Relationship between P-glycoprotein expression and cyclosporin A in kidney. An immunohistological and cell culture study.

P-glycoprotein (P-gp), encoded in humans by the mdr-1 gene, acts physiologically as an efflux pump to expel hydrophobic substances from cells. This glycoprotein is closely related to multidrug resistance in tumor cells and can be modulated by cyclosporin A (CsA). We investigated the relationship between CsA and P-gp in 52 renal allograft biopsies and in cultures of Madin-Darby canine kidney (MDCK) renal tubule cells to determine whether the intrarenal accumulation of CsA or chronic stimulation with the drug modified the expression of P-gp. Expression of P-gp and CsA was analyzed by immunohistochemistry. Immunostaining was evaluated semiquantitatively. Modulation of P-gp in MDCK cells after chronic stimulation with CsA for 7, 30, and 60 days was analyzed by flow cytometry. P-gp and CsA immunostaining in renal post-transplant biopsies showed considerable overlap in all cases (Spearman's test, r = 0.577, P < 0.001). After 7 days in vitro, the number of cells expressing P-gp increased progressively; a further increase in mean fluorescence was found after 60 days (P < 0.001, Student's t-test). Our findings suggest that in non-neoplastic cells, CsA may stimulate P-gp as a mechanism of detoxification. Individual differences in the adaptive responses to glycoprotein may be responsible for the appearance of nephrotoxicity or a CsA-resistant rejection reaction in cases of overexpression on lymphocytes and macrophages.

Influence of intrarenal deposits of ciclosporin A on acute renal transplant rejection.

Immunohistochemical techniques were used to study the presence of ciclosporin A (CsA) and leukocyte subsets in 36 posttransplant renal biopsy specimens histologically diagnosed as acute graft rejection. Glomeruli from patients with CsA deposits contained more leukocytes (p < 0.05) than glomeruli from tissues without deposits. In contrast, the interstitium from patients without deposits contained significantly more B lymphocytes than interstitia from kidneys with CsA deposits. In both glomeruli and interstitia, the CD4/CD8 ratios were higher in tissues without deposits, although the difference was not significant. The plasma levels of creatinine increased with the intensity of renal CsA deposits, and significantly more patients on hemodialysis had deposits as compared with patients not on hemodialysis. Our findings suggest two types of acute nonvascular rejection: (1) predominantly interstitial, with a good prognosis, characterized by low numbers of intrarenal CsA deposits and a predominance of B lymphocytes and (2) predominantly glomerular, with a poor prognosis, characterized by high levels of intrarenal CsA and a predominance of CD8-positive cells and macrophages.

Immunohistochemical study of 30 cases of cyclosporin A-induced gingival overgrowth.

Immunohistochemical techniques were used to study the presence of cyclosporin A (CsA) and leukocyte subsets in 30 gingival biopsies of renal transplant subjects with gingival overgrowth (GO). Statistical analysis revealed significant differences in the total number of inflammatory cells determined by monoclonal antibody CD45, the monocyte/macrophage (CD68) subset, the plasmatic cells (EMA), and the total of T-lymphocytes (CD3) (P < 0.001, Student t test) between the treated subjects and the healthy control group. Differences were found in the helper/inducer T lymphocytes CD4 (P < 0.001 Student t test) and cytotoxic/suppressor T lymphocyte (CD8) (P < 0.01, Student t test) subsets between both groups. The CD4/CD8 ratio was greater in the transplant subjects than in the control group (1.82 +/- 0.16 versus 1.35 +/- 0.05 respectively) (P < 0.05 Student t test). There was no significant difference in the populations CD16+, CD57+, and CD20+. The CD45+ CD4+, and CD68+ cells increased in number along with the degree of GO. The number of epithelial cells/mm2 which displayed a deposit of CsA increased in accordance with the degree of GO (P < 0.05, Kruskal-Wallis's test). Likewise, the intraepithelial deposit of CsA in the GO region was found to be related to the inflammatory infiltrate CD4+, CD8+, and CD68+ (r = 0.7432; r = 0.7346; r = 0.77005, respectively). Our findings suggest that the intraepithelial deposit of CsA and the inflammatory infiltrate play a predominantly pathogenic role and are both related to the degree of GO.

[Suprarenal carcinoma of an unusual size]. / Carcinoma suprarrenal de tamaño inusual.

Suprarenal carcinoma is an unusual entity, rarely surpassing 4,000 gr. In general, tumors of such big size are not functional. We present a case of a 31-years-old woman with a suprarenal carcinoma weighting 5,200 gr, in which hormonal production was clinically and biochemically demonstrated.

[Lymphomatoid papulosis evolving into malignant lymphoma. Clinico-pathological and immunohistochemical study of 3 cases]. / Papulosis linfomatoide con evolución a linfoma maligno. Estudio clinicopatológico e inmunohistoquímico de 3 casos.

Lymphomatoid papulosis is a disorder characterized by recurrent skin lesions with histological features suggestive of malignant lymphoma. In most cases the cutaneous lesions heal spontaneously but the course of the disease is long-lasting and an evolution into a Hodgkin's disease and non-Hodgkin lymphomas may be seen. We report herein the clinical, pathological and immunohistochemical study of three patients having a long-standing lymphomatoid papulosis, which turned into Hodgkin's disease, mycosis fungoides and nodular paragranuloma, respectively. Immunohistochemical analysis showed that the immunophenotype of atypical cells in lymphomatoid papulosis was similar to that observed in Reed-Sternberg cells in Hodgkin's disease and the neoplastic cells of mycosis fungoides. However, the immunohistochemical profile of cells in lymphomatoid papulosis differed from those observed in cells of nodular paragranuloma, developed by one of the three patients. The relationship between lymphomatoid papulosis and malignant lymphomas associated to lymphomatoid papulosis is discussed. The results show that no definitive criteria can be infered from an immunohistochemical study in lymphomatoid papulosis, in predicting the clinical evolution of the disease.

[Gastric emptying of solids in chronic alcoholic hepatopathy: role of autonomic insufficiency]. / Vaciamiento gástrico de sólidos en la hepatopatía etílica crónica: responsabilidad de la insuficiencia autonómica.

Thirty one subjects are studied, 15 healthy (controls) and 16 presenting chronic alcoholic hepatopathy, in whom the existence of an autonomic insufficiency syndrome (AIS) was evaluated measuring the variations in heart rate while breathing (R index) and after standing up [O(B) index]. Vagal functioning was also studied when evaluating gastric emptying of digestible solids (VGS) and non digestible (VGSND). VGS after 45, 75 and 105 minutes in alcoholic patients was slower than in healthy controls (p less than 0.05) and in 50% of them it was slow after 105 minutes. VGSND was similar in both groups. R and O(B) indexes in alcoholic patients was smaller than in the control group (p less than 0.001), presenting 94% of them some index altered. An elevated percentage of patients suffering chronic alcoholic hepatopathy present a AIS which involves several organs, being R and O(B) indexes a better diagnostic method than VGS study.