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M Cozzi

Publications and source records attributed to M Cozzi.

At least 19 recordsLinked to original sources
PubMed1997

Establishment of HHV-8-positive and HHV-8-negative lymphoma cell lines from primary lymphomatous effusions.

Primary lymphomatous effusions are represented by cases of non-Hodgkin's lymphoma (NHL) which grow in liquid phase in the serous body cavities in the absence of solid tumour masses. Based on morphologic, immunophenotypic, virologic and genotypic features, primary lymphomatous effusions are distinguished into body cavity-based lymphoma (BCBL), Burkitt's lymphoma (BL) and immunoblastic large-cell lymphoma. The histogenesis and pathogenesis of primary lymphomatous effusions are virtually unclarified. In this study, we have established 2 cell lines (CRO-AP/1 and CRO-AP/2) representative of 2 distinct categories of primary lymphomatous effusion, BCBL (CRO-AP/2) and BL (CRO-AP/1). Both CRO-AP/1 and CRO-AP/2 carry monoclonal re-arrangements of the immunoglobulin genes which are identical to those of the respective parental tumours. Consistent with its BCBL origin, CRO-AP/2 is characterised by a non-B, non-T phenotype and harbours infection by HHV-8 (approx. 100 viral copies/cell) and Epstein-Barr virus. Conversely, CRO-AP/1 expresses several B cell-associated antigens, lacks HHV-8 infection and carries the genetic hallmark of BL, i.e., a chromosomal breakpoint of band 8q24. CRO-AP/1 and CRO-AP/2 may be valuable for the biologic characterization of primary lymphomatous effusions, particularly since the number of available cell lines derived from such lymphomatous effusions is extremely limited.

Ascites↗
PubMed1997

High CD40 membrane expression in AIDS-related lymphoma B cell lines is associated with the CD45RA+, CD45RO+, CD95+ phenotype and high levels of its soluble form in culture supernatants.

CD40 is a membrane glycoprotein expressed on normal and neoplastic B lymphocytes. Stimulation through CD40 regulates important cellular functions, but the effects depend on its membrane density. While extensive studies have characterized CD40 in non-Hodgkin lymphomas of immunocompetent individuals, little is known on the characteristics of this molecule in lymphomas arising in immunocompromised hosts. The aim of this study was to characterize the pattern of CD40 expression in an in vitro model constituted by AIDS small non-cleaved lymphoma (SNCCL) cell lines. The analysis of CD45 isoforms, a group of molecules alternatively spliced during B cell differentiation, has been chosen to correlate this process to the number of CD40 molecules per cell in these cell lines. Since Apo 1/Fas expression is upregulated on B lymphocytes after CD40 ligation and this expression is functionally relevant, we wanted to know whether a different CD40 pattern in AIDS-SNCCL cell lines could influence CD95 expression. We have shown that 3 of these cell lines (PA 682, Es III, and HBL-2) have high membrane CD40 expression (> 100,000 molecules/cell); they release large amounts of soluble CD40 (sCD40) in culture supernatants (>500 pg/ml), are CD45RA/RO double labelled, and express the Apo 1/Fas (CD95) antigen. On the contrary, low CD40 membrane antigen cell lines (BRGIgA, HBL-2, NC 71, AS 283A, and LAM C3+, < 50,000 molecules/cell) release low amounts of sCD40 (<300 pg/ml), are CD45RA+ but CD45RO-, and do not express CD95. EBV has no role in CD40 and CD45 isoform behaviour, because EBV superinfection of the EBV negative, low membrane CD40 HBL-2 cell line does not modify CD40 membrane expression, sCD40 production, or CD45 isoform and CD95 expression. Our data suggest that membrane CD40 in AIDS-SNCCL cell lines might be a key element in the regulation of their pathophysiology by influencing the expression of CD45 isoforms and of CD95, and by the release of its soluble form.

Antigens, CD↗
PubMed1996

Human osteoclasts and preosteoclast cells (FLG 29.1) express functional c-kit receptors and interact with osteoblast and stromal cells via membrane-bound stem cell factor.

Bone remodeling requires cooperation between osteoclasts and other specialized or accessory bone cell populations by mechanisms that have not been completely elucidated. Here we describe the expression and functional role of the proto-oncogene c-kit and of its specific ligand stem cell factor (SCF) on human osteoclasts, osteoblasts, and stromal cells derived from different sources. Our results indicate that primary osteoclasts in imprints of metaphyseal bone and giant cell tumors (GCTs) of bone, as well as a bone marrow-derived preosteoclast cell line of human origin (FLG 29.1), expressed immunodetectable c-kit protein. In contrast, tissue osteoclasts did not react with anti-SCF antibodies, and barely detectable levels of SCF mRNA and protein were found in FLG 29.1 cells. Conversely, a strong expression of membrane bound-SCF was found in primary cultured bone marrow stromal cells, in a stromal cell line (C433) derived from the mononuclear component of GCT of bone, and in a human cell line with osteoblast features (Saos-2). FLG 29.1 preosteoclast cells displayed about 29,000 binding sites/cell of a single class of high affinity c-kit receptors (Kd 6.12 x 10(-10) mol/L) with a molecular weight of about 140 kDa, along with a structurally normal c-kit mRNA. Proliferation of FLG 29.1 preosteoclast cells was stimulated by exogenous SCF, indicating that c-kit was capable of transducing growth signals. Finally, in vitro adhesion of FLG 29.1 cells to primary bone marrow stromal cells, GCT-derived stromal cells (C433), and Saos-2 osteoblast cells was significantly inhibited by an excess of soluble SCF or by monoclonal antibodies recognizing SCF binding sites on the c-kit receptor. These results indicate that c-kit is constitutively expressed on human osteoclasts and that it may be directly implicated in cell contact-dependent interaction of osteoclasts with other specialized or accessory cell populations of the bone microenvironment. Our observations suggest a role for SCF in human diseases characterized by abnormal bone resorption and remodeling.

Bone Marrow↗
PubMed1995

High frequency of EBV association with non-random abnormalities of the chromosome region 1q21-25 in AIDS-related Burkitt's lymphoma-derived cell lines.

Chromosome 1q abnormalities represent the second most frequent cytogenetic lesion of Burkitt lymphoma (BL) and acute lymphoblastic leukemia (ALL)-L3. The most frequent change is partial duplication of the long arm of chromosome 1, involving variable bands but consistently including 1q23. Among AIDS-related BL similar chromosome 1q abnormalities have also been found. We have now characterized in detail the chromosome 1q abnormalities of 4 AIDS-BL cell lines and compared them to other molecular features of the tumor clone, namely infection by Epstein Barr virus (EBV). Immunophenotypic characteristics were also assessed by conventional in situ immunocytochemical and flow cytometric procedures. The B-cell origin of all cell lines was demonstrated by the expression of B-cell-restricted markers (e.g., CD19). Analysis of Ig light chains confirmed their monoclonal nature. The t(8;14) was present in 3 of the 4 lines, whereas variant translocation t(8;22) was detected in the remaining cell line. Additional chromosomal changes were found in all cases, with chromosome 1 being involved in all. Structural changes encompassed in each case the 1q21-25 bands, in either duplication or partial trisomy. EBER ISH studies identified EBV association in 3 of the 4 AIDS-BL cell lines in contrast to previous studies of BL of immunocompetent individuals. Our findings of a high frequency of chromosome 1q abnormalities in EBV-infected AIDS-related BL cell lines demonstrate that such chromosomal abnormality and EBV positivity are not mutually exclusive and are possibly independent factors, whereas their close association in AIDS may be related to the immunodeficiency.

Burkitt Lymphoma↗
PubMed1994

CD26/dipeptidyl peptidase IV expression in human lymphomas is restricted to CD30-positive anaplastic large cell and a subset of T-cell non-Hodgkin's lymphomas.

CD26 is identical to the cell surface ectoenzyme dipeptidyl peptidase IV (DPPIV). CD26/DPPIV is associated with T-cell activation and proliferation and also may function as an auxiliary adhesion factor. Although CD26/DPPIV has been previously studied on lymphoid populations and on leukemias/lymphomas of B- and T-cell phenotype, little is known about its expression and functional role in some specific types of lymphomas, such as CD30-positive anaplastic large cell (ALC) lymphomas and Hodgkin's disease (HD). A series of 81 lymphoma samples, including 23 cases of HD, 17 cases of CD30-positive ALC lymphomas, 41 cases of other non-Hodgkin's lymphomas (NHL), and a panel of HD- or ALC lymphoma-derived human cell lines were evaluated for CD26/DPPIV expression by enzyme histochemistry and immunohistochemistry on frozen sections and cell smears. CD26/DPPIV protein was expressed on neoplastic cells in 12 of 17 (71%) ALC lymphomas irrespective of their antigenic phenotype and in seven of 15 (47%) T-cell NHLs. In contrast, we did not detect CD26/DPPIV expression in tumor cells from 26 cases of B-cell NHL other than ALC lymphomas or in Reed Sternberg (RS) cells and variants of 21 of 23 HD cases. Accordingly, CD26/DPPIV expression was maintained on the CD30-positive ALC lymphoma cell line Karpas 299, but the molecule was not detected on HD-derived cell lines of B, T, or non-B non-T phenotype. These results may support a new potential tool for the phenotypic separation of ALC lymphomas from HD based on the differential expression of the CD26/DPPIV molecule. Moreover, given the demonstration that CD26/DPPIV is identical to the human adenosine deaminase (ADA) binding protein, it could be speculated that CD26/DPPIV also may function by interacting with ADA to regulate the growth of CD26/DPPIV expressing neoplastic cells in ALC lymphomas.

Dipeptidyl Peptidase 4↗
PubMed1990

Immunohistocytochemical correlation of DAP IV-CD 26 reactivity with immunologic markers of lymphocyte activation in human lymphoid tissues.

The topographic distribution of the dipeptidylaminopeptidase IV (DAP IV-CD 26) and II (DAP II) positive T-cell population in six reactive lymph nodes and seven follicular B-cell non-Hodgkin's lymphomas (NHL) was analysed with regard to the distribution of activated T-cells, as visualized by a panel of monoclonal antibodies including Tac-CD 25, HLA-DR, OKT 9-CD 71, ICAM-1-CD 54, LFA-1-CD 11a. For comparative studies serial frozen sections of the lymph nodes were tested by enzyme histochemistry and immunohistochemistry. In addition, cell suspensions obtained from 10 B-NHL and interleukin-2 (IL-2) activated T-cells were investigated by a combined cytochemical and immunological method for simultaneous visualization of DAP IV-CD 26 cytoplasmic activity and surface immunostaining for markers of lymphocyte activation. Both in reactive and lymphomatous lymph nodes the topographic distribution of DAP IV-CD 26+ and DAP II+ lymphocytes was rather similar to that of Tac-CD 25+ lymphocytes. On the contrary, the DAP IV-CD 26 and DAP II distribution pattern substantially differed from that of the other immunologic markers. In a cell suspension of IL-2 activated T-cells, more than 80% of the cells with a blastic morphology were DAP IV-CD 26+; DAP IV-CD 26+ cells coexpressing Tac-CD 25, OKT 9-CD 71, HLA-DR positivity, relative to the total number of DAP IV-CD 26 positive cells, were 90.5%, 70.5% and 87% respectively. Only small (not activated) lymphocytes expressed a focal cytoplasmic DAP II positivity. In cell suspensions from 10 cases of B-NHL the mean percentage of DAP IV-CD 26+ Tac-CD 25+ cells was 75.8. Only a small number of DAP IV-CD 26+ cells coexpressed HLA-DR, the mean percentage being 9.6. The results support the view that DAP IV-CD 26 may be considered as a marker of lymphocyte activation; this marker seems to be restricted to T lymphocytes that reside in the T dependent areas of reactive lymph nodes and to non malignant T-cells surrounding neoplastic follicles of follicular NHL.

Antigens, CD↗
PubMed1989

Dipeptidylaminopeptidase IV activity in T lymphocyte subsets in B cell non-Hodgkin's lymphomas.

The total T cell population and T cell subsets in ten lymph nodes with reactive lymphoid hyperplasia (RLH) and 23 specimens (21 lymph nodes, one stomach, and one small bowel) involved by histologically and immunohistologically diagnosed B cell non-Hodgkin's lymphomas (NHLs) were determined by reactivity with monoclonal antibodies Leu 4-CD3, Leu 3-CD4, and Leu 2-CD8 in cytospin preparations from cell suspensions. T cell populations were also investigated for the coexpression of dipeptidylaminopeptidase IV (DAP IV) activity, which was visualized simultaneously with cell surface immunostaining by a combined cytochemical and immunocytochemical method. The mean absolute percentage of Leu 4-CD3+ (total T) and Leu 3-CD4+ cell populations was significantly lower in B cell NHL cases than in RLH cases (35% v 54%, P less than .001; 29.5% v 44.4%, P less than .01). No difference in the mean absolute percentage of the Leu 2-CD8+ T cell subset was found between the RLH cases and the B cell NHL cases classified as other than category A as described by the Working Formulation (WF) of NHLs. The relative percentage of Leu 4-CD3+ and Leu 2-CD8+ cells coexpressing DAP IV reactivity was lower in B cell NHL cases than in RLH cases (27.3% v 39.5%, P less than .05; 13.5% v 24.4%, P less than .10). There was no difference in the proportion of Leu 3-CD4+ cells expressing DAP IV reactivity between the NHL and RLH groups (34.5% v 36.1%). Since the mean relative percentage of Leu 2-CD8+ cells expressing DAP IV reactivity in the B cell NHL group in the other than category A according to the WF was lower than that of the RLH group (12.5% v 24.4%), and whereas the mean absolute percentage of total Leu 2-CD8+ cells was similar in the two groups (16.6% and 16.6%), a possible defective role of this Leu 2-CD8+ DAP IV+ subset, at least in B cell NHLs in the other than category A according to the WF, may be hypothesized.

Antibodies, Monoclonal↗
PubMed1989

Intermediate lymphocytic lymphoma encompassing diffuse and mantle zone pattern variants. A distinct entity among low-grade lymphomas?

Intermediate lymphocytic lymphoma has been operationally included among low-grade lymphomas, but few clinical data appeared to support definitely such an inclusion. The clinicopathologic features of 13 out of 14 cases of intermediate lymphocytic lymphoma either encompassing diffuse or mantle-zone pattern variants (ILL or MZL, respectively), diagnosed by conventional histology according to established criteria, are reported. Frozen section immunophenotypic analysis was also performed in 10 cases and enzyme studies were done in five. The 14 cases formed 6.9% of 203 non-Hodgkin's lymphomas (NHL) histologically diagnosed over a 2-year period. Among the 13 cases studied, there were nine males (five with ILL and four with MZL) and four females (one with ILL and three with MZL). Median age was 59 years. Splenomegaly (46%), high stage diseases (100%), involvement of bone marrow (92%) and peripheral blood (38%), and diffusion to and/or involvement of extranodal sites (38%), all were common findings at presentation. The 34 low-grade NHL of the total series classified according to the Working Formulation did not significantly differ from the ILL/MZL group in terms of frequency of involvement of bone marrow (69%) and peripheral blood (56%) as well as diffusion to and/or involvement of extranodal sites (26%). In ILL/MZL, therapy modalities were not uniform and the short follow-up time precluded firm conclusions on prognosis. Immunohistology demonstrated that ILL/MZL diagnosed by adequate morphologic criteria is a fairly homogeneous entity, also sharing most of its consistent immunological features with low-grade NHL. Thus, ILL/MZL is a relatively frequent and consistently recognizable clinical and pathological entity that may deserve a distinct place among NHL according to the Working Formulation. Proper clinical studies are needed to establish on a firmer basis the prognosis and optimal treatment of ILL/MZL.

Adenosine Triphosphatases↗
PubMed1989

A combined cytochemical and immunocytochemical method for simultaneous visualization of cytoplasmic enzyme reactivity and cell surface antigens in cell suspensions.

Immunocytochemical methods were used in combination with enzyme cytochemistry to visualize simultaneously cytoplasmic enzyme reactivity (for dipeptidyl[amino]peptidase [DAP IV], acid phosphatase [AcP], chloroacetyl esterase [CAE]) and cell surface antigens (Leu-3a, Leu-4, Leu-14, Leu-M1, OKT4, OKT8, OKB7) in cytospin preparations from cell suspensions of human reactive lymphoid tissues (four lymph nodes and three tonsils). Different fixative solutions were tested. Enzyme and immunocytochemical reactions were carried out in different orders of sequence to establish which was the better direction for the combination of the two methods. The following immunocytochemical methods were tested: three stages, avidin-biotin complex, peroxidase-antiperoxidase, alkaline phosphatase-antialkaline phosphatase (APAAP) (using both peroxidase and alkaline phosphatase as labeling enzyme). Acetone or buffered formalin acetone gave the best results both for cytochemical and immunologic reactions. DAP IV and AcP reactivities could be visualized only when cytochemical reactions were performed before immunocytochemistry. CAE reactivity could be demonstrated either before or after immunocytochemistry. Cell surface antigens could be demonstrated with most immunocytochemical methods: however, the APAAP method was preferred for its sensitivity and effectiveness when combined with enzyme cytochemistry. By this approach, cells expressing only immunologic markers and cells expressing only cytochemical markers could easily be distinguished from those coexpressing both markers, because cytochemistry and immunocytochemistry could be combined without affecting the reactivity of each marker, and the reaction products did not hamper the interpretation of preparations.

Antigens, Surface↗
PubMed1987

The effect of pre-stretch on mechanical efficiency of human skeletal muscle.

The mechanical efficiency of positive work was studied in six subjects performing three different types of exercises. On the first occasion the subjects ran on a motor-driven treadmill at 3.33 m s-1; the second and the third exercises consisted of performing rhythmical vertical jumps for 1 min both in rebound (RJ) and no-rebound (NRJ) conditions. The mechanical efficiency calculated in NRJ, which reflects only the conversion of biochemical energy into mechanical work, was found to be lower than the corresponding observation in RJ, 17.2 vs. 27.8% (P less than 0.001), respectively. These differences could not be explained by only the storage and recoil of elastic energy occurring in RJ compared with NRJ. The calculated extra work delivered 'free' was greater than the potential elastic energy which could be stored within the leg extensor muscles (187 vs. 124 J for each jump, P less than 0.05). It is likely that other factors might be responsible for the extra work found in NRJ. It was suggested that the difference in the length of time to perform positive work between a simple shortening contraction and a stretch-shortening muscular activity could be also responsible for the enhanced efficiency observed in RJ. This suggestion was supported by the high relationship (P less than 0.001) found between the time to perform positive work and the mechanical efficiency measured in jumping and estimated during running.

Adult↗
PubMed1985

Immunocytochemical evidence of common-ALL antigen in null-ALL.

4 cases of acute lymphoblastic leukaemia (ALL), diagnosed as null-ALL by indirect immunofluorescence using monoclonal antibodies, were similarly investigated using a sensitive immunoperoxidase method. The Avidin-Biotin system was employed. The immunoenzymatic results were in agreement with those obtained with immunofluorescence techniques for all antigens except common-ALL (C-ALL). The C-ALL antigen, recognized by the J5 antibody, was detected only by the immunoperoxidase method on cell membranes of the 4 ALL. This paper discusses the possibility of false negative results in testing for C-ALL antigen by conventional indirect immunofluorescence as suggested by refined immunocytochemical screening. Moreover, the ability of the immunoperoxidase system to identify antigens on cell membranes, even at very low density, is discussed. The clinical significance of the presence of C-ALL antigen at weak intensity in cases of null-ALL is also considered.

Antibodies, Monoclonal↗
PubMed1984

A two-year survey of mucocutaneous lymph node syndrome in northeastern Italy. Epidemiological and clinical findings.

A two-year retrospective survey of cases of mucocutaneous lymph node syndrome (MLNS, Kawasaki disease) was conducted by a collaborative research group in Northeastern Italy (Friuli Venezia-Giulia) by reviewing the records of all patients admitted in the paediatric wards of this area from January 1, 1981 to December 31, 1982. 19 cases of MLNS were identified representing an overall incidence in the two-year period of 14.7 cases per 100,000 children younger than 5 years of age. Seasonal clustering of cases was observed, 17 out of 19 cases occurring either in spring or autumn (P = 0.0004, binomial distribution) and 11 out of 19 cases occurring in spring alone (P = 0.0023). No evidence for direct contact between cases or common source exposure emerged, and no risk factors were identified. The clinical spectrum of the disease was similar to that described elsewhere, carditis, uveitis, arthritis and urethritis being the most frequent complications. One infant died, and in this case coronary artery aneurysms were demonstrated by two-dimensional echocardiography. In the remaining cases recovery was complete without sequelae. This study suggests that MLNS is more frequent than expected and that the real incidence of the disease is probably underestimated. The evidence of seasonal clustering of cases strongly suggests the presence of a yet unidentified exogenous factor playing a role in the etiology of the disease.

Child↗