal changes. MRI, MRS, and MRS imaging studies have emphasized that axonal loss or damage in MS can be both substantial and early. The dynamic observations that are allowed by these noninvasive measures of pathology have demonstrated direct correlations between these axonal changes and disability, making a compelling case for increased emphasis on finding treatments of MS that may limit damage to CNS axons or salvage injured axons.

Journal ArticleDOI
TL;DR: This finding supports the hypothesis that flutamide reduces androgen synthesis through restoration of ovulation, although a direct block of the steroidogenic enzymes of androgen biosynthesis in ovarian thecal cells cannot be excluded.
Abstract: Anovulation in women with polycystic ovary syndrome (PCOS) is the direct effect of high local androgen concentrations on the ovary. Antiandrogens are substances that prevent androgens from expressing their activity on target tissues. Flutamide is a nonsteroid antiandrogen that has been found effective in hirsute patients, although its mechanism of action is unclear. Eight girls, ranging in age from 16–19 yr, with moderate to severe hirsutism and menstrual irregularities were enrolled in this study. The basal hormonal pattern showed anovulatory cycles; increased concentrations of LH, androstenedione, and testosterone; and increased LH/FSH ratio. A baseline ultrasound scan revealed polycystic ovaries in all patients. All were given 250 mg flutamide twice a day for 6 months. LH, FSH, androstenedione, testosterone, estradiol, and progesterone were evaluated before treatment, every 4 days during the third month of treatment, and on day 24 of the sixth month of treatment. Hirsutism improved, androgen levels dro...

Journal ArticleDOI
TL;DR: It appears that the presence of TNF receptors is necessary for the development of BLM-induced lung injury, and signaling through these receptors may contribute to the regulation of the TGF-beta 1 mRNA expression observed in response to bleomycin.
Abstract: Bleomycin (BLM) induction of lung fibrosis in mice is an established model to study the mechanism of pulmonary fibrosis. Cytokine secretion has been implicated as a fundamental component of the lung fibrotic process observed in response to BLM. Among the cytokines implicated in lung fibrosis, Tumor necrosis factor (TNF) alpha has been considered to play a fundamental role. In the present study, we characterized the cellular sources of TNF during BLM-induced lung injury and examined the importance of TNF receptors in this process. To characterize the expression of TNF, we utilized two strains of mice, one sensitive (C57BL/6) and one resistant (BALB/c) to BLM-induced lung injury. Mice received BLM (120 mg/kg total) or saline, as control, by multiple subcutaneous injections. BLM induced the development of inflammation in subpleural areas only in the lungs of BLM-sensitive mice. These subpleural areas were characterized by infiltration of CD68-positive macrophages and increased collagen deposition. BLM enhanced the expression of TNF mRNA in BLM-sensitive, but not in BLM-resistant, mice. In situ hybridization studies localized the expression of TNF in the areas of BLM-induced inflammation in 6% and 27% of macrophages at 14 and 21 days post BLM treatment. In addition to TNF, BLM exposure resulted in the upregulated expression of transforming growth factor (TGF)-beta 1, but not interleukin (IL)-1, mRNA in the lungs of both murine strains at 14 and 21 days. This upregulated expression of TGF-beta 1 mRNA was greater in the lungs of BLM-sensitive mice. In separate experiments, double TNF receptor knockout mice were exposed to BLM. These animals demonstrated an increased expression of TNF, but not TGF-beta 1, mRNA in response to BLM and did not exhibit histologic evidence of lung injury following BLM exposure. In summary, the upregulation of TNF mRNA in macrophages correlated with the appearance of inflammation following BLM exposure and was limited to the BLM-sensitive strain. Furthermore, in addition to the release of the TNF ligand, it appears that the presence of TNF receptors is necessary for the development of BLM-induced lung injury, and signaling through these receptors may contribute to the regulation of the TGF-beta 1 mRNA expression observed in response to bleomycin. These results provide further support for a role of macrophages and TNF in the induction of lung inflammation.

Journal ArticleDOI
TL;DR: Current knowledge on bacterial NSAPs is reviewed, together with analytical tools that may be useful for their characterization, and an overview is presented concerning the use of bacterialNSAPs in biotechnology.
Abstract: Bacterial nonspecific acid phosphohydrolases (NSAPs) are secreted enzymes, produced as soluble periplasmic proteins or as membrane-bound lipoproteins, that are usually able to dephosphorylate a broad array of structurally unrelated substrates and exhibit optimal catalytic activity at acidic to neutral pH values. Bacterial NSAPs are monomeric or oligomeric proteins containing polypeptide components with an M(r) of 25-30 kDa. On the basis of amino acid sequence relatedness, three different molecular families of NSAPs can be distinguished, indicated as molecular class A, B and C, respectively. Members of each class share some common biophysical and functional features, but may also exhibit functional differences. NSAPs have been detected in several microbial taxa, and enzymes of different classes can be produced by the same bacterial species. Structural and phyletic relationships exist among the various bacterial NSAPs and some other bacterial and eucaryotic phosphohydrolases. Current knowledge on bacterial NSAPs is reviewed, together with analytical tools that may be useful for their characterization. An overview is also presented concerning the use of bacterial NSAPs in biotechnology.

Journal ArticleDOI
TL;DR: Female penguins made on average longer foraging trips than males, ranged greater distances more frequently and consumed larger quantities of krill and fed more extensively on fish throughout chick rearing while males made shorter journeys to closer foraging grounds during the guard period.
Abstract: Consistent sex differences in foraging trip duration, feeding locality and diet of breeding Adelie penguins (Pygoscelis adeliae) were demonstrated at two widely separated locations over several breeding seasons. Differences in foraging behaviour were most pronounced during the guard stage of chick rearing. Female penguins made on average longer foraging trips than males, ranged greater distances more frequently and consumed larger quantities of krill. In contrast, males made shorter journeys to closer foraging grounds during the guard period and fed more extensively on fish throughout chick rearing. Mean guard stage foraging trip durations over four seasons at Bechervaise Island, Eastern Antarctica and over two seasons at Edmonson Point, Ross Sea ranged between 31 and 73 h for females and 25 and 36 h for males. Ninety percent of males tracked from Bechervaise Island by satellite during the first 3 weeks post-hatch foraged within 20 km of the colony, while the majority (60%) of females travelled to the edge of the continental shelf (80–120 km from the colony) to feed during this period.

Journal ArticleDOI
TL;DR: FPP was successful in more than 70% of patients; the barbecue rotation had slightly less successful but more immediate results; both methods enable otoconial debris to migrate into the posterior canal.
Abstract: Horizontal-canal paroxysmal positional vertigo (HC-PPV) is a vestibular syndrome due to canalolithiasis of the horizontal canal. The more common posterior-canal paroxysmal positional vertigo has a well defined and effective therapy, while there have been few reports on physical therapy for HC-PPV, and these have been tried in relatively few patients. We report the results of two different types of treatment of HC-PPV in 92 patients. A group of 21 untreated patients acted as a control group. One method, known as forced prolonged position (FPP), proposes liberating the affected canal by gravitation, and involves having the patient lie on the healthy side for many hours. The other method (the barbecue rotation) is a liberatory manoeuvre which proposes to expel the otoconia from the canal by rotating the patient 270° around the longitudinal axis of the body in rapid steps of 90°. FPP was successful in more than 70% of our patients; the barbecue rotation had slightly less successful but more immediate results....

Journal ArticleDOI
TL;DR: The dephosphorylating activity common to all these proteins supports the definition of this phosphatase motif and the inclusion of these enzymes into a superfamily of phosphohydrolases that is proposed to indicate as “DDDD” after the presence of the four invariant aspartate residues.
Abstract: Members of a new molecular family of bacterial nonspecific acid phosphatases (NSAPs), indicated as class C, were found to share significant sequence similarities to bacterial class B NSAPs and to some plant acid phosphatases, representing the first example of a family of bacterial NSAPs that has a relatively close eukaryotic counterpart. Despite the lack of an overall similarity, conserved sequence motifs were also identified among the above enzyme families (class B and class C bacterial NSAPs, and related plant phosphatases) and several other families of phosphohydrolases, including bacterial phosphoglycolate phosphatases, histidinol-phosphatase domains of the bacterial bifunctional enzymes imidazole-glycerolphosphate dehydratases, and bacterial, eukaryotic, and archaeal phosphoserine phosphatases and threalose-6-phosphatases. These conserved motifs are clustered within two domains, separated by a variable spacer region, according to the pattern [FILMAVT]-D-[ILFRMVY]-D-[GSNDE]-[TV]-[ILVAM]-[AT S VILMC]-X-?YFWHKR)-X-?YFWHNQ?-X( 102,191)-?KRHNQ?-G-D-?FYWHILVMC?-?QNH?-?FWYGP?-D -?PSNQYW?. The dephosphorylating activity common to all these proteins supports the definition of this phosphatase motif and the inclusion of these enzymes into a superfamily of phosphohydrolases that we propose to indicate as "DDDD" after the presence of the four invariant aspartate residues. Database searches retrieved various hypothetical proteins of unknown function containing this or similar motifs, for which a phosphohydrolase activity could be hypothesized.

Journal Article
TL;DR: The contrasting results found in the present study could be a stimulus for the organization of new projects, which may lead to the identification of an optimal therapeutic approach for fibromyalgic patients, also using tramadol for long periods.
Abstract: This study assessed the analgesic action of tramadol compared with placebo in patients suffering from fibromyalgia syndrome. Twelve patients (11 females, one male) were treated according to a double-blind crossover experimental design. Each patient, after signing informed consent, was randomly allocated to either tramadol (100 mg ampul in 100 ml given intravenously in 15 min doses) or placebo for a single dose treatment. At the second visit, patients crossed over to the other drug for a further single dose treatment. There was a wash-out period of 1 week. Nine patients completed the study, while in three cases (two tramadol, one placebo) the study was discontinued due to the onset of side effects. The assessment of efficacy, carried out at the baseline and 15 min and 2 hours after administration of each dose, involved the use of a visual analog scale (VAS 100 mm) for spontaneous pain and pressure dolorimetry (kg/cm2) at 12 "symptomatic" tender points and nine "control" tender points for fibromyalgic pain. During the first treatment cycle effective control of spontaneous pain was achieved with tramadol, which determined a reduction of 20.6% while with the placebo spontaneous pain increased by 19.8%. With pressure dolorimetry there were no clinically important differences observed after either active treatment or placebo. The contrasting results found in the present study could be a stimulus for the organization of new projects, which may lead to the identification of an optimal therapeutic approach for fibromyalgic patients, also using tramadol for long periods.

Journal ArticleDOI
TL;DR: This parallel group study involved 143 patients recruited in a practicebased research network of 11 offices in 7 countries to evaluate the applicability of the documented added benefits of GTR in the treatment of intrabony defects to different populations and the generalizability ofthe expected results to different clinicians.
Abstract: Background: Several studies have shown that GTR therapy of intrabony defects results in significantly better outcomes than access flap alone. Most of the available data, however, have been produced in highly controlled research environments by a small group of investigators. Generalizability of results to different clinicians and different subject populations has not been evaluated so far. Methods: This parallel group study involved 143 patients recruited in a practicebased research network of 11 offices in 7 countries. It was designed to evaluate: 1) the applicability of the documented added benefits of GTR in the treatment of intrabony defects to different populations, and 2) the generalizability of the expected results to different clinicians. GTR was compared to access flap alone. Defects, one in each patient, were accessed with a previously described papilla preservation flap in both the test and control group. In addition, GTR sites received application of a bioabsorbable poly-D,L-lactide-co-glycoli...

Journal ArticleDOI
TL;DR: A procedure for the recursive approximation of the feasible parameter set of a linear model with a set membership uncertainty description is provided and several approximation strategies for polytopes are presented.

Journal ArticleDOI
TL;DR: The identification, cloning, and oncogenic activity of the murine CK2α′ subunit is reported, suggesting that unbalanced expression of a CK2 catalytic subunit synergizes with Ha-ras in cell transformation.

Journal ArticleDOI
TL;DR: Species with relatively high PSH reactivity and glucose 6-phosphate dehydrogenase activity, such as the rat, had a higher antioxidant capacity than species (calf) in which these parameters were relatively low, and species with relatively low antioxidant capacity showed a relatively low capacity to restore normal values after oxidative stress.

Journal ArticleDOI
TL;DR: It is proven that multilayer perceptrons with sigmoidal units and a number of hidden units less or equal than the number of inputs are unable to model patterns distributed in typical clusters, since these networks draw open separation surfaces in the pattern space.
Abstract: Discusses the ability of multilayer perceptrons (MLPs) to model the probability distribution of data in typical pattern recognition and verification problems. It is proven that multilayer perceptrons with sigmoidal units and a number of hidden units less or equal than the number of inputs are unable to model patterns distributed in typical clusters, since these networks draw open separation surfaces in the pattern space. When using more hidden units than inputs, the separation surfaces can be closed but, unfortunately it is proven that determining whether or not a MLP draws closed separation surfaces in the pattern space is NP-hard. The major conclusion of the paper is somewhat opposite to what is believed and reported in many application papers: MLPs are definitely not adequate for applications of pattern recognition requiring a reliable rejection and, especially, they are not adequate for pattern verification tasks.

Journal ArticleDOI
TL;DR: The structure of β-mercaptoethanol-inhibited urease from Bacillus pasteurii, a highly ureolytic soil micro-organism, was solved at 1.65 A using synchrotron X-ray cryogenic diffraction data as discussed by the authors.
Abstract: The structure of β-mercaptoethanol-inhibited urease from Bacillus pasteurii, a highly ureolytic soil micro-organism, was solved at 1.65 A using synchrotron X-ray cryogenic diffraction data. The structure clearly shows the unexpected binding mode of β-mercaptoethanol, which bridges the two nickel ions in the active site through the sulfur atom and chelates one Ni through the OH functionality. Another molecule of inhibitor forms a mixed disulfide with a Cys residue, thus sealing the entrance to the active site cavity by steric hindrance. The possible implications of the results on structure-based molecular design of new urease inhibitors are discussed.

Journal ArticleDOI
TL;DR: The functional properties of the RyR3 channels are in agreement with a potential qualitative contribution of this channel to Ca2+ release in skeletal muscle and in other tissues.
Abstract: Single-channel analysis of sarcoplasmic reticulum vesicles prepared from diaphragm muscle, which contains both RyR1 and RyR3 isoforms, revealed the presence of two functionally distinct ryanodine receptor calcium release channels. In addition to channels with properties typical of RyR1 channels, a second population of ryanodine-sensitive channels with properties distinct from those of RyR1 channels was observed. The novel channels displayed close-to-zero open-probability at nanomolar Ca2+ concentrations in the presence of 1 mM ATP, but were shifted to the open conformation by increasing Ca2+ to micromolar levels and were not inhibited at higher Ca2+ concentrations. These novel channels were sensitive to the stimulatory effects of cyclic adenosine 5'-diphosphoribose (cADPR). Detection of this second population of RyR channels in lipid bilayers was always associated with the presence of the RyR3 isoform in muscle preparations used for single-channel measurements and was abrogated by the knockout of the RyR3 gene in mice. Based on the above, we associated the novel population of channels with the RyR3 isoform of Ca2+ release channels. The functional properties of the RyR3 channels are in agreement with a potential qualitative contribution of this channel to Ca2+ release in skeletal muscle and in other tissues.

Journal ArticleDOI
TL;DR: The formation, reactivity and toxicity of aldehydes originating from lipid peroxidation of cellular membranes are reviewed, and 4-HNE was the most cytotoxic aldehyde and was then assumed as a model molecule of oxidative stress.
Abstract: The formation, reactivity and toxicity of aldehydes originating from lipid peroxidation of cellular membranes are reviewed. Very reactive aldehydes, namely 4-hydroxyalkenals, were first shown to be formed in autoxidizing chemical systems. It was subsequently shown that 4-hydroxyalkenals are formed in biological conditions, i.e. during lipid peroxidation of liver microsomes incubated in the NADPH-Fe systems. Our studies carried out in collaboration with Hermann Esterbauer which led to the identification of 4-hydroxynonenal (4-HNE) are reported. 4-HNE was the most cytotoxic aldehyde and was then assumed as a model molecule of oxidative stress. Many other aldehydes (alkanals, alk-2-enals and dicarbonyl compounds) were then identified in peroxidizing liver microsomes or hepatocytes. The in vivo formation of aldehydes in liver of animals intoxicated with agents that promote lipid peroxidation was shown in further studies. In a first study, evidence was forwarded for aldehydes (very likely alkenals) bound to liver microsomal proteins of CCl4 or BrCCl3-intoxicated rats. In a second study, 4-HNE and a number of other aldehydes (alkanals and alkenals) were identified in the free (non-protein bound) form in liver extracts from bromobenzene or allyl alcohol-poisoned mice. The detection of free 4-HNE in the liver of CCl(4) or BrCC1(3)-poisoned animals was obtained with the use of an electrochemical detector, which greatly increased the sensitivity of the HPLC method. Furthermore, membrane phospholipids bearing carbonyl groups were demonstrated in both in vitro (incubation of microsomes with NADPH-Fe) and in vivo (CC1(4) or BrCCl(3) intoxication) conditions. Finally, the results concerned with the histochemical detection of lipid peroxidation are reported. The methods used were based on the detection of lipid peroxidation-derived carbonyls. Very good results were obtained with the use of fluorescent reagents for carbonyls, in particular with 3-hydroxy-2-naphtoic acid hydrazide (NAH) and analysis with confocal scanning fluorescence microscopy with image video analysis. The significance of formation of toxic aldehydes in biological membranes is discussed.

Journal ArticleDOI
TL;DR: The metallo-beta-lactamase produced by Chryseobacterium meningosepticum, which is the flavobacterial species of greatest clinical relevance, was purified and characterized and showed significant sequence similarity to other class B beta- lactamases.
Abstract: The metallo-beta-lactamase produced by Chryseobacterium (formerly Flavobacterium) meningosepticum, which is the flavobacterial species of greatest clinical relevance, was purified and characterized. The enzyme, named BlaB, contains a polypeptide with an apparent Mr of 26000, and has a pI of 8.5. It hydrolyses penicillins, cephalosporins (including cefoxitin), carbapenems and 6-beta-iodopenicillanate, a mechanism-based inactivator of active-site serine beta-lactamases. The enzyme was inhibited by EDTA, 1-10 phenanthroline and pyridine-2,6-dicarboxylic acid, with different inactivation parameters for each chelating agent. The C. meningosepticum blaB gene was cloned and sequenced. According to the G+C content and codon usage, the blaB gene appeared to be endogenous to the species. The BlaB enzyme showed significant sequence similarity to other class B beta-lactamases, being overall more similar to members of subclass B1, which includes the metallo-enzymes of Bacillus cereus (Bc-II) and Bacteroides fragilis (CcrA) and the IMP-1 enzyme found in various microbial species, and more distantly related to the metallo-beta-lactamases of Aeromonas spp. (CphA, CphA2 and ImiS) and of Stenotrophomonas maltophilia (L1).

Journal ArticleDOI
01 Mar 1998-Stroke
TL;DR: In patients with VBD, superimposed atheromatous changes of the posterior circulation may have an important role in precipitating ischemia, however, other factors related to the severity of the dolichoectasia also favor ischemIA and in some cases are the only factors responsible.
Abstract: Background and Purpose—Vertebrobasilar dolichoectasia (VBD) may produce symptoms by direct compression of cranial nerves or the brain stem, by obstructive hydrocephalus, or by ischemia in the vertebrobasilar arterial territory. This study was undertaken to examine and characterize clinical and imaging findings in patients with stroke associated with VBD and compare these data with those for patients with VBD who did not have a stroke. Methods—We studied 40 consecutive stroke patients with associated VBD. All were evaluated by CT scan (n=9), MRI (n=6), or both (n=25). The diameter of the basilar artery (BA), height of bifurcation, and transverse position were evaluated. Clinical and imaging findings were compared with those found in a group of 40 VBD patients without stroke. Results—More than half of the patients (24 of 40) had infratentorial infarcts, located mainly in the midpons. Sixteen patients had supratentorial lesions localized in the thalamus (n=8) or in the superficial arterial territory of the p...

Journal ArticleDOI
TL;DR: There are no data in the literature about anxiety disorders, but subjects with seasonal affective disorder show a peak of births in May, and data on personality, eating and ‘neurotic’ disorders are less consistent.
Abstract: Numerous studies suggest that seasonal birth may play a pathogenic role in the development of mental disorders. A birth excess of 10% during winter and spring has been shown in schizophrenia. The few studies carried out on affective disorders revealed a significant increase of births in the first quarter of the year in bipolar disorders and major depressive disorder. Subjects with seasonal affective disorder show a peak of births in May. Data on personality, eating and 'neurotic' disorders are less consistent. At the moment there are no data in the literature about anxiety disorders.

Book ChapterDOI
TL;DR: In this article, the structure and properties of copper-zinc superoxide dismutases are discussed and a natural monomeric species has been isolated from the periplasmic space of an Escherichia coli strain.
Abstract: Publisher Summary This chapter discusses structure and properties of copper–zinc superoxide dismutases. The superoxide radical anion is physiologically produced in controlled amounts in animals and plants from the one-electron reduction of dioxygen occurring in several metabolic pathways. Under pathological conditions, large amounts of superoxide and related active oxygen species are released. Thus, a twofold aspect of superoxide effects on living organisms emerges from the available experimental data. The actual role of superoxide dismutase enzymes in living organisms needs to be reconsidered in view of this wider framework. A natural monomeric species has been isolated from the periplasmic space of an Escherichia coli strain. This CuZnSOD displays a catalytic activity comparable to that of bovine SOD, but is highly sensitive to proteases. A comparison of sequences of different Cu 2 Zn 2 SODs shows that amino acids are invariant, and that most of them are residues close to or part of the active site.