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G Esposito

Publications and source records attributed to G Esposito.

At least 109 records · Page 6Linked to original sources
PubMed1999

Context-dependent, neural system-specific neurophysiological concomitants of ageing: mapping PET correlates during cognitive activation.

We used PET to explore the neurophysiological changes that accompany cognitive disability in ageing, with a focus on the frontal lobe. Absolute regional cerebral blood flow (rCBF) was measured in 41 healthy volunteers, evenly distributed across an age range of 18-80 years, during two task paradigms: (i) the Wisconsin Card Sorting Test (WCST), which depends heavily on working memory and is particularly sensitive to dysfunction of the dorsolateral prefrontal cortex (DLPFC); and (ii) Raven's Progressive Matrices (RPM), which may also have a working memory component, but depends more on visuo-spatial processing and is most sensitive to dysfunction of postrolandic regions. We used voxel-wise correlational mapping to determine age-related changes in WCST and RPM activation and developed a method to quantitate and localize statistical differences between the correlation maps for the two task paradigms. Because both WCST and RPM performance declined with age, as expected, correlational analyses were performed with and without partialling out the effect of task performance. Task-specific reductions of rCBF activation with age were found in the DLPFC during the WCST and in portions of the inferolateral temporal cortex involved in visuo-spatial processing during the RPM. We also found reduced ability to suppress rCBF in the right hippocampal region during the WCST and in mesial and polar portions of the prefrontal cortex during both task conditions. Task-dependent alterations with age in the relationship between the DLPFC and the hippocampus were also documented; because the collective pattern of changes in the hippocampal-DLPFC relationship with ageing was opposite to that seen in a previous study using dextroamphetamine, we postulated a dopaminergic mechanism. These results indicate that, despite some cognitive overlap between the two tasks and the age-related cognitive decline in both, many of the changes in rCBF activation with age were task-specific, reflecting functional alteration of the different neural circuits normally engaged by young subjects during the WCST and RPM. Reduced activation of areas critical for task performance (i.e. the DLPFC during the WCST and posterior visual association areas of the inferolateral temporal cortex during the RPM), in conjunction with the inability to suppress areas normally not involved in task performance (i.e. the left hippocampal region during the WCST and mesial polar prefrontal cortex during both the WCST and RPM), suggest that, overall, reduced ability to focus neural activity may be impaired in older subjects. The context dependency of the age-related changes is most consistent with systems failure and disordered connectivity.

Adolescent↗
PubMed1999

Combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) anf erythropoietin (EPO) for the treatment of advanced non-responsive chronic lymphocytic leukemia.

We report the use of a colony-stimulating granulocyte-macrophage factor (GM/CSF) and erythropoietin (EPO) combination as salvage treatment in four heavily-pretreated patients with refractory/ recurrent B-CLL. Induction therapy was subcutaneous GM-CSF 2.5 microg/ kg, and EPO, 150 units/kg both daily for the first 14 d. Maintenance therapy was GM-CSF on days 1, 3 and 5 and Epo on days 2, 4 and 6 at the same doses with weekly recycling. All the patients responded favourably. A significant reduction of lymphocytosis, lymphoadenomegaly, and organomegaly was obtained within one month of therapy. The number of infections and transfusional requirement decreased dramatically. The hemoglobin increased to over 11 g/dl in 3 out of 4 patients. With a median follow-up of 11 months (range 5-13) we observed 4 partial responses (NCI/IWCLL) and only one progression after a 10-month partial response. This combination regimen seems very active, safe and easy to administer. It may represent a promising therapeutical option in heavily pretreated patients. Further clinical and biological studies on a larger cohort of patients are needed to confirm these preliminary data, to clarify the hypothetical interactions between these cytokines and B-CLL cell proliferation pathways, and to establish if this therapy may have an impact on survival.

Administration, Cutaneous↗
PubMed1999

[Vascular complications during laparoscopy. An analysis of a personal case].

Vascular complications of laparoscopy most often occur during Veress needle or primary trocar placement. Veress needle punctures are insignificant and require no further treatment, whereas trocar induced vascular injuries can be catastrophic. The frequency of vascular or viscus injuries is difficult to calculate since several complications are not published. A vascular complication occurred in a young girl with neurologic problems and a kyphoscoliosis operated on in laparoscopy for a gastroesophageal reflux is discussed. After the establishment of pneumoperitoneum, an important hemoperitoneum was rapidly evident at insertion of the laparoscope. An open laparotomy was performed showing right common iliac vessel injuries and several intestinal perforations. After a complex vascular reconstruction and a multiple intestinal suture, the Nissen fundoplication with pyloroplasty was performed traditionally and the patient leave the hospital free of symptoms after 20 days. In laparoscopy, as in all areas of surgery, experience knowledge and meticulous attention to details are the most important factors in order to avoid complications. The authors believe that the open approach with Hasson cannula is the most important factor in avoiding complications.

Child, Preschool↗
PubMed1998

Effect of naloxone on morphine-induced changes in striatal dopamine metabolism and glutamate, ascorbic acid and uric acid release in freely moving rats.

Recent findings have shown that systemic morphine increases extracellular dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), ascorbic acid (AA) and uric acid concentrations in the striatum of freely moving rats. The morphine-induced increase in DA oxidative metabolism is highly correlated with that of xanthine. In the present study, we evaluated the effects of subcutaneous (s.c.) naloxone (1 mg/kg) on morphine-induced changes in DA, DOPAC, HVA, 5-hydroxyindoleacetic acid (5-HIAA), AA, uric acid and glutamate in the striatum of freely moving rats using microdialysis. Dialysates were assayed by high performance liquid chromatography with electrochemical detection or (glutamate) ultraviolet detection. Morphine (5-20 mg/kg) given s.c. increased DA, DOPAC+HVA, 5-HIAA, AA and uric acid and decreased glutamate dialysate concentrations over a 3 h period after morphine. Morphine (1 mM), given intrastriatally, did not affect all the above parameters, with the exception of an early short-lasting decrease in AA concentration. Naloxone antagonised all morphine-induced changes with the exception of AA increase and glutamate decrease in dialysate concentrations. Systemic or intrastrial (0.2-2 mM) naloxone increased AA and decreased glutamate dialysate concentrations. When given intranigrally, morphine (1 mM) increased DOPAC+HVA, AA and uric acid and decreased glutamate dialysate concentrations over a 2 h period after morphine; DA and 5-HIAA concentrations were unaffected. These results suggest that: (i) morphine increases striatal DA release and 5-hydroxytryptamine oxidative metabolism by a micro-opioid receptor-mediated mechanism mainly at extranigrostriatal sites; (ii) morphine increases DA and xanthine oxidative metabolism and affects glutamate and AA release by a micro-opioid receptor mediated mechanism acting also at nigral sites; and (iii) a micro-opioid receptor-mediated mechanism tonically controls at striatal sites extracellular AA and glutamate concentrations.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

NMR studies on the structure/function correlations of T-cell-epitope analogs from pertussis toxin.

A synthetic tridecapeptide, corresponding to the 30-42 fragment of the S1 subunit of pertussis toxin, has been structurally characterised by using NMR spectroscopy. The molecule corresponds to a T-cell epitope of the bacterial toxin which has been extensively analysed with the alanine scanning approach to check the relevance of each residue for the biological activity of the peptide. Five of these Ala-substituted analogs have also been spectroscopically studied. In the experimental conditions used, different extents of helicity were found for the six peptides in a way which cannot be related to their capabilities of of binding to major histocompatibility complex (MHC) class II and inducing T-cell proliferation. Backbone flexibility around helical transient conformations seems to constitute the structural intermediate step between the structure of the corresponding sequence within the parental protein and in the MHC class II complex. A model of the latter complex, which accounts for the different biological activities of the analogs, is proposed.

Amino Acid Sequence↗
PubMed1998

Changing patterns of brain activation during maze learning.

Recent research has found that patterns of brain activation involving the frontal cortex during novel task performance change dramatically following practice and repeat performance. Evidence for differential left vs. right frontal lobe activation, respectively, during episodic memory encoding and retrieval has also been reported. To examine these potentially related issues regional cerebral blood flow (rCBF) was measured in 15 normal volunteers using positron emission tomography (PET) during the naive and practiced performance of a maze task paradigm. SPM analysis indicated a largely right-sided, frontal lobe activation during naive performance. Following training and practice, performance of the same maze task elicited a more posterior pattern of rCBF activation involving posterior cingulate and precuneus. The change in the pattern of rCBF activation between novel and practiced task conditions agrees with results found in previous studies using repeat task methodology, and indicates that the neural circuitry required for encoding novel task information differs from that required when the same task has become familiar and information is being recalled. The right-sided preponderance of activation during naive performance may relate to task novelty and the spatially-based nature of the stimuli, whereas posterior areas activated during repeat performance are those previously found to be associated with visuospatial memory recall. Activation of these areas, however, does not agree with previously reported findings of left-sided activation during verbal episodic memory encoding and right-sided activation during retrieval, suggesting different neural substrates for verbal and visuospatial processing within memory.

Adult↗
PubMed1998

Lymphoproliferative disease in human peripheral blood mononuclear cell-injected SCID mice. IV. Differential activation of human Th1 and Th2 lymphocytes and influence of the atopic status on lymphoma development.

Intraperitoneal transfer of PBMC from EBV+ donors into SCID mice leads to high human Ig levels in mouse serum and B cell lymphoproliferative disease. As these events depend on the activation of coinjected human T cells, we addressed the behavior of the Th1 and Th2 subsets in this model. Production of IFN-gamma, but not of Th2 cytokines such as IL-4, was detected in culture supernatants of PBMC stimulated in vitro with mouse splenocytes. Moreover, anti-CD3 stimulation of the human cells recovered from mice brought about IFN-gamma, but not IL-4, synthesis; on the other hand, PCR and in situ hybridization analysis of ex vivo-recovered cells disclosed the presence of mRNA for both cytokines following in vitro restimulation, thus suggesting posttranscriptional regulation of IL-4 gene expression. When SCID mice were inoculated with PBMC from atopic donors, whose Th1/Th2 profile displays an imbalance toward Th2 cells, tumor development rates were lower, and tumor latency was higher, compared with those in mice injected with PBMC from normal donors. Isotypic analysis of human Ig in mouse serum showed the exclusive presence of IFN-gamma-driven IgG subclasses; in addition, human IgE were low or undetectable in most cases. These findings indicate that following transfer into SCID mice, human Th1 lymphocytes undergo preferential activation, whereas Th2 function is down-regulated. Th1 lymphocytes probably are a major component in promoting EBV+ B cell expansion and tumor development; the individual Th1/Th2 profile could in part account for the as yet unexplained donor variability in tumor generation in this experimental model.

Adult↗
PubMed1998

Selective NMR Experiments on Macromolecules: Implementation and Analysis of QUIET-NOESY.

The QUIET-NOESY experiment (Zwahlen et al., J. Am. Chem Soc. 116, 362-368, 1994) is applied to measure the mobility of the flexible extensions in the large aggregate (800 kDa) of a small heat-shock protein. The proper choices of the experimental protocol and parameters are discussed in order to employ a simplified data analysis procedure. Further experimental verification of the proposed strategy is also presented using the cyclic peptide gramicidin S as a model compound. Under suitable conditions, the determinations based on the analysis of QUIET-NOESY data are affected to a negligible extent by the approximations that are introduced by the proposed approach. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Mapping voxel-based statistical power on parametric images.

Using a classic technique based on the noncentral F-distribution method for computing statistical power, we developed a general approach to the estimation of voxel-based power in functional brain image data analysis. We applied this method to PET data from a large sample (N = 40) of subjects performing the Wisconsin Card Sorting (WCST) paradigm analyzed with SPM95, produced statistical power maps for a range of samples sizes and smoothing filter widths, and examined the effects of sample size and image smoothing on the expected reliability of activation findings. At an uncorrected alpha of 0.01, a fixed filter size of 10 mm3, and a range of power thresholds, maps revealed that the power to reject the null hypothesis in brain regions implicated in the task at Ns of 5 and 10 may not be sufficient to ensure reliable replication of significant findings and so should be interpreted with caution. At sample sizes approaching 20 subjects, sufficient power was found in the right dorsolateral prefrontal cortex (BA 46/9), right and left inferior parietal lobule (BA 40), and left inferior temporal lobe (BA 37), comprising the cortical network typically observed during the WCST. Filter size needed to maximize power varied widely, but systematically, across the brain, tending to follow known neuroanatomical landmarks. Statistical power considerations in brain imaging studies are critical for controlling the rate of false negatives and assuring reliable detection of cognitive activation. The variation of filter size for maximizing power across the brain suggests that the underlying neuroanatomy of functional units is an important consideration in the a priori selection of filter size.

Algorithms↗
PubMed1998

Uncoupling cognitive workload and prefrontal cortical physiology: a PET rCBF study.

Working memory is a fundamental cognitive building block involved in the short-term maintenance and transformation of information. In neuropsychological studies, working memory has been shown to be of limited capacity; however, the neurophysiological concomitants of this capacity limitation have not been explored. In this study we used the [15O] water PET rCBF technique and statistical parametric mapping to examine normal subjects while they performed two cognitive tasks, both individually and simultaneously. One task was the Wisconsin Card Sorting Test, a complex reasoning task involving working memory, and the other was a rapidly paced auditory verbal shadowing task. When both tasks were performed simultaneously, there were significant decrements in performance compared with the individual task performance scores, indicating that cognitive workload had been increased. Analysis of the rCBF maps showed that when the two tasks were performed together, in contrast to when they were performed separately, there was less prefrontal activation. These results suggest that increases in cognitive workload do not necessarily recruit and then sustain cortical neurophysiological resources to a maximum, but rather may actually be accompanied by a diminution in cortical activity.

Adult↗
PubMed1997

Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women.

There is considerable evidence from animal studies that gonadal steroid hormones modulate neuronal activity and affect behavior. To study this in humans directly, we used H215O positron-emission tomography to measure regional cerebral blood flow (rCBF) in young women during three pharmacologically controlled hormonal conditions spanning 4-5 months: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate (Lupron), Lupron plus estradiol replacement, and Lupron plus progesterone replacement. Estradiol and progesterone were administered in a double-blind cross-over design. On each occasion positron-emission tomography scans were performed during (i) the Wisconsin Card Sorting Test, a neuropsychological test that physiologically activates prefrontal cortex (PFC) and an associated cortical network including inferior parietal lobule and posterior inferolateral temporal gyrus, and (ii) a no-delay matching-to-sample sensorimotor control task. During treatment with Lupron alone (i.e., with virtual absence of gonadal steroid hormones), there was marked attenuation of the typical Wisconsin Card Sorting Test activation pattern even though task performance did not change. Most strikingly, there was no rCBF increase in PFC. When either progesterone or estrogen was added to the Lupron regimen, there was normalization of the rCBF activation pattern with augmentation of the parietal and temporal foci and return of the dorsolateral PFC activation. These data directly demonstrate that the hormonal milieu modulates cognition-related neural activity in humans.

Adult↗
PubMed1997

Effects of two hypertrophic cardiomyopathy mutations in alpha-tropomyosin, Asp175Asn and Glu180Gly, on Ca2+ regulation of thin filament motility.

The functional properties of wild type alpha-tropomyosin expressed in E. coli with an alanine-serine N-terminal leader (AS-alpha-Tm) were compared with those of AS-alpha-Tm with either of two missense mutations (Asp175Asn and Glu180Gly) shown to cause familial hypertrophic cardiomyopathy (FHC). Wild type AS-alpha-Tm and AS-alpha-Tm(Asp175Asn) binding to actin was indistinguishable from rabbit skeletal muscle ab-tropomyosin whilst the affinity of AS-alpha-Tm(Glu180Gly) was about threefold weaker. In vitro motility assays were performed with AS-alpha-tropomyosin incorporated into skeletal muscle actin-rhodamine phalloidin filaments moving over skeletal muscle heavy meromyosin. Under relaxing conditions (pCa9), troponin added to actin filaments containing AS-alpha-tropomyosin or mutant tropomyosins resulted in normal switch-off, with a decrease in the fraction filaments moving from >80% to <20%. Under activating conditions (pCa5), troponin had a minor effect upon actin-AS-alpha-tropomyosin filament velocity (increased by 5 +/- 1%, n=10), whereas the velocity increased by 18 +/- 3% (n=7) with actin filaments containing AS-alpha-tropomyosin(Asp175Asn) and by 21 +/- 2% (n=8) with filaments containing AS-alpha-tropomyosin(Glu180Gly) (p<0.05 compared with AS-alpha-tropomyosin). Thus FHC mutations in alpha-tropomyosin produce detectable changes in the Ca2+-regulation of thin filaments, presumably via altered interaction with troponin.

Actins↗
PubMed1997

Structural comparison between retro-inverso and parent peptides: molecular basis for the biological activity of a retro-inverso analogue of the immunodominant fragment of VP1 coat protein from foot-and-mouth disease virus.

Antibodies induced against intact foot-and-mouth disease Virus (FMDV) particles bind to the retro-inverso analogue of fragment 141-159 of the viral coat protein VP1 of FMDV, variant A, equally well as to the parent peptide. A conformational investigation of this retro-inverso peptide was carried out by nmr spectroscopy and restrained molecular modeling in order to identify the structural basis for the antigenic mimicry between these retro-inverso and parent peptides. In 100% trifluoroethanol a well-defined left-handed alpha-helical region exists from residue 150 to residue 159, which is consistently present in all conformational families obtained from restrained modelling. A less-defined left-handed helical region is present in the tract 144-148, which is also consistent for all structures. Conformational flexibility exists about Gly149, which leads to two types of structures, either bent or linear. In the bent structures, a three-residue inverse tight turn is found, which can be classified as an inverse gamma-turn centered at Gly149. The overall structural features of the retro-inverso peptide are shown to be similar to those of the parent L-peptide. The two molecules, however, are roughly mirror images because they share inherently chiral secondary structure elements. By comparing these conformational conclusions with the x-ray structure of the Fab complex of a corresponding VP1 antigenic fragment, a rationale is proposed to account for the topological requirements of specific recognition that are implied by the equivalent antigenic activity of the natural and retro-inverso compounds.

Amino Acid Sequence↗
PubMed1997

Electrostatic effects in homeodomain-DNA interactions.

We report here an investigation of the role of electrostatics in homeodomain-DNA interactions using techniques based around the use of the Poisson-Boltzmann equation. In the present case such a study is of particular interest, since in contrast to other proteins previously studied with this method, the homeodomain is a small, highly charged protein that forms extensive ion pairs upon binding DNA. We have investigated the salt dependence of the binding constant for specific association and for a variety of models for non-specific association. The results indicate that, in line with the models proposed by Manning and Record, the entropy of counterion release accounts for a significant fraction of the salt dependence of the binding free energy, though this is perhaps due to fortuitous cancellation of other contributing terms. The thermodynamic effects of a number of specific homeodomain mutants were also investigated, and partly rationalized in terms of favorable electrostatic interactions in the major goove of DNA. Investigation of the temperature-dependence of the free energy of association indicates that the electrostatic contributions become increasingly favorable as the temperature rises. For this particular system, however, there appears to be no significant electrostatic contribution to the delta(delta C(p)) of association. Finally, an analysis of the free energy of interaction when the homeodomain is moved ca one Debye length from the DNA suggests that pure electrostatic forces are able to steer the homeodomain into a partially correct orientation for binding to the DNA.

Amino Acid Sequence↗
PubMed1997

Inflammatory polyarthropathy and bone remodeling in HTLV-I Tax-transgenic mice.

Transgenic mice carrying the tax gene of human T-cell lymphotropic virus type I displayed a high prevalence of arthropathy. The percentage of affected animals increased with age, reaching a peak of 43% at 20 months. Southern analysis of deoxyribonucleic acid (DNA) from tissue samples indicated that disease development was related to tax copy number. Histopathologic evaluation of the ankle joints disclosed deep erosion of the synovial lining, fibrous tissue proliferation together with angiogenesis, mononuclear cell infiltration, and activation of osteoclasts. Radiologic examination confirmed joint involvement and revealed bone architecture modifications. The phenotype exhibited by the affected animals closely resembles that of seronegative arthritis in humans, and may indicate tax protein as a causal agent of arthropathy observed in HTLV-I infected individuals.

Age Factors↗
PubMed1997

Effect of morphine on striatal dopamine metabolism and ascorbic and uric acid release in freely moving rats.

Recent ex vivo findings have shown that morphine increases dopamine (DA) and xanthine oxidative metabolism and ascorbic acid (AA) oxidation in the rat striatum. In the present study, we evaluated the effects of subcutaneous daily morphine (20 mg/kg) administration on DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), AA and uric acid in the striatum of freely moving rats using microdialysis. Dialysates were assayed by high performance liquid chromatography with electrochemical detection. On the first day, morphine administration caused a significant increase in extracellular DA, DOPAC, HVA, AA and uric acid concentrations over a 3 h period after morphine. In all treated rats (n = 7), individual concentrations of DOPAC + HVA were directly correlated with individual AA and uric acid concentrations. Last morphine administration on the 4th day increased DOPAC, HVA, AA and uric acid concentrations but failed to increase those of DA. Individual DOPAC + HVA concentrations were still directly correlated with individual AA and uric acid concentrations. These results suggest that systemic morphine increases both striatal DA release and DA and xanthine oxidative metabolism. Only the former effect undergoes tolerance. The increase in DA oxidative metabolism is highly correlated with that of xanthine. The subsequent enhancement in reactive oxygen species production may account for the increase in extracellular AA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Lysine as helix C-capping residue in a synthetic peptide.

The structure of the synthetic peptide CH3CO(Leu-Ser-Leu-Leu-Leu-Ser-Leu)3Lys-NH2 in trifluoroethanol/water 60/40 (volume ratio) was characterized by two-dimensional nmr spectroscopy. The peptide, closely related to the amphiphilic helix models designed by W. F. De-Grado and co-workers to mimic protein ion channels [(1988) Science, Vol. 240, p. 1177-1181], folds into a regular helix spanning residues 1-20. Evidence for a helix C-terminal capping conformation, involving the terminal lysine residue, was observed from Overhauser effects and checked for consistency by restrained molecular dynamics simulations. The side-chain amino group of Lys22 forms a hydrogen bond with the carbonyl of Leu18, and the distorted helical geometry of the terminal dipeptide allows the inclusion of a water bridge between the backbone NH of the Lys22 residue and the carbonyls of Leu19 and Ser20.

Amino Acid Sequence↗