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G Comi

Publications and source records attributed to G Comi.

At least 37 records · Page 2Linked to original sources
PubMed1998

A rapid method for the identification and partial serotyping of Listeria monocytogenes in food by PCR and restriction enzyme analysis.

Two highly specific primers for Listeria monocytogenes were used to yield from foods such as milk, soft cheese and meat, PCR products that were cleaved with the restriction enzyme HindIII. The fragments generated allowed a distinction between two groups of L. monocytogenes serovars: serovars 1/2a and 1/2c cluster in one group and serovars 1/2b, 3b and 4b in the other subgroup. Since this procedure can be completed in 24 h, an epidemiological association between human disease and suspected sources can be rapidly confirmed at the subgroup level in the laboratory.

Animals↗
PubMed1998

A longitudinal brain MRI study comparing the sensitivities of the conventional and a newer approach for detecting active lesions in multiple sclerosis.

Monthly dual-echo spin-echo (SE) and enhanced magnetic resonance imaging (MRI) after the injection of a standard dose (SD) of gadolinium (Gd) is the conventional approach to monitor short-term disease activity in multiple sclerosis (MS). In this study, the sensitivity of this approach in detecting active lesions in MS was compared with that of monthly fast fluid attenuated inversion recovery (FLAIR) scans associated with enhanced MRI after the injection of a triple dose (TD) of Gd. Thirteen patients with relapsing-remitting MS entered the study. Monthly MRI scans were obtained on four occasions in two separate sessions (interval between 12 and 24 h). In one session, dual-echo conventional SE and SD Tl-weighted scans were obtained; in the other, fast-FLAIR and TD Tl-weighted scans. The order of the two sessions was randomized. Three observers counted the number of active lesions detected by each of the two approaches. One hundred and four active lesions were detected by the conventional approach and 199 by the newer approach (average increase per patient = 75%, range = 0-325%). The mean number of active lesions per month per patient was 2.0 for the conventional approach and 3.8 for the new approach (P = 0.004). Scans with active lesions were 34/52 (65%) with the conventional approach and 37/52 (71%) with the new approach. Our data indicate that the combined use of monthly fast-FLAIR and TD enhanced Tl-weighted scans increases the number of active lesions detected on serial MRI scans from patients with MS.

Adult↗
PubMed1998

Quantitative volumetric analysis of brain magnetic resonance imaging from patients with multiple sclerosis.

We compared the volumes of the brain as a whole and of different cerebral structures from patients with multiple sclerosis (MS) and normal subjects. In the patients, we also correlated brain volumes with T2 and T1 lesion loads and disability. A magnetization-prepared rapid acquisition gradient echo (MP RAGE) sequence with subsequent reconstruction of axial 1-mm thick slices and a dual-echo sequence were obtained in 15 patients with relapsing-remitting or secondary progressive MS and 15 sex-, age-, height- and weight-matched normal subjects. The brains and the different cerebral structures studied (cerebral hemispheres, cerebellum and brainstem) were segmented manually by a single observer on the 1-mm MP RAGE scans. The hyperintense lesion volumes seen on dual-echo scans and the hypointense lesion volumes seen on the 1-mm MP RAGE scans were measured using a semi-automated segmentation technique based on local thresholding. Compared to the normal volunteers, patients had significantly lower cerebral (P = 0.008), hemispheric (P = 0.01) and brainstem (P = 0.03) volumes. Cerebral atrophy was detected in seven (47%) MS patients. Patients with brainstem signs had significantly lower mean brainstem volume than the others (P = 0.04). No significant correlations were found between the cerebral volumes and the EDSS scores, the hyperintense lesion volumes and the hypointense lesion volumes. We conclude that cerebral atrophy is a relatively frequent finding in MS, but its relationship with physical disability is modest.

Adult↗
PubMed1998

A one year study of new lesions in multiple sclerosis using monthly gadolinium enhanced MRI: correlations with changes of T2 and magnetization transfer lesion loads.

In this study, 14 patients with either relapsing-remitting or secondary progressive multiple sclerosis (MS) were scanned monthly using gadolinium enhanced magnetic resonance imaging (MRI). At the start of the study and at 1 year follow up, T2-weighted and magnetization transfer (MT) scans were also performed. The correlation between the frequency and extent of enhancement and changes of lesion load over a 1 year period on T2-weighted and MT images were assessed. For all patients, and for the relapsing-remitting patients only, the number and volume of enhancing lesions per month showed no significant correlation with the change between baseline and 1 year follow up of lesion volumes on T2 and MT images. However, strong correlations were found between the number and volume of gadolinium enhancing lesions with changes of T2 (r = 0.93, P = 0.02) and MT (r = 0.82, P = 0.04) lesion loads in patients with secondary progressive MS. Strong correlations were also found between the lesion loads on T2-weighted scans and on MT images both at baseline and at 1 year follow up (r = 0.83, P = 0.003). In addition, the changes in lesion load over 1 year, detected using the two techniques, were moderately correlated (r = 0.51, P = 0.05). This study provides further evidence that the pathological processes in MS are at different stages in relapsing-remitting and secondary progressive MS. It also suggests that the effectiveness of recovery mechanisms within lesions might be one of the major factors responsible for such a difference.

Adult↗
PubMed1998

IL-12 is involved in the induction of experimental autoimmune myasthenia gravis, an antibody-mediated disease.

IL-12 has been shown to be involved in the pathogenesis of Th1-mediated autoimmune diseases, but its role in antibody-mediated autoimmune pathologies is still unclear. We investigated the effects of exogenous and endogenous IL-12 in experimental autoimmune myasthenia gravis (EAMG). EAMG is an animal model for myasthenia gravis, a T cell-dependent, autoantibody-mediated disorder of neuromuscular transmission caused by antibodies to the muscle nicotinic acetylcholine receptor (AChR). Administration of IL-12 with Torpedo AChR (ToAChR) to C57BL/6 (B6) mice resulted in increased ToAChR-specific IFN-gamma production and increased anti-ToAChR IgG2a serum antibodies compared with B6 mice primed with ToAChR alone. These changes were associated with earlier and greater neurophysiological evidence of EAMG in the IL-12-treated mice, and reduced numbers of AChR. By contrast, when IL-12-deficient mice were immunized with ToAChR, ToAChR-specific Th1 cells and anti-ToAChR IgG2a serum antibodies were reduced compared to ToAChR-primed normal B6 mice, and the IL-12-deficient mice showed almost no neurophysiological evidence of EAMG and less reduction in AChR. These results indicate an important role of IL-12 in the induction of an antibody-mediated autoimmune disease, suggest that Th1-dependent complement-fixing IgG2a anti-AChR antibodies are involved in the pathogenesis of EAMG, and help to account for the lack of correlation between anti-AChR levels and clinical disease seen in many earlier studies.

Animals↗
PubMed1998

Proinflammatory cytokines regulate antigen-independent T-cell activation by two separate calcium-signaling pathways in multiple sclerosis patients.

Central nervous system (CNS) lesions typical of multiple sclerosis (MS) are characterized by demyelinating inflammatory infiltrates that contain few CNS antigen-specific autoreactive T cells and a multitude of pathogenic non-antigen-specific mononuclear cells. Here, we report that in patients with MS the combined action of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-2, and IL-6 leads to the activation of most peripheral T cells (mainly CD4 memory) by promoting a persistent intracellular calcium increase via two independent signaling pathways. The activation of these pathways, one activated by IFNgamma and the other by the combination TNFalpha/IL-2/IL-6, is independent from myelin antigens and precedes by 2 weeks phases of disease activity (eg, clinical relapses and/or appearance of gadolinium-enhancing lesions on brain magnetic resonance imaging scans during 1 year of follow-up). Our results indicate that an appropriate combination of the four cytokines, three with a proinflammatory profile and one necessary for T-cell growth and differentiation, can activate in an antigen-independent fashion most peripheral T cells from MS patients. This mechanism is likely to contribute to the recruitment of nonspecific lymphocytes into the cellular activation processes leading to CNS demyelination and may represent a major target for immune intervention in MS.

Antigens↗
PubMed1998

Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis.

Serial monthly magnetization transfer (MT) imaging was performed to evaluate whether a change of the normal appearing white matter (NAWM), which precedes the appearance of enhancing lesions, is seen in patients with multiple sclerosis (MS). Every 4 weeks for 3 months, 10 patients with relapsing-remitting MS were scanned with a T1-weighted sequence, 20 minutes after injection with 0.3 mmol/kg gadolinium-DTPA (Gd-DTPA). During each of the monthly sessions, MT and dual echo scans were also performed before Gd-DTPA injection. On coregistered images, the MT ratio (MTR) was measured in NAWM subsequently involved by enhancing lesions, in NAWM areas on the same slices but outside any present or future MR abnormality, and in enhancing lesions at the time of their appearance. Forty-eight new enhancing lesions with no corresponding abnormalities on previous scans were identified. Their average MTR was 33.1% (+/-8.4%). Three, 2, and 1 month before enhancement appearance, the mean MTR in NAWM, measured from areas corresponding to future enhancing lesions, was significantly lower than the mean MTR in NAWM outside enhancing areas; the MTR decreased steadily as the time when the enhanced lesion approached. These results suggest that changes in the NAWM of patients with MS occur before lesions become evident on conventional MRI scans.

Adult↗
PubMed1998

Event-related desynchronization to contingent negative variation and self-paced movement paradigms in Parkinson's disease.

The event-related desynchronization (ERD) to voluntary movement is an indicator of cortical activation with a high time resolution and a specific spatial representation. We have evaluated 10 patients affected by Parkinson's disease (PD), free from L-dopa treatment for at least 12 hours, and 10 control subjects. Each subject underwent ERD examination during self-paced movement (SPM) and during contingent negative variation (CNV) paradigms. ERD was measured as the percentage decrease of alpha band power and calculated for frequency bands of 1 Hz, ranging between 8 and 12 Hz. For group comparisons, the frequency showing the highest ERD was selected for each subject and for each side. In the control group, ERD in the CNV paradigm began over the contralateral centroparietal electrodes 1475 ms before movement onset of the right hand and 1375 ms for the left. In the SPM paradigm, ERD started over the contralateral central electrodes 2150 ms and 1775 ms before movement onset of the right and left hand, respectively. In the PD group, ERD started over the contralateral central areas 800 ms and 475 ms before movement onset of the right and left hand, respectively, for CNV paradigm and 1200 ms and 750 ms for the right and left hand, respectively, for SPM paradigm. Therefore, contralateral ERD began closer to movement onset in PD compared with the control group in both paradigms. ERD over the sensorimotor areas ipsilateral to the movement was not significantly different in PD compared with the control group. The finding of delayed contralateral ERD in PD is according to the view that functional cortical activation related to movement preparation is impaired in PD. The lack of group differences in the onset of ipsilateral ERD, which appears close to movement execution than contralateral ERD both in normal subjects and in PD, suggests that different mechanisms may be involved in generating ERD over the hemispheres ipsilateral and contralateral to the movement, and that only the latter are impaired in PD.

Adult↗
PubMed1998

Development of a PCR microplate-capture hybridization method for simple, fast and sensitive detection of Salmonella serovars in food.

The authors have developed an easy and rapid detection and identification system for Salmonella spp. in food. The gene inv A was selected as the target sequence. Oligonucleotides derived from conserved regions of this gene were able to exclusively prime the amplification of a 389 bp fragment when Salmonella spp. DNA was used as the template. An internal Salmonella spp. specific DNA probe was used for confirmation of the amplified polymerase chain reaction(PCR)product, by Southern blot or microplate-capture hybridization assay. In this fashion the sensitivity of the method was increased 100-fold (4.5 fg total DNA). To validate the method, a total of 75 food samples were tested. The PCR-microplate capture hybridization assay is easy to perform and much faster than traditional detection methods for Salmonella spp. in food. Hybridization in microtitre plates is more readily observed than in Southern blot and is more sensitive than conventional agarose gel electrophoresis.

Biotin↗
PubMed1998

EEG coherence in Alzheimer's disease.

EEG coherence can be used to evaluate the functionality of cortical connections and to get information about the synchronization of the regional cortical activity. We studied EEG coherence in patients affected by clinically probable Alzheimer's disease (AD) in order to quantify the modifications in the cortico-cortical or cortico-subcortical connections. The EEGs were recorded in 10 AD patients (with mild or moderate degrees of dementia) and in 10 normal age-matched subjects, at rest and eye-closed, from 16 electrodes with linked-ears reference. Spectral parameters and coherence were calculated by a multichannel autoregressive model using 50 artifact-free epochs, 1 s duration each. Alpha coherence was significantly decreased in 6 patients, the decrease being more accentuated in the area near the electrode taken into account; a significant delta coherence increase was found in a few patients between frontal and posterior regions. The AD group showed a significant decrease of alpha band coherence, in particular in temporo-parieto-occipital areas, more evident in patients with a more severe cognitive impairment. These abnormalities could reflect two different pathophysiological changes: the alpha coherence decrease could be related to alterations in cortico-cortical connections, whereas the delta coherence increase could be related to the lack of influence of subcortical cholinergic structures on cortical electrical activity.

Aged↗
PubMed1998

How does brain MRI lesion volume change on serial scans in patients with multiple sclerosis?

Although lesion load changes on conventional T2-weighted brain magnetic resonance imaging (MRI) scans from patients with multiple sclerosis (MS) are used to monitor the effect of treatment, there is no clear definition of how lesion load changes over years according to the lesion load present at a baseline evaluation. In the present study, we evaluated the relationship between lesion load changes over time and lesion load at a baseline evaluation in a group of untreated patients with MS. We scanned nineteen patients on two separate occasions with a mean interval 16.4 months between the two examinations. In each scanning session, a scan with forty contiguous 3-mm-thick axial slices was acquired. We assessed MRI lesion loads using a semi-automated local thresholding technique. Both a linear (p < 0.0001) and a quadratic component (p = 0.0008) of the baseline volume were significant in describing the follow-up volume. The equation to model this finding was as follows: Vf = beta0 Vb + beta1 (Vb)2, where Vf is the lesion volume at follow-up, Vb is the lesion volume at baseline, beta0 = 0.834 (SE = 0.098), and beta1 = 0.014 (SE = 0.003) (mL)(-1). Our data indicate that lesion volume changes detectable on serial brain MRI studies from patients with MS are dependent on the extent of lesion burden present on the baseline MRI scans. This finding has to be considered when planning phase III trials.

Adult↗
PubMed1998

Brain MRI lesion volume measurement reproducibility is not dependent on the disease burden in patients with multiple sclerosis.

We evaluated the potential effect of the lesion burden on the reproducibility of repeated lesion volume (LV) measurements from brain magnetic resonance imaging (MRI) scans of patients with multiple sclerosis (MS). Dual-echo, conventional spin echo brain MRI scans were obtained from 107 patients with MS. On proton density-weighted images, LV was assessed three times by the same raters, using a semi-automated, local thresholding technique for lesion segmentation. Mean LV (MLV) was 16.1 mL (range = 0.7-57.3 mL). The mean intra-observer coefficient of variation (COV) for the three measurement replicates was 2.6% (range = 0.2-7.2%). The intra-observer measurement variance (Var) increased with MLV and the fitted model was Var = 0.00187 MLV1.84. This indicates that LV measurements can be considered as measures whose variances are proportional to the square of their mean values, i.e., these measures have constant COV. Using a semi-automated, local thresholding segmentation technique, the reproducibility of LV measurements from brain MRI scans of patients with MS is not significantly influenced by varying lesion burdens.

Analysis of Variance↗
PubMed1998

Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that is triggered in genetically predisposed individuals by common anesthetics and muscle relaxants. The ryanodine receptor (RYR1) is mutated in a number of MH pedigrees, some members of which also have central core disease (CCD), an inherited myopathy closely associated with MH. Mutation screening of 6 kb of the RYR1 gene has identified four adjacent novel mutations, C6487T, G6488A, G6502A, and C6617T, which result in the amino acid alterations Arg2163Cys, Arg2163His, Val2168Met, and Thr2206Met, respectively. Collectively, these mutations account for 11% of MH cases and identify the gene segment 6400-6700 as a mutation hot spot. Correlation analysis of the in vitro contracture-test data available for pedigrees bearing these and other RYR1 mutations showed an exceptionally good correlation between caffeine threshold and tension values, whereas no correlation was observed between halothane threshold and tension values. This finding has important ramifications for assignment of the MH-susceptible phenotype, in genotyping studies, and indicates that assessment of recombinant individuals on the basis of caffeine response is justified, whereas assessment on the basis of halothane response may be problematic. Interestingly, the data suggest a link between the caffeine threshold and tension values and the MH/CCD phenotype.

Female↗
PubMed1998

A multi-centre longitudinal study comparing the sensitivity of monthly MRI after standard and triple dose gadolinium-DTPA for monitoring disease activity in multiple sclerosis. Implications for phase II clinical trials.

In this study we assessed the safety, efficacy and cost-effectiveness of the use of triple dose gadolinium-DTPA (Gd) in serial monthly brain MRI of patients with multiple sclerosis, such as could be selected for clinical trials. The number of enhancing lesions, the number of new enhancing lesions and the number of active scans were used to evaluate the sensitivity of the contrast-enhanced MRI to disease activity. The dose of Gd, and the effect of introducing a delay between the contrast injection and the scan were both appraised. Every 4 weeks for 3 months, and in two separate sessions, scans were obtained from 40 patients with relapsing-remitting or secondary progressive multiple sclerosis, 5 min (early) and 20 min (delayed) after a standard dose (0.1 mmol/kg) or triple dose (0.3 mmol/kg) Gd injection. There were 435 enhancing lesions (242 of which were new) on the early standard dose scans, 479 (263 new) on the delayed standard dose, 772 (365 new) on the early triple dose and 827 (404 new) on the delayed triple dose. There were 109 scans revealing active disease on the early standard dose scans, 112 on the delayed standard dose, 119 on the early triple dose and 120 on the delayed triple dose. Statistical simulations indicated that the sample sizes needed for both cross-over and parallel-group trials with similar powers are lower if serial monthly triple dose MRI is used. No side-effects were reported and no significant changes in blood test parameters were found throughout the study. This study shows that the serial use of triple dose Gd is safe, and that it increases the sensitivity of serial monthly enhanced MRI in detecting multiple sclerosis activity significantly. Its use should enable preliminary trials of experimental therapies for multiple sclerosis to be conducted in small patient populations, over a short period of time.

Adult↗