[Orthotopic autografts of ovarian slices in pregnant rats]. / Autogreffes orthotopiques de fragments ovariens chez le rat avec grossesses.

We carried out orthotopic autografts of ovarian tissue on 15 Wistar rats. One ovary has been removed and cut in 2 or 3 slices. The other ovary has been removed, and the controlateral slices grafted in the empty ovarian bursa by mean of a microscope, without vascular anastomosis. The endocrine function of the graft was assessed by checking the vaginal smears. The animals were mated. Two of them became pregnant with normal offsprings, two others has vaginal bleeding which could be miscarriages. This experimentation suggests that the orthotopic autograft of ovarian slices is possible in rats. The endocrine function of the ovary is restored with a very good rate. Fertility is restored for a small proportion of animals.

[Immunohistochemical study of lesions in Horton's temporal arteritis before and during corticotherapy]. / Etude immunohistochimique des lésions d'artérite temporale de Horton avant et au cours de la corticothérapie.

The immunohistochemical study was performed on temporal artery biopsies from eight patients with giant cell (temporal) arteritis: three before treatment, four after a short period of corticosteroid therapy (from 1 day to 7 days) and one during relapse occurring after a treatment of 9 years; from four subjects with clinical symptoms but without histological features of giant cell arteritis and from five negative controls. Before treatment, biopsies of patients with temporal arteritis showed an inflammatory infiltrate with macrophages and T cells, essentially CD4+ and memory T cells (CD45 RO+), expressing the markers of activation IL2 receptor and HLA DR. Few B and NK cells were also detected. Adhesion molecules, LFA1 and I-CAM1, were strongly expressed by T cells and macrophages. In contrast, the ligand to the CD2, the CD58 marker, was rarely detected. These immunohistochemical features were also observed after a short corticosteroid treatment (by intravenous methylprednisolone or oral prednisone), with presence of activated T cells, memory T cells, macrophages and I-CAM1 and LFA1 expressing cells in the infiltrate. A temporal biopsy, performed after a long time of corticosteroid therapy, showed activated T cells, macrophages and memory cells in o,ne arteriole. In controls, this study showed some mononuclear cells dispersed in intima and adventia, but without activated or memory T cells. Our results support the presence of immune local response in temporal arteritis, incompletely improved by a short corticosteroid treatment.

[Neuroendocrine primary cutaneous carcinoma. Therapeutic aspects in 13 patients]. / Carcinomes neuro-endocrines cutanés primitifs. Aspects thérapeutiques chez 13 malades.

INTRODUCTION: Since the description by Toker in 1972, neuroendocrine carcinoma or Merkel cell carcinoma, is a well identified clinical entity although the appropriate treatment is still debated. Wide surgical exeresis is indicated as first line treatment in all cases but the question concerning protocols for adjuvant radiotherapy or chemotherapy remains open. We analyzed retrospectively our series of 13 patients with neuroendocrine carcinoma looking for an association between radiotherapy and surgery. PATIENTS: There were 7 women and 6 men in our study population (age range 43-88 years). Two cancers of the rectum and one prostate cancer were associated. In 6 cases, the tumor was localized on the limbs, in 5 on the face and in 2 on the buttocks. Mean delay to diagnosis was 2.5 months. At diagnosis, only 1 patient had satellite nodes. The pathology examination evidenced intermediary cell type and architecture. Immunohistochemistry tests were positive for NSE, NF, KII and the ultrastructure confirmed the diagnosis. Nine patients were treated with surgical exeresis with wide 1 cm margins and was completed with radiotherapy of the tumoral bed at homogeneous doses of 45 to 60 Gy. Surgery alone was used in 4 patients. RESULTS: Mean follow-up was 27 months (5-98). Among the 13 operated patients, 11 have survived, 1 died due to the neoplasia and in 1 other from another cause. Local and regional recurrence rate after exercise alone was 50 p. 100 (2/4) with concomitant development of metastasis in both cases. When local or locoregional post-operative radiotherapy was given, local or regional recurrence rate was 33 p. 100 (2/6). DISCUSSION: Cutaneous neuroendocrine carcinoma or Merkel cell carcinoma is an uncommon skin tumor. It is difficult to determine the management protocol on the basis of data in the literature. Due to risk of locoregional recurrence, we currently propose post-operative radiotherapy of the tumor bed and drainage nodes in all patients.

Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA).

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.

[Inguinal mastocytosis with histiocytic infiltrate]. / Mastocytose inguinale avec infiltrat histiocytaire.

INTRODUCTION: The diagnosis of mastocytosis is usually not difficult in cases with typical skin lesions. Intertrigo is exceptional. CASE REPORT: An 83-year-old patient developed inguinal intertrigo bilaterally. The lesions contained maculopapulous elements without Darier's sign. The histology examination revealed a mixed mast cell infiltration predominated by histiocytes. The ultrastructure confirmed the diagnosis of cutaneous mastocytosis. No extension was observed. DISCUSSION: Skin folds are rarely involved in infiltrating diffuse mastocytosis. Two cases have been reported in the literature including one doubtful case. Mastocytosis should thus be included in the possible diagnoses in patients with macupopapulous intertrigo. In addition, the mastocytic and histiocytic polymorphism observed here is rare.

[Cutaneous reactions to gold salts]. / Réactions cutanées aux sels d'or.

OBJECTIVE: Evaluate the clinical features of skin reactions to gold salts. INTRODUCTION: Gold dermatitis is described in the literature as a group of reactions non-specifically associated with these drugs. PATIENTS AND METHODS: Ten patients (7 males, 3 females, mean age 59.6 years [corrected] with a skin reaction were studied over a 6 year period. All were treated with Allochrysine for rheumatoid arthritis (n = 8), rhizomelic pseudopolyarthritis (n = 1) or arthropathic psoriasis (n = 1). RESULTS: The delay to the first signs was from 2 weeks to 8 months. Three lichenoid eruptions (including two with buccal lesions and two which followed an autonomous course), 2 pityriasis rosea (one with eosinophilia and one with liver disease), 2 eczematoid dermatoses and one urticaria were observed. Pathology examinations (8/10) were in agreement with clinical diagnosis. Imputability was 14 (1 case), 13 (8 cases) and 12 (1 case). DISCUSSION: The clinical features observed were variable and in agreement with a particular clinical situation. They were not specific to gold salts and cannot be qualified as "gold dermatitis". Two autonomous and severe lichenoid eruptions were observed. Generalized lesions were associated with biological signs. This situation must be considered as a marker of severity.

Production of interleukin 6 by granulomas of giant cell arteritis.

IL-6 serum levels are increased in patients suffering from GCA, and this cytokine may play a role in the systemic symptoms associated with this disease. We analyzed by in situ hybridization and immunohistochemistry whether IL-6 production originates from arterial granulomas in GCA. Seven arterial biopsy specimens taken from patients with histologically proved GCA were studied. IL-6 production was detected in all cases at both the mRNA and the protein levels. IL-6-producing cells were distributed in the intima, in the media, and in the adventitia. Positive cells were clearly enriched in the media, however, and particularly in contact with the internal elastic lamina. The morphology of the IL-6-producing cells showed that they belonged to several cell populations. In the media, most IL-6-producing cells were macrophages, whereas fibroblasts also produced IL-6 in the intima. Neither endothelial cells nor giant cells were found to express the IL-6 gene. Increased IL-6 serum concentrations returned to normal levels in most patients after administration of corticosteroids, indicating that inhibition of IL-6 production by GCA granuloma cells may be one of the mechanisms of action of corticosteroids in this condition. Production of IL-6 in abnormal arteries may thus participate to the systemic manifestations of GCA.

[Immunohistochemical study of lesions of temporal arteritis in Horton's disease]. / Etude en immunohistochimie des lésions d'artérite temporale de la maladie de Horton.

Fourteen monoclonal antibodies were used to immunohistochemically label 22 temporal artery biopsy specimens taken from patients with temporal arteritis before treatment (n = 10), after 1.3 days of corticotherapy (n = 6) and after 12-30 days of steroids (n = 6). Histological sections from untreated patients revealed an inflammatory infiltrate comprised of approximately equal proportions of macrophages and T lymphocytes; the majority of the latter belonged to the CD4+ subset (the CD4+/CD8+ ratio varied from 2/1 to 4/1, depending upon the biopsy). These cells expressed high levels of HLA DR and low levels of interleukin-2 (IL2) receptors. A few B lymphocytes and plasmocytes were seen, mainly in the adventitia. Antigen-presenting cells (APC) were always found in the damaged media and natural killer cells (few in number) were sometimes present. Some macrophages were positively immunolabeled for IL6. A short, 1-to-3-day course of corticosteroids did not appreciably modify the lesions: cells remained highly activated, APC were seen in half the biopsies and IL6 immunolabeling persisted. The findings were essentially the same in treated but poorly controlled patients. Biopsies from 2 patients in clinical and biological remission revealed the persistence of an active immunological process. These observations indicate that the immunological process is poorly controlled by corticosteroid therapy.

Inhibitory effects of AcSDKP on the mixed lymphocyte reaction (MLR). Part I. MLR with mouse spleen cells.

AcSDKP (inhibitor of entry into cycle of pluripotent hemopoietic stem cells) is able to decrease mixed lymphocyte reaction intensity when H-2 incompatible allogeneic spleen cells are used as stimulators. This is a first approach to determining whether AcSDKP has potential therapeutic value for clinical bone marrow transplantation.

Inhibitory effects of AcSDKP on the mixed lymphocyte reaction (MLR). Part II. Human whole blood cells.

AcSDKP is a physiological negative regulator of hematopoietic stem cell proliferation. To investigate the applicability of AcSDKP in the prevention of graft-versus-host disease, this tetrapeptide was tested in mice and showed an inhibitory effect on the mixed lymphocyte reaction (MLR). In this paper we report MLR using human whole blood cells. The maximum inhibitory effect (50%) was obtained at 2.5 ng/ml AcSDKP. All experiments showed a constant dose response. Experiments are now being conducted to elucidate the mechanism of this inhibition.

Constitutive IL-2 expression in HTLV-I-infected leukaemic T cell lines.

An IL-2 autocrine growth circuit has been proposed as a major mechanism in HTLV-I-related leukaemogenesis. We have developed a polymerase chain reaction combined with reverse transcription RT-PCR to detect IL-2 transcripts and a sensitive immunostaining method for IL-2 protein. Combination of these two methods with in situ hybridization demonstrated that most cells of the T cell line IARC 301.5, whose proliferation is stimulated by autocrine IL-2, constitutively synthesize IL-2. This pattern was also found in the HTLV-I T cell lines HUT, MT2 and C 8166/45, and in the HTLV-I-negative T cell lines Jurkat and HSB2 but not MOLT4. Four non-lymphoid cell lines and cultured fibroblasts were negative, in agreement with the T cell specificity of IL-2 synthesis. Hence, most T cell lines tested, whether HTLV-I-infected or not, constitutively synthesize IL-2, suggesting a possible common feature of leukaemic T cell lines. The presence of IL-2 transcript and protein in most cells of the reacting cell lines is consistent with an autocrine process possibly involved at some stage in acquiring growth autonomy.