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We studied the occurrence of diabetes mellitus in 6 children receiving corticosteroid therapy after renal transplantation. The first hyperglycemic episode occurred in all cases before the fortieth day of treatment but other episodes were observed thereafter. All children were glycosuric, without ketonuria. The diabetes has always been transient, and easily managed with insulin treatment and usual diabetic diet. A glucose tolerance test was performed 3 to 6 months after these episodes; glycemic response to glucose was abnormal in 2 of 6 children; in all cases, the insulin response to the glucose load was inadequate. In 2 children, the fasting blood glucose is still abnormal after a follow-up of 3 years. The other patients have recovered despite sustained corticotherapy. No specific background (genetics, HLA groups) or specific circumstances of treatment were identified. Therefore, we recommend to follow closely glycemia in children after renal transplantation, with a daily glycemic determination especially during the first 3 weeks.

The present study investigates whether the metabolic abnormalities in cystinotic cells could affect nonspecific immune responses. Lymphocytes showed normal antibody-dependent cellular cytotoxicity and natural killer activity. However, cystinotic polymorphonuclear and mononuclear phagocytes exhibited altered oxidative responses as monitored by a luminol dependent chemiluminescence (CL) assay. Both isolated polymorphonuclear and mononuclear phagocytes in the absence of stimuli showed significantly increased CL production which was not found when cells were tested directly within whole blood. CL responses to a panel of stimuli differed markedly according to the type of cells and agents tested. Indeed, isolated polymorphonuclear demonstrated increased CL responses to soluble but not particulate agents, whereas isolated mononuclear phagocytes and overall cell CL responses in whole blood were found to be within the normal range regardless of the type of stimulus used. We also studied some membrane related properties of phagocytic cells. Fc and C3b receptors were normally expressed as tested by erythrocyte-antibody and erythrocyte-antibody-complement rosette-forming cells. Nevertheless, cystinotic polymorphonuclear and mononuclear phagocytes presented decreased random and directed migrations in an under-agarose chemotaxis assay. Finally, cystinotic granulocytes showed an impaired adhesiveness in a nylon fiber assay.

The successful transplantation of a human malignant histiocytosis into nude mice allowed the examination of its atypical histiocytic cell proliferation. Histiocytic type cells were identified by positive reactions with acid phosphatase and non-specific esterase and with anti human DR or OKI1 antisera. Presence of OKT9 antigen and negative results obtained with most OKT antisera, rosettes, erythrophagocytosis and lysozyme corroborate the histiocytic immature state of the cells and preclude another type of tumor. All positive tests to prove a mature mononuclear phagocytic origin were attributable to the murine host cell reaction.

Human polymorphonuclear neutrophils, monocytes, and lymphocytes were studied for their ability to synthesize Paf-acether when stimulated with the ionophore A 23187 (Io) or with specific secretagogues. When stimulated with Io, neutrophils produced 100 +/- 8.5 pmol Paf-acether 1 X 10(6) cells (mean +/- 1 SD, n = 5); monocytes were less efficient (44 +/- 3.3 pmol Paf-acether/1 X 10(6) cells), whereas lymphocytes were practically unable to form this mediator (1.0 +/- 0.4 pmol Paf-acether/1 X 10(6) cells). Neutrophils and monocytes released in the extracellular medium 49 and 37% of Paf-acether that they formed, respectively. We attempted to correlate the amount of Paf-acether produced by the various cell types with that of its precursors, 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine and 1-O-alkyl-sn-glycero-3-phosphocholine (2-lyso Paf-acether). In the three cell types, the amount of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine was sufficient to ensure the formation of 2-lyso Paf-acether and consequently that of Paf-acether. The quantity of 2-lyso Paf-acether formed appeared to be the limiting factor only in the case of the neutrophils. These cells increased their synthesis of Paf-acether in the presence of exogenous 2-lyso Paf-acether. To investigate the failure of lymphocytes to produce the mediator, the acetylating step of Paf-acether formation was studied, and we found a very weak activity (0.5 +/- 0.1 nmol Paf-acether/10 min/mg protein) in this cell type as opposed to monocytes (4.0 +/- 2.3 nmol Paf-acether/10 min/mg protein) and neutrophils (17.8 +/- 5.3 nmol Paf-acether/10 min/mg protein). These activities were doubled in Io-stimulated cells. Thus, the modulation of acetyl-transferase activity appears to be a key step in the regulation of Paf-acether biosynthesis. Also, the availability of 2-lyso Paf-acether could regulate Paf-acether synthesis in human neutrophils.

Three human lymphocyte differentiation antigens, specific of the entire T-cell population, of the helper/inducer T-cell subset, and of the cytotoxic/suppressor T-cell subset have been identified, using mouse monoclonal antibodies obtained from Dr. P. Kung. Various T-cell populations were radio-labelled, the antigens were isolated by immunoprecipitation with the monoclonal antibodies and the resulting immune complexes subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The OKT3 antigen, present on peripheral T-lymphocytes and on functionally mature thymocytes has been identified as an oligomeric protein, composed of 23,000 mol. wt subunits. The OKT4 antigen, specific for the helper/inducer subset, is a single protein of 53,000 mol. wt. The OKT8/OKT5 antigen, defining the cytotoxic/suppressor subpopulation is composed of two subunits of 31,000 and 33,000. From co-capping experiments and biochemical data, the hypothesis is established that OKT5 recognizes a dimer of 140,000 mol. wt and OKT8 recognizes a determinant present on both the monomer 70,000 and the dimer. This hypothesis could explain the OKT5- OKT8+ phenotype of some T-cells.

The effects of intravenous Nitrogen Mustard (NM), given with a total cumulative dose of 0.8 mg/kg BW, were studied in 60 children with idiopathic nephrotic syndrome (INS). Thirty patients were frequent relapser with corticosteroid dependence. In this group the actuarial remission rate was 43, 30 and 15% after 1, 2 and 3 years respectively. The relapse rate per year was decreased from 2.76 +/- 1.56 to 0.88 +/- 0.79 after NM. Ten of the 17 patients showing a partial response to steroids went into complete remission after NM but 6 of them relapsed. Of the 13 patients who did not respond to steroids only 3 went into remission for a short time. Vomiting and leukopenia were noted in one third of cases. The data indicate that NM may improve the course of corticosteroid dependent INS, being less effective in partial responders and probably without effect in non responders.

Thirty-five children (12 girls, 23 boys), aged from 1 year and 5 months to 14 years at the onset of idiopathic nephrotic syndrome, received cyclosporin A (CyA) because of steroid toxicity or failure to respond to steroids. The initial oral dose was 6 mg/kg per day and this was adjusted to obtain trough plasma levels of 50-150 ng/ml. The duration of treatment was between 2 and 8 months. In patients who responded to CyA treatment, the dosage was tapered off; treatment was stopped if found to be ineffective. Of the 35 children, 20 were frequent-relapsing steroid responders who suffered serious side-effects from steroid therapy. Seventeen of them either went into remission or did not relapse despite the withdrawal of prednisone. Prednisone doses could be lowered but not stopped in 1 patient and the remaining 2 patients relapsed when prednisone was tapered off. At the final examination, 10 of the 12 children in whom CyA was tapered off and who had initially responded to CyA had relapsed. A second course was given to these 10 patients and 3 failed to respond. Five children were partial steroid responders and CyA induced a remission in 1 and a partial remission in another. Among the 10 children who were steroid resistant, only 1 responded to CyA, 2 had a partial response and 7 failed to respond to CyA. A reduction of glomerular filtration rate occurred in 8 patients, 7 of whom had either persistent nephrotic syndrome or were in relapse, which suggests that factors other than CyA nephrotoxicity may have been operative. Complete reversal occurred in only 4 patients. Significant histological changes, likely to be related to CyA, were seen in 2 repeat renal biopsies out of the 11 performed.