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L Battistini

Publications and source records attributed to L Battistini.

29 records · Page 2Linked to original sources
PubMed1996

CD1b is expressed in multiple sclerosis lesions.

Recent observations have shown that CD1 molecules act as restriction elements in the presentation of antigens to specialized subsets of T cells. To examine the expression of CD1 molecules in multiple sclerosis (MS) lesions, frozen sections of central nervous system (CNS) tissues from nine MS and three other neurological disease (OND) patients, one patient with Wilson's disease, and one non-neurological control were stained by immunocytochemistry. In chronic-active MS lesions, CD1b immunoreactivity was prominent on perivascular inflammatory cells whereas macrophages within the lesion showed little reactivity. At the lesion edge, intense immunoreactivity for CD1b was found on hypertrophic astrocytes. High level expression of CD1b in MS lesions was found to colocalize with the presence of GM-CSF in astrocytes. In chronic-silent lesions, CD1b expression was found on only a few perivascular astrocytic foot processes and the occasional perivascular macrophage. CD1b was not found in the tissues studied for control purposes. In contrast, MHC class II expression was detected on microglia in all tissues examined. The relatively low level expression of CD1b in normal-appearing tissues, chronic-silent lesions and in the OND controls supports the conclusion that the expression of CD1b in active MS lesions is significantly upregulated and could contribute to lesion development.

Adult↗
PubMed1995

Multiple sclerosis: limited diversity of the V delta 2-J delta 3 T-cell receptor in chronic active lesions.

T lymphocytes bearing the gamma delta T-cell receptor have been found in the central nervous system of patients with multiple sclerosis in association with demyelinated lesions. Although the biological function of these cells remains to be established, it has been proposed that they are involved in the response to highly conserved antigens, such as heat shock proteins (hsp), expressed during tissue damage and thus may contribute to the development of an autoimmune response. Using polymerase chain reaction, we probed for the presence of T-cell receptor gamma delta cells in fresh-frozen early autopsy brain tissue from patients with multiple sclerosis and patients with non-multiple sclerosis conditions. The results demonstrated the presence of two major V-J combinations of the T-cell receptor delta chain--V delta 2-J delta 3, V delta 2-J delta 1--and we used a direct sequencing technique to determine whether this gamma delta T-cell population was clonal or diverse. In chronic-active plaques from 9 patients with multiple sclerosis, we found a striking predominant gene rearrangement within the V delta 2-J delta 3 T-cell receptor population that was not present in central nervous system tissue from patients with other neurological diseases. In contrast, within the V delta 2-J delta 1 T-cell receptor population, a predominant rearrangement pattern was detected in only 1 of the multiple sclerosis patients. The sequence of the predominant V delta 2-J delta 3 gene rearrangement was confirmed by cloning and sequencing the gene products from 1 multiple sclerosis patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Cytokine localization in multiple sclerosis lesions: correlation with adhesion molecule expression and reactive nitrogen species.

The relative levels and cellular distribution of proinflammatory and regulatory cytokines have been examined by immunohistochemistry in multiple sclerosis (MS) lesions of differing activity and compared with CNS tissue from other neurologic diseases with an inflammatory or noninflammatory component. Results show widespread distribution of cytokines in association with both perivascular inflammatory cells and glial cells in all types of inflammatory lesions. Although no obvious pattern of proinflammatory versus regulatory cytokines could be determined in MS lesions, proinflammatory cytokines were rarely noted in normal and noninflammatory conditions, whereas regulatory cytokines were readily detectable in the same diseases. The possible relevance of these cytokine patterns to adhesion molecule expression and the presence of reactive nitrogen species is also addressed.

Amino Acid Oxidoreductases↗
PubMed1995

Gamma delta T cell receptor analysis supports a role for HSP 70 selection of lymphocytes in multiple sclerosis lesions.

BACKGROUND: Interactions between gamma delta T cells and heat shock proteins (HSP) have been proposed as contributing factors in a number of diseases of possible autoimmune etiology but definitive evidence to support this hypothesis has been lacking. In multiple sclerosis (MS), a chronic inflammatory neurologic disease, HSP and gamma delta T cells are known to colocalize in brain lesions. Analysis of T cell receptor (TCR) gene usage in these lesions has detected evidence of clonality within both the V delta 2-J delta 1 and V delta 2-J delta 3 populations of gamma delta T cells. In our own studies, using direct sequence analysis, a dominant V delta 2-J delta 3 TCR sequence was found in 9 MS brain samples, suggesting a response to a common antigen. In this report, we have examined gamma delta T cell receptor gene usage in MS peripheral blood T cell lines selected for reactivity to HSP 70. MATERIALS AND METHODS: TCR rearrangement patterns for V delta 2-J delta 1 and V delta 2-J delta 3 were studied using the polymerase chain reaction (PCR) and a direct sequencing technique in populations of peripheral blood mononuclear cells (PBMC) cultured with Mycobacterium tuberculosis (M. tuberculosis) purified protein derivative (PPD) and then selected for reactivity to a 70-kD heat shock protein (HSP70). Cells were obtained from health donors, patients with MS, and patients with tuberculosis (TB). PCR products were subjected to direct sequence analysis to look for evidence for clonality within these T cell lines and to define the sequence of the V-D-J (CDR3) region of the TCR. RESULTS: In freshly isolated PBMC, both V delta 2-J delta 1 and V delta 2-J delta 3 gene rearrangement patterns were detected, whereas in HSP70+ T cell lines the predominant delta chain rearrangement pattern was V delta 2-J delta 3. Direct sequence analyses indicated that in cells reactive with HSP70 the V delta 2-J delta 3 sequences were usually oligoclonal and used D delta 3 exclusively. In four of four MS and two of three TB patients, the oligoclonal sequences in the HSP70+ T cell lines were identical to one another and to a dominant sequence previously detected in MS brain lesions. In two of three HSP70+ T cell lines from healthy controls, the oligoclonal sequences differed from those found in both groups of patients but were identical to one another except for a small region of heterogeneity in the second N region. In contrast, in freshly isolated PBMC or in PPD+HSP70- T cell lines, the V delta 2-J delta 3 gene rearrangement patterns were usually polyclonal and dominant sequences were rarely identified. CONCLUSIONS: These results support the conclusion that a subpopulation of gamma delta T cells in MS lesions are responding to HSP 70 and that non-CNS-specific antigens contribute to the pathogenesis of MS.

Amino Acid Sequence↗
PubMed1994

Development of a method for measuring cell number: application to CNS primary neuronal cultures.

In the present work we further develop a method for counting cell number that is totally independent from the permeability or uptake conditions of the cells, from the state of activation of intracellular enzymes, and from cellular metabolism. We provide a visual characterization of the method and show that it is highly suitable for cells not growing as monolayers as well as for cultures containing numerous aggregates. We also extend the applicability of this method to CNS primary neuronal cultures and show its direct comparison with alternative means for cellular quantification. The technique is fast, does not require tedious procedures or long washes, and offers advantages such as a high sensitivity and no background.

Animals↗
PubMed1994

Reactive nitrogen intermediates in human neuropathology: an overview.

Nitric oxide (NO) is a recently recognized messenger molecule that has been shown to possess pleiotropic properties, including vasodilation, neurotransmission, cytotoxicity and antimicrobial activity. Constitutive and inducible forms of NO synthase (NOS) have been identified. Activation of cNOS releases relatively low levels of NO for short periods of time whereas induction of iNOS releases high levels of NO for extended periods of time. In rodents, iNOS is predominantly found in cells of the monocyte/macrophage series, including microglia, where it is induced by a combination of bacterial products and cytokines. cNOS and iNOS have also been reported in rodent astrocytes. Activation of iNOS in the CNS could be toxic to many different cell types, including neurons and oligodendrocytes. iNOS, however, has been difficult to demonstrate in human peripheral blood cells, suggesting that the regulation of expression of this enzyme in humans is different from that found in rodents. In this overview, we show that in human glial cells cultured in vitro, astrocytes, but not microglia, can be induced by cytokines to express NO-like activity. Bacterial products are without effect, but a combination of IL-1 and TNF alpha or IFN gamma is a potent stimulus. NO production by astrocytes inhibits Cryptococcus neoformans growth in vitro. In vivo, we show in acute multiple sclerosis lesions, intense NADPH-diaphorase activity is present in hypertrophic astrocytes in the lesion center and at the lesion edge, whereas microglia are nonreactive. Increased NADPH-diaphorase activity colocalizes with immunoreactivity for IL-1 and TNF. These results suggests that the induction of reactive nitrogen intermediates in humans differs from that found in rodents, and supports the conclusion that hypertrophic astrocytes are the major source of NO-like activity in the inflamed CNS.

Amino Acid Oxidoreductases↗
PubMed1994

Hepatitis C virus infection in thalassemia patients undergoing allogeneic bone marrow transplantation.

Ninety-eight patients with homozygous-beta thalassemia who had undergone allogeneic bone marrow transplantation (BMT) between May 1990 and March 1992 were tested for hepatitis C antibodies (anti-HCV) before and after BMT. Anti-HCV positivity was detected in 50 of the 98 patients (51%) before BMT. Seroconversion was demonstrated in seven of the 40 evaluable seronegative patients. In four cases it was probably due to the different sensitivity of first and second generation ELISA. Of the 46 evaluable seropositive patients 4 had transient and 5 persistent negativity for HCV antibodies after BMT. The high prevalence of anti-HCV positivity in thalassemic patients is related to the continuous requirement for blood transfusions. We found a strong correlation between biochemical and histological evidence of liver damage and anti-HCV positive status in multi-transfused patients. In our experience HCV hepatitis does not influence the outcome of BMT.

Adolescent↗
PubMed1993

Recombinant human insulin-like growth factor I exerts a trophic action and confers glutamate sensitivity on glutamate-resistant cerebellar granule cells.

Cerebellar granule cells grown in the presence of a serum complex differentiate but are resistant to the lethal action of excitatory amino acids. When these cells are grown also in the presence of insulin-like growth factor I (IGF-I) they become fully susceptible to the toxic, lethal action of glutamate. The glutamate-sensitizing action of IGF-I is dependent on concentration (half-maximal effect at 2-4 ng/ml) and time (half-maximal effect at 2-4 days in vitro) and is paralleled by the appearance of functionally active, glutamate-activated, Ca2+ channels and of voltage-gated Na+ and late K+ channels. IGF-I-induced glutamate sensitivity is rapidly reversible (t1/2 = 30-60 min) after removal of this somatomedin. The action of IGF-I is not mimicked by IGF-II, nerve growth factor, basic or acidic fibroblast growth factor, platelet-derived growth factor, or tumor necrosis factor alpha. We postulate that the constitutive phenotype of cerebellar granule cells is glutamate-resistant and becomes responsive to excitatory amino acids under the action of epigenetic cues among which IGF-I may be one of those operative in vivo.

Animals↗
PubMed1993

Cerebellar neurones: differentiation and modulation of sensitivity to excitotoxic treatment.

The neurite outgrowth and adhesion complex (NOAC), isolated from rabbit sera has been dissociated in its major components by reverse-phase chromatography in HPLC by using a C18 column. SDS-PAGE analysis of the active fractions revealed the presence of three major bands of approximately 100, 70 and 50 kDa. Studies on the biological activity of NOAC were carried out on rat cerebellar granule cells. NOAC-cultured cells exhibit a marked resistance to excitotoxic stimuli carried by glutamate.

Animals↗