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Introduction: The aim of this study was to investigate the presence and the role of the parathyroid hormone-related protein (PTH-rP) in the inflamed pulp. Materials and Methods: Thirty-four pulp tissue specimens (24 inflamed and 10 normal pulps) from extracted third molars were studied. The presence of PTH-rP was observed by using immunohistochemistry. Negative controls were performed using non immunized rabbit or mouse serum, omitting the primary antibody. Results: The analysis of all the sections of normal pulps showed the presence of PTHrP positive cells only in the odontoblastic zone and in few fibroblasts. Instead all inflamed pulps showed PTHrP positive cells both in vascular zone and in pulp stroma, as well as in the odontoblastic and subodontoblastic zone. Conclusion: Several works proved that this peptide plays a role even in angiogenesis process, but its function is controversial. It is possible to hypothesize that PTHrP stimulates angiogenesis, but it is recommended to further conduct research on this area. [ABSTRACT FROM AUTHOR]

Objectives. Cyclooxygenase-2 (COX-2) seems to be involved in critical steps of cancer onset and progression. Abnormalities of epidermal growth factor receptor (EGFR) and Her-2/neu have been actively investigated in ovarian cancer and associated with unfavorable clinical outcome. The involvement of COX-2 in ErbB family pathways has been proposed. We investigated by immunohistochemistry the expression of COX-2, EGFR, and Her-2/neu in a series of advanced primary ovarian cancers.Methods. The study included 76 consecutive stage IIIC–IV ovarian cancer patients with measurable disease after first surgery. Immunohistochemistry was performed on paraffin-embedded sections with rabbit antiserum against COX-2, murine monoclonal antibody (MoAb) 300G9 against Her-2/neu, and monoclonal antibody 108 against EGFR.Results. No association among COX-2, EGFR, and HER-2/neu was found. COX-2 positivity was found in a statistically significant higher percentage of unresponsive cases (80.0%) than in patients responding to chemotherapy (35.7%) (P = 0.0008). The association between COX-2 positivity and poor chance of response to treatment was retained in multivariate analysis. In the subgroup of patients who underwent explorative laparotomy COX-2-positive cases showed a shorter overall survival (P = 0.049).Conclusions. COX-2 could represent a possible new marker of sensitivity to platin-based chemotherapy in ovarian cancer. The lack of association of COX-2 with EGFR or Her-2/neu suggests that the ability of COX-2 to predict tumor sensitivity to chemotherapy is not dependent on EGFR or Her-2/neu status and could be independently associated with prognosis. In this context, the availability of agents able to specifically interfere with COX-2, Her-2/neu, or EGFR tyrosine kinase is of potential interest. [Copyright &y& Elsevier]

Expression of 20-alpha-hydroxysteroid dehydrogenase (20α-SDH), a putative T cell marker in the murine system, has been examined in human haematopoietic cells. Higher levels of enzymatic activity were expressed by human peripheral blood mononuclear cells (PBMC) in comparison with thymocytes. When PBMC were fractionated into T and non T cell subsets, the greatest values of 20α-SDH activity were associated with the non T cell population. Cells from bone marrow exhibited lower levels of 20a-SDH than PBMC and thymocytes. Both myeloid and lymphoid leukaemic cells expressed significant 20α-SDH activity. In addition our data in U-937 and CM-S human cell lines indicate that cells belonging to the myelomonocytic precursor compartment constitutively expressed 20α- SDH activity. Furthermore, this activity was less expressed when these cells were induced to monocyte-macrophage differentiation. In conclusion, our data in the human system indicate that 20α-SDH should not be viewed as a lymphoid lineage-restricted marker enzyme. [ABSTRACT FROM AUTHOR]

The inhibitory effect of glucocorticoids on the in vitro response to phytohaemagglutinin of the residual circulating T lymphocytes in renal transplant patients during maintenance immunosuppressive therapy with glucocorlicostcroids and azathioprine has been investigated. As in normal subjects, the steroid-induced inhibition of transplanted patients' lymphocyte response was inversely correlated with the mitogen concentration used. On the other hand, the response of the various lymphocyte preparations from transplanted patients appeared less inhibited by steroids than the corresponding preparations from normal subjects. The addition lo the culture of the adherent cell product interleukin I was effective in removing to a similar extent the steroid inhibitory effect on lymphocytes from normal and transplanted subjects. Thus, the lesser inhibitory effect of glucocorticoids on transplanted patient lymphocytes could be explained by the higher percentages of monocytes present in all peripheral blood mononuclear cell preparations. These results suggest that during immunosuppressive therapy with glucocorticoids and azathioprine the residual circulating lymphocytes have a responsiveness to in vitro dexamethasone suppression similar to that of normal peripheral blood lymphocytes. [ABSTRACT FROM AUTHOR]

The relationship between the expression of T3 and T6 antigens and the capacity lo respond to phytohaemagglutinin (PHA) has been studied in the lymphocyte component of nine human thymomas. It appears that there is a positive correlation between the mitogen responsiveness of thymoma lymphocytes and the relative proportion of T3 positive (T3+),T6 negative (T6- ), peanut receptor negative and IgM-Fc receptor positive cells. Moreover we have comparatively investigated the dexamethasone (Dex) inhibitory effect on the mitogenesis of T lymphocytes from thymoma, normal thymus and peripheral blood. In the presence of the macrophage product interleukin 1, the capacity of Dex to inhibit the mitogenesis of peripheral blood purified T cells (PBT) is inversely correlated with the PHA concentration used. Conversely. Dex completely (>90%) inhibits thymocyte mitogenesis irrespective of PHA concentration. The entity of Dex inhibitory effect on thymoma lymphocyte mitogenesis shows a great variability ranging between that observed in normal thymocytes and that observed in PBT. In each thymoma case the degree of inhibition appears to be dependent on the size of the more mature thymocyte pool being positively correlated with the number of T6+ but negatively with that of T3+ cells. Our data demonstrate a high degree of variability among thymomas relative to the phenotypic and functional properties of their lymphocyte component. On the other hand, in some thymomas the phenotypic and functional characteristics of lymphocyte component seem to represent only a narrow span of normal thymocyte maturative pathway. In this respect, human thymoma may constitute a profitable tool for studying the intrathymic T lymphocyte maturative steps. [ABSTRACT FROM AUTHOR]

Human thymocytes were separated into 10 fractions by continuous Percoll density gradient centrifugation. Almost all the cells able to proliferate in response to phytohaemagglutinin (PHA) and about 80%Y of the thymocytes carrying the mature T3 marker were contained within the first two lightest fractions (Fr1 and Fr2). However, cells in Fr1 and in Fr2 were clearly different in terms of their interleukin requirement for mitogenesis. i.e. in the presence of interleukin-1 (IL-l). Fr1 thymocytes showed proliferative responses to PHA that were three to five times greater than those of the Fr2 cells, whereas in the presence of exogenous IL-2 both Fr1 and Fr2 cells had mitogenic responses of a similar magnitude. These differences could not be explained by accessory cell contamination or by different kinetics of the proliferative responses. Furthermore, in the presence of exogenous IL-l. Fr1 thymocytes showed a greater capacity for producing IL-2, In contrast, there was no difference in the expression of functional IL-2 receptors between the two fractions. It can be concluded that the mature thymocyte subpopulation contains at least two functionally distinct subsets, which differ in density, and that during intrathymic maturation the capacities to produce and to respond to II.-2 do not develop simultaneously. Although both the number and the binding characteristics of glucocorticoid (GC) receptor sites did not differ significantly between Fr1 and Fr2 thymocytes, dexamethasone was more effective in inhibiting the PHA-induced mitogenesis of Fr2 than of Fr1 cells. Thus, the GC sensitivity of T-cell mitogenesis is not directly correlated with receptorrelated variables. In contrast with observations made on peripheral T cells, the Inhibitory activity of GC on thymocyte mitogenesis was only partially reversed by the addition of exogenous IL-2. Thus, the inhibitory action of GC on thymocyte mitogenesis cannot be explained only by the steroid-induced inhibition of IL-l-IL-2 production; it must also be due to a GC-inhibitory effect on the IL-2-rcsponsivc cell proliferation. [ABSTRACT FROM AUTHOR]

Interleukin-1 (IL-1) production by the human monocyte-like cloned cell line CM-SM has been investigated as a function of the state of cell differentiation. CM-SM cells were induced to differentiate along the monocyte-macrophage lineage by bacterial lipopolysaccharides (LPS) or by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Cell differentiation was studied by various morphological, functional, cytochemical, and immunological variables, whereas IL-1 activity in the supernatants was measured by the lectin-primed thymocyte proliferation assay. Unstimulated CM-SM cells constitutively produced cell differentiation, but the effect was reversible, and the cells, in general, did not acquire a capacity for phagocytosis. IL-1 levels were increased about 10-fold over the controls. TPA induced further cell differentiation to macrophage-like cells capable of phagocytosis. IL-1 activity could not be measured directly in the supernatants owing to the synergistic effect of TPA in the assay system. Unequivocal removal of the phorbol was not achieved, but the data indicated that the ‘real’ levels of IL-1 in the TPA-induced cultures were not significantly higher than those from LPS-induced cultures. [ABSTRACT FROM AUTHOR]