Organ culture in the study of human tumors with special reference to nephroblastoma.
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Biomedical subjects
Publications and source records attributed to C Nezelof.
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We have studied by ultrastructural histo-autoradiography, in a primary immunological response, the behavior of three types of guinea-pig histiocytic cells exposed to 125I-flagellin, lymph node histiocytes, alveolar macrophages and skin Langerhans cells, making use of the experimental model of Nossal et al. (1964). Whereas latero cave lymph node histiocytes exposed to 125I-flagellin by in vivo injection of the labelled antigen into the hind foot of the guinea-pig trap the flagellin as do 20% of alveolar macrophages incubated in vitro in a culture medium containing 125I-flagellin, skin Langerhans cells exposed in vivo (intradermal and hypodermal injection of the antigen) and in vitro, as was done for alveolar macrophages, are never labelled. These results suggest that, despite the fact that it belongs to the mononuclear phagocytic system, the Langerhans cell is not a common essentially phagocytic macrophage but represents a cell lineage involved in more complex immune reactions requiring the cooperation of sensitized lymphocytes.
The authors discuss the W.H.O. classification of neoplastic disorders of lymphatic and haematopoietic tissue proposed by G. Mathé and H. Rappaport. They note the points in common with previously published new classifications and make a number of remarks and criticisms. They stress the point most open to discussion: maintenance of the concept of reticulosarcoma. They propose the parallel use of several classifications, including the old nomenclature of Rappaport, in routine histopathology during the comming years.
A case of Krabbe's leucodystrophy is reported after photon and delayed ultrastructural microscopic study. Cerebroside overload within the cerebral globoid cells was shown as well as in the interstitial histiocytic infiltration of the peripheral nerves. Reviewed with the published literature, the characteristics of the inclusions observed seem to be unspecific and, from a morphological standpoint, Krabbe's disease may be related to the gangliosidoses.
Following exposure to phorbol ester (TPA), DEL cell line, a human malignant histiocytosis (MH) cell line, is able to differentiate along a macrophage phenotype and thus it provides a suitable model for analyzing the sequential and differential gene expression associated with monocyte/macrophage differentiation. C-myc, c-myb, c-fos, c-sis and c-fms expression were determined by Northern analysis at various times following TPA treatment. The results showed that TPA down-modulated the constitutive expression of c-myc, c-myb, and c-fms, mRNA to low but still detectable levels. Conversely, TPA-induced differentiation resulted in transient appearance of c-fos, whereas no change in the level of c-sis and actin transcripts were observed. Thus, the c-fms and c-sis genes appear to be regulated in a specific manner in this malignant histiocytosis derived cell line. Furthermore, these investigations demonstrated a constitutive CSF-1 gene expression which transiently increased at mRNA and also at protein level as evaluated by a murine bone marrow CFU bioassay. Through this drug-induced modulation, the DEL cell line offers an additional model for studying some of the subtle interrelations existing between a growth factor (CSF-1) and its receptor (c-fms) in the monocyte/macrophage system.
The production of TNF-alpha and IL-1 alpha and beta molecules has been shown to be associated with the proliferation and activation of cells of the monocyte/macrophage series, the intermediate steps in the synthesis of these molecules have been less investigated. Unstimulated and TPA stimulated DEL cells (a CD30-positive, t(5;6)(q35;p21) malignant histiocytosis cell line) were used to study the expression of TNF-alpha and IL-1 genes and to evaluate, by nuclear run-on assay and biological measurements, the control of their transcription and the level of protein production. To refine this analysis, the effects of cycloheximide and actinomycin D were also evaluated in this investigation. Following TPA stimulation, transcription of TNF-alpha (constitutively present) increased threefold as early as 30 mins and started decreasing by 24h. Cycloheximide superinduced the expression of TNF-alpha mRNA and, accordingly, the release of its protein. By contrast, transcription of IL-1 molecules appeared de novo and did not result in a biologically detectable protein. Measurements of RNA half line after actinomycin D indicated that TNF-a and IL-1 alpha mRNAs are not as stable as that of IL-1 beta. These results indicate that, despite their common synergistic activity, the transcriptional and post-transcriptional mechanisms regulating the synthesis of TNF-alpha and IL-1 alpha and IL-1 beta involve different pathways.