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Biomedical subjects

E Tabone

Publications and source records attributed to E Tabone.

At least 37 records · Page 2Linked to original sources

Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens.

LFA-3, ICAM-1, HLA.ABC and HLA.DR expression was analyzed on 66 neuroblastoma specimens. HLA.ABC was expressed on 26 specimens, HLA.DR on 2, LFA-3 on 20 and ICAM-1 on 10. HLA.ABC and LFA-3 were positive on ganglioneuroblastoma or ganglioneuroma, but they were negative on neuroblastoma, independently of the clinical staging; HLA.ABC and LFA-3 were induced in vivo by chemotherapy in parallel with tumoral cell differentiation, in both the primary and the metastases. The expression of ICAM-1 was restricted to 5 of the 10 low-grade stage-1 or stage-2 specimens, 1 stage-3 specimen, and the primary tumors of 2 patients with stage-4 disease, analyzed hence at diagnosis and after chemotherapy (4 specimens); metastatic cells obtained in 1 of these patients were negative. HLA.ABC and LFA-3 expressed on both mycN-negative and -positive specimens, whereas ICAM-1 was restricted to MYCN-negative specimens. LFA-3 diffusely stained partially differentiated neuroblasts, Schwann cells and ganglion cells. The expression of HLA.ABC on differentiated neuroblasts varied from one sample to another and within the same tumor; Schwann cells were strongly positive, but ganglion cells were negative. In positive samples, ICAM-1 was expressed on differentiated neuroblasts and Schwann cells, but negative on ganglion cells; however, most of the differentiated tumors were ICAM-1-negative, suggesting ICAM-1 induction by unknown local signal. The 4 markers were negative on undifferentiated neuroblasts. The distribution of these 4 markers on clinical specimens was in agreement with their reactivity on fetal tissues, as well as with results obtained on neuroblastoma cell lines before and after in vitro treatment with IFN-gamma.

Alkaline Phosphatase↗

Alteration of the inner surface of venous catheters by antineoplastic drugs.

Septic complications and thrombosis are frequent causes of long-term venous catheter implantation failure and tend to occur more frequently in oncology than in patients using catheters for hyperalimentation only. The purpose of this in vitro study was to study extensively the inner surface behaviour and the possible changes in their mechanical properties of various silicone and polyurethane catheters after exposure to a flow of the most common antineoplastic drugs. Silicone catheters appeared to be the best choice for cytostatic drug infusions because of their chemical stability, but the addition of an opacifier imposes a protective inner and outer layer to improve their surface properties for biocompatibility.

Antineoplastic Agents↗

Immunolocalization of transforming growth factor-beta 1 in the bovine adrenal cortex using antipeptide antibodies.

Eight- to 12-amino acid long peptides, representing fragments of transforming growth factor-beta 1 (TGF beta 1) and TGF beta 2 were selected on the basis of their potential immunogenicity and were used to generate polyclonal antibodies. Anti-TGF beta 1-(91-103) antibodies recognized specifically TGF beta 1, prevented TGF beta 1 binding to NRK-49F cells, and neutralized the biological activity of TGF beta 1 in adrenocortical cells (consisting in the inhibition of angiotensin-II-induced cortisol production). Antibodies raised against TGF beta 2-(65-73) appeared to recognize TGF beta 2 with a better affinity than TGF beta 1, but were unable to block the binding of either TGF beta 1 or TGF beta 2 to their receptors or to inhibit their biological activity. These observations are in line with a prominant role of the C-terminal domain of TGF beta 1 in its interaction with its receptor(s) and, hence, in its biological activity. Using anti-TGF beta 1-(91-103) antibodies, we could localize immunoreactive TGF beta 1-like material in the cortex of adult bovine adrenal glands. No reactivity was detected in the capsule or adrenal medulla. The reactivity was maximal in the zona fasciculata/reticularis and weaker in the zona glomerulosa. TGF beta-like material was present in a latent form in the conditioned medium from primary cultures of bovine adrenocortical cells. These cells secreted about 5 ng heat-activatable TGF beta-like material/24 h of culture.10(6) cells. Taken together with our previous reports that bovine adrenocortical cells possess high affinity TGF beta 1 receptors and secrete a TGF beta 1-like molecule under a latent form, the present observations further support the hypothesis that TGF beta 1 or a closely immunologically related protein acts as an autocrine regulator of adrenocortical steroidogenic functions.

Adrenal Cortex↗

Extracellular matrix and intermediate filaments in the first stages and repair of experimental gingivitis in man.

By the indirect immunoperoxidase labelling procedure the expressions of type I and III collagens, laminin and fibronectin and of KL1 cytokeratin and vimentin were examined in the first stages and repair of experimental gingivitis in young subjects. A two month longitudinal study was performed using the tissue from buccal marginal gingival biopsies of four subjects taken sequentially at five specific times: before and during plaque accumulation, and during plaque elimination. The sites examined microscopically were the coronal half of the junctional epithelium and the underlining infiltrated connective tissue fraction. No clinical change could be observed during the study period. Histological examination showed reversible cellular changes during the accumulation of plaque. There were increases in vascularization and cellularity and loss of collagen. They recovered 56 days after plaque elimination their baseline level. Electron microscopic examination showed myofibroblastic aspects in some fibroblasts. The changes in the expression of laminin, fibronectin and KL1 in the J.E. might be due to a proliferation rate enhancement, and suggest an adaptation to the alterations brought about by the inflammatory process. They also reinforce the hypothesis that this epithelium resembles a developmental tissue. Type I collagen demonstrated the "collagen loss-repair" cycle shown in connective tissue by the histological study. The rise in type III collagen and the vimentin fall, both at the initial stage, suggest that these protein profiles may yield information for clinical research purposes during the very early inflammatory process. The variations in fibronectin indicate its key role in the early inflammatory and repair processes. Finally, the variations in matrix and cytoskeletal proteins variations, as well as the morphological modifications observed, were nearly all reversible.

Adolescent↗

Platelet-melanoma cell interaction is mediated by the glycoprotein IIb-IIIa complex.

A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa-like GPs. When the melanoma cells were preincubated with LYP 18, tumor-platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions.

Antibodies, Monoclonal↗

[Detection of micrometastases in excised regional lymph nodes in cancer of the breast. Systematic use of KL1 anticytokeratin monoclonal antibodies in a prospective series of 120 T2 N- patients].

A series of 120 patients (T2, No, N1a according to UICC classification) with mammary cancer treated by mastectomy and regional lymph node dissection, classified T2N-after Hemalun-Phloxine Safran (HPS) standard sections, have a positive reaction with immunohistochemical staining (IHM) using monoclonal antibodies (anti KL1) so that IHM improve the detection of lymph node metastases. 13 patients out of 120 presumed N-after HPS technic became positive with IHM staining. We examined 2108 lymph nodes and noticed 19 N+, the size of which was less than 2 millimeters. Microscopically, three main aspects are follows. Micrometastases made of clusters of malignant cells; micrometastases with single cells in file, and a composite aspect from both previous ones. Metastatic cells detected by anti KL1 have an excellent contrast due to clear nucleus surrounded by a large rim of dark cytoplasm. Although T2N-has a better prognosis than T2N+, 10 to 20% of patients relapsed within ten years after surgical treatment. It is important to determine whether the detection of occult micrometastases permits to predict recurrence. Is it a relevant correlation or not? if such a connection does'not exist, micrometastasis detection became irrelevant; on the contrary, if it exists, the therapists can launch on adequate adjuvant treatment - useful only - for patients with high risk of relapse.

Antibodies, Monoclonal↗

[Surface changes of intravenous catheters after antineoplastic chemotherapy].

During long-term venous catheter implantation, septic and thrombotic complications are quite frequent. In the case reported, the failure of systemic and local antibiotic therapy during repeated septicaemia due to Bacillus cereus at the time of intensive chemotherapy led to a scanning electron microscopy study of the used silicone catheter. There were marked changes of the inner surface with a lot of cellular remains, in contrast with the usual non thrombogenic property of the silicone. An in vitro study was carried out with antitumour agents. Duration of exposure and drug concentration were identical to those used in in vivo perfusions. There were marked changes of the inner surface, which could lead to important modifications of the properties of the silicone. The damage depended on the drug. Silicone was slightly sensitive to vicristin and carmustin, but highly sensitive to cisplatin and doxorubicin. The compatibility of catheter material with the drugs used, especially for oncologic chemotherapy, must be tested systematically.

Antineoplastic Agents↗

[Polyurethane catheters and antineoplastic chemotherapy. An experimental study].

An in vitro study of the effect of cytotoxic drugs on polyurethane catheters was carried out. The drugs used--vincristine, doxorubicin, cisplatin and carmustine--damage the surface of silicone elastomer catheters. The irregularities produced seem to be preferential sites for thrombus formation and adhesion of bacterial microcolonies. Electron microscopy examination of the catheters dipped in the drug solutions for different time intervals revealed the appearance of different patterns of damage. The irregularities produced seemed to be less pronounced than for silicone catheters. Polyurethane was highly sensitive to doxorubicin. These changes could well have clinical repercussions. The compatibility of catheters and drugs should be routinely tested before being put on the market.

Antineoplastic Combined Chemotherapy Protocols↗

Paracrine regulation of testicular function.

Data from several experimental approaches have been reviewed and the findings clearly indicate the existence of multiple interactions between testicular cells and the potential role of these interactions in the paracrine control of testicular functions. Both testicular interstitial fluid and spent media from cultured Sertoli cells had an acute steroidogenic effect on Leydig cells, and this effect is not species specific. The secretion of this steroidogenic factor(s), which is probably a protein, is enhanced by previous FSH treatment of Sertoli cells. Coculture for 2-3 days of pig Leydig cells with homologous or heterologous Sertoli cells enhances Leydig cell specific functions (hCG receptor number and hCG responsiveness) and induces Leydig cell hypertrophy. A similar but less pronounced trophic effect is seen when Leydig cells are cultured with spent media from Sertoli cells cultured in the presence of FSH and high concentrations of insulin, but the spent media from Sertoli cells cultured in the absence of these two hormones inhibits Leydig cell specific functions. Somatomedin-C might play an important role in the positive trophic effect of Sertoli cells on Leydig cells, since this peptide is secreted by Sertoli cells and it has trophic effects on the specific function of Leydig cells. Moreover, Sertoli cells, probably through a diffusible factor and cell-to-cell contacts, control the multiplication, meiotic reduction and maturation of germ cells. In turn, the activity of Sertoli cells is modulated by the stage of neighbouring germ cells. Thus, if a normal Sertoli cell function (which depends not only on FSH but also on Leydig and myoid cell secretory products) is an absolute requirement for germ cell multiplication and maturation, these cells, in turn, cyclically regulate Sertoli cell function and through these cells the size and probably the function of Leydig cells.

Animals↗

Paracrine control of Leydig cell activity by FSH dependent proteins from Sertoli cells: an in vitro study.

The regulating effect of follicle-stimulating hormone (FSH) on Leydig cell function was studied using a model of immature porcine Leydig and Sertoli cells cultured in a hormone supplemented defined medium. FSH pretreatment for 2 days of Leydig cells cultured alone was with no effect. FSH pretreatment of Leydig cells cocultured with Sertoli cells increases Leydig cell activity in an FSH dose-dependent manner with a maximal effect observed at 50 ng/ml porcine FSH (pFSH). Leydig cells cultured for 2 days in conditioned medium (CM) by FSH stimulated (FSH-CM) Sertoli cells, as compared to CM by unstimulated (control) (C-CM) Sertoli cells show an increase of their activity with a maximal effect observed at 50 ng/ml pFSH. Leydig cells cultured in CM as compared to non CM, show a marked development of organelles (smooth endoplasmic reticulum and mitochondria) involved in the steroidogenic activity. The activity of FSH-CM as compared to C-CM on Leydig cell function was non dialyzable and trypsin sensitive. These data suggest that Sertoli cells exert a regulatory action on Leydig cell steroidogenic activity via FSH dependent secreted proteins.

Animals↗

Paracrine role of Sertoli cells.

Data from several experimental approaches strongly suggest that Sertoli cells exert a paracrine control of the two main testicular functions, androgen secretion and spermatogenesis. Further evidence supporting this role of Sertoli cells was obtained by coculture of Sertoli cells with other testicular cells. Coculture of pig or rat Sertoli cells with pig Leydig cells produces an increase in the hCG receptor number and an increase in the steroidogenic activity of Leydig cells. Pretreatment with FSH further increases the values of these two parameters. These biochemical changes were associated with ultrastructural changes in Leydig cells. The effects of Sertoli cells on Leydig cells depend upon the ratio of the two cells and on the substrate in which the cells are cultured. Moreover, Leydig cells produce an increase in the FSH receptor number and in the FSH stimulation of plasminogen activator production by Sertoli cells. Coculture of rat or pig Sertoli cells with rat germ cells, induces an increase in the RNA and DNA biosynthetic activities of germ cells. Most of the stimulatory effects seemed to be mediated by diffusible factors, secreted by Sertoli cells, but full expression of the stimulatory action was observed when germ cells were in contact with other cells. In this coculture system, a fraction of rat germ cells containing mainly mature forms of spermatocytes inhibited rat Sertoli cell RNA and DNA synthesis, but had no effect on pig Sertoli cells. On the contrary, a fraction of rat germ cells richer in spermatogonias and preleptotene spermatocytes, stimulated rat Sertoli cell DNA synthesis but was without effect on pig Sertoli cells. These results clearly show that the stimulatory effects of Sertoli cells on Leydig and on germ cells which are not species specific are mediated mainly by diffusible factors, the secretion of which is regulates by FSH.

Animals↗

FSH regulates cultured Leydig cell function via Sertoli cell proteins: an in vitro study.

The effects of follicular stimulating hormone (FSH) on testicular steroidogenic activity has been studied by testing the capacity of conditioned medium (CM) by both unstimulated (control) Sertoli cells (C-CM) and FSH stimulated Sertoli cells (FSH-CM) to influence porcine cultured Leydig cell activity. Leydig cells cultured in FSH-CM for 48 hrs, as compared to C-CM, show a significant (P less than 0.05) increase in [125I]-hCG binding (150% +/- 4) and hCG-stimulated testosterone (T) secretion (266% +/- 42). In addition, the stimulating effect of FSH-CM on Leydig cell function as compared to C-CM, is trypsin sensitive, non dialyzable, heat stable, acid resistant and is chromatographed following gel filtration (Sephadex G 100) into two different peaks of activity. These data suggest that FSH regulates Leydig cell function via (at least two types of) Sertoli cell secreted proteins.

Animals↗

Cultured Sertoli cell-mediated FSH stimulatory effect on Leydig cell steroidogenesis.

To determine the precise role of Sertoli cells in the stimulating effects of follicle stimulating hormone (FSH) on Leydig cell activity, porcine purified Leydig and Sertoli cells were cultured separately or together in a chemically defined medium in the absence or presence of porcine, FSH 50 ng/ml. Leydig cell activity was evaluated using two parameters: human chorionic gonadotropin (hCG) binding sites; and hCG-stimulated cAMP production and testosterone secretion. First, it was found that FSH increases Leydig cell activity in crude Leydig cell preparations (40-60% of Leydig cells), whereas it exerts no effect on purified Leydig cells (greater than 90% of Leydig cells). Second, FSH stimulates the activity of Leydig cells cocultured with Sertoli cells, whereas it remains without effect on purified Leydig cells cultured alone. This stimulating effect of FSH on Leydig cell activity is dependent on the Sertoli cell number in the coculture. These data 1) show that the stimulating effect of FSH on Leydig cell function is mediated by Sertoli cells and 2) support the concept of local control of Leydig cell function originating from Sertoli cells.

Animals↗

Interactions between immature porcine Leydig and Sertoli cells in vitro. An ultrastructural and biochemical study.

Interactions between Leydig and Sertoli cells, as well as a stimulatory effect of FSH on Leydig cell activity, have been reported in many studies. In order to investigate these interactions, the ultrastructure of immature pig Leydig cells under different culture conditions has been studied. When cultured alone in a chemically defined medium, there is a marked regression of the Leydig cell smooth endoplasmic reticulum and a swelling of the mitochondria. Addition of FSH or hCG does not prevent these phenomena. Co-culturing of Leydig cells with Sertoli cells from the same animal maintains the smooth endoplasmic reticulum at the level seen in vivo and in freshly isolated Leydig cells. The addition of FSH to the co-culture stimulates its development and increases Leydig cell activity, as assessed by an increase in hCG binding sites and an increased steroidogenic response to hCG. These results suggest that Sertoli cells exert a trophic effect on Leydig cells, and that the stimulatory effect of FSH on Leydig cell function is mediated via the Sertoli cells. These results reinforce the concept of a local regulatory control of Leydig cell steroidogenesis.

Animals↗