Biomedical subjects

A Kowitz

Publications and source records attributed to A Kowitz.

At least 19 recordsLinked to original sources

PubMed1999

[The dawn of the profession: odontology among the Etruscans].

The Etruscans were a group of agricultural people who evolved into an urban population of craftsmen, traders, and navigators who lived in a network of cities and dominated the area of the Mediterranean around Italy in the 8th and 9th centuries BC. What has come to be known, and is of importance in our study of the history of dentistry are a significant number of very interesting works of art which include gold dental prostheses. The Etruscan prostheses are remarkable because they used gold bands which were soldered into rings instead of the gold ones which are seen in other cultures (Egyptians, Phoenicians) of the same time.

Art↗

PubMed1998

Inhibitory effect of 1alpha,25-dihydroxyvitamin D3 on allogeneic lymphocyte stimulation and Langerhans cell maturation.

1alpha,25-Dihydroxyvitamin D3 (calcitriol) has been shown to inhibit the proliferation of peripheral blood mononuclear cells induced by allogeneic Langerhans cells in a human mixed epidermal cell lymphocyte reaction. The potent antigen-presenting function of Langerhans cells is gained during culture. We tried to dissect the effect of calcitriol on lymphocyte proliferation and Langerhans cell maturation in a murine mixed epidermal cell lymphocyte reaction using unfractioned epidermal cells as a source for Langerhans cells. First, calcitriol was added upon setup of the mixed epidermal cell lymphocyte reaction using cultured epidermal cells as antigen-presenting cells, and this was found to inhibit the proliferation of lymphocytes in a time- and concentration-dependent manner. When calcitriol was added only during preculture of freshly isolated epidermal cells, the subsequent mixed epidermal cell lymphocyte reaction was also inhibited. In addition, the growth of keratinocytes and the production of granulocyte/macrophage colony-stimulating factor during preculture of epidermal cells was completely inhibited. Supplementation with this growth factor only partially restored the proliferative response of lymphocytes. These results suggest that calcitriol inhibits both the alloantigen-driven stimulation of naive T cell and Langerhans cells maturation. Further experiments with purified Langerhans cells are required to elucidate the mechanism of action of calcitriol on Langerhans cell maturation.

Animals↗

PubMed1993

L1 adhesion molecule on mouse leukocytes: regulation and involvement in endothelial cell binding.

L1 is a cell surface glycoprotein of the immunoglobulin superfamily which was initially shown to mediate adhesion between neural cells. Recently we have reported that L1 is expressed by bone marrow cells and the majority of mature lymphocytes (Kowitz et al., Eur. J. Immunol. 1992. 22: 1199-1205). To analyze the function of L1 on leukocytes we studied its regulation following cell activation. In vitro activation of B lymphocytes with lipopolysaccharide or T lymphocytes with phorbol 12-myristate 13-acetate/Ca2+ ionophore, concanavalin A or anti-CD3 monoclonal antibody as well as in vivo activation of V beta 8+ T cells with staphylococcal enterotoxin B (SEB) revealed a down-regulation of L1 within 48 h. A rapid loss of L1 expression was seen when mouse neutrophils were activated with PMA alone. This rapid loss paralleled the shedding of L-selectin. We also studied a possible role of L1 in the binding of leukocytes to endothelial cells. ESb-MP lymphoma cells with a high expression of L1 (L1hi) could bind to bend3 endothelioma cells without prior activation with inflammatory cytokines. The interaction was inhibited by anti-L1 antibodies. In contrast, ESb-MP cells with low L1 expression (L1lo) were only marginally bound. Latex beads coated with affinity-isolated L1 antigen were also able to bind to the endothelioma cells in a specific fashion. The binding of ESb-MP lymphoma cells required Ca2+ and Mg2+ ions and was sensitive to cold temperature. Since the endothelioma cells did not express L1 the binding mechanism studied here is distinct from the established L1-L1 homotypic interaction. It is possible that the novel L1-mediated adhesion pathway involves an unidentified ligand and could play a role in leukocyte migration.

Animals↗

PubMed1993

Expression of L1 cell adhesion molecule is associated with lymphoma growth and metastasis.

The cell adhesion molecule (CAM) L1 is involved in homotypic and heterotypic adhesion between neural cells. It has recently also been identified on leucocytes. We have investigated the expression of L1 on hematopoietic tumor cell lines and found that several tumors including the ESb-MP lymphoma are positive for L1. A potential role for L1 in spontaneous metastasis formation was examined using these cells. From wild-type (wt) L1high lymphoma cells we selected by a fluorescence-activated cell sorter (FACS) stable L1low expression variants. Syngeneic DBA/2 mice injected subcutaneously with L1low clones showed faster primary tumor growth, developed visceral metastases significantly faster and died earlier than animals carrying L1high wt cells. L1 high revertants from the L1low variants showed again a reduced metastatic capacity and a malignancy similar to the wt cells. Expression of L1 on the tumor variants and revertants correlated directly with their homotypic aggregation behaviour in vitro. L1 expression correlated negatively with metastatic capacity. These results suggest that L1 molecules may contribute to the overall malignant potential of the lymphoma cells, presumably by interfering with cell-cell interactions critical for tumor growth and dissemination.

Animals↗

PubMed1992

Expression and function of the neural cell adhesion molecule L1 in mouse leukocytes.

The neural cell adhesion molecule L1 is a cell surface glycoprotein of the immunoglobulin superfamily which mediates adhesion between neural cells. The possibility that similar cell-cell recognition mechanisms may be shared by the nervous and immune systems prompted us to study the expression and function of L1 in cells of the hematopoietic system. Immunofluorescence analysis using monoclonal L1 antibody revealed that the molecule is expressed in the bone marrow, spleen, and thymus of the mouse. This observation was confirmed by amplifying cDNA derived from these organs by the polymerase chain reaction with L1-specific oligonucleotide primers. Two-color fluorescence analysis indicated that bone marrow lymphoid and granulocyte precursor cells express low and high levels of L1, respectively. In the thymus L1 is primarily expressed by mature cells that have a strong expression of CD3 and in the spleen both B cells and T cells express L1. The possible function of L1 in lymphoid cells was studied using subcloned ESb-MP lymphoma cells having high or low densities of L1 on the cell surface as well as activated splenic B lymphoblasts. Parental and subcloned ESb-MP cells that strongly expressed L1 could form homotypic aggregates in the presence of low Ca2+ levels, whereas subcloned ESb-MP cells with a weak expression of L1 did not aggregate, suggesting that L1 mediates the Ca(2+)-independent aggregation of the parental ESb-MP cells. Furthermore, the aggregation of activated B lymphoblasts under physiological concentrations of Ca2+ and Mg2+ was inhibited by 30% in the presence of Fab fragments of polyclonal L1 antibodies, implying that L1 also mediates adhesion among normal lymphoid cells. A possible role of L1 on lymphocytes in stimulating the innervation of lymphoid organs is discussed.

Animals↗

PubMed1990

The neural cell adhesion molecule N-CAM enhances L1-dependent cell-cell interactions.

On neural cells, the cell adhesion molecule L1 is generally found coexpressed with N-CAM. The two molecules have been suggested, but not directly shown, to affect each other's function. To investigate the possible functional relationship between the two molecules, we have characterized the adhesive interactions between the purified molecules and between cultured cells expressing them. Latex beads were coated with purified L1 and found to aggregate slowly. N-CAM-coated beads did not aggregate, but did so after addition of heparin. Beads coated with both L1 and N-CAM aggregated better than L1-coated beads. Strongest aggregation was achieved when L1-coated beads were incubated together with beads carrying both L1 and N-CAM. In a binding assay, the complex of L1 and N-CAM bound strongly to immobilized L1, but not to the cell adhesion molecules J1 or myelin-associated glycoprotein. N-CAM alone did not bind to these glycoproteins. Cerebellar neurones adhered to and sent out processes on L1 immobilized on nitrocellulose. N-CAM was less effective as substrate. Neurones interacted most efficiently with the immobilized complex of L1 and N-CAM. They adhered to this complex even when its concentration was at least 10 times lower than the lowest concentration of L1 found to promote adhesion. The complex became adhesive for cells only when the two glycoproteins were preincubated together for approximately 30 min before their immobilization on nitrocellulose. The adhesive properties between cells that express L1 only or both L1 and N-CAM were also studied. ESb-MP cells, which are L1-positive, but N-CAM negative, aggregated slowly under low Ca2+. Their aggregation could be completely inhibited by antibodies to L1 and enhanced by addition of soluble N-CAM to the cells before aggregation. N2A cells, which are L1 and N-CAM positive aggregated well under low Ca2+. Their aggregation was partially inhibited by either L1 or N-CAM antibodies and almost completely by the combination of both antibodies. N2A and ESb-MP cells coaggregated rapidly and their interaction was similarly inhibited by L1 and N-CAM antibodies. These results indicate that L1 is involved in two types of binding mechanisms. In one type, L1 serves as its own receptor with slow binding kinetics. In the other, L1 is modulated in the presence of N-CAM on one cell (cis-binding) to form a more potent receptor complex for L1 on another cell (trans-binding).

Animals↗

PubMed1990

Functional cooperation between the neural adhesion molecules L1 and N-CAM is carbohydrate dependent.

The neural cell adhesion molecules L1 and N-CAM have been suggested to interact functionally by formation of a complex between the two molecules (Kadmon, G., A. Kowitz, P. Altevogt, and M. Schachner. 1990. J. Cell Biol. 110:193-208). To determine the molecular mechanisms underlying this functional cooperation, we have studied the contribution of carbohydrates to the association of the two molecules at the cell surface. Aggregation or adhesion between L1- and N-CAM-positive neuroblastoma N2A cells was reduced when the synthesis of complex and/or hybrid glycans was modified by castanospermine. Fab fragments of polyclonal antibodies to L1 inhibited aggregation and adhesion of castanospermine-treated cells almost completely, whereas untreated cells were inhibited by approximately 50%. Fab fragments of polyclonal antibodies to N-CAM did not interfere with the interaction between castanospermine-treated cells, whereas they inhibited aggregation or adhesion of untreated cells by approximately 50%. These findings indicate that cell interactions depending both on L1 and N-CAM ("assisted homophilic" binding) can be reduced to an L1-dominated interaction ("homophilic binding"). Treatment of cells with the carbohydrate synthesis inhibitor swainsonine did not modify cell aggregation in the absence or presence of antibodies compared with untreated cells, indicating that castanospermine-sensitive, but swainsonine-insensitive glycans are involved. To investigate whether the appropriate carbohydrate composition is required for an association of L1 and N-CAM in the surface membrane (cis-interaction) or between L1 on one side and L1 and N-CAM on the other side of interacting partner cells (trans-interaction), an L1-positive lymphoid tumor cell line was coaggregated with and adhered to neuroblastoma cells in the various combinations of castanospermine-treated and untreated cells. The results show that it is the cis-interaction between L1 and N-CAM that depends on the appropriate carbohydrate structures.

Alkaloids↗

PubMed1990