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Biomedical subjects

A Tessitore

Publications and source records attributed to A Tessitore.

At least 19 recordsLinked to original sources
PubMed2006

Subcortical motor plasticity in patients with sporadic ALS: An fMRI study.

OBJECTIVE: To address the potential contribution of subcortical brain regions in the functional reorganization of the motor system in patients with sporadic ALS (sALS) and to investigate whether functional changes in brain activity are different in sALS patients with predominant upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction. METHODS: We studied 16 patients with sALS and 13 healthy controls, using BOLD-fMRI, while they performed a simple visually paced motor task. Seven patients had definite clinical UMN signs while nine patients had prevalent clinical and electrophysiological LMN involvement. fMRI data were analyzed with Brain Voyager QX. RESULTS: Task-related functional changes were identified in motor cortical regions in both patients and healthy controls. Direct group comparisons revealed relatively decreased BOLD fMRI responses in left sensorimotor cortex, lateral premotor area, supplementary motor area and right posterior parietal cortex (p < 0.05 corrected) and relatively increased responses in the left anterior putamen (p < 0.001 uncorrected) in sALS patients. Additional analyses between the two patients subgroups demonstrated significant BOLD fMRI response differences in the anterior cingulate cortex and right caudate nucleus (p < 0.001 uncorrected) with more robust activation of these areas in patients with greater UMN burden. Importantly, there were no significant differences in performance of the motor task between sALS patients and controls as well as between sALS patient subgroups. CONCLUSIONS: Our data demonstrate a different BOLD fMRI pattern between our sALS patients and healthy controls even during simple motor behavior. Furthermore, patients with sALS and greater UMN involvement show a different reorganization of the motor system compared to sALS patients with greater LMN dysfunction.

Adult↗
PubMed2006

Gangliosides as apoptotic signals in ER stress response.

Renewed attention has been given lately to gangliosides and to their function as intracellular messengers of the adaptive responses to stress. Gangliosides are vital components of cell membranes; therefore, deleterious consequences can result from changes in their chemical composition and concentration, that is, membrane dynamics and structure can be altered as can the behavior of other membrane proteins. The importance of gangliosides in human health is evident in neurodegenerative diseases associated with defects in their degradation. As key modulators of intracellular calcium flux, gangliosides are involved in cellular processes downstream of calcium signaling. In this review, we focus on the effect of ganglioside accumulation on the endoplasmic reticulum calcium homeostasis and on the integrity of the mitochondrial membranes. We discuss how these events elicit an apoptotic program that ultimately leads to cell death. Owing to interorganelle crosstalk, these events are not necessarily self-contained, and gangliosides may serve as the common factor.

Animals↗
PubMed2006

Novel P53 mutations detected by FAMA in colorectal cancers.

BACKGROUND: The aim of the study was to identify p53 gene mutations by FAMA (fluorescence-assisted mismatch analysis) in colorectal cancers. PATIENTS AND METHODS: Analytical scanning of the p53 gene (exons 5-9) was performed in colon cancer samples from 44 consecutive patients by FAMA. FAMA is a semiautomatic scanning approach based on the chemical cleavage of the mismatch in fluorescently labeled heteroduplex DNA, obtained from the combination of a normal and a mutated allele. FAMA has already shown optimal levels of diagnostic accuracy and sensitivity in detecting gene mutations (nucleotide substitutions, insertions/deletions) both at the germline and somatic level. The peculiar feature of FAMA is its ability to detect and localize mutations, by a redundant pattern of signals due to fluorescent DNA fragments generated by chemical cleavage. Moreover, previous data have demonstrated that normal contaminating DNA from stromal cells in the sample does not affect the sensitivity of the procedure, leading to the identification of the mutation even when the ratio mutant/normal allele is 10%. RESULTS: Eighteen mutations (12 missense, one nonsense, two deletions, three nucleotide substitutions at the level of the splice-junctions) and two polymorphisms were detected by FAMA in 17 patients (39%) and then confirmed by automated sequence analysis. Six of 18 mutations (33%) were not previously reported for colon cancer samples and two of 18 lesions (11%) were identified as novel p53 mutations. CONCLUSIONS: Analytical scanning of the p53 gene by FAMA in DNA from colon cancer samples provides a sensitive, accurate and specific diagnostic procedure for routine clinical application.

Colorectal Neoplasms↗
PubMed2006

Physiological and technical aspects of ''6-a-side'' soccer drills.

AIM: The purposes of the present study were: 1) to evaluate heart rate and technical-tactical differences, if any, during ''6-a-side'' drills, played on 2 pitch dimensions (30x40 m and 50x40 m) and duration (3 min and 8 min); 2) to assess the variability of data between repeated experimental sessions; 3) to evaluate training intensities from heart rate at lactate threshold. METHODS: Laboratory measurements of maximal oxygen consumptions, maximum heart rates and lactate thresholds were performed on 9 soccer players who played at Regional level. For test and retest field sessions, the exercise intensities were calculated from heart rate monitoring and match analysis (number of actions, consecutive passes, players involved in a single action) was performed. RESULTS: No significant differences were found in heart rate frequency distributions between test and retest sessions. Statistically significant differences in frequency distributions of heart rate were found only between the 3 min and 8 min drills played on the 40x50 m pitch. Regarding exercise intensity, significant differences (P<0.01) were found for pitch dimension, with higher intensities shown during the 30x40 m pitch trials. When technical data were related to time units, no differences were found among experimental settings. CONCLUSIONS: These data indicate that coaches could better modulate the training intensity by varying the pitch dimension, with the smaller individual playing area (30x40 m) having a large impact on the metabolic demands of exercise.

Adult↗
PubMed2005

Characterization of a novel HLA-Cw*02 variant, Cw*0208, in a Caucasian individual.

We describe an additional HLA-Cw*02 variant, HLA-Cw*0208, which has been identified in a renal transplant recipient of Caucasian origin (Italy). After performing preliminary serological typing, we analyzed exons 2 and 3 of the HLA-C locus polymorphism by cloning the amplified DNA and using a sequence-based typing method. The new allele differs from Cw*020202 by one nucleotide substitution at nucleotide 61 (G-->A) of exon 2, which translates to a difference of one amino acid at residue 21 (His-->Arg) of the HLA-C heavy chain. We propose that Cw*0208 was generated by a random point mutation in codon 21 from the Cw*020202 allele, or through gene conversion of Cw*020202 with another allele, probably the Cw*1205 and Cw*1602 alleles.

Alleles↗
PubMed2005

Identification of a novel HLA-A*02 allele, A*027401*.

A novel HLA-A*02 allele was detected in a Caucasian patient from central Italy, requiring a hematopoietic cell transplantation. Direct sequencing identified a variation in one nucleotide position, which was confirmed by cloning. The name A*027401 was officially assigned by the WHO Nomenclature Committee in November 2004. A*027401 differs from A*02010101 by a single G to A substitution at nucleotide position 595 in exon 3. The new variant would lead to a nonsynonymous nucleotide change (GGG to AGG) at codon 175, resulting in a basic Arg in the alpha-helix of the alpha2-domain, in place of a non-polar Gly. The presence of an uncommon variation at a highly conserved nucleotide position could have implications in unrelated hematopoietic cell transplantation.

Alleles↗
PubMed2004

Human leukocyte antigen-A, -B, and -Cw polymorphism in a Berber population from North Morocco using sequence-based typing.

Class I human leukocyte antigen (HLA) polymorphism was examined in a Berber population from North Morocco, named Metalsa (ME). All data were obtained at high-resolution level, using sequence-based typing. The most frequent alleles were: HLA-A*0201 and A*0101; HLA-B*44 (B*4403 and B*4402); B*0801 and the B*50 allele group (B*5001 and B*5002); HLA-Cw*0602; and Cw*07 group (Cw*070101, Cw*070102, Cw*0702, Cw*0704, and Cw*0706), and Cw*040101. The novel HLA-B*570302 allele was identified. It differs at position 486 and position 855 from B*570301, resulting in synonymous Thr and Val. The analysis also evidenced some alleles common in Africans (A*3402, A*6802, A*7401, B*1503, B*4102, B*4202, B*7801, B*5802, Cw*1701, and Cw*1703) and some uncommon alleles (A*3004, B*2702, B*2703, B*5001,02, B*3503, and Cw*0706). The predominant HLA-A-Cw-B-DRB1-extended haplotypes in ME population were A*0101-Cw*0501-B*4402-DRB1*0402, A*240201-Cw*0701-B*0801-DRB1*030101, A*2301-Cw*040101-B*4403-DRB1*040501, A*0201-Cw*040101-B*4403-DRB1*1302, and A*3002-Cw*0602-B*5002-DRB1*0406. This study demonstrates a strong relatedness of ME to other Moroccan and North African populations, some characteristics of sub-Saharan Africans and evidenced the influence of various immigrations during centuries. Nevertheless, this study highlights some unique genetic traits of the ME population compared to other ethnic groups within Morocco, which could be of great interest for clinical aims, transplantation, and diseases.

Adult↗
PubMed2003

Prognostic value of p53 molecular status in high-risk primary breast cancer.

BACKGROUND: Mutations in the p53 gene are the most common genetic alterations in human primary breast carcinoma and these mutations are often associated with worse prognosis and chemo/radioresistance. PATIENTS AND METHODS: The analysis of the p53 gene was performed by fluorescence-assisted mismatch analysis in 13 consecutive high-risk primary breast cancer (HR-BC) patients with 10 or more involved axillary nodes to evaluate its prognostic value. RESULTS: Three p53 mutations (23%) and four allelic variants were detected. After a median follow-up of 52 months the HR-BC disease-free survival (DFS) was 51% and overall survival 79%. All patients harboring a p53 mutation (p53(mut)) relapsed within 10 months of the median DFS while 67% of those showing a wild-type p53 status (p53(wt)) survive disease-free at a median follow-up of 43 months. One p53(mut) patient is still alive while all the p53(wt) patients survive at 56 months median follow-up. Two out of the four p53(wt) relapsing breast cancer patients showed the Arg72Pro allelic variant; one of these died at 75 months. CONCLUSIONS: p53 mutations may help identify a subset of very high risk breast cancer patients (vHR-BC) with worse prognosis.

Breast Neoplasms↗
PubMed2002

Neurophysiological correlates of age-related changes in human motor function.

BACKGROUND: There are well-defined and characteristic age-related deficits in motor abilities that may reflect structural and chemical changes in the aging brain. OBJECTIVE: To delineate age-related changes in the physiology of brain systems subserving simple motor behavior. METHODS: Ten strongly right-handed young (<35 years of age) and 12 strongly right-handed elderly (>50 years of age) subjects with no evidence of cognitive or motor deficits participated in the study. Whole-brain functional imaging was performed on a 1.5-T MRI scanner using a spiral pulse sequence while the subjects performed a visually paced "button-press" motor task with their dominant right hand alternating with a rest state. RESULTS: Although the groups did not differ in accuracy, there was an increase in reaction time in the elderly subjects (mean score plus minus SD, young subjects = 547 +/- 97 ms, elderly subjects = 794 +/- 280 ms, p < 0.03). There was a greater extent of activation in the contralateral sensorimotor cortex, lateral premotor area, supplementary motor area, and ipsilateral cerebellum in the elderly subjects relative to the young subjects (p < 0.001). Additional areas of activation, absent in the young subjects, were seen in the ipsilateral sensorimotor cortex, putamen (left > right), and contralateral cerebellum of the elderly subjects. CONCLUSIONS: The results of this study show that elderly subjects recruit additional cortical and subcortical areas even for the performance of a simple motor task. These changes may represent compensatory mechanisms invoked by the aging brain, such as reorganization and redistribution of functional networks to compensate for age-related structural and neurochemical changes.

Adult↗
PubMed2002

Identification of the novel allele B*4427 and a confirmatory sequence (B*44022).

This report presents a novel allele, HLA-B*4427, which was identified in a bone marrow donor of Caucasian origin, and a confirmatory sequence (B*44022). Sequence analysis revealed the new allele differs from B*44021 by a single nucleotide exchange at position 668 (C-->T), which is located in exon 4. At the protein level, it is the only B*44 variant to produce an Ala in place of a Val at codon 199. Its structure suggests that it may have originated from a point mutation in B*44021 or by gene conversion with a variety of HLA-B alleles. Cloning and sequencing of the allele B*44022 revealed a sequence identical to B*44021 and B*44 exon 4, with the codon GTC (Val) in position 199.

Alleles↗
PubMed2001

Heart rate and match analysis in pre-pubescent soccer players.

The aim of this study was to compare match analysis (using video recordings) and the physiological load (heart rate measured every 5 s, blood lactate measured after the warm-up, first half and second half) of six 11-year-old soccer players during official games of eleven-a-side on a regular-sized pitch (100 x 65 m) and of seven-a-side on a smaller pitch (60 x 40 m). In both games, heart rate exceeded 170 beats x min(-1) 84% of the time, while blood lactate ranged from 1.4 to 8.1 mmol l(-1). No significant differences were recorded for the physiological parameters. For both matches, walking comprised 38% of total time, running 55%, inactivity 3% and jumping 3%. Although there were no significant differences between halves or matches, running for less than 10 s was 10% more frequent in the seven-a-side game. In the seven-a-side game, there were significantly more passes and significantly fewer tackles, suggesting that seven-a-side matches played on smaller pitches may be more suitable for pre-pubescent soccer players.

Analysis of Variance↗
PubMed2000

Molecular defects in the alpha-N-acetylglucosaminidase gene in Italian Sanfilippo type B patients.

Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is a rare autosomal recessive disorder characterized by the inability to degrade heparan sulfate because of a deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). We performed mutation screening in a group of 20 patients, identyifing 28 mutations, 14 of which were novel (L35F, 204delC, 221insGCGCG, G82D, W156C, 507delC, IVS3+1G-->A, E336X, V501G, R520W, S534Y, W649C, 1953insGCCA, 2185delAGA). Four of these mutations were found in homozygosity and only one was seen in two different patients, showing the remarkable molecular heterogeneity of the disease. Mutation IVS3+1G-->A produces aberrant RNA splicing: it represents a base substitution from G to A of the invariant GT dinucleotides at the splicing donor site of intron 3 resulting in the skipping of exon 3 and both exons 2 and 3. Transient transfection of COS cells, by DNA mutagenized with NAGLU mutations, produced enzymatic molecules without activity, demonstrating the deleterious nature of the defects. Metabolic labeling of transfected mutants suggested a normal synthesis of the involved polypeptide for missense alterations, whereas increased protein or mRNA instability was shown for nonsense and most of the frameshift mutations.

Acetylglucosaminidase↗
PubMed2000

Tolosa-Hunt syndrome preceded by facial palsy.

The Tolosa-Hunt syndrome consists of a painful ophthalmoplegia related to a granulomatous inflammatory process in the cavernous sinus, which may be documented by cerebral magnetic resonance imaging with gadolinium enhancement. Two cases of Tolosa-Hunt syndrome preceded by facial palsy observed in 1998 at the Department of Neurosurgery of the Second University of Naples are presented here. Both patients developed Tolosa-Hunt syndrome following an ipsilateral facial palsy that resolved in about 15 days with medical treatment. Cerebral magnetic resonance imaging with gadolinium enhancement showed, in both cases, inflammatory tissue in the cavernous sinus. The patients underwent corticosteroid therapy (prednisolone, 80 mg per day, intravenously) with pain regression. In the first case, the patient experienced recurrence of the syndrome that was definitively resolved with further corticosteroid treatment. The rare reports of facial palsy in patients with Tolosa-Hunt syndrome suggest the inclusion of this disease in the so-called multiple cranial nerve palsy syndrome. It is probable that Tolosa-Hunt syndrome has an inflammatory pathogenesis.

Adult↗
PubMed1999

Angiotensin II stimulates intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells and increases soluble ICAM-1 release in vivo.

BACKGROUND: We evaluated whether angiotensin II (Ang II) influenced intercellular adhesion molecule (ICAM)-1 expression by human vascular endothelial cells derived from umbilical cord veins (HUVECs) and plasma soluble ICAM-1 levels in vivo. METHODS AND RESULTS: Cultured HUVECs were incubated with Ang II (from 10(-9) to 10(-6) mol/L) with or without candesartan and PD12319 (inhibitors of Ang II AT(1) and AT(2) receptors, respectively) for various times up to 4 hours. Total RNA was then extracted from HUVECs, and Northern blots were probed with a 1.9-kb ICAM-1 cDNA fragment. HUVEC supernatants were used to assess soluble ICAM-1 release by ELISA. Northern blot analysis detected a strong increase of ICAM-1 mRNA after 2-hour incubation with Ang II. The response was inhibited by candesartan. Soluble ICAM-1 release by HUVECs also increased (P<0. 002) after 2-hour Ang II stimulation. In vivo, Ang II (at an initial rate of 1.0 ng. kg(-1). min(-1), to be increased each 30 minutes by 2.0 ng. kg(-1). min(-1) to the final rate of 7.0 ng. kg(-1). min(-1)) was infused in 8 normotensive and 12 essential hypertensive individuals. In the latter, Ang II was reinfused after 4 weeks on either placebo (n=3), losartan (50 mg UID, n=5), or atenolol (50 mg UID, n=4) treatment. Plasma soluble ICAM-1 levels increased after Ang II infusion in hypertensives and normotensives (P<0.0001 after 90 minutes). Losartan reduced baseline soluble ICAM-1 levels (P<0.05) and Ang II-related ICAM-1 increments. CONCLUSIONS: Ang II upregulates ICAM-1 expression by HUVECs and stimulates in vitro and in vivo soluble ICAM-1 release. AT(1) receptor blockade inhibits such endothelial effects of Ang II.

Adult↗
PubMed1999

A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene.

We report a novel case of multiple endocrine neoplasia type 2A (MEN 2A) associated with two mutations of the protooncogene RET. One affects codon 634 and causes a cysteine to arginine substitution; the second at codon 640 causes an alanine to glycine substitution in the transmembrane region. The two mutations were present on the same RET allele and were detected in germline and tumor DNA. Both mutations were de novo, i.e. they were not found in the DNA of the parents or relatives. Immunohistochemical and RT-PCR analysis showed that the pheochromocytoma expressed calcitonin as well as both RET alleles. A cell line established from the tumor and propagated in culture sustained the expression of RET and calcitonin, as did the original pheochromocytoma. Because the patient presented with medullary thyroid carcinoma and pheochromocytoma without parathyroid gland involvement, we speculate that this clinical picture could be correlated with the two RET mutations and to the unusual calcitonin production. This is the first report of a MEN 2A case due to two mutations of the RET gene and associated with a calcitonin-producing pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1998

Two gamma-interferon-activation sites (GAS) on the promoter of the human intercellular adhesion molecule (ICAM-1) gene are required for induction of transcription by IFN-gamma.

We describe the molecular features of the interferon (IFN)-gamma-mediated transcription of the human intercellular adhesion molecule (ICAM-1) gene. We identified putative IFN-gamma-activated sites (GAS) distributed throughout a large segment of the ICAM-1 promoter (4.0 kb region). Using computer-assisted search, these sequences were similar to potential IFN-gamma responsive elements that have a core sequence 5'-TTNCNNNAA-3'. In this report we show that in the ICAM-1 promoter a GAS site is located at -115 from the translation initiation site, and binds with strong affinity to IFN-gamma-activated Signal Transducers and Activators of Transcription (STAT1) homodimers. The same sequence is responsible for the IFN-gamma-mediated transcription of the ICAM-1 gene. Moreover, we present evidence that a more distal GAS element that maps at -2787 from the translation initiation site, binds IFN-gamma-activated STAT1 dimers with lower affinity. Multimeric copies of such GAS sequence inserted into a tkCAT minimal promoter can drive transcription, demonstrating that the -2787 bp GAS element has an independent functional activity upon binding of IFN-gamma-activated STAT1 proteins as documented by in vitro binding assays. Furthermore, using recombinant ICAM-CAT mutants, we show that, in vivo, the -2787 GAS, but not a mutagenized -2787 GAS site, when coupled to the more proximal -115 GAS element, has an additive effect in enhancing the IFN-gamma-mediated transcription of ICAM-1 promoter. Nevertheless, using a recombinant construct bearing the wild type -2787 GAS element and a mutagenized -115 GAS element, we could not detect any transcription after transfection of U937 recipient cells, suggesting that the -2787 bp GAS element is not sufficient as such for gene activation, but can cooperate with its cognate proximal sequence to give full function to the ICAM-1 promoter during the IFN-gamma response. Taken together these data provide evidence that two GAS sites are required for the full potential activity in the mechanism of ICAM-1 gene activation by IFN-gamma.

5' Untranslated Regions↗
PubMed1997

Transcriptional regulation of intercellular adhesion molecule 1 by phorbol ester in human neuroblastoma cell line SK-N-SH involves jun- and fos-containing activator protein 1 site binding complex(es).

In this study, the regulatory elements involved in ICAM-1 transcriptional response to phorbol ester (12-0-tetradecanoylphorbol-13-acetate; TPA) have been investigated in the human neuroblastoma cell line, SK-N-SH. TPA induced intercellular adhesion molecule 1 (ICAM-1) protein expression in SK-N-SH cells within 24 h of treatment as judged by indirect immunofluorescence. Basal ICAM-1 mRNA levels were barely detectable in untreated SK-N-SH cells but were induced by TPA to a maximal level with 4 h and were reduced thereafter. Analysis of the 5' promoter sequence of ICAM-1 revealed two regions that functioned equally in the TPA induction of ICAM-1 transcription. The first region (-145 to -227) contained a nuclear factor-kappa B (NF kappa B) element. The second region (-316 to -390) contained a putative TPA-responsive element (TRE; TGATTCA) and a TATA box. Deletion and point mutation of the latter region indicated that the TRE was indeed the functional element within this region and acted fully and independently of all other elements including the TATA box at position -352. This TRE bound TPA induced specific nuclear complexes in vitro containing junD, c-jun, c-fos, and fra2 but not cAMP-responsive element binding/activating transcription factor family proteins. ICAM-TRE binding activity was induced within 30 min following TPA treatment. This preceded the appearance of ICAM-NF kappa B site binding activity. Cotransfection of c-jun and c-fos expression vectors into SK-N-SH cells induced transactivation from ICAM-1 promoter constructs containing the intact but not mutated TRE site. Primer extension analyses revealed that TPA had induced transcription exclusively at two sites -40 and -41 bp upstream of the translation start site. These data show that the ICAM-TRE and its cognate jun- and fos-containing transcription factors play a predominant role in the transcriptional response of ICAM-1 to the protein kinase C activator TPA in SK-N-SH cells.

Cyclic AMP Response Element-Binding Protein↗