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Biomedical subjects

C Milanese

Publications and source records attributed to C Milanese.

At least 73 records · Page 4Linked to original sources

Phenotype analysis of unstimulated lymphocytes and anti-CD3-stimulated proliferating T-cells from cerebrospinal fluid and peripheral blood in patients with multiple sclerosis and other neurological diseases.

In 15 patients with multiple sclerosis (MS) and in 11 patients with other neurological diseases (OND), the phenotype of fresh unstimulated CSF and PB mononuclear cells and of "in vitro" expanded T-cells was studied by monoclonal antibody stain and cytofluorimeter analysis. A compartment-specific decrease of CD8+Leu8+ and CD8+Leu8- cells in CSF was detected; moreover, lower levels of CD8+Leu8- cells were seen in MS than in OND patients, both in CSF and in PB. Although the percentages of unstimulated CSF CD4+ cells did not differ between MS and OND, a higher proportion of "in vitro" expanded CD4+ T-cells was obtained from MS patients than from OND. Among MS patients, T-cell growth was very scarce or absent in those sampled during relapses. The results suggest alterations both within the CD4+ "helper" and the CD8+ "suppressor-cytotoxic" populations in the CSF of MS patients, and stress the relevance of functional analysis in conjunction with phenotype studies.

Adult↗

Short-term neurophysiological monitoring in multiple sclerosis bouts. Evaluation of steroid treatment.

Visual (VEP) and brainstem auditory (BAEP) evoked potentials (EP) were recorded in 21 multiple sclerosis (MS) patients in acute relapse before and after steroid treatment. VEPs were abnormal in 14/21 patients and BAEPs in 10/21 patients before treatment. In 4 patients with acute optic neuritis (ON), an improvement of VEPs paralleled clinical evolution in 3 cases. Substantial and contrasting changes in VEPs or BAEPs, with no clinical counterpart, were related to a spontaneous fluctuation of EPs in acute relapses of MS. These changes suggest frequent subclinical (multifocal and, possibly, sequential) central nervous system involvement in MS bouts. Group analysis showed nonsignificant changes in EP parameters before and after treatment. Our results indicate that evoked potentials (EPs) are of limited value for monitoring the short-term effect of steroid treatment in MS in bouts.

Adult↗

Synthesis of digoxigenin-labeled cDNA as a test for mRNA integrity.

The nucleotide analogue digoxigenin-11-dUTP is widely used as a nonradioactive marker in a broad range of techniques including dot blots, Southern and Northern blots, colony and plaque screenings and in situ hybridizations. In this report, we describe the incorporation of this molecule into a cDNA synthesized by reverse transcriptase as a novel application for digoxigenin. This reaction can be performed as a useful control to check the integrity of a bulk mRNA preparation in the construction of a cDNA library, since the ability of mRNA to direct the synthesis of long molecules of first-strand cDNA is a sign of its integrity.

DNA↗

Overview of azathioprine treatment in multiple sclerosis.

The efficacy of azathioprine in the treatment of multiple sclerosis was assessed by meta-analysis of the results of all published blind, randomised, controlled trials. 793 patients were enrolled in 5 double-blind and 2 single-blind studies. After 1 year of treatment, the increase in Kurtzke disability status score was no different in treated and control groups, but at 2 years there was a small difference (-0.22; 95% confidence interval [CI] -0.43, 0.003) in favour of azathioprine treatment; this difference was sustained, but not increased, after 3 years. The probability of freedom from any relapse during 1, 2, and 3 years' treatment was significantly greater in the azathioprine-treated group (relative odds over 3 years 1.97; 95% Cl 1.27, 3.04), but it is debatable whether the slight clinical benefits of azathioprine outweigh its side-effects.

Azathioprine↗

HLA antigens in Italian multiple sclerosis patients.

We analyzed HLA-A, -C, -B, -DR and -DQ specificities in 104 Italian multiple sclerosis patients and in 905 healthy controls. The frequencies of HLA-A23, A26, Cw4, DR3 and, especially DR5 antigens were significantly higher in multiple sclerosis patients than in controls. Patients with progressive course were characterized by high frequencies of B7, B8 and DR3 antigens: Cw1 and DRw11 shows a negative correlation with the extent of intrathecal IgG production. These data confirm that the HLA system may influence the clinical expression and the immune responses to the disease.

HLA Antigens↗

Analysis of peripheral blood lymphocyte phenotype and function during dexamethazone treatment of progressive multiple sclerosis.

Five patients with chronic progressive multiple sclerosis (MS) and three control patients with lumbar disc herniation were treated with dexamethazone during 14 days. The effect on peripheral blood T-cell subsets and on the proliferative response of peripheral blood mononuclear cells (PBMC) to pokeweed mitogen (PWM) and anti-mu antibody was analyzed. Before treatment, the proportion of CD3+ and CD4+ PBMC was similar in MS and control patients, but the proportion of CD8+ and DR+ PBMC was lower and the PBMC were less responsive to anti-mu stimulation in MS patients compared to controls. Steroid treatment induced reversible granulocytosis and lymphocytosis. CD3+ and CD4+ cells increased and DR+ cells decreased in MS patients but not in controls. Proliferation of anti-mu stimulated PBMC increased in MS-patients during the two weeks of treatment, but decreased in controls. The enhancement in the MS patients of pre-existing immune abnormalities suggests that a cautious attitude is warranted in the use of steroid treatment in chronic progressive MS.

Adult↗

HLA and multiple sclerosis in Italy: a review of the literature.

HLA antigens of locus A, C, B, DR and DQ were typed in 104 Italian multiple sclerosis patients and in 905 healthy controls; the results have been compared with those published in the Italian literature. The Italian studies have been reviewed regarding the ethnic origin of the typed population and the corresponding prevalence of the disease. The data suggest a lack of association between A3 and B7 antigens and Italian multiple sclerosis and a relevance of other DR locus antigens (mainly DR4 and DR5), in addition to DR2, in the susceptibility to the disease.

HLA Antigens↗

Double blind study of intrathecal beta-interferon in multiple sclerosis: clinical and laboratory results.

Sixteen patients with clinically definite MS admitted to a double blind randomised controlled trial of intrathecal natural beta-IFN were followed for a mean of 22 months including the six month treatment period. Clinical response, evaluated in terms of relapse frequency and of progression rate, showed an increase in relapse rate in treated patients during the six month treatment period and, overall, no benefit in treated versus placebo patients. Serial evaluations were made of cerebrospinal fluid (CSF) cells, IgG, myelin basic protein and CSF and blood T-cell subsets. A rise in CSF IgG Index, MBP and DR+ cells in IFN-treated patients suggested an activation of intrathecal immune response in treated patients.

Adolescent↗

Development of an enzyme-linked immunosorbent assay with a monoclonal antibody prepared against alpha 1-antitrypsin for diagnostic screening of inflammatory disorders.

A monoclonal antibody, designated A2a18b8, of IgG1 class prepared against human alpha 1-antitrypsin, cross-reacts with alpha 1-antitrypsin in the serum of rat and baboon, but not with alpha 1-antitrypsin in serum of rabbit, pig, hamster, guinea pig, dog, or turtle. We used A2a18b8 in an enzyme-linked immunosorbent assay (ELISA) developed for human alpha 1-antitrypsin. Preliminary ELISA screening of 247 serum samples from patients with various inflammatory disorders indicated that the concentration of a specific epitope(s) on alpha 1-antitrypsin recognized by this monoclonal antibody was increased significantly in patients with active systemic lupus erythematosus, mixed connective tissue disease, and rheumatoid arthritis, but not in patients with sclerodermic disorders or Sjögren's syndrome. Evidently, A2a18b8 has diagnostic value in that it selectively recognizes a specific epitope(s) on alpha 1-antitrypsin that is (are) apparently exposed during selective inflammatory disorders.

Animals↗

CSF T-cell subsets in multiple sclerosis: relationship to cerebrospinal fluid myelin basic protein and clinical activity.

Cerebrospinal fluid myelin basic protein and cerebrospinal fluid and peripheral blood T-cell subsets have been studied in patients with multiple sclerosis and other inflammatory and non-inflammatory nervous system diseases. These biological parameters have been correlated with clinical disease activity. No changes in peripheral blood T-cell subsets were seen in multiple sclerosis patients. Low cerebrospinal fluid T8+ cells occurred only in multiple sclerosis, while high cerebrospinal fluid T4+ cells were detected both in clinically active multiple sclerosis and in inflammatory nervous system diseases. A close relationship was found between cerebrospinal fluid T4/T8 ratio and myelin basic protein in relapsing multiple sclerosis patients.

Adolescent↗

Double-blind randomized trial of ACTH versus dexamethasone versus methylprednisolone in multiple sclerosis bouts. Clinical, cerebrospinal fluid and neurophysiological results.

30 patients with acute exacerbations of multiple sclerosis were treated by ACTH, dexamethasone or methylprednisolone in a double-blind randomized study. Clinical parameters were assessed; cerebrospinal fluid and neurophysiological parameters (visual- and brainstem-evoked potentials) were evaluated at the beginning and at the end of treatment. Dexamethasone was more effective than ACTH and 6-methylprednisolone in shortening bout duration. Neither CSF nor neurophysiological parameters were significantly affected by therapy.

Adolescent↗

Brainstem auditory evoked potential abnormalities and magnetic resonance imaging in posterior fossa lesions.

Brainstem auditory evoked potentials (BAEPs) were evaluated in a series of 15 patients with extra-axial cerebello-pontine angle tumors (3 cases), demyelinating plaques (11 cases), and intra-axial tumor (1 case), verified by magnetic resonance imaging (MRI). A satisfactory correlation between the location of the lesions and the type of BAEP abnormalities was found in 11 cases. In 2 other cases, definite MRI brainstem lesions located outside the acoustic pathways were associated with normal BAEPs. In the opposite situation (2 cases of BAEP abnormalities with normal MRI), the inability of MRI to detect demyelinating lesions may be due to the temporal evolution of the lesions themselves. The results of this BAEP-MRI comparative study confirm that BAEP is a sensitive diagnostic tool in revealing brainstem dysfunction, although its localizing power appears to be debatable. The most satisfactory MRI/BAEP topodiagnostic correlation was found with lesions involving the acoustic nerve in its intracranial tract or the caudal pons and bulbopontine junctions.

Adolescent↗

Double blind controlled randomized study on azathioprine efficacy in multiple sclerosis. Preliminary results.

The preliminary results of a double blind controlled prospective randomized trial of Azathioprine for therapeutic efficacy in 38 patients with Multiple Sclerosis are reported. Progression of the disease is significantly reduced in Azathioprine-treated group in comparison to Placebo-treated patients, but this effect is reached only after 3 years of treatment (P less than 0.025) regardless of the clinical course and without affecting relapse rate.

Adult↗

Magnetic resonance imaging in multiple sclerosis: diagnostic value and clinical correlations.

101 patients with multiple sclerosis (MS) (53 definite, 22 probable, 8 possible and 18 suspected according to the McDonald and Halliday criteria) were investigated by magnetic resonance imaging (MRI), to evaluate its diagnostic sensitivity compared to other diagnostic parameters such as cerebrospinal fluid (CSF) findings and auditory brainstem responses (ABR). In addition, correlations between severity of lesions on MRI and clinical data (disability duration of the disease and progression rate) and CSF immunoglobulin abnormalities were evaluated. MRI detected multiple demyelinating lesions in 96% of definite, 77% of probable, 50% of possible and 56% of suspected MS. In the same groups CSF was positive for oligoclonal banding in 85%, 68%, 50% and 37% and ABR in 82%, 50%, 80% and 28% respectively. Severity of MRI was found to correlate with disability and duration of the disease, but not with progression rate. The presence of CSF oligoclonal bands and a raised and IgG index were usually associated with more extensive white matter involvement as evaluated by MRI.

Brain↗

Human T lymphocyte activation.

The T lymphocyte receptor for antigen and histocompatibility molecules is a molecular complex comprised of five polypeptide chains. Both the 49KD alpha and 43KD beta chains are immunoglobulin-like and thus contain variable domains responsible for ligand binding. In contrast, the 20-25KD T3 gamma, delta and epsilon chains are monomorphic structures presumably involved in transmembrane signalling. The alpha and beta subunits are disulfide bonded to each other and held in noncovalent association with the T3 chains. T3-Ti receptor crosslinking leads to conformational modification of a second T lineage specific molecule, termed the 50KD T11 structure and in turn, protein kinase C activation, elevation in intracytoplasmic free calcium and Na+/H+ antiport stimulation.

Cell Differentiation↗

Cerebrospinal fluid and peripheral blood T-lymphocyte subsets in multiple sclerosis: monoclonal antibody analysis and correlations with clinical activity.

Enumeration of cerebrospinal fluid and peripheral blood T-lymphocyte subsets (T-total, T-helper and T-suppressor) was performed by monoclonal antibody technique in 18 patients with Multiple Sclerosis and in 4 patients with non-inflammatory neurological diseases. While no differences were observed in peripheral blood subsets among the various phases of the disease, a marked rise in cerebrospinal fluid helper-suppressor ratio was seen in acute relapses. The results give further support to the concept of a strict compartimentalization in immune response abnormalities in Multiple Sclerosis patients.

Cerebrospinal Fluid↗