D. Zarcone - Academia.edu (original) (raw)

Papers by D. Zarcone

Research paper thumbnail of A scanning electron microscopy (SEM) analysis of human cytotoxic cell subsets and of their mode of conjugation with tumor cell targets

Scanning microscopy

ABSTRACT

Research paper thumbnail of Human T cells expressing the gamma/delta T-cell receptor (TcR-1): C gamma 1- and C gamma 2-encoded forms of the receptor correlate with distinctive morphology, cytoskeletal organization, and growth characteristics

Proceedings of the National Academy of Sciences

BB3 and 6-TCS1 monoclonal antibodies identify two distinct nonoverlapping populations of T-cell r... more BB3 and 6-TCS1 monoclonal antibodies identify two distinct nonoverlapping populations of T-cell receptor (TcR) y/6 (TcR-1)-positive cells, which express a disulfidelinked and a nondisulfide-linked form of TcR, respectively. BB3+ cells represented the majority of circulating TcR-1 cells, but they were virtually undetectable in the thymus. On the other hand, 8-TCS1+ cells were largely predominant among TcR-1l thymocytes but represented a minority in peripheral blood (PB). Similar distributions were observed by clonal analysis of thymocytes or PB TcR-1 populations. The use of joining region (J)-specific probes indicated that BB3+ and 8-TCS1+ clones displayed different patterns of J rearrangement. Thus, the disulfide-linked form of TcR-1 (BB3+ clones) was associated with the expression of J segments upstream to the Cyl gene segment, whereas the nondisulfide-linked form (6-TCS1+ clones) was associated with the expression of J segments upstream to Cy2. 6-TCS1+ clones, in most instances, exhibited a

Research paper thumbnail of Adhesion molecule expression on B-cell chronic lymphocytic leukemia cells: Malignant cell phenotypes define distinct disease subsets

Blood

Expression of surface adhesion molecules of the lg superfamily (CD54 and CD58), of the integrin f... more Expression of surface adhesion molecules of the lg superfamily (CD54 and CD58), of the integrin family (pl, &, and a3 chains), of the selectin family (L-selectin), and of the lymphocyte homing receptor (CD44) was analyzed on 6cell chronic lymphocytic leukemia (6-CLL) cells from 7 4 patients. The aim of the study was the definition of phenotypically distinct disease subsets and the correlation of adhesion molecule phenotypes with clinical parameters. Expression of CD58 on 6-CLL cells defined more advanced disease stages. In comparison with p chain-positive cases, patients whose cells did not express B1, &, and p3 integrin chains fell into the most favorable prognostic group, with lower lymphocytosis and the absence of splenomegaly, diffuse bone marrow infiltration, and therapy requirement. A of Italy (Target Projects: BTBS and ACRO) and ,from the Italian

Research paper thumbnail of CTLA-4 (CD152) inhibits the specific lysis mediated by human cytolytic T lymphocytes in a clonally distributed fashion

The Journal of Immunology

Since the functional outcome of effector T lymphocytes depends on a balance between activatory an... more Since the functional outcome of effector T lymphocytes depends on a balance between activatory and inhibitory receptors, we studied the ability of CTLA-4 (CD152) to inhibit the cytolytic function of CTL. In 22 TCR alpha/beta+ CD3+ 8+ CTL clones, activation induced by anti-CD3, anti-CD28, or anti-CD2 mAb was inhibited by anti-CD152 mAb in a redirected killing assay. In eight clones inhibition was >40%, in 10 it ranged between 20-40%, and in four it was <20%. This suggests the existence of a clonal heterogeneity as well as for the ability of CTLA-4 to inhibit CD3/TCR-, CD28-, or CD2-mediated CTL activation. To support further this contention, we used an experimental model based upon Ag-specific CTL. Eight Ag-specific T cell clones that lyse autologous EBV-infected B lymphocytes, but are unable to lyse allogeneic EBV-infected B cell lines, were used in a cytolytic assay in which anti-CD152 mAb or soluble recombinant receptor (i.e., CTLA-4 Ig) were included. In this system, at var...

Research paper thumbnail of Molecules that inhibit T-cell functions: cytochemical localization and shuttling

European journal of histochemistry: EJH

Adaptive immune responses to antigens are mediated by specific receptors expressed on B cells (BC... more Adaptive immune responses to antigens are mediated by specific receptors expressed on B cells (BCR's) and T cells (TCR's). Effector cells and memory cells are produced following a proliferative wave that accounts for clonal expansion. If not down-regulated, clonal expansion might lead to uncontrolled lymphoproliferation that would be harmful for the organism. Several mechanisms that account for the down-sizing of activated lymphocyte clones are briefly reviewed here. We next consider in detail one such mechanism that deals with the functional characterization and the immunocytochemical localization of two T-cell inhibitory molecules, namely the Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) and the HP-F1 antigen, both present in all T lymphocytes. CTLA-4 and HP-F1 inhibit CD4+ T-helper cell proliferation and the lytic ability of CD8+ T-cytotoxic cells in non-specific and in antigen-specific cytolytic assays. Interestingly, a clonal distribution exists as for the ability of CTLA-4...

Research paper thumbnail of Functional and clinical relevance of CD44 variant isoform expression on B-cell chronic lymphocytic leukemia cells

Haematologica

Recent studies have shown that expression of adhesion molecules of the Ig superfamily, of integri... more Recent studies have shown that expression of adhesion molecules of the Ig superfamily, of integrins and of selectins allows definition of high vs low risk B-cell chronic lymphocytic leukemia (B-CLL). The proteoglycan CD44 is an adhesion molecule that may be expressed as a standard form of 85-95 KD or as several variant isoforms. The presence of certain CD44 variant (v) isoforms on neoplastic cells indicates poor prognosis in epithelial and lymphoid malignancies, as it is associated with tumor progression and metastasis. The expression of CD44 v3, 4, 5, 6, 7, 9 and 10 was analyzed in cells from 85 B-CLL patients. Indirect immunofluorescence and flow cytometry were used to identify CD44v. Functional studies were performed by analysis of adhesion to hyaluronate (HA), one CD44 ligand, and HA-induced Ca2+ influx. A variety of statistical methods were used to define phenotypic and functional differences between the various clones, to calculate survival curves, and for multivariate analyse...

Research paper thumbnail of Posterior headache as a warning symptom of vertebral dissection: a case report

The journal of headache and pain, 2005

Cervicocerebral arterial dissection is an important cause of stroke in young adults; the onset is... more Cervicocerebral arterial dissection is an important cause of stroke in young adults; the onset is often characterised by severe occipital headache, followed by nausea, vomiting and vertigo, mimicking a migraine attack. We describe herewith a case of vertebral arterial dissection with cerebellar infarction, which started with a posterior headache and neurovegetative symptoms, without other signs. Recommendations for recognition of similar cases, potentially dangerous and treatable, are discussed.

Research paper thumbnail of Molecules that inhibit T-cell functions: cytochemical localization and shuttling

European journal of histochemistry : EJH, 2000

Adaptive immune responses to antigens are mediated by specific receptors expressed on B cells (BC... more Adaptive immune responses to antigens are mediated by specific receptors expressed on B cells (BCR's) and T cells (TCR's). Effector cells and memory cells are produced following a proliferative wave that accounts for clonal expansion. If not down-regulated, clonal expansion might lead to uncontrolled lymphoproliferation that would be harmful for the organism. Several mechanisms that account for the down-sizing of activated lymphocyte clones are briefly reviewed here. We next consider in detail one such mechanism that deals with the functional characterization and the immunocytochemical localization of two T-cell inhibitory molecules, namely the Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) and the HP-F1 antigen, both present in all T lymphocytes. CTLA-4 and HP-F1 inhibit CD4+ T-helper cell proliferation and the lytic ability of CD8+ T-cytotoxic cells in non-specific and in antigen-specific cytolytic assays. Interestingly, a clonal distribution exists as for the ability of CTLA-4...

Research paper thumbnail of Functional and clinical relevance of CD44 variant isoform expression on B-cell chronic lymphocytic leukemia cells

Haematologica, 1998

Recent studies have shown that expression of adhesion molecules of the Ig superfamily, of integri... more Recent studies have shown that expression of adhesion molecules of the Ig superfamily, of integrins and of selectins allows definition of high vs low risk B-cell chronic lymphocytic leukemia (B-CLL). The proteoglycan CD44 is an adhesion molecule that may be expressed as a standard form of 85-95 KD or as several variant isoforms. The presence of certain CD44 variant (v) isoforms on neoplastic cells indicates poor prognosis in epithelial and lymphoid malignancies, as it is associated with tumor progression and metastasis. The expression of CD44 v3, 4, 5, 6, 7, 9 and 10 was analyzed in cells from 85 B-CLL patients. Indirect immunofluorescence and flow cytometry were used to identify CD44v. Functional studies were performed by analysis of adhesion to hyaluronate (HA), one CD44 ligand, and HA-induced Ca2+ influx. A variety of statistical methods were used to define phenotypic and functional differences between the various clones, to calculate survival curves, and for multivariate analyse...

Research paper thumbnail of CTLA-4 (CD152) inhibits the specific lysis mediated by human cytolytic T lymphocytes in a clonally distributed fashion

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1999

Since the functional outcome of effector T lymphocytes depends on a balance between activatory an... more Since the functional outcome of effector T lymphocytes depends on a balance between activatory and inhibitory receptors, we studied the ability of CTLA-4 (CD152) to inhibit the cytolytic function of CTL. In 22 TCR alpha/beta+ CD3+ 8+ CTL clones, activation induced by anti-CD3, anti-CD28, or anti-CD2 mAb was inhibited by anti-CD152 mAb in a redirected killing assay. In eight clones inhibition was >40%, in 10 it ranged between 20-40%, and in four it was <20%. This suggests the existence of a clonal heterogeneity as well as for the ability of CTLA-4 to inhibit CD3/TCR-, CD28-, or CD2-mediated CTL activation. To support further this contention, we used an experimental model based upon Ag-specific CTL. Eight Ag-specific T cell clones that lyse autologous EBV-infected B lymphocytes, but are unable to lyse allogeneic EBV-infected B cell lines, were used in a cytolytic assay in which anti-CD152 mAb or soluble recombinant receptor (i.e., CTLA-4 Ig) were included. In this system, at var...

Research paper thumbnail of Role of adhesion molecules in the mechanism of non-MHC (major histocompatibility complex) restricted cell-mediated cytotoxicity

Scanning microscopy, 1993

Adhesion molecules involved in the interaction between immune system effector cells and tumor tar... more Adhesion molecules involved in the interaction between immune system effector cells and tumor targets are surface molecules which contribute to the formation of cell-to-cell contacts and belong to the integrin family. In this paper, the role played by the adhesion molecules in the process of cell-mediated cytotoxicity is reviewed. Furthermore, the contact area between effector and target cells has been analyzed by scanning electron microscopy. This region, termed "closed chamber", seems to contribute to killing efficiency by creating an intimate contact region in which cytotoxic factors can easily induce lethal hit in target cell. Thus, the extension of the closed chamber seems to be positively related to effector cell killing potential as well as to target cell sensitivity and, in this context, the adhesion molecules prove to play a pivotal role. In fact, a receptor-ligand interaction occurs between CD11a/CD18 (LFA-1) and CD2 molecules, expressed on the effector cells, an...

Research paper thumbnail of Antibodies to CD44 trigger effector functions of human T cell clones

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1993

mAb against the lymphocyte homing receptor CD44/Hermes up-regulate the proliferation of human T P... more mAb against the lymphocyte homing receptor CD44/Hermes up-regulate the proliferation of human T PBL induced by anti-CD3 or anti-CD2 mAb. Moreover, certain anti-CD44 mAb can activate human resting T cells and mouse cytotoxic T cells in the absence of anti-CD3 or anti-CD2 mAb. Here, we show that anti-CD44 mAb trigger proliferation of human CD3+/CD4+ T cell clones in a fashion similar to that observed with mAb to CD3. Such an effect is IL-2-dependent, as shown by IL-2 production induced by anti-CD44 mAb and by complete inhibition of cell proliferation in the presence of anti-IL-2 antibodies or cyclosporin A. Moreover, anti-CD44 mAb trigger human cytolytic T cell clones to lyse Fc gamma-R+ P815 cells in the absence of additional stimuli. The magnitude of the cytolytic response induced by anti-CD44 mAb is comparable to that observed in the presence of anti-CD3 mAb for both CD4+ and CD8+ TCR-alpha/beta+ clones, and for V delta 1 or V delta 2 TCR-gamma/delta+ clones. By contrast, in CD3-/C...

Research paper thumbnail of Adhesion molecule expression on B-cell chronic lymphocytic leukemia cells: malignant cell phenotypes define distinct disease subsets

Blood, Jan 15, 1993

Expression of surface adhesion molecules of the Ig superfamily (CD54 and CD58), of the integrin f... more Expression of surface adhesion molecules of the Ig superfamily (CD54 and CD58), of the integrin family (beta 1, beta 2, and beta 3 chains), of the selectin family (L-selectin), and of the lymphocyte homing receptor (CD44) was analyzed on B-cell chronic lymphocytic leukemia (B-CLL) cells from 74 patients. The aim of the study was the definition of phenotypically distinct disease subsets and the correlation of adhesion molecule phenotypes with clinical parameters. Expression of CD58 on B-CLL cells defined more advanced disease stages. In comparison with beta chain-positive cases, patients whose cells did not express beta 1, beta 2, and beta 3 integrin chains fell into the most favorable prognostic group, with lower lymphocytosis and the absence of splenomegaly, diffuse bone marrow infiltration, and therapy requirement. A novel finding was the expression of beta 3 chains on cells from a minority (12 of 74) of B-CLL cases. beta 3 chains were always coexpressed with beta 1 and beta 2 cha...

Research paper thumbnail of Relationship between target cell cycle and susceptibility to natural killer lysis

Cancer research, 1987

Studies from several laboratories have evaluated the role of cell surface antigenic molecules on ... more Studies from several laboratories have evaluated the role of cell surface antigenic molecules on target cells in natural killer (NK)-mediated cytotoxicity. A number of these cell surface molecules are associated with cell proliferation and may be expressed preferentially during one phase of the cell cycle. The purpose of this investigation was to evaluate the role that target cell cycle plays in susceptibility to NK lysis. Enrichment (greater than 80%) of cells from NK-resistant and NK-sensitive cell lines in the G0G1, S, and G2M phases of the cell cycle was achieved by centrifugal elutriation. We demonstrate that there was no influence of cell cycle on NK-mediated lysis of NK-resistant or susceptible cell lines.

Research paper thumbnail of A scanning electron microscopy analysis of human cytotoxic cell subsets and of their mode of conjugation with tumor cell targets

Scanning microscopy, 1989

In this study we describe the surface features of non-MHC (Major Histocompatibility Complex)-rest... more In this study we describe the surface features of non-MHC (Major Histocompatibility Complex)-restricted cytotoxic cells isolated from human peripheral blood. Purified populations of CD3-, natural killer (NK) cells were allowed to interact with NK-sensitive (K562) and NK-resistant (THP-1-0) tumor cell targets. The type of effector to target cell binding was investigated by scanning electron microscope (SEM) analysis. A different interaction with the effectors is described for NK-resistant targets in comparison with NK-susceptible tumor cells. SEM was also used to investigate the relationship between interleukin 2 (IL2)-activated cytotoxic cells (lymphokine-activated killer, LAK, cells) and the tumor targets. We also describe the unique growth features of certain clones of cytotoxic T cells expressing gamma delta antigen receptors which support the contention that these cells may have a special ability of homing into tissues. We conclude that non-specific cytotoxic cells constitute a ...

Research paper thumbnail of Expression of adhesion molecules in lymphoproliferative disorders

Leukemia, 1992

We review the role of adhesion molecule expression on malignant lymphoid cells as delineated by e... more We review the role of adhesion molecule expression on malignant lymphoid cells as delineated by experimental studies and clinical observation. Adhesion molecules of the Ig superfamily, integrins, selectins, and the lymphocyte homing receptor CD44 mediate cell-to-cell and cell-to-extracellular matrix interactions. These molecules have been investigated with the aim (i) of defining certain biological features of the malignant cells, (ii) of providing a rationale to understand tumor organization, metastasis and organ specificity, and (iii) of detecting disease subsets and prognostic groups.

Research paper thumbnail of A novel inhibitory receptor regulates T-cell function

Research paper thumbnail of Modulation of the effector cell-target cell interaction by antibodies to CD2 and CD11a/CD18

Cell Biology International Reports, 1990

Research paper thumbnail of ACUTE STROKE IN A YOUNG ADULT: A CLINICAL REPORT OF COCAINE ABUSE AND TABAGISM

… NAZIONALE DELLA SNO

... 466 ACUTE STROKE IN A YOUNG ADULT: A CLINICAL REPORT OF COCAINE ABUSE AND TABAGISM MERELLO M.... more ... 466 ACUTE STROKE IN A YOUNG ADULT: A CLINICAL REPORT OF COCAINE ABUSE AND TABAGISM MERELLO M., MAZZUCCHELLI F., BERNASCONI S., DI FALCO M., ZARCONE D. Stroke Unit, UO Neurologia, Ospedale San Antonio Abate, Gallarate (VA). Page 471. ...

Research paper thumbnail of Systemic inflammation and neurodegeneration in a mouse model of multiple sulfatase deficiency

Proceedings of the National Academy of Sciences, 2007

Sulfatases are involved in several biological functions such as degradation of macromolecules in ... more Sulfatases are involved in several biological functions such as degradation of macromolecules in the lysosomes. In patients with multiple sulfatase deficiency, mutations in the SUMF1 gene cause a reduction of sulfatase activities because of a posttranslational modification defect. We have generated a mouse line carrying a null mutation in the Sumf1 gene. Sulfatase activities are completely absent in Sumf1 ؊/؊ mice, indicating that Sumf1 is indispensable for sulfatase activation and that mammals, differently from bacteria, have a single sulfatase modification system. Similarly to multiple sulfatase deficiency patients, Sumf1 ؊/؊ mice display frequent early mortality, congenital growth retardation, skeletal abnormalities, and neurological defects. All examined tissues showed progressive cell vacuolization and significant lysosomal storage of glycosaminoglycans. Sumf1 ؊/؊ mice showed a generalized inflammatory process characterized by a massive presence of highly vacuolated macrophages, which are the main site of lysosomal storage. Activated microglia were detected in the cerebellum and brain cortex associated with remarkable astroglyosis and neuronal cell loss. Between 4 and 6 months of age, we detected a strong increase in the expression levels of inflammatory cytokines and of apoptotic markers in both the CNS and liver, demonstrating that inflammation and apoptosis occur at the late stage of disease and suggesting that they play an important role in both the systemic and CNS phenotypes observed in lysosomal disorders. This mouse model, in which the function of an entire protein family has been silenced, offers a unique opportunity to study sulfatase function and the mechanisms underlying lysosomal storage diseases.

Research paper thumbnail of A scanning electron microscopy (SEM) analysis of human cytotoxic cell subsets and of their mode of conjugation with tumor cell targets

Scanning microscopy

ABSTRACT

Research paper thumbnail of Human T cells expressing the gamma/delta T-cell receptor (TcR-1): C gamma 1- and C gamma 2-encoded forms of the receptor correlate with distinctive morphology, cytoskeletal organization, and growth characteristics

Proceedings of the National Academy of Sciences

BB3 and 6-TCS1 monoclonal antibodies identify two distinct nonoverlapping populations of T-cell r... more BB3 and 6-TCS1 monoclonal antibodies identify two distinct nonoverlapping populations of T-cell receptor (TcR) y/6 (TcR-1)-positive cells, which express a disulfidelinked and a nondisulfide-linked form of TcR, respectively. BB3+ cells represented the majority of circulating TcR-1 cells, but they were virtually undetectable in the thymus. On the other hand, 8-TCS1+ cells were largely predominant among TcR-1l thymocytes but represented a minority in peripheral blood (PB). Similar distributions were observed by clonal analysis of thymocytes or PB TcR-1 populations. The use of joining region (J)-specific probes indicated that BB3+ and 8-TCS1+ clones displayed different patterns of J rearrangement. Thus, the disulfide-linked form of TcR-1 (BB3+ clones) was associated with the expression of J segments upstream to the Cyl gene segment, whereas the nondisulfide-linked form (6-TCS1+ clones) was associated with the expression of J segments upstream to Cy2. 6-TCS1+ clones, in most instances, exhibited a

Research paper thumbnail of Adhesion molecule expression on B-cell chronic lymphocytic leukemia cells: Malignant cell phenotypes define distinct disease subsets

Blood

Expression of surface adhesion molecules of the lg superfamily (CD54 and CD58), of the integrin f... more Expression of surface adhesion molecules of the lg superfamily (CD54 and CD58), of the integrin family (pl, &, and a3 chains), of the selectin family (L-selectin), and of the lymphocyte homing receptor (CD44) was analyzed on 6cell chronic lymphocytic leukemia (6-CLL) cells from 7 4 patients. The aim of the study was the definition of phenotypically distinct disease subsets and the correlation of adhesion molecule phenotypes with clinical parameters. Expression of CD58 on 6-CLL cells defined more advanced disease stages. In comparison with p chain-positive cases, patients whose cells did not express B1, &, and p3 integrin chains fell into the most favorable prognostic group, with lower lymphocytosis and the absence of splenomegaly, diffuse bone marrow infiltration, and therapy requirement. A of Italy (Target Projects: BTBS and ACRO) and ,from the Italian

Research paper thumbnail of CTLA-4 (CD152) inhibits the specific lysis mediated by human cytolytic T lymphocytes in a clonally distributed fashion

The Journal of Immunology

Since the functional outcome of effector T lymphocytes depends on a balance between activatory an... more Since the functional outcome of effector T lymphocytes depends on a balance between activatory and inhibitory receptors, we studied the ability of CTLA-4 (CD152) to inhibit the cytolytic function of CTL. In 22 TCR alpha/beta+ CD3+ 8+ CTL clones, activation induced by anti-CD3, anti-CD28, or anti-CD2 mAb was inhibited by anti-CD152 mAb in a redirected killing assay. In eight clones inhibition was >40%, in 10 it ranged between 20-40%, and in four it was <20%. This suggests the existence of a clonal heterogeneity as well as for the ability of CTLA-4 to inhibit CD3/TCR-, CD28-, or CD2-mediated CTL activation. To support further this contention, we used an experimental model based upon Ag-specific CTL. Eight Ag-specific T cell clones that lyse autologous EBV-infected B lymphocytes, but are unable to lyse allogeneic EBV-infected B cell lines, were used in a cytolytic assay in which anti-CD152 mAb or soluble recombinant receptor (i.e., CTLA-4 Ig) were included. In this system, at var...

Research paper thumbnail of Molecules that inhibit T-cell functions: cytochemical localization and shuttling

European journal of histochemistry: EJH

Adaptive immune responses to antigens are mediated by specific receptors expressed on B cells (BC... more Adaptive immune responses to antigens are mediated by specific receptors expressed on B cells (BCR's) and T cells (TCR's). Effector cells and memory cells are produced following a proliferative wave that accounts for clonal expansion. If not down-regulated, clonal expansion might lead to uncontrolled lymphoproliferation that would be harmful for the organism. Several mechanisms that account for the down-sizing of activated lymphocyte clones are briefly reviewed here. We next consider in detail one such mechanism that deals with the functional characterization and the immunocytochemical localization of two T-cell inhibitory molecules, namely the Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) and the HP-F1 antigen, both present in all T lymphocytes. CTLA-4 and HP-F1 inhibit CD4+ T-helper cell proliferation and the lytic ability of CD8+ T-cytotoxic cells in non-specific and in antigen-specific cytolytic assays. Interestingly, a clonal distribution exists as for the ability of CTLA-4...

Research paper thumbnail of Functional and clinical relevance of CD44 variant isoform expression on B-cell chronic lymphocytic leukemia cells

Haematologica

Recent studies have shown that expression of adhesion molecules of the Ig superfamily, of integri... more Recent studies have shown that expression of adhesion molecules of the Ig superfamily, of integrins and of selectins allows definition of high vs low risk B-cell chronic lymphocytic leukemia (B-CLL). The proteoglycan CD44 is an adhesion molecule that may be expressed as a standard form of 85-95 KD or as several variant isoforms. The presence of certain CD44 variant (v) isoforms on neoplastic cells indicates poor prognosis in epithelial and lymphoid malignancies, as it is associated with tumor progression and metastasis. The expression of CD44 v3, 4, 5, 6, 7, 9 and 10 was analyzed in cells from 85 B-CLL patients. Indirect immunofluorescence and flow cytometry were used to identify CD44v. Functional studies were performed by analysis of adhesion to hyaluronate (HA), one CD44 ligand, and HA-induced Ca2+ influx. A variety of statistical methods were used to define phenotypic and functional differences between the various clones, to calculate survival curves, and for multivariate analyse...

Research paper thumbnail of Posterior headache as a warning symptom of vertebral dissection: a case report

The journal of headache and pain, 2005

Cervicocerebral arterial dissection is an important cause of stroke in young adults; the onset is... more Cervicocerebral arterial dissection is an important cause of stroke in young adults; the onset is often characterised by severe occipital headache, followed by nausea, vomiting and vertigo, mimicking a migraine attack. We describe herewith a case of vertebral arterial dissection with cerebellar infarction, which started with a posterior headache and neurovegetative symptoms, without other signs. Recommendations for recognition of similar cases, potentially dangerous and treatable, are discussed.

Research paper thumbnail of Molecules that inhibit T-cell functions: cytochemical localization and shuttling

European journal of histochemistry : EJH, 2000

Adaptive immune responses to antigens are mediated by specific receptors expressed on B cells (BC... more Adaptive immune responses to antigens are mediated by specific receptors expressed on B cells (BCR's) and T cells (TCR's). Effector cells and memory cells are produced following a proliferative wave that accounts for clonal expansion. If not down-regulated, clonal expansion might lead to uncontrolled lymphoproliferation that would be harmful for the organism. Several mechanisms that account for the down-sizing of activated lymphocyte clones are briefly reviewed here. We next consider in detail one such mechanism that deals with the functional characterization and the immunocytochemical localization of two T-cell inhibitory molecules, namely the Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) and the HP-F1 antigen, both present in all T lymphocytes. CTLA-4 and HP-F1 inhibit CD4+ T-helper cell proliferation and the lytic ability of CD8+ T-cytotoxic cells in non-specific and in antigen-specific cytolytic assays. Interestingly, a clonal distribution exists as for the ability of CTLA-4...

Research paper thumbnail of Functional and clinical relevance of CD44 variant isoform expression on B-cell chronic lymphocytic leukemia cells

Haematologica, 1998

Recent studies have shown that expression of adhesion molecules of the Ig superfamily, of integri... more Recent studies have shown that expression of adhesion molecules of the Ig superfamily, of integrins and of selectins allows definition of high vs low risk B-cell chronic lymphocytic leukemia (B-CLL). The proteoglycan CD44 is an adhesion molecule that may be expressed as a standard form of 85-95 KD or as several variant isoforms. The presence of certain CD44 variant (v) isoforms on neoplastic cells indicates poor prognosis in epithelial and lymphoid malignancies, as it is associated with tumor progression and metastasis. The expression of CD44 v3, 4, 5, 6, 7, 9 and 10 was analyzed in cells from 85 B-CLL patients. Indirect immunofluorescence and flow cytometry were used to identify CD44v. Functional studies were performed by analysis of adhesion to hyaluronate (HA), one CD44 ligand, and HA-induced Ca2+ influx. A variety of statistical methods were used to define phenotypic and functional differences between the various clones, to calculate survival curves, and for multivariate analyse...

Research paper thumbnail of CTLA-4 (CD152) inhibits the specific lysis mediated by human cytolytic T lymphocytes in a clonally distributed fashion

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1999

Since the functional outcome of effector T lymphocytes depends on a balance between activatory an... more Since the functional outcome of effector T lymphocytes depends on a balance between activatory and inhibitory receptors, we studied the ability of CTLA-4 (CD152) to inhibit the cytolytic function of CTL. In 22 TCR alpha/beta+ CD3+ 8+ CTL clones, activation induced by anti-CD3, anti-CD28, or anti-CD2 mAb was inhibited by anti-CD152 mAb in a redirected killing assay. In eight clones inhibition was >40%, in 10 it ranged between 20-40%, and in four it was <20%. This suggests the existence of a clonal heterogeneity as well as for the ability of CTLA-4 to inhibit CD3/TCR-, CD28-, or CD2-mediated CTL activation. To support further this contention, we used an experimental model based upon Ag-specific CTL. Eight Ag-specific T cell clones that lyse autologous EBV-infected B lymphocytes, but are unable to lyse allogeneic EBV-infected B cell lines, were used in a cytolytic assay in which anti-CD152 mAb or soluble recombinant receptor (i.e., CTLA-4 Ig) were included. In this system, at var...

Research paper thumbnail of Role of adhesion molecules in the mechanism of non-MHC (major histocompatibility complex) restricted cell-mediated cytotoxicity

Scanning microscopy, 1993

Adhesion molecules involved in the interaction between immune system effector cells and tumor tar... more Adhesion molecules involved in the interaction between immune system effector cells and tumor targets are surface molecules which contribute to the formation of cell-to-cell contacts and belong to the integrin family. In this paper, the role played by the adhesion molecules in the process of cell-mediated cytotoxicity is reviewed. Furthermore, the contact area between effector and target cells has been analyzed by scanning electron microscopy. This region, termed "closed chamber", seems to contribute to killing efficiency by creating an intimate contact region in which cytotoxic factors can easily induce lethal hit in target cell. Thus, the extension of the closed chamber seems to be positively related to effector cell killing potential as well as to target cell sensitivity and, in this context, the adhesion molecules prove to play a pivotal role. In fact, a receptor-ligand interaction occurs between CD11a/CD18 (LFA-1) and CD2 molecules, expressed on the effector cells, an...

Research paper thumbnail of Antibodies to CD44 trigger effector functions of human T cell clones

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1993

mAb against the lymphocyte homing receptor CD44/Hermes up-regulate the proliferation of human T P... more mAb against the lymphocyte homing receptor CD44/Hermes up-regulate the proliferation of human T PBL induced by anti-CD3 or anti-CD2 mAb. Moreover, certain anti-CD44 mAb can activate human resting T cells and mouse cytotoxic T cells in the absence of anti-CD3 or anti-CD2 mAb. Here, we show that anti-CD44 mAb trigger proliferation of human CD3+/CD4+ T cell clones in a fashion similar to that observed with mAb to CD3. Such an effect is IL-2-dependent, as shown by IL-2 production induced by anti-CD44 mAb and by complete inhibition of cell proliferation in the presence of anti-IL-2 antibodies or cyclosporin A. Moreover, anti-CD44 mAb trigger human cytolytic T cell clones to lyse Fc gamma-R+ P815 cells in the absence of additional stimuli. The magnitude of the cytolytic response induced by anti-CD44 mAb is comparable to that observed in the presence of anti-CD3 mAb for both CD4+ and CD8+ TCR-alpha/beta+ clones, and for V delta 1 or V delta 2 TCR-gamma/delta+ clones. By contrast, in CD3-/C...

Research paper thumbnail of Adhesion molecule expression on B-cell chronic lymphocytic leukemia cells: malignant cell phenotypes define distinct disease subsets

Blood, Jan 15, 1993

Expression of surface adhesion molecules of the Ig superfamily (CD54 and CD58), of the integrin f... more Expression of surface adhesion molecules of the Ig superfamily (CD54 and CD58), of the integrin family (beta 1, beta 2, and beta 3 chains), of the selectin family (L-selectin), and of the lymphocyte homing receptor (CD44) was analyzed on B-cell chronic lymphocytic leukemia (B-CLL) cells from 74 patients. The aim of the study was the definition of phenotypically distinct disease subsets and the correlation of adhesion molecule phenotypes with clinical parameters. Expression of CD58 on B-CLL cells defined more advanced disease stages. In comparison with beta chain-positive cases, patients whose cells did not express beta 1, beta 2, and beta 3 integrin chains fell into the most favorable prognostic group, with lower lymphocytosis and the absence of splenomegaly, diffuse bone marrow infiltration, and therapy requirement. A novel finding was the expression of beta 3 chains on cells from a minority (12 of 74) of B-CLL cases. beta 3 chains were always coexpressed with beta 1 and beta 2 cha...

Research paper thumbnail of Relationship between target cell cycle and susceptibility to natural killer lysis

Cancer research, 1987

Studies from several laboratories have evaluated the role of cell surface antigenic molecules on ... more Studies from several laboratories have evaluated the role of cell surface antigenic molecules on target cells in natural killer (NK)-mediated cytotoxicity. A number of these cell surface molecules are associated with cell proliferation and may be expressed preferentially during one phase of the cell cycle. The purpose of this investigation was to evaluate the role that target cell cycle plays in susceptibility to NK lysis. Enrichment (greater than 80%) of cells from NK-resistant and NK-sensitive cell lines in the G0G1, S, and G2M phases of the cell cycle was achieved by centrifugal elutriation. We demonstrate that there was no influence of cell cycle on NK-mediated lysis of NK-resistant or susceptible cell lines.

Research paper thumbnail of A scanning electron microscopy analysis of human cytotoxic cell subsets and of their mode of conjugation with tumor cell targets

Scanning microscopy, 1989

In this study we describe the surface features of non-MHC (Major Histocompatibility Complex)-rest... more In this study we describe the surface features of non-MHC (Major Histocompatibility Complex)-restricted cytotoxic cells isolated from human peripheral blood. Purified populations of CD3-, natural killer (NK) cells were allowed to interact with NK-sensitive (K562) and NK-resistant (THP-1-0) tumor cell targets. The type of effector to target cell binding was investigated by scanning electron microscope (SEM) analysis. A different interaction with the effectors is described for NK-resistant targets in comparison with NK-susceptible tumor cells. SEM was also used to investigate the relationship between interleukin 2 (IL2)-activated cytotoxic cells (lymphokine-activated killer, LAK, cells) and the tumor targets. We also describe the unique growth features of certain clones of cytotoxic T cells expressing gamma delta antigen receptors which support the contention that these cells may have a special ability of homing into tissues. We conclude that non-specific cytotoxic cells constitute a ...

Research paper thumbnail of Expression of adhesion molecules in lymphoproliferative disorders

Leukemia, 1992

We review the role of adhesion molecule expression on malignant lymphoid cells as delineated by e... more We review the role of adhesion molecule expression on malignant lymphoid cells as delineated by experimental studies and clinical observation. Adhesion molecules of the Ig superfamily, integrins, selectins, and the lymphocyte homing receptor CD44 mediate cell-to-cell and cell-to-extracellular matrix interactions. These molecules have been investigated with the aim (i) of defining certain biological features of the malignant cells, (ii) of providing a rationale to understand tumor organization, metastasis and organ specificity, and (iii) of detecting disease subsets and prognostic groups.

Research paper thumbnail of A novel inhibitory receptor regulates T-cell function

Research paper thumbnail of Modulation of the effector cell-target cell interaction by antibodies to CD2 and CD11a/CD18

Cell Biology International Reports, 1990

Research paper thumbnail of ACUTE STROKE IN A YOUNG ADULT: A CLINICAL REPORT OF COCAINE ABUSE AND TABAGISM

… NAZIONALE DELLA SNO

... 466 ACUTE STROKE IN A YOUNG ADULT: A CLINICAL REPORT OF COCAINE ABUSE AND TABAGISM MERELLO M.... more ... 466 ACUTE STROKE IN A YOUNG ADULT: A CLINICAL REPORT OF COCAINE ABUSE AND TABAGISM MERELLO M., MAZZUCCHELLI F., BERNASCONI S., DI FALCO M., ZARCONE D. Stroke Unit, UO Neurologia, Ospedale San Antonio Abate, Gallarate (VA). Page 471. ...

Research paper thumbnail of Systemic inflammation and neurodegeneration in a mouse model of multiple sulfatase deficiency

Proceedings of the National Academy of Sciences, 2007

Sulfatases are involved in several biological functions such as degradation of macromolecules in ... more Sulfatases are involved in several biological functions such as degradation of macromolecules in the lysosomes. In patients with multiple sulfatase deficiency, mutations in the SUMF1 gene cause a reduction of sulfatase activities because of a posttranslational modification defect. We have generated a mouse line carrying a null mutation in the Sumf1 gene. Sulfatase activities are completely absent in Sumf1 ؊/؊ mice, indicating that Sumf1 is indispensable for sulfatase activation and that mammals, differently from bacteria, have a single sulfatase modification system. Similarly to multiple sulfatase deficiency patients, Sumf1 ؊/؊ mice display frequent early mortality, congenital growth retardation, skeletal abnormalities, and neurological defects. All examined tissues showed progressive cell vacuolization and significant lysosomal storage of glycosaminoglycans. Sumf1 ؊/؊ mice showed a generalized inflammatory process characterized by a massive presence of highly vacuolated macrophages, which are the main site of lysosomal storage. Activated microglia were detected in the cerebellum and brain cortex associated with remarkable astroglyosis and neuronal cell loss. Between 4 and 6 months of age, we detected a strong increase in the expression levels of inflammatory cytokines and of apoptotic markers in both the CNS and liver, demonstrating that inflammation and apoptosis occur at the late stage of disease and suggesting that they play an important role in both the systemic and CNS phenotypes observed in lysosomal disorders. This mouse model, in which the function of an entire protein family has been silenced, offers a unique opportunity to study sulfatase function and the mechanisms underlying lysosomal storage diseases.