Search PubMed⌕ Search

Biomedical subjects

C Milanese

Publications and source records attributed to C Milanese.

At least 91 records · Page 5Linked to original sources

Value of otoneurological tests in the staging of multiple sclerosis.

We looked for correlations between otoneurological findings and neurological signs in multiple sclerosis (MS). 41 patients were tested for: spontaneous and caloric nystagmus, horizontal pursuit eye tracking, full-field optokinetic nystagmus and eye movements. The findings were compared with the course of the disease (progressive or remitting), age at onset of MS and disability, in order to test the predictive value of this type of test. The correlation between otoneurological abnormalities and lesion site is very high for brainstem lesions. Subclinical brainstem lesions were detected in 66% of patients with optic neuritis only and in 42% of those with spinal cord involvement only. Eye movement disorders are more frequent (p less than 0.1) in disease of long duration. The vestibular examination was altered in 100% of patients with clinically definite and probable MS, in 91% of those with possible and in 80% of those with suspected MS. No specific otoneurological pattern was identified. No significant correlation with age at onset or with disability was found.

Adult↗

Prognostic value of cerebrospinal fluid electrophoresis in optic neuritis and suspected multiple sclerosis.

The prognostic significance of cerebrospinal fluid electrophoresis and IgG-index has been investigated in 44 patients, of whom 10 had optic neuritis and 34 suspected, possible or probable multiple sclerosis. The predictive value of CSF oligoclonal banding for future disease dissemination is very high in the suspected multiple sclerosis subgroup, where after a follow-up of 4.4 years, 7 out of 7 band-positive patients displayed further disease activity. The absence of CSF oligoclonal bands seems to carry a relatively benign short-term (follow-up 3.4 years) prognosis in suspected MS cases.

Adult↗

Retraction of data.

Explore the source record for details and available documents.

Retraction Notice↗

A lymphokine that activates the cytolytic program of both cytotoxic T lymphocyte and natural killer clones.

A 10-12 kD lymphokine, herein termed TCAF, was recently shown to be secreted from Th after crosslinking of their antigen/MHC (T3-Ti) receptors. TCAF stimulates resting T lymphocyte proliferation via binding to surface components of the T11 pathway. To determine whether TCAF could induce antigen-independent activation of the lytic machinery of cytotoxic cells, the present studies were conducted. In the presence of TCAF, both T8+ class I MHC-specific and T4+ class II MHC-specific cytotoxic T cell clones were induced to kill targets, including those lacking the appropriate MHC molecules. This effect was unique to TCAF, since IL-1, IL-2, IFN-gamma could not stimulate lytic activity. Furthermore, both T3+T11+ and T3-T11+ NK clones were triggered to lyse NK-resistant target cells. These findings suggest that TCAF can function in an antigen-independent fashion to amplify cytotoxic effector responses.

Antibodies, Monoclonal↗

Identification of a T helper cell-derived lymphokine that activates resting T lymphocytes.

A novel lymphokine with apparent molecular size of 10 to 12 kilodaltons is secreted from helper T cell clones within hours after cross-linking their T cell antigen-MHC (major histocompatibility complex) receptors (T3-Ti). This lymphokine, termed interleukin-4A (IL-4A), stimulates resting lymphocytes by binding to a surface component (or components) of the alternative T11 pathway and subsequently by inducing interleukin-2 (IL-2) receptors. The activation process is neither dependent on antigen specificities of the recruited population or the presence of macrophages. It appears, therefore, that IL-4A is a mediator involved in amplifying the T cell immune response.

Antibodies, Monoclonal↗

Selective inhibition of interleukin 2 gene function following thymocyte antigen/major histocompatibility complex receptor crosslinking: possible thymic selection mechanism.

Considerable evidence now exists to support the notion that the 50-kDa sheep erythrocyte-binding protein, T11, represents an essential cell surface component of a human T-cell lineage activation pathway. Furthermore, it is known that the human T3-Ti T-cell antigen/major histocompatibility complex receptor complex is capable of regulating cell growth mediated by the T11 structure. Here we show that, within the T3+ thymocyte compartment, T3-Ti crosslinking rapidly inhibits T11-initiated interleukin 2 (IL-2) gene transcription and translation. This inhibition is restricted to the IL-2 gene (IL2) as transcription of both the IL-2-receptor gene (IL2R) and the Ti beta-chain gene (TCRB) are not affected (human gene designations are in parentheses). Perhaps more importantly, T3-Ti-mediated IL-2 inhibition of this type is not operational in peripheral T lymphocytes. The results imply that the majority of T3+ thymocytes are functionally distinct from peripheral T lymphocytes despite their T3+ phenotype and must possess a unique endogenous regulatory component for suppressing IL-2 gene activity. Moreover, since IL-2 is likely rate-limiting for growth within the thymus, the findings provide one plausible mechanism for thymic selection--namely, T3-Ti crosslinking of thymocytes upon interaction with self-major histocompatibility complex inhibits clonal expansion of high-affinity autoreactive cells.

Antigens, Differentiation, T-Lymphocyte↗

The human T-cell receptor.

Recent studies using cloned antigen-specific T lymphocytes and monoclonal antibodies directed at their various surface glycoprotein components have led to the identification of the human T-cell antigen receptor as a surface complex comprised of a clonotypic 90-kD Ti heterodimer and the invariant 20- and 25-kD T3 molecules. Approximately 30,000-40,000 Ti and T3 molecules exist on the surface of human T lymphocytes. These glycoproteins are acquired and expressed during late thymic ontogeny, thus providing the structural basis for immunologic competence. The alpha and beta subunits of Ti bear no precursor-product relationship to one another and are encoded by separate genes. Moreover, the presence of unique peptides following proteolysis of different Ti molecules isolated by non-cross-reactive anticlonotypic monoclonal antibodies supports the notion that variable regions exist within both the alpha and the beta subunits. N-Terminal amino acid sequencing and molecular cloning of the Ti beta subunit further show that it bears an homology to the first V-region framework of immunoglobulin light chains and represents the product of a gene that rearranges specifically in T lymphocytes. Triggering of the T3-Ti receptor complex gives rise to specific antigen-induced proliferation through an autocrine pathway involving endogenous IL-2 production, release, and subsequent binding to IL-2 receptors. The implications of these findings for understanding human T-cell growth and its regulation in disease states are discussed.

Amino Acid Sequence↗

Murine monoclonal antibodies as probes for the phenotypical, functional, and molecular analysis of a discrete peripheral blood lymphocyte population exerting natural killer activity in vitro.

Two monoclonal antibodies (AB8.28 and A10) reacting with large granular lymphocytes were extensively studied and characterized. The two peripheral blood lymphocyte subsets positive for the expression of AB8.28 and A10 determinants were isolated by cell sorting and the phenotype analyzed using a panel of anti-lymphocyte reagents. Both subsets displayed the characteristics of "null cells." Moreover, these subsets encompassed a significant amount of the natural killer activity, since preparations of peripheral blood lymphocytes deprived of AB8.28+ and A10+ cells showed a remarkable reduction of such activity. The analysis of the distribution of the AB8.28 and A10 epitopes has been carried out using a variety of cells, i.e., normal tissues, tumor cells, established cell lines, and preparations obtained from patients with different leukemic disorders. The structure bearing the epitopes recognized by the two monoclonal antibodies was characterized immunologically (immunoprecipitation, SDS-PAGE analysis, immunomodulation, and competition with other antibodies) and by various functional assays. On the basis of inhibition tests, the AB8.28 molecule seems to be related functionally and/or structurally with the IgG Fc receptor. By contrast, the A10 structure does not share this activity and so far has eluded any precise biological characterization.

Antibodies, Monoclonal↗

MHC class II gene products specific autoreactive T cell clones provide inducer as well as amplifier function for B cell Ig production.

Autoreactive T lymphocytes were generated by culturing human peripheral blood mononuclear cells with an antigen-specific/MHC restricted autologous inducer T cell, termed RW17C and subsequently cloned in soft agar. The majority of such clones expressed the T3+T4+T8-T11+Ia+ phenotype and were directed at autologous class II MHC gene products found on B cells, macrophages and B lymphoblastoid cells as judged by their proliferative response to the latter. For this recognition, the clones employed a T3-Ti molecular complex and a T4 structure analogous to those found on allospecific T cells. Perhaps more importantly, it was observed that the same AC (autoreactive clone) induced autologous B cells to produce high levels of immunoglobulin in the absence of exogenous antigen and could synergize with the RW17C clone to effect maximal B cell Ig production. In addition, supernatant from T3-Ti triggering of AC clone induced both polyclonal proliferation and differentiation of small B lymphocytes. These results support the notion that such autoreactive cells can function in a physiologic amplifier role by facilitating induction via an internal set of signals (i.e. autologous MHC).

Antibodies, Monoclonal↗

Clonal analysis of B cell growth and differentiation activities induced from T lymphocytes upon triggering of T3-Ti and T11 pathways.

The cellular origin of B cell growth factors (BCGF) and differentiation factors (BCDF) was investigated in the present study. For this purpose, T4+ and T8+ T cell clones were obtained from human peripheral blood, activated via stimulation of either the antigen/MHC receptor (T3-Ti molecular complex) or the antigen-independent alternative pathway (T11 molecule), and subsequently examined for their capacity to induce B cell proliferation and immunoglobulin production. The results showed that 1) BCGF is produced by both T4+ and T8+ T cells at the population level as well as at the clonal level; 2) BCDF activity, in contrast, is largely but not exclusively restricted to the T4+ subset; and 3) both the T3-Ti and T11 pathways activate individual clonal T cell populations to promote B cell growth and differentiation.

Antibody Formation↗

Characterization of a murine monoclonal antibody specific for human early lymphohemopoietic cells.

This paper summarizes the results of the characterization of A10, a murine monoclonal antibody which recognizes an epitope not restricted to cells of a definite lineage, but which seems to be specific for an early differentiation antigen present on precursors of circulating T and B cells. The structure recognized by the A10 monoclonal antibody, although strikingly structurally similar to the HLA-A,B,C complex, is immunologically different both from histocompatibility antigens and from beta 2 microglobulin. Furthermore, the distribution of the A10 antigen is analyzed in different cell and tissue samples, both in health and disease conditions.

Animals↗

Clonotypic surface structure on human T lymphocytes: functional and biochemical analysis of the antigen receptor complex.

Recent studies using cloned antigen-specific T lymphocytes and monoclonal antibodies directed at their various surface glycoprotein components have led to identification of the human T cell antigen receptor as a surface complex comprised of a clonotypic 90KD Ti heterodimer and the monomorphic 20/25KD T3 molecules. Approximately 30,000-40,000 Ti and T3 molecules exist on the surface of human T lymphocytes. These glycoproteins are acquired and fully expressed during late thymic ontogeny, thus providing the structural basis for immunologic competence. The alpha and beta subunits of Ti bear no precursor-product relationship to one another and are encoded by separate genes. The presence of unique peptides following proteolysis of different Ti molecules isolated by noncrossreactive anticlonotypic monoclonal antibodies supports the notion that variable regions exist within both the alpha and beta subunits. Moreover, N-terminal amino acid sequencing of the Ti beta subunit shows that it bears homology to the first V-region framework of immunoglobulin light chains and represents the product of a gene that rearranges specifically in T lymphocytes. Soluble or Sepharose-bound anti-Ti monoclonal antibodies, like physiologic ligand (antigen/MHC), enhanced proliferative responses to purified IL-2 by inducing a 6-fold increase in surface IL-2 receptor expression. In contrast, only Sepharose-bound anti-Ti or physiologic ligand triggered endogenous clonal IL-2 production and resulted in subsequent proliferation. The latter was blocked by antibodies directed at either the IL-2 receptor or IL-2 itself. These results suggest that induction of IL-2 receptor expression but not IL-2 release occurs in the absence of T3-Ti receptor crosslinking. Perhaps more importantly, the findings demonstrate that antigen-induced proliferation is mediated through an autocrine pathway involving endogenous IL-2 production, release, and subsequent binding to IL-2 receptors.

Antibodies, Monoclonal↗

Generation and characterization of murine monoclonal antibodies against HLA Class II molecules.

HLA Class II antigens (human la) are coded by Major Histocompatibility Complex and play important biological roles in health and disease. In this report we describe the generation and characterization of nine murine monoclonal antibodies (MoAbs) specific for determinants localized on the human la molecules. The reactivity of these MoAbs inferred from serological analysis along with the data obtained from biochemical characterization of the target structures allowed a classification of these reagents as monomorphic and polymorphic. Two monomorphic MoAbs, identifying different subsets of human la molecules, were studied in detail.

Animals↗

Brainstem auditory evoked potentials in the diagnosis of multiple sclerosis.

Brainstem auditory evoked potentials (BAEPs) have been investigated in 34 patients affected by multiple sclerosis. Abnormalities were found in 68% of the patients. Silent lesions of the brainstem were detected in 60% of the clinically definite and in 44% of the probable cases. The diagnostic value of these findings is discussed.

Adolescent↗

Oculomotor disturbances in Balint's syndrome: anatomoclinical findings and electrooculographic analysis in a case.

A 67-year-old man had repeated cerebral ischemic attacks, which resulted in a clinical picture combining paralysis of visual fixation, optic ataxia and impairment of visuospatial orientation, consistent with the definition of Balint's syndrome. Postmortem examination showed multiple lesions involving the occipital cortex of both sides and the white matter underlying the right insular cortex. EOG recording demonstrated a marked impairment of refixation saccades and saccades on verbal command. Smooth pursuit movements were completely abolished. Visual fixation was randomly achieved after many erratic exploratory movements and steadily maintained on the target (spasmodic fixation). During spasmodic fixation, EOG recording detected an ocular flicker resulting in a continuous instability of eye position. It is suggested that these findings may all be accounted for by the loss of panoramic vision due to a bilateral impairment of cortical areas 18 and 19.

Aged↗