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Biomedical subjects

L P Ruco

Publications and source records attributed to L P Ruco.

At least 37 records · Page 2Linked to original sources
PubMed1996

Expression of ICAM-1 and VCAM-1 in human malignant mesothelioma.

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are cytokine-inducible adhesion molecules which recognize ligands that are highly expressed on leukocytes. Expression of ICAM-1 and VCAM-1 was investigated in tissue sections of 16 cases of malignant mesothelioma (seven epithelial, eight biphasic, and one sarcomatoid) using immunohistochemistry. Neoplastic cells were diffusely and intensely stained for ICAM-1 in all cases. VCAM-1 was detected in 14 of 16 cases. The percentage of VCAM-1-positive tumour cells was more than 50 per cent in eight cases and the staining was observed mainly in epithelial-like cells. VCAM-1 was rarely expressed in other malignant tumours of epithelial origin, being present in only 1 of 58 cases of carcinoma originating from different anatomical sites. At the cellular level, ICAM-1 and VCAM-1 appeared co-distributed, the staining for both being cytoplasmic with a membrane reinforcement. The regulation of VCAM-1 expression by neoplastic mesothelial cells was investigated in vitro using 14 mesothelioma cell lines. ICAM-1 was expressed by cultured cells of all mesothelioma cell lines, even in the absence of cytokines. VCAM-1 was detected in 10-50 per cent of the cells in three non-stimulated mesothelioma cell lines (mero-95, mero-96, and mero-134), and was absent or poorly expressed in the remaining 11. Exposure of a negative cell line (mero-48a) to an optimal concentration of tumour necrosis factor alpha (TNF alpha) or interleukin-13 (IL-13) for 6-18 h resulted in the induction of VCAM-1 mRNA synthesis and in VCAM-1 expression at the membrane level in 60-70 per cent of the cells. These findings are consistent with the possibility that TNF alpha, IL-13, or other activating signals are released in the tumour micro-environment and regulate the expression of VCAM-1 in malignant mesothelioma cells.

Blotting, Northern↗
PubMed1996

Expression of Met protein in thyroid tumours.

Met protein is a transmembrane 190 kD heterodimer with tyrosine kinase activity, encoded by c-MET oncogene. It serves as a high affinity receptor for hepatocyte growth factor (HGF)/scatter factor (SF), a cytokine which stimulates cell proliferation, motility, and invasion. Expression of Met protein was investigated in 116 thyroid tumours using an anti-Met mouse monoclonal antibody (DQ-13) active on paraffin-embedded material. Reactivity for DQ-13 was observed in 77 per cent of papillary carcinomas, in 70 per cent of Hürthle cell tumours, and rarely in other tumours. The staining was either uniformly present throughout the tumour or limited to nests of infiltrating tumour cells. In some Hürthle cell tumours, prominent accumulation of the protein was observed in the Golgi area. Reactivity for Met protein was decreased or absent in poorly differentiated tumours and was not influenced by tumour size, presence of lymph node metastases, or age of the patient. Immunostaining for Ki-67 revealed that cytoplasmic accumulation of Met protein was not associated with enhanced proliferation of tumour cells. Overexpression of Met protein in thyroid papillary carcinoma may result in increased motility of tumour cells, which in turn may account for intraglandular multifocal dissemination and early lymph node metastasis.

Adenocarcinoma↗
PubMed1996

Expression of adhesion molecules and extracellular matrix proteins in glioblastomas: relation to angiogenesis and spread.

We studied the immunohistochemical expression of inducible adhesion molecules, integrins and extracellular matrix proteins in 10 cases of glioblastoma multiforme in order to investigate their angiogenesis, local invasiveness, poor metastasizing properties and their lack of tumour infiltrating leukocytes. In glioblastomas endothelial proliferations represent the majority of vascular structures; they were positive for endothelial markers (vWF, CD31, VE-cadherin) and negative for macrophage markers (CD68, PAM-1). Immunohistologically, they were subtyped into: 1 solid-glomeruloid ICAM-1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1 negative; 2 channelled-branching ICAM-1 negative and alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1 positive; 3 channelled-telangiectatic ICAM-1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1 positive. In channelled proliferations, the expression and distribution of tenascin and merosin in the basal membrane was similar to that of normal brain vessels. The expression of all these molecules might indicate different steps of maturation of endothelial proliferations. The majority of endothelial proliferations may be immunohistologically considered as incomplete vascular structures; this might account for the low metastasizing tendency and low recruitment of leukocytes by these tumours. Neoplastic astrocytes were GFAP-1, ICAM-1, VCAM-1, alpha 2 beta 1, alpha 3 beta 1 and alpha 5 beta 1 immunoreactive and alpha 6 beta 4 negative: this allows them to interact with extracellular matrix proteins and might, in part, explain the tendency of glioblastomas to infiltrate locally.

Brain Neoplasms↗
PubMed1995

The lymphoepithelial organization of the tonsil: an immunohistochemical study in chronic recurrent tonsillitis.

Interactions between leukocytes and crypt epithelium were extensively investigated in 12 cases of chronic recurrent tonsillitis, using immunohistochemistry and cytofluorimetric analysis of cell suspensions. Intraepithelial leukocytes are a mixed cell population composed of 50 per cent CD20-positive B lymphocytes, 40 per cent T lymphocytes with a 2.7 CD4/CD8 ratio, and 10 per cent CD68-positive macrophages. About 4 per cent of intraepithelial leukocytes are proliferating cells, as indicated by Ki-67 staining. Leukocyte infiltration is associated with expression on epithelial cells of the adhesion molecules ICAM-1 and VCAM-1. Crypt epithelium is supported by a basement membrane showing frequent interruptions and connected with the reticular stroma of the lymphoid tissue, which was stained for fibronectin, tenascin, collagen, and laminin. Extracellular matrix (ECM) distribution was correlated with integrin expression on B and T lymphocytes. It was found that the ECM was arranged differently in the follicles and in the extrafollicular area and that B and T lymphocytes exhibited different patterns of integrin expression.

Adolescent↗
PubMed1994

Co-expression of endothelial cell and macrophage antigens in Kaposi's sarcoma cells.

The histopathogenesis of Kaposi's sarcoma (KS) was investigated using immunocytochemistry in 12 skin biopsies obtained from two AIDS patients, nine patients with the classic form, and one organ-transplant patient. KS cells revealed a peculiar antigenic profile, being characterized by co-expression of endothelial and macrophage markers. KS cells were stained for von Willebrand factor (vWF); for vascular endothelial (VE) cadherin, an endothelial specific adhesion molecule; and for PECAM/CD31. In addition, they expressed the macrophage antigens PAM-1, CD68, and CD14, and were positive for vitronectin receptor and alpha-1,5,6/beta-1 integrins. KS cells were weakly stained for ICAM-1 in 6 of 12 cases and were negative for VCAM-1 and E-selectin.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in undifferentiated nasopharyngeal carcinoma (lymphoepithelioma) and in malignant epithelial tumors.

Immunoreactivity for intercellular adhesion molecule-1 (ICAM-1) and for vascular cell adhesion molecule-1 (VCAM-1), two adhesion molecules of the immunoglobulin (Ig) superfamily, was tested and measured on tissue sections from 16 undifferentiated nasopharyngeal carcinomas (U-NPC), 12 keratinizing squamous cell carcinomas (SCCs) of the head and neck region, and 54 malignant epithelial tumors of various origin. Neoplastic cells of all cases of U-NPC were diffusely and intensely stained for ICAM-1 and VCAM-1. Moreover, ICAM-1 messenger RNA (mRNA) and VCAM-1 mRNA were detected by Northern blot analysis of RNA extracts from two tumors. In the other epithelial tumors focal or diffuse staining for ICAM-1 was observed in 40 cases (66%), whereas reactivity for VCAM-1 was detected in a single case of metastatic undifferentiated carcinoma of unknown origin. The biopsy specimens of U-NPC showed variable infiltration by leukocytes, which were positive for the integrins lymphocyte function antigen-1 (LFA-1) and alpha-4/beta-1, the corresponding ligands for ICAM-1 and VCAM-1. The possibility that ICAM-1 and VCAM-1 on neoplastic cells may favor the intratumoral recruitment of leukocytes in a way similar to that occurring in crypt epithelium of the palatine tonsil is discussed.

Adolescent↗
PubMed1994

Adhesion molecules and lymphocyte recruitment in lymphocytic thyroiditis, thyroid papillary carcinoma and parotid adenolymphoma.

Lymphocytic infiltrates are usually present in chronic lymphocytic thyroiditis, thyroid papillary carcinoma and parotid adenolymphoma. We selected these conditions to investigate the mechanisms of recruitment and organization of lymphocytic infiltrates in extranodal tissues. MoAbs in immunoperoxidase were used to identify the expression of ICAM-1 and VCAM-1 on endothelial cells (EC), and of their ligands LFA-1 and VLA-4 on lymphocytes and accessory cells. VCAM-1 positive EC were rarely observed in thyroids devoid of lymphocyte infiltration. Conversely, EC in chronic lymphocytic thyroiditis and in papillary carcinoma showed positive immunostaining for VCAM-1 and ICAM-1. These findings were associated with the presence of lymphocytes positive for the ligands VLA-4 and LFA-1. The upregulated expression of VCAM-1 on perifollicular capillaries was co-distributed with an accumulation of VLA-4 positive lymphocytes. In adenolymphoma, all EC were ICAM-1 positive, whereas the majority of vessels were VCAM-1 negative. Consequently the majority of lymphoid cells were LFA-1 positive and VLA-4 negative. We suggest that ICAM-1 and VCAM-1 expression on EC play a role in the recruitment of lymphocyte infiltration in chronic lymphocytic thyroiditis and papillary carcinoma. Furthermore, the upregulation of VCAM-1 and VLA-4 in thyroid reactive and neoplastic conditions may be linked to an immune response possibly related to thyroid tissue antigens.

Adenolymphoma↗
PubMed1994

Characterization of EN4 monoclonal antibody: a reagent with CD31 specificity.

EN4 MoAb was originally described as a MoAb that reacts specifically with human endothelial cells, and the reagent was not assigned to any of the presently known CD. Here, we provide evidence indicating that EN4 reacts with the CD31 antigen. Thus, EN4 stains strongly murine fibroblasts transfected with the human CD31 gene. Furthermore, SDS-PAGE analysis of immunoprecipitates of cell lysates from surface-iodinated Jurkart T cells demonstrated that EN4 and reference CD31 MoAb recognized the same antigen, of 130 kD mol. wt. Finally, both EN4 and CD31 gave the same pattern of reactivity when tested on tonsillar or peripheral blood lymphoid cells by FACS analysis or by immunohistochemistry on sections of a variety of human tissues. EN4, however, proved consistently more efficient than the reference anti-CD31 MoAb as judged by both the intensity of fluorescence or of tissue staining. This property has thus allowed a better characterization of the tissue and cellular distribution of CD31.

Antibodies, Monoclonal↗
PubMed1994

Cytokine production and expression of adhesion molecules and integrins in tumor infiltrating lymphomononuclear cells of non-small cell carcinomas of the lung.

Localization of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and of their ligands, lymphocyte function-associated antigen-1 and very late activation antigen-4, was determined in non-small cell lung carcinomas and tumor-free lung. Messenger RNA expression for interleukins (IL) IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, tumor necrosis factor-alpha, transforming growth factor-beta, interferon-gamma, granulocyte-macrophages colony stimulating factor, and human perforin-1 was assessed by in situ hybridization on the same tissues. Intercellular adhesion molecule-1 was expressed in all blood vessels, whereas only a low number of vessels displayed vascular cell adhesion molecule-1 immunoreactivity. Tumor infiltrating lymphomononuclear cells consisted of lymphocyte function-associated antigen-1-positive cells and of a lower number of very late activation antigen-4-positive cells. All squamous cell carcinomas consisted of intercellular adhesion molecule-1-positive neoplastic cells infiltrated by lymphocyte function-associated antigen-1-positive tumor infiltrating lymphomononuclear and CD-la-positive Langerhans cells, whereas only a minor number of adenocarcinomas displayed a consistent number of intercellular adhesion molecule-1-positive neoplastic cells. Tumor infiltrating lymphomononuclear cells showed a wider production of cytokines when compared to bronchus-associated lymphoid tissue of tumor-free lung. Moreover, cells producing interferon-gamma, IL-4, and IL-5 were more numerous in squamous cell carcinomas than in adenocarcinomas. These findings indicate that the lung squamous cell carcinoma might represent a neoplastic microenvironment able to induce activation of tumor infiltrating lymphomononuclear cells more efficiently than the adenocarcinoma.

Aged↗
PubMed1993

Molecular mechanisms involved in intraepithelial lymphocyte migration: a comparative study in skin and tonsil.

Intraepithelial lymphocyte migration is a biological process frequently observed in skin and tonsil. Using immunohistochemistry, we have studied the molecular bases of this process in seven skin biopsies involved by mycosis fungoides (MF) and in 12 tonsils, four involved by B-chronic lymphocytic leukaemia (B-CLL) and eight by lymphoid follicular hyperplasia (LH). In the skin, intraepidermal T-lymphocyte infiltration was associated with narrowing and fragmentation of the basement membrane, as shown by an anti-collagen type IV antibody. Immunostaining of serial sections with an anti-collagenase type IV antibody revealed that collagenase type IV was localized in the upper dermis and strictly co-distributed with collagen type IV, suggesting that enzymatic digestion played a role in the alterations of the basement membrane. Further migration through the epidermis was mediated by expression on keratinocytes of intercellular adhesion molecule-1 (ICAM-1) and of leukocyte-function associated antigen-1 (LFA-1) on infiltrating lymphocytes. In the tonsil, intraepithelial infiltration was mediated by the expression of vascular cell adhesion molecule-1 (VCAM-1) by epithelial cells and of very late antigen-4 (VLA-4) by infiltrating lymphocytes. Further intraepithelial lymphocyte migration was then established, as already shown in the skin, by ICAM-1/LFA-1 interaction. Lymphocyte recruitment from the systemic circulation was studied using antibodies directed against endothelial leukocyte adhesion molecule-1 (ELAM-1), ICAM-1, and VCAM-1. These adhesion molecules were highly expressed by blood vessels in the upper dermis of MF and the percentage of ELAM-1+/VCAM-1+ vessels was significantly higher than that observed in tonsils.(ABSTRACT TRUNCATED AT 250 WORDS)

Basement Membrane↗
PubMed1993

Vascular activation in the histopathogenesis of Hodgkin's disease: potential role of endothelial tissue factor in intravascular thrombosis and necrosis.

Endothelial cell activation and alterations of intravascular coagulation were investigated in 27 cases of Hodgkin's disease (HD), in five cases of anaplastic large cell lymphoma (ALCL), and in ten reactive lymph nodes. Lymph node sections were immunostained for E-selectin, a molecule present on cytokine-activated endothelial cells; for tissue factor (TF), a cellular initiator of the coagulation cascade; for glycoprotein (gp) II/III, a platelet-specific antigen; and for fibrin. In HD, vascular activation was particularly prominent in the nodular sclerosis subtype, as indicated by a larger number of E-selectin-positive blood vessels (72 +/- 49) compared with mixed cellularity (22 +/- 37). High expression of E-selectin was associated with alterations of intravascular coagulation, as indicated by immunostaining of some vascular endothelial cells for TF, by a higher incidence of intravascular thrombi, and by the extensive presence of areas of fibrin exudation and necrosis. In ALCL, the levels of endothelial cell activation and intravascular coagulation were comparable to those of HD nodular sclerosis. In reactive nodes, some E-selectin-positive blood vessels were observed only in 3/10 cases; immunostaining for TF was not detected on endothelial cells; and alterations of intravascular coagulation were rarely observed.

Adolescent↗
PubMed1993

Expression of adhesion molecules in Langerhans' cell histiocytosis.

Expression of adhesion molecules was investigated in six biopsy specimens of Langerhans' cell histiocytosis using immunocytochemistry. Cells with Langerhans' cell histiocytosis morphology were stained for ICAM-1, for the beta-1 integrins alpha-4 (VLA-4) and alpha-5 (VLA-5) , and for the beta-2 integrins LFA-1, MAC-1 and p150,95. This pattern of reactivity was different from that of epidermal Langerhans' cells of the normal skin which were not immunostained. A variable number of CD68+ multinucleated giant cells was present in five biopsies. They were less reactive than the cells of Langerhans' cell histiocytosis for alpha-4 (VLA-4) and LFA-1, were positive for MAC-1 and p150,95 and were characterized by prominent expression of the beta-1 integrins alpha-2 (VLA-2), alpha-3 (VLA-3) and of VnR (alpha-v/beta-3). The repertoire of adhesion molecules expressed by giant cells is indicative of profound cell-matrix interactions, whereas that of Langerhans' histiocytosis cells suggests particularly active cell-cell interactions. Blood vessels of the lesions were stained for beta-1 integrins, for vitronectin receptor and for molecules involved in adhesion and trans-endothelial migration of circulating leukocytes, such as ICAM-1, VCAM-1 and E-selectin. Additional findings were the observation of CD1a + multinucleated giant cells in a single case, suggesting a possible lineage relationship with the histiocytosis cells, and the demonstration of some Ki-67+ Langerhans' cell histiocytosis cells and CD1a+ mitotic figures in four of six cases, indicating local proliferation of Langerhans' histiocytosis cells.

Adult↗
PubMed1993

Tissue distribution of very late activation antigens-1/6 and very late activation antigen ligands in the normal thymus and in thymoma.

The expression of very late activation antigens (VLAs)-1/6 was correlated with that of the VLA ligands fibronectin, laminin, collagen, and vascular cell adhesion molecule-1 in sections of normal thymus, in thymocyte suspensions, and in 10 cases of thymoma. Capsular epithelial cells are VLA-2+, VLA-3+, and VLA-6+ and face the thymic basement membrane, which is rich in fibronectin, laminin, and collagen type IV. Cortical epithelial cells are VLA-2+ and are embedded in a reticular meshwork of nonorganized extracellular matrix (ECM) that is rich in fibronectin. Cortical thymocytes, identified as CD3dim cells by using immunofluorescence in suspension, are highly positive for VLA-4, a fibronectin ligand. Most cortical macrophages are positive for vascular cell adhesion molecule-1, a molecule recognized by VLA-4. Medullary epithelial cells are VLA-2+/VLA-3+ and are codistributed with fibrous strands of organized ECM that are positive for fibronectin, collagen, and laminin. Medullary thymocytes, identified as CD3bright cells, are positive for VLA-4 and VLA-6, a ligand for laminin. Our findings suggest that intrathymic thymocyte maturation is associated with changes in expression of VLA molecules, which are apparently correlated with the presence of VLA ligands in the tissue microenvironment. Thymomas were classified as cortical (three), common (five), or medullary (two) type. Expression of VLA molecules and distribution of ECM in the three histological subtypes were reminiscent of those observed in the respective regions of the normal thymus. All cases of thymoma were characterized by overexpression of VLA molecules on neoplastic cells, which was associated with increased deposition of organized ECM rich in fibronectin, laminin, and collagen.

Antigen-Presenting Cells↗
PubMed1992

A novel endothelial-specific membrane protein is a marker of cell-cell contacts.

mAbs were raised in mice against cultured human endothelial cells (EC) and screened by indirect immunofluorescence for their ability to stain intercellular contacts. One mAb denoted 7B4 was identified which, out of many cultured cell types, specifically decorated cultured human EC. The antigen recognized by mAb 7B4 is bound at the appositional surfaces of cultured EC only as they become confluent and is stably expressed at intercellular boundaries of confluent monolayers. EC recognition specificity was maintained when the antibody was assayed by immuno-histochemistry in tissue sections of many normal and malignant tissues and in blood vessels of different size and type. The antigen recognized by 7B4 was enriched at EC intercellular boundaries similarly in vitro and in situ. In vitro, addition of mAb 7B4 to confluent EC increased permeation of macromolecules across monolayers even without any obvious changes of cell morphology. In addition, when EC permeability was increased by agents such as thrombin, elastase, and TNF/gamma IFN, its distribution pattern at intercellular contact rims was severely altered. mAb 7B4 immunoprecipitated a major protein of 140 kD from metabolically and surface-labeled cultured EC extracts which appeared to be an integral membrane glycoprotein. On the basis of its distribution in cultured cells and in tissues in situ, 7B4 antigen is distinct from other described EC proteins enriched at intercellular contacts. NH2-terminal sequencing of the antigen, immunopurified from human placenta, and sequencing of peptides from tryptic peptide maps revealed identity to the cDNA deduced sequence of a recently identified new member of the cadherin family (Suzuki, S., K. Sano, and H. Tanihara. 1991. Cell Regul. 2:261-270.) These data indicate that 7B4 antigen is an endothelial-specific cadherin that plays a role in the organization of lateral endothelial junctions and in the control of permeability properties of vascular endothelium.

Amino Acid Sequence↗
PubMed1992

Expression and cell distribution of the intercellular adhesion molecule, vascular cell adhesion molecule, endothelial leukocyte adhesion molecule, and endothelial cell adhesion molecule (CD31) in reactive human lymph nodes and in Hodgkin's disease.

The immunocytochemical expression of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelial leukocyte adhesion molecule (ELAM-1), endothelial cell adhesion molecule (EndoCAM CD31), and HLA-DR antigens was investigated in sections of 24 reactive lymph nodes and in 15 cases of Hodgkin's disease. ICAM-1 was detected in sinus macrophages, follicular dendritic reticulum cells (FDRCs), interdigitating reticulum cells (IDRCs), epithelioid macrophages, Hodgkin's cells (HCs), and vascular endothelium. ICAM-1 expression was often associated with that of HLA-DR antigens. VCAM-1 was detected in FDRCs, in fibroblast reticulum cells (FRCs), in macrophages, and in rare blood vessels. EndoCAM (CD31) was constitutively expressed in all types of endothelial cells, sinus macrophages, and in epithelioid granulomas. ELAM-1 was selectively expressed by activated endothelial cells of high endothelium venules (HEVs). When expression of the inducible adhesion molecules ICAM-1, VCAM-1 and ELAM-1 was comparatively evaluated in HEVs, it was found that ICAM-1 + HEVs were present in all reactive and HD nodes, whereas ELAM-1 and/or VCAM-1 were expressed only in those pathologic conditions characterized by high levels of interleukin-1/tumor necrosis factor (IL-1/TNF) production, such as granulomatosis and Hodgkin's disease. In Hodgkin's disease, the expression of ELAM-1/VCAM-1 was more pronounced in cases of nodular sclerosis and was associated with a significantly higher content of perivascular neutrophils.

Cell Adhesion Molecules↗