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The effect of several natural products of Stevia rebaudiana on glucose production and oxygen uptake in rat renal cortical tubules was investigated. Steviol, isosteviol and glucosilsteviol decreased glucose production and inhibited oxygen uptake. The sweet principle stevioside, and steviolbioside, however, were without effect on gluconeogenesis and oxygen uptake.

The phosphorylation and dephosphorylation of proteins in neutrophils from normal children and patients with chronic granulomatous disease (CGD) were studied with two-dimensional gel electrophoresis and autoradiography, followed by densitometric scanning. In normal neutrophils the radioactivities of 11 spots among approximately 50 radioactive spots were changed by stimulation with phorbol 12-myristate 13-acetate (PMA) and 6 of the 11 spots were also changed by stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP) and NaF. The phosphorylation of only two spots (Mr = 48 000 and 62 000) was inhibited by 2-deoxyglucose and N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W-7), which inhibits superoxide production, while it was not affected by dibutyryl cAMP, KCN and ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA), which do not affect superoxide production. The observation indicates that the Mr = 48 000 and 62 000 proteins may be involved in the activation process of superoxide production. When the neutrophils of four male and two female CGD patients were examined, the changes in 11 spots on stimulation were similar to those of normal children, indicating that the (de)phosphorylation of the proteins which seems to be involved in the activation process is not affected in CGD neutrophils.

Adult and fetal human kidneys were investigated for the reactivities of monoclonal antibodies, BA-1, BA-2 and BA-3 against human leukocytes. In developing metanephros, their reactivities changed reflecting the stage of nephrogenesis. Thus BA-1 stained both metanephric blastema and ureteric bud. Glomerular and proximal tubular development was characterized by the disappearance of BA-1 reactive antigen and the appearance of CALLA defined by BA-3. Immuno-electron-microscopically CALLA was solely located on the glomerular epithelial membrane and on the microvilli of the proximal tubules. BA-2 constantly stained ureteric bud-derived tissues. These observations were applied for the analysis of histogenesis of Wilms' tumour. Tumour blastema of the classical type reacted only with BA-1. Epithelial components in the classical as well as the epithelial type reacted both with BA-1 and BA-2. CALLA was only detectable in glomeruloid and the connecting tubular structures, while these were unstained by BA-1. Stromal components in the classical and the sarcomatous type did not express any of these antigens. Staining patterns were identical in surgically removed and xenotransplanted tumours. These studies establish that each component of Wilms' tumour can clearly be interpreted regarding its histogenesis and that epithelial components corresponding to proximal tubules are identified in Wilms' tumour.

We have developed a mouse monoclonal antibody 5C11 (IgG2a) against cell surface antigen of Ewing's sarcoma (ES). 5C11 specifically reacted with ESs but not with other small round cell tumours in childhood, i.e. neuroblastomas, primitive neuroectodermal tumours (PNETs), rhabdomyosarcomas and malignant lymphomas. 5C11 did not react with any other tumours in children except for hepatoblastomas. No reactivity has been identified in normal tissues with the exception of fetal hepatocytes. Immunoelectron microscopically, 5C11 reactive antigen was located on cell membrane of ES cells. Biochemically, 5C11 immunoprecipitated a cell surface protein having molecular weight of 81,000 Da. 5C11 is the first antibody which can clearly distinguish ES from neurogenic tumours, especially from PNETs which were recently reported to have common features to ESs regarding chromosal abnormality and proto-oncogene expression but show evident differentiation into neurogenic direction. The results strongly indicate the usefulness of 5C11 not only for diagnostic purpose when no specific marker is available but also for studying the histogenesis of ES. In addition, no reactivity in normal tissue implies its potential application as a therapeutic reagent when the management of ES patients is still a great problem in clinical field.

Two infants with malignant histiocytosis, as diagnosed by morphological and cytochemical examinations of malignant cells infiltrating pleural effusion, skin, and bone marrow, are described. Surface marker analysis of the malignant cells with monoclonal antibodies showed these cells to express markers of T-lymphocytes and HLA-DR antigen, but not those of B-lymphocytes, granulocytes, or monocytes. These immunological findings demonstrated that the neoplastic cells in malignant histiocytosis of infancy may be of T-cell origin, rather than histiocytic or monocytic origin.

Seventeen cases of pediatric malignant neoplasm with pulmonary and/or pleural lesions shown by chest radiography at initial diagnosis were reviewed and analyzed. Respiratory symptoms such as dyspnea, tachypnea, and chest pain were observed on admission in approximately one-half of them. The initial chest radiography showed pleural lesions in 7 of the 17, pulmonary lesions in 8, and both pulmonary and pleural lesions in 2. Unilateral or bilateral pleural fluids were observed in all of the seven patients with pleural lesions, and malignant cells were confirmed in the pleural fluid of all patients. The radiographic patterns of the eight patients with pulmonary lesions were solitary nodule in two, multiple nodules in two, diffuse miliary nodules in three, and diffuse honeycomb in one. Histological examination of the pulmonary lesion was performed in six patients at the initial diagnosis or after death, while in the remaining two primary or other metastatic sites were examined. The two patients with both pulmonary and pleural lesions showed multiple nodules or infiltrates with pleural fluid on chest radiography. Increased malignant cells were detected in the pleural fluid of both patients. In all cases, the lesions gradually or rapidly disappeared with multidrug chemotherapy. The review confirms the need for a combination of complete radiographic and pathological analysis at the time of initial diagnosis of malignant neoplasm in children to distinguish other causes such as infectious complications.

Surface marker analysis of atypical cells, present at elevated levels in the peripheral blood of a 2-yr-old patient with familial erythrophagocytic lymphohistiocytosis (FEL), was performed with monoclonal antibodies. The atypical cells expressed T11, T8, Ia and LeuM2 antigens, markers of suppressor/cytotoxic T lymphocyte and monocyte. The monoclonal antibody-defined surface markers were thus distinguishable from those of other lymphoproliferative disorders clinically resembling FEL.