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A Uccelli

Publications and source records attributed to A Uccelli.

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

Differential display analysis of murine encephalitogenic mRNA.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease which can be induced by inoculation with activated CD4+ T lymphocytes specific for myelin proteins. It has been postulated that autoreactive Th1-type CD4+ cells are responsible for the lesions, whereas autoreactive Th2-type cells suppress or modulate the disease. However, the mechanisms involved in the development of inflammatory lesions and neurologic deficits in EAE have not been fully described, and probably involve a complex array of mediators and alternative or redundant pathways. To identify additional factors associated with the pathological role of T cells in EAE, we adapted the differential mRNA display technique to fingerprint the transcripts expressed by encephalitogenic and non-encephalitogenic T cells. Using 60 primer combinations, 21 differentially expressed cDNAs were identified. Among them 13 are known sequences, including IL-3 in non-encephalitogenic lymphocytes. Their relevance for the disease process is discussed.

Animals↗
PubMed1998

Effect of copolymer-1 on serial gadolinium-enhanced MRI in relapsing remitting multiple sclerosis.

We examined the effect of Copolymer-1 (Cop1) on magnetic resonance (MR) imaging changes in 10 patients with relapsing-remitting multiple sclerosis (RRMS). Monthly gadolinium (Gd)-enhanced MR imaging was performed for 9 to 27 months in the pretreatment period followed by 10 to 14 additional months during Cop1 treatment. MR images were evaluated by two radiologists (F.S. and R.C.P.) masked to the scan date. We found a 57% decrease in the frequency of new Gd-enhancing lesions and in the mean area/month of new Gd-enhancing lesions in the Cop1 treatment period compared with the pretreatment period (0.92 versus 2.20 lesions per month and 22 mm2 versus 43 mm2 area/month; p = 0.1, Wilcoxon signed rank test). Percentage change in lesion load area on T2-weighted images showed a decrease in the accumulation of lesion area during treatment, which was significant for the patient group with a longer pretreatment period (p = 0.05, Friedman test). These results demonstrate a reduction in the number of new Gd-enhancing lesions and in the lesion load during Cop1 treatment compared with the preceding period without therapy and are suggestive of an effect of Cop1 on MR abnormalities observed in multiple sclerosis.

Gadolinium↗
PubMed1998

An open-label trial of gabapentin treatment of paroxysmal symptoms in multiple sclerosis patients.

We conducted an open-label trial of gabapentin (GBP) as therapy for paroxysmal symptoms (PS) in 21 MS patients, including trigeminal neuralgia (6 patients), painful tonic spasms (11), dysesthetic or paresthetic symptoms (3) and ocular ataxia (1). Complete resolution of symptoms or partial improvement was obtained, respectively, in 14 and 4 of 18 patients who ended the study. Sustained improvement with minor side effects was obtained at dosages ranging from 600 to 1200 mg/d. Our findings suggest that GBP may be effective for PS in MS and warrant a further study in a double-blind placebo-controlled trial.

Acetates↗
PubMed1997

Characterization of the TCRB chain repertoire in the New World monkey Callithrix jacchus.

Callithrix jacchus is an outbred New World primate characterized by a naturally occurring bone marrow chimerism, restricted polymorphism at many MHC loci, and unusual susceptibility to viral pathogens, adenocarcinoma, colitis, and, following immunization with myelin antigens, a demyelinating disease of the central nervous system closely resembling human multiple sclerosis. Here we characterize the TCRB repertoire in this species, representing the first such analysis in a New World monkey. Two TCRBC, 13 BJ, 2 BD, and 15 BV genes were identified. Overall, a high degree of similarity with human TCRBV-D-J-C gene sequences was observed, indicating a close phylogenetic relationship. Biased usage in favor of genes from the TCRBC1-BJ1 cluster was present in 77% of sequences, in contrast to preferential usage of BC2-BJ2 genes known to occur in humans and mice. Complementarity-determining region 3 averaged 10 amino acids in length and were diverse. Framework regions of TCRBV genes were extensively conserved. Phylogenetic analysis of TCRBV sequences from different species indicated that TCR genes are highly stable across primates. Thus, a diverse TCRB repertoire is generated in C. jacchus despite the limited polymorphism of class I MHC loci. Extensive homology to human TCR genes, natural chimerism, and susceptibility to inflammatory disorders are characteristics of C. jacchus that create a useful model system for the study of human autoimmunity.

Amino Acid Sequence↗
PubMed1997

Local-clonal expansion of infiltrating T lymphocytes in chronic encephalitis of Rasmussen.

Rasmussen's syndrome is a progressive and intractable form of epilepsy characterized pathologically by focal brain inflammation with large numbers of infiltrating T lymphocytes. To better understand the nature of the T cell response in this disease, we analyzed TCR expression in the brain lesions using PCR for quantitative assessment of TCRBV gene transcripts, together with size and sequence analysis of the third complementarity-determining region (CDR3) of the dominant TCR rearrangements. Restricted (oligoclonal) BV family usage was not observed, as all of the 22 BV PCR products were usually detected at levels exceeding the background. However, significant individual biases in the frequencies of different TCR families was evident. The distinct pattern of BV expression by infiltrating lymphocytes detected in the original PCR screening suggested a specific immune response. The primary structure of the rearranged CDR3 sequences for the BV family expressed at highest level in each sample was studied by size and sequence analysis. The data showed that predominant TCR BV families expressed in diseased brain tissue displayed limited size heterogeneity and extensive repetition of in-frame CDR3 nucleotide motifs. These findings demonstrate that the local immune response in Rasmussen's syndrome includes restricted T cell populations that have likely expanded from a few precursor T cells responding to discrete antigenic epitopes.

Amino Acid Sequence↗
PubMed1995

Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that serves as a model for the human disease multiple sclerosis. We evaluated rolipram, a type IV phosphodiesterase inhibitor, for its efficacy in preventing EAE in the common marmoset Callithrix jacchus. In a blinded experimental design, clinical signs of EAE developed within 17 days of immunization with human white matter in two placebo-treated animals but in none of three monkeys that received rolipram (10 mg/kg s.c. every other day) beginning 1 week after immunization. In controls, signs of EAE were associated with development of cerebrospinal fluid pleocytosis and cerebral MRI abnormalities. In the treatment group, there was sustained protection from clinical EAE, transient cerebrospinal fluid pleocytosis in only one of three animals, no MRI abnormality, and marked reduction in histopathologic findings. Rolipram-treated and control animals equally developed circulating antibodies to myelin basic protein. Thus, inhibition of type IV phosphodiesterase, initiated after sensitization to central nervous system antigens, protected against autoimmune demyelinating disease.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Intravenous immunoglobulin, plasmalymphocytapheresis and azathioprine in chronic progressive multiple sclerosis.

Five patients with a severe form of chronic progressive multiple sclerosis no longer responsive to steroid therapy were treated for six months with high-dose intravenous immunoglobulin associated with plasmalymphocytapheresis and azathioprine. In spite of an apparent initial stabilization of the course of the disease, EDSS assessment after six and twelve months of therapy revealed progressive disability in all patients.

Adult↗
PubMed1994

Hereditary motor and sensory neuropathy with myelin outfolding: clinical, genetic and neuropathological study of three cases.

We describe 3 patients affected by a congenital motor and sensory neuropathy with excessive myelin outfoldings (MOs). Clinical and electrophysiological features supported the diagnosis of hereditary motor and sensory neuropathy (HMSN). The genetic study failed to demonstrate either the duplication in chromosome 17p11.2 or the mutations at exons 1 and 2 of the myelin protein gene, PMP-22, recently observed in HMSN type Ia, and suggested an autosomal recessive (AR) inheritance. Sural nerve biopsy revealed a demyelinating process with prominent hypertrophic changes and excessive MOs formation. The percentage of MOs was significantly higher than in 3 age-matched HMSN Ia patients. MOs were morphologically and morphometrically different from tomacular-like thickenings of myelin. Myelin thickness was significantly lower than in the three HMSN Ia controls and linear regression showed a thinner myelin related to axon diameter. The reported cases demonstrate that HMSN with MOs is a well defined variant of HMSN and that a primary defect in the myelination process may be proposed as a possible pathogenic mechanism.

Adolescent↗
PubMed1994

17p11.2 duplication is a common finding in sporadic cases of Charcot-Marie-Tooth type 1.

We investigated the presence of duplication in chromosome 17p11.2 in 4 individuals with sporadic Charcot-Marie-Tooth disease (CMT 1) and 1 isolated case where a definite differential diagnosis between CMT 1 and Déjérine-Sottas disease was not achieved. The 5 affected cases and their parents and relatives were submitted to a complete clinical, neurophysiologic and genetic evaluation. A sural nerve biopsy was performed in all the isolated patients. Paternity was tested and confirmed. The presence of DNA duplication was detected in all the sporadic cases and was absent in all parents and relatives, thus confirming that a de novo dominant mutation is commonly present also in patients without a familial history and that there is a practical relevance of the genetic study in distinguishing isolated cases of CMT 1 from other forms of hereditary motor and sensory neuropathies or demyelinating neuropathies.

Adolescent↗
PubMed1993

Induction of experimental autoimmune encephalomyelitis in rats and immune response to myelin basic protein in lipid-bound form.

Encephalitogenic activity of myelin basic protein (MBP) isolated in a form retaining binding to all myelin lipids was tested in Lewis rats. Immunization with this new stable lipid-bound and native-like preparation (LB-MBP), induced experimental autoimmune encephalomyelitis (EAE) as intensively as the classical lipid free MBP (LF-MBP). During the course of the disease, high affinity specific response to LB-MBP and high frequency of LB-MBP specific precursors was observed in peripheral lymphoid organs, indicating that the disease occurred in presence of anti LB-MBP specific T-cell responsivity. Short term lines, generated from lymphocytes collected at the onset of the disease from LB-MBP immunized rats, showed a strong dose-dependent response to LB-MBP, but not to LF-MBP. The present data indicate that in rat, LB-MBP maintains encephalitogenic activity and induces expansion of a specific T-cell population. These data suggest also that LB-MBP is a new autoantigen that may be relevant in human diseases.

Animals↗
PubMed1992

Charcot-Marie-Tooth disease: evidence of a duplication at D17S122 locus.

The presence of 17p11.2 duplication in CMT 1 Italian families was studied. Fourteen families were tested with pVAW409R3a probe which detects the duplication at D17S122 locus. The duplication was found in all affected individuals, but not in the unaffected relatives and in the unrelated spouses. Also two sporadic cases were investigated: the duplication was present in both patients confirming this mutation as cause of the disease.

Charcot-Marie-Tooth Disease↗
PubMedDate not supplied

Interindividual variability of cranioencephalic relationships as predicted by CT.

To validate a procedure assembling CT scans in a three-dimensional (3D) array, the interindividual variability of cranioencephalic relationships, as estimated by our technique, was compared with that of the normal population. To this purpose the position of the habenulopineal complex (HPC) with respect to skull references was investigated in 41 normal subjects. In particular the x, y, and z, coordinates of individual HPCs were determined after each CT was assembled in a 3D multislice array. Thereafter, distances of the HPC from the frontal and occipital poles, the vault, and the base of the skull were measured and compared with the anatomicoradiological norms. From our estimates the distances of the HPC from both the frontal pole and the vault of the skull proved to vary as a function of the maximal skull diameter with no distortion of cranioencephalic relationships. The proposed assembling method can be regarded as a reliable tool for a quantitative evaluation of data collected from CT or other reconstructive tomography techniques in anatomicoclinical studies. This method enables a generalized (i.e., not confined to neurosurgical procedures) application of stereotactic principles.

Adult↗
PubMedDate not supplied

Conventional perimetry, short-wavelength automated perimetry, frequency-doubling technology, and visual evoked potentials in the assessment of patients with multiple sclerosis.

PURPOSE: To evaluate the diagnostic power of conventional, achromatic, automated perimetry (CAP), short-wavelength automated perimetry (SWAP), frequency-doubling technology (FDT) perimetry, and visual evoked potentials (VEP) in a group of patients with multiple sclerosis (MS) with or without a history of optic neuritis. METHODS: Thirty eyes of 15 patients (5 male, 10 female, average age 38+/-7 years) with confirmed diagnosis of MS underwent CAP, SWAP (Humphrey 750-II VFA, program central 30-2, full-threshold strategy), FDT perimetry (program N-30), and pattern VEPs. Sixteen eyes (53.3%) had no history of ocular involvement and a negative ophthalmologic examination. They were matched with a control group of 10 healthy volunteers (4 male, 6 female, average age 31+/-10 years). The mean deviation (MD) and the pattern standard deviation (PSD) of the two groups were compared (t-test). Fourteen eyes (46.7%) had, on the contrary, a history of optic neuritis. Inside this group, the MD and the PSD of the three techniques were correlated (Spearman's rank test), in order to investigate whether any significant differences might be revealed by these techniques in pointing out the total amount of visual field damage. RESULTS: When comparing MS patients without signs or symptoms of ocular involvement and a control group, no significant differences were found for CAP MD, CAP PSD, and FDT PSD. Significant differences were found, on the contrary, for SWAP MD (p=0.0014), SWAP PSD (p=0.0001), and FDT MD (p=0.0001). When considering the MD and the PSD of the three techniques in the group of MS patients who had a history of optic neuritis, a significant correlation was found only between CAP MD and SWAP MD (r=0.0057), with a tendency by SWAP to reveal a higher rate of visual field loss. The other correlations were not significant. According to predefined criteria, the group of asymptomatic subjects had abnormal CAP in 1 eye (6.25%), abnormal SWAP in 9 (56.2%), abnormal FDT in 11 (68.7%), and abnormal VEPs in 7 (43.7%). The combined use of all techniques allowed us to identify silent optic nerve impairment in 15 (93.7%) eyes. CONCLUSIONS: Short-wavelength automated perimetry and FDT perimetry are two non-conventional perimetric techniques that were mainly developed for the early detection of glaucomatous damage. The results of this study demonstrate their efficacy also in detecting early visual field deficits in MS patients without clinical signs of optic neuropathy. Frequency doubling perimetry, in particular, proved to be an easy, fast, and sensitive technique in the assessment of patients with MS. Our results also suggest that subclinical visual involvement in MS can be better diagnosed using multiple (neurophysiologic and psychophysical) tests.

Adult↗