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Biomedical subjects

G Tedeschi

Publications and source records attributed to G Tedeschi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Functional fields in human auditory cortex revealed by time-resolved fMRI without interference of EPI noise.

The gradient switching during fast echoplanar functional magnetic resonance imaging (EPI-fMRI) produces loud noises that may interact with the functional activation of the central auditory system induced by experimental acoustic stimuli. This interaction is unpredictable and is likely to confound the interpretation of functional maps of the auditory cortex. In the present study we used an experimental design which does not require the presentation of stimuli during EPI acquisitions and allows for mapping of the auditory cortex without the interference of scanner noise. The design relies on the physiological delays between the onset, or the end, of stimulation and the corresponding hemodynamic response. Owing to these delays and through a time-resolved acquisition protocol it is possible to analyze the decay of the stimulus-specific signal changes after the cessation of the stimulus itself and before the onset of the EPI-acoustic noise related activation (decay-sampling technique). This experimental design, which might permit a more detailed insight in the auditory cortex, has been applied to the study of the cortical responses to pulsed 1000 Hz sine tones. Distinct activation clusters were detected in the Heschl's gyri and the planum temporale, with an increased extension compared to a conventional block-design paradigm. Furthermore, the comparison of the hemodynamic response of the most anterior and the posterior clusters of activation highlighted differential response patterns to the sound stimulation and to the EPI-noise. These differences, attributable to reciprocal saturation effects unevenly distributed over the superior temporal cortex, provided evidence for functionally distinct auditory fields.

Acoustic Stimulation↗
PubMed2001

T2 relaxometry of brain in myotonic dystrophy.

We investigated the nature and extent of brain involvement in myotonic dystrophy (DM), examining possible T2 relaxation abnormalities in the brain of 20 patients with adult-onset DM and 20 sex- and age-matched normal controls. Brain MRI was performed at 0.5 T, and T2 values were calculated from signal intensity in two echoes. Regions of interest included: frontal, parietal, temporal, occipital and callosal (rostral and splenial) normal-appearing white matter; frontal, occipital, insular and hippocampal cortex; caudate nucleus, putamen, globus pallidus and thalamus. All white-matter and occipital and right frontal cortex regions showed a significantly longer T2 in the patients. Multiple regression analysis, including grey- and white-matter T2 as dependent variables, plus age at onset and at imaging, disease duration, muscular disability, brain atrophy and CTG trinucleotide repeats as independent variables, revealed that only white-matter T2 elongation and disease duration correlated positively. White-matter involvement in DM is more extensive than previously reported by MRI and neuropathological studies and seems to be progressive in the course of disease.

Adolescent↗
PubMed2001

Primary structure of kappa-casein isolated from mares' milk.

In this work the purification and the complete primary structure of kappa-casein from equine milk are reported for the first time. Mares' milk casein was separated by RP-HPLC into four fractions. Complete primary sequence was obtained by sequence analysis of the protein in the fastest eluting peak isolated by chromatography. This sequence was 95% identical to that reported for the C-terminal portion of the zebras' kappa-casein and showed high similarity with kappa-caseins from sources other than Equidae, confirming that this protein was indeed kappa-casein in equine milk. The presence of post-translational modifications in equine kappa-casein was investigated by mass spectroscopy, after enzymic dephosphorylation. Two main components were found, the smaller component being more abundant. Equine kappa-casein was recognized by a lectin specific for one of the glucosidic bonds in the saccharide moiety of bovine kappa-casein. Sequence comparison with prevision studies showed that the distribution of charged and hydrophobic regions in equine kappa-casein was similar, but not identical, to that found in the bovine protein; these regions are associated with the role of kappa-casein in the formation and stabilization of the micellar structure of casein in milk.

Amino Acid Sequence↗
PubMed2001

Dilated Virchow-Robin spaces in myotonic dystrophy: frequency, extent and significance.

To study the frequency, extent and significance of dilated Virchow-Robin spaces (VRSs) in dystrophia myotonica (DM), we evaluated the cranial magnetic resonance imaging (MRI) of 41 patients with the adult form of DM and 41 healthy controls. Dilated VRSs and white matter lesions (WMLs) were rated according to semiquantitative methods. Convexity VRSs were more frequent (68 vs. 34%; p < 0.01) and severer (median scores: 4 vs. 0; p < 0.01) in DM patients than in controls, while lenticulostriate VRSs did not show significant differences in frequency (83 vs. 70%; p > 0.05) and severity (median scores: 4 vs. 3; p > 0.05). WMLs were more frequent (66 vs. 22%; p < 0.01) and severer (median scores: 5 vs. 0; p < 0.01) in patients. Disease duration was negatively correlated with convexity VRSs and positively with lobar (centrum semiovale) WML scores. Dilated convexity VRSs might be one of the initial findings in cranial MRI of DM, preceding the appearance of lobar WMLs.

Adolescent↗
PubMed2001

Limited proteolysis of a disulfide-linked apoA-I dimer in reconstituted HDL.

The apolipoprotein A-I(Milano) (apoA-I(M)) is a molecular variant of apoA-I characterized by the Arg(173)-->Cys substitution, leading to the formation of homodimers A-I(M)/A-I(M). Upon interaction with palmitoyloleoylphosphatidylcholine, A-I(M)/A-I(M) forms only two species of reconstituted HDL (rHDL) particles, with diameters of 7.8 and 12.5 nm. We used limited proteolysis to analyze the conformation of A-I(M)/A-I(M) in the two rHDL particles, in comparison with that of apoA-I in rHDL of similar size. ApoA-I in the small, 7.8-nm rHDL is degraded to a greater extent (50% after 6 h) than in the large rHDL (<10% degraded after 6 h). The protease susceptibility of A-I(M)/A-I(M) in small and large rHDL is instead remarkably the same, with A-I(M)/A-I(M) being much more sensitive to proteolytic digestion (50% degraded after 10 min) than apoA-I. The identification of the proteolytic fragments by immunoblotting, N-terminal sequencing, and molecular mass determination, shows that the N-terminus of both proteins is resistant to proteolysis, with six cleavage sites located in the central and carboxy-terminal portions of the molecules. Cleavage in the middle of apoA-I occurs at distinct sites in 7.8-nm (Lys(118)) and 12.7-nm (Arg(123)) rHDL, indicating a different conformation in small and large rHDL particles. The A-I(M)/A-I(M) instead adopts a unique and identical conformation in small and large rHDL, with the carboxy-terminal portion of the molecule being remarkably more accessible to the proteases than in apoA-I. This suggests the presence of a novel carboxy-terminal domain in A-I(M)/A-I(M), not organized in a compact structure and not shared by wild-type apoA-I, which may account for the unique functional properties of A-I(M)/A-I(M).

Antibodies, Monoclonal↗
PubMed2001

[Cardiovascular risk factors and diseases in centenarians].

Aging is considered a product of an interaction between genetic, environmental and lifestyle factors. Are centenarians, who have almost arrived at the maximum life-span (120 yrs), free of cardiovascular disease or do they have an increased resistance? How many cardiovascular risk factors are present? We have studied a group of 148 centenarians selected from registered residents of Rome (average age 101.8 +/- 1.9; range 100-108). Their health was assessed through direct 1.5 hour interviews, conducted by physicians with geriatric training at the patient's residence, which includes geriatric assessment scales' submission. The prevalence of cardiovascular disease of our centenarians is 16.7%, represented by heart failure (8%), myocardial infarction (4.7%) and angina pectoris (4%). Among the cardiovascular risk factors, hypertension (31.1%) and hypercholesterolemia are the most frequent, while diabetes is not present. These data, compared with younger samples, point out a lower percentage of cardiovascular disease and risk factors. Moreover centenarians have always conducted a healthy lifestyle (Mediterranean diet, smoking abstention, physical activity, low levels of anxiety and depression). Finally, having identified the golden mean which allows us to carry out a programmed intervention for the prevention of cardiovascular risk factors and diseases, we will be able to increase longevity, allowing a larger number of subjects to reach the maximum human life-span.

Age Factors↗
PubMed2000

Tubulin anchoring to glycolipid-enriched, detergent-resistant domains of the neuronal plasma membrane.

After incubation of intact living cultured rat cerebellar granule cells at 37 degrees C with a new GM1 ganglioside analog, carrying a diazirine group and labeled with (125)I in the ceramide moiety, followed by photoactivation, a relatively small number of radiolabeled proteins were detected in a membrane-enriched fraction. A protein of about 55 kDa with a pI of about 5 carried a large portion of the radioactivity even if incubation and cross-linking were performed at 4 degrees C and in the presence of inhibitors of endocytosis, suggesting that it is cross-linked at the plasma membrane. Immunoprecipitation and Western blotting experiments showed the positivity of this protein for tubulin. Trypsin treatment of intact cells ruled out the involvement of a plasma membrane surface tubulin. Release of radioactivity from cross-linked tubulin after KOH treatment (but not hydroxylamine treatment) suggested that the photoactivated ganglioside reacts with an ester-linked fatty acid anchor of tubulin. Low buoyancy, detergent-resistant membrane fractions, isolated from cells after incubation with the GM1 analogue and photoactivation, proved their enrichment in endogenous and radioactive GM1 ganglioside, sphingomyelin, cholesterol, signal transduction proteins, and tubulin. It is noteworthy that radioactive tubulin was also detected in this fraction, indicating the presence of tubulin molecules carrying a fatty acid anchor in detergent-resistant, ganglioside-enriched domains of the plasma membrane. Parallel experiments carried out with a phosphatidylcholine analogue, also carrying a diazirine group and labeled with (125)I in the fatty acid moiety, showed the specificity of tubulin interaction with GM1. Taken together, these results indicate that some tubulin molecules are associated with a lipid anchor to detergent-resistant glycolipid-enriched domains of the plasma membrane. This novel feature of membrane domains can provide a key for a better understanding of their biological role.

Animals↗
PubMed2000

Telephone counseling as adjuvant treatment for nicotine replacement therapy in a "real-world" setting.

BACKGROUND: Physicians prescribing nicotine replacement therapy (NRT), or health plans covering NRT, often want their patients to receive adjuvant behavioral treatment. However, how to do that in a "real world" is unclear. This paper reports results from a public health program that uses proactive telephone counseling as support for physician advice and provides adjuvant treatment for NRT users. METHODS: Participants were NRT users (N = 8,832) who called the California Smokers' Helpline, a statewide cessation service that provides proactive counseling, one session before NRT use and multisessions after the smokers received NRT. After receiving NRT, some participants discontinued the counseling while others continued with follow-up sessions. A subset of the 8,832 participants (n = 664) was interviewed 13 months later for quitting status. RESULTS: After receiving NRT, 79% of the participants continued with counseling and received 4.2 sessions on average, while 21% of them received only one session. Overall, 82.8% of all participants made a quit attempt. Nicotine patch users were more likely to make an attempt than nicotine gum users (85.2% vs 66.3%), but the relapse probability was the same for these attempts. Those who received multiple counseling were more likely to make an attempt than those receiving single counseling (84.4% vs 77.1%) and were more likely to stay quit for 1 year (25.6% vs 16.1%). CONCLUSIONS: Proactive telephone counseling is a promising adjuvant treatment for NRT users in a "real-world" setting: a convenient referral service for supporting health plans or physicians who advise their patients to quit smoking.

Adolescent↗
PubMed2000

Cloning, overexpression, and purification of Escherichia coli quinolinate synthetase.

Quinolinate synthetase catalyzes the second step of the de novo biosynthetic pathway of pyridine nucleotide formation. In particular, quinolinate synthetase is involved in the condensation of dihydroxyacetone phosphate and iminoaspartate to form quinolinic acid. To study the mechanism of action, the specificity of the enzyme and the interaction with l-aspartate oxidase, the other component of the so-called "quinolinate synthetase complex," the cloning, the overexpression, and the purification to homogeneity of Escherichia coli quinolinate synthetase were undertaken. The results are presented in this paper. Since the overexpression of the enzyme resulted in the formation of inclusion bodies, a procedure of renaturation and refolding had to be set up. The overexpression and purification procedure reported in this paper allowed the isolation of 12 mg of electrophoretically homogeneous quinolinate synthetase from 1 liter of E. coli culture. A new, continuous, method for the evaluation of quinolinate synthetase activity was also devised and is presented. Finally, our data definitely exclude the possibility that other enzymes are involved in the biosynthesis of quinolinic acid in E. coli, since it is possible to synthesize quinolinic acid from l-aspartate, dihydroxyacetone phosphate, and O(2) by using only nadA and nadB gene overexpressed products.

Base Sequence↗
PubMed2000

Does abnormal neuronal excitability exist in myotonic dystrophy? I. Effects of the antiarrhythmic drug hydroquinidine on slow saccadic eye movements.

The abnormal neuronal excitability hypothesized in myotonic dystrophy (MD) might contribute to psychomotor and behavioral disturbances of MD patients. To gain new insights into the pathophysiology of MD, we determined whether the antiarrhythmic drug hydroquinidine would ameliorate slow saccadic eye movements (SEMs), apathy and hypersomnia in MD patients. SEMs were selected as simple modality for psychomotor investigation. The study was conducted in a randomized, placebo-controlled, double-blind, crossover manner. Ten ambulatory patients without contraindications to hydroquinidine administration were enrolled. Hydroquinidine (450 mg/day) or placebo was given orally for 6 weeks with a washout period of 6 weeks between treatments. SEMs were recorded by electrooculography and analyzed by a computer system. Two patients withdrew in the first week of active treatment because of nausea and epigastralgia. Hydroquinidine significantly increased the normalized peak saccadic velocity and shortened the saccadic reaction time compared to placebo. The drug's effects on apathy and hypersomnia are presented in a companion paper.

Adult↗
PubMed2000

Does abnormal neuronal excitability exist in myotonic dystrophy? II. Effects of the antiarrhythmic drug hydroquinidine on apathy and hypersomnia.

An abnormal neuronal excitability in myotonic dystrophy (MD) might contribute to psychomotor and behavioral disturbances of MD patients. To gain new insights into the pathophysiology of MD, we determined whether the antiarrhythmic drug hydroquinidine could ameliorate apathy and hypersomnia besides slow saccadic eye movements in these patients. The study was conducted in a randomized, placebo-controlled, double-blind, crossover manner. Ten ambulatory patients without contraindications to hydroquinidine administration were enrolled. Hydroquinidine (450 mg/day) or placebo was given orally for 6 weeks with a washout period of 6 weeks between treatments. Apathy was evaluated by means of the apathy evaluation scale (AES) and hypersomnia by a sleep diary. Two patients withdrew in the first week of active treatment because of nausea and epigastralgia. The drug significantly reduced AES scores and daily sleep time compared to placebo. Thus, hydroquinidine can ameliorate apathy and hypersomnia in MD. However, the possibility of proarrhythmia and the high frequency of cardiac disturbances in MD seriously limit the therapeutic perspective. The effects on eye movements are presented in a companion paper.

Anti-Arrhythmia Agents↗
PubMed2000

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients.

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.

Adult↗
PubMed2000

Purification and primary structure of a new bovine spermadhesin.

Z13 is a new seminal plasma protein made up of two disulfide-linked 13-kDa subunits that was identified in our laboratory by 2D PAGE. In this report we present the purification of Z13 from bovine seminal plasma. In solution, the protein is a nonglycosylated dimer that presents one interchain disulfide bond and does not show heparin-binding properties. The complete primary structure and the localization of the S-S bridges are reported. The results suggest that Z13 is a new protein of the spermadhesin family whose members are thought to play a prominent role in different aspects of fertilization.

Amino Acid Sequence↗
PubMed2000

A centralised telephone service for tobacco cessation: the California experience.

OBJECTIVE: To provide an overview of the California Smokers' Helpline, an increasingly popular telephone program for tobacco cessation in California since 1992. As many states, regions, and nations are contemplating various telephone programs as part of large scale anti-tobacco campaigns, this paper presents a practical model. DESIGN: The Helpline provides Californians with free cessation services that include counselling, self help quit kits, and cessation related information. Services are provided in six spoken languages plus a line for the hearing impaired. The program is promoted statewide by media campaigns, health care providers, local tobacco control programs, and the public school system. SETTING: The Helpline is centrally operated through the University of California, San Diego and provides services statewide via telephone. RESULTS: The Helpline has served over 100 000 tobacco users and has become the chief cessation resource for the Comprehensive Tobacco Control Program in California. Media was the most important referral source for Helpline callers (50%), followed by health care providers (20%). About one third of the callers were ethnic minorities and 17% were 24 years old or younger. Compared to California smokers in general, the callers were more dependent on nicotine and more likely to live with other smokers, but they were also more likely to have tried to quit recently and were more ready to try again. Two randomised trials have demonstrated the efficacy of the Helpline's counselling protocol. CONCLUSION: A centralised helpline operation can be an accessible and effective service for tobacco users and should be included in any large scale, comprehensive tobacco control program.

Adolescent↗
PubMed2000

Proton MR spectroscopic imaging without water suppression.

To improve reproducibility in proton magnetic resonance (MR) spectroscopic imaging in human brain, simultaneous acquisition of the internal water reference and metabolite signals was evaluated. Measurements in healthy volunteers showed that the increase in dynamic range from signal oversampling was sufficient to avoid digitization errors. In addition, use of singular value decomposition techniques and finite impulse response filters proved effective in separating water and metabolite signals and providing estimates of the metabolite concentrations.

Adult↗
PubMed1999

Cloning and heterologous expression of NAD(P)H:quinone reductase of Arabidopsis thaliana, a functional homologue of animal DT-diaphorase.

In higher plants, NAD(P)H:quinone reductase (NQR) is the only flavoreductase known to reduce quinone substrates directly to hydroquinones by a two-electron reaction mechanism. This enzymatic activity is believed to protect aerobic organisms from the oxidative action of semiquinones. For this reason plant NQR has recently been suggested to be related to animal DT-diaphorase. A cDNA clone for NQR of Arabidopsis thaliana was identified, expressed in Escherichia coli, purified and characterized. Its amino acid sequence was found related to a number of putative proteins, mostly from prokaryotes, with still undetermined function. Conversely, in spite of the functional homology, sequence similarity between plant NQR and animal DT-diaphorase was limited and essentially confined to the flavin binding site.

Amino Acid Sequence↗
PubMed1999

Structure of L-aspartate oxidase: implications for the succinate dehydrogenase/fumarate reductase oxidoreductase family.

BACKGROUND: Given the vital role of NAD+ in cell metabolism, the enzymes involved in bacterial de novo NAD+ biosynthesis are possible targets for drug design against pathogenic bacteria. The first reaction in the pathway is catalysed by L-aspartate oxidase (LASPO), a flavoenzyme that converts aspartate to iminoaspartate using either molecular oxygen or fumarate as electron acceptors. LASPO has considerable sequence homology with the flavoprotein subunits of succinate dehydrogenase (SDH) and fumarate reductase (FRD). RESULTS: The crystal structure of the apoform of LASPO from Escherichia coli has been determined to 2.2 A resolution. The enzyme shows a novel fold for an FAD-dependent protein, comprising a three-domain structure: an FAD-binding domain with the dinucleotide-binding fold, a C-terminal three-helical bundle domain, and an alpha + beta capping domain, which is topologically similar to the small subunit of spinach ribulose-1,5-bisphosphate carboxylase/oxygenase. The interface between the FAD-binding and capping domains defines a cleft in which the active site is located. CONCLUSIONS: A number of strictly conserved residues present in all three domains indicate that LASPO, SDH and FRD share the same overall folding topology. Many of these conserved residues are in the FAD-binding site and active centre, suggesting a similar catalytic mechanism. Thus, LASPO, SDH and FRD form a class of functionally and structurally related oxidoreductases that are all able to reduce fumarate and to oxidise a dicarboxylate substrate.

Amino Acid Oxidoreductases↗