The intestinal chalones 1 and 2, extracted from the intestine of the adult newt, are known to inhibit the G1 and G2 phases of the cell cycle in the embryonic intestine. The effects of these intestinal chalones on the proliferation and differentiation of intestinal cells of newt embryos were studied with special attention to the dose-response relationship, the embryonic stage and the duration of treatment. The chalone 2 triggered a linear, dose-dependent inhibition between two concentration thresholds; nevertheless about 25% of the cycling cells were not inhibited either by the highest doses injected or by repeated injections. Sensitivity to chalone 2 appeared in the intestinal epithelium at the end of embryonic development (stage 34) but the cells were not delayed in the G2 phase for more than about 20 h in spite of repeated injections. It was inferred from the doseresponse curve of the mitotic inhibition by chalone 1, that the intestinal cell population was heterogeneous: about 50% of the cycling cells were inhibited by low concentrations of chalone 1; an additional proportion of about 25% of cycling cells was inhibited by 100 x more concentrated chalone 1 and the remaining 25% was insensitive to the inhibitor. Repeated injections of chalone 1 blocked about 50% of the cycling cells definitively in the G1 phase, speeded up digestion of yolk platelets, promoted the differentiation of goblet cells and depressed the number of stem cells in the proliferative compartment located beneath the epithelium. A kinetics model of cell proliferation and cell differentiation in the intestinal cell lineages was elaborated and it was suggested that the arrest of mitotic activity and the completion of differentiation in an embryonic cell depends on two incoming signals: one is intracellular and appears when the required number of cell cycles has occured in the cell lineage, leading to a committed stem cell sufficiently differentiated to synthesise chalone and to respond to chalone; the other signal is extracellular and appears when the chalone concentration is high enough: i.e. when the required number of cells is obtained in this tissue.

Differentiation of the intestinal epithelium ofPleurodeles occurs during the last period of embryogenesis (stage 34) and is completed during the first stages of larval development before the onset of feeding (stage 37). In the course of this 4-day period the intestinal epithelium, which is a closed endodermal cylinder at stage 34, becomes a functional epithelium constituted by columnar absorbing cells and goblet cells. During intestinal differentiation, the cell number rises although the growth fraction decreases from 52% to 22%. At stage 34, mitoses are randomly distributed throughout the endoderm, but at stage 36 they become confined to cell nests which appear beneath the epithelium.The cell nests correspond to the proliferating compartment which produces an equal number of dividing cells and of resting cells: these cells are arrested in the G1 phase of the generative cycle and differentiate. Such a pattern of proliferation and differentiation maintains a constant number of proliferating stem cells which subserve the renewing function in the intestinal epithelium after the onset of feeding. The relationships between cell proliferation and differentiation in the developing intestinal epithelium ofPleurodeles are closely similar to those observed in Mammals and suggest particularly that the intestinal cell nests of Urodela are analogous to the crypts of Lieberkühn in higher Vertebrates.

Changes in the intestinal wall ofAlytes obstetricans (Amphibia, Anura) were quantified during thyroxine treatment. The relative proportion of each intestinal wall component was determined in tissue sections. Autoradiographic studies on intestine with3H-thymidine revealed the distribution and frequency of labeled nuclei.The labeling index in the primary epithelium falls to zero by 3 days. Thyroxine treatment induces a decrease in the growth rate of this tissue, just before its degeneration and complete elimination by 14 days.Three days after T4-treatment, a secondary epithelium develops from basal stem cells. Its labeling index rises to a maximum of about 50% by 9 days, and thereafter declines. Cell proliferation is less marked in the extraepithelial zone, which nevertheless thickens during this thyroxine-induced metamorphosis.

In irradiated mice engrafted with hemopoietic cells, the thymus is repopulated more rapidly by bone marrow-derived than by spleen-derived cells. Admixing thymic cells with the restorative suspension stimulates the thymic repopulation by spleen-derived cells whereas it has no effect on the repopulation by bone marrow-derived cells.

Following injection of bone marrow cells in lethally irradiated mice, previously infected with BCG regenerating hemopoietic cell populations differentiate along the leucocyte pathway to the detriment of erythroid lineage. Such a phenomenon persisting even if anemia of infected mice is increased by bleeding just before irradiation and reconstitution supports the hypothesis of preferential differentiation of stem cells.

The author described a case of extensive total hemispherectomy extending to the red nucleus, gave a review of the literature of such conditions together with a brief historical review. He analysed in detail the secondary degenerative changes of the nervous tracts within the brainstem. The histological study of the remaining hemisphere, the cerebellum and the membranes revealed the following: 1) a false sub-dural membrane within the surgical space, proliferation of the arachnoidal cells and a granular ependymitis, changes which were interpreted as an attempt to fill the empty space resulting from the operation; 2) an inflammatory meningo-encephalitis with rare intra-nuclear inclusions quite suggestive of a reaction due to a slow virus or of a slow resorptive process. From a clinico-pathological point of view, this case, an almost experimental model, illustrated the possibility that only one hypothalamus would be sufficient to maintain a good hormonal equilibrium.

The authors report two new cases of encephalitis occurring in association with immunity deficiency. The first concerns a child suffering from Bruton type congenital hypogammaglobulinemia. Histological examination of the brain under light microscopy shows important lesions of panencephalitis with parenchymal atrophy : the latter was more marked in the cerebellar lamellae. Ultra-structural examination showed numerous nuclear bodies in the nuclei of the macroglial cells and tubular inclusions situated in the cytoplasm of the capillary endothelial cells. The second case is that of a man of 44 years of age who had undergone a kidney transplant for malignant arterial hypertension, who after 3 months immunodepressive treatment suffered from temporo-spatial confusion together with a pyramidal tract syndrome. He died after 3 weeks evolution of the disease. Microscopical examination of the encephalon showed the presence of microglial nodules with aspects of neurophagia, suggestive of a polioencephalitis. These lesions were situated in the temporal cortex and the brain stem. The lymphocytic reaction was very slight in the second case.

The role played by different components of thymic microenvironment in T-cell-maturation is examined: antibodies to a soluble thymic factor (STF) were thus shown to inhibit T-cell maturation in the chicken while incubation of bursal "null" cells with STF could induce the differentiation of some of them into T cells. In addition to STF, whose properties resemble those of other soluble thymic factors, an insoluble thymic factor (ITF) is described: it is localized mainly in membranes associated with medullary blood vessels, and its injection to mice provokes an influx of marrow stem cells into the thymus.

The host-virus interactions of several murine C type viruses with cell lines established in vitro from a mouse teratocarcinoma were studied. The cells used in this study were the multipotential stem cells, or embryonal carcinoma cells, and the differentiated cells derived from a same tumor.

Following the intravenous injection of 1 mg of BCG into Mice an anemia with erythroblastopenia is observed in spite of a high level of erythropoietin. A preferential differentiation of hematopoietic stem cells to leucocytes is observed with a concomitant of the differentiation to erythrocytes.

After a short description of the gastro-intestinal syndrome (for a single "acute" irradiation) and a discussion of the importance of fractionation in radiotherapy, the authors report their experimental results on intestinal tolerance in mice after fractionated irradiation. Intestinal tolerance was assessed from LD50 after abdomen irradiation. Variation of LD50 was first studied as a function of the fraction number N (keeping constant the overall time T). From these data iso-effect curves were calculated which can be used for clinical applications for correcting the total dose when the fraction number has to be modified (for T constant). In a second series of experiments, variation of LD50 was studied as a function of overall time T (keeping constant the fraction number N), this study confirms the large recovery capability of the intestinal mucosa, which is due to the combination of 2 mechanisms: shortening of the mitotic cycle of the surviving stem cells and increase of the size of the stem cell compartment. These 2 mechanisms were evaluated quantitatively for a fractionated irradiation. The data obtained for intestine are compared to similar data obtained for other tissues (skin, lung). The authors emphasize the risk of applying to late effects the conclusions obtained for early effets.

The authors report two anatomo-clinical cases of striato-nigral degeneration with trial of L-Dopa; one of them included an olivoponto-cerebellar degeneration. The features of this degeneration are compared with the literature and related to heredo-degenerative diseases of the nervous system.

One and two months after section of the hypophyseal stalk in the male frog. Rana esculenta, and involution of numerous gonadotrophic cells, contrasting with the normal aspect of the eosinophilic cells can be observed.

Bone marrow suspensions from non hematologic patients have been cultured in methyl cellulose, with conditioned medium prepared with normal peripheral blood cells. The granulocytic-monocytic colony forming cell (G-CFC) can give rise to colonies, which were counted on the 14th day. The mean G-CFC number is 38 +/- 26 when 2.10(5) cells are cultured. The striking disparity from one patient to an other cannot be explained by the culture conditions, nor by the clinical status. There is no sex difference; older patients have a significant reduction of the colony numbers compared to younger patients.

Grafting of haemopoietic organs was performed at several developmental stages between diploid and autotetraploid individuals of Pleurodeles waltlii. The difference in size between diploid and tetraploid cells is so obvious that their identification is possible by direct microscopic examination. To avoid immunological rejection, the grafts have been made with inbred animals. 2. After grafting the spleen, the host cells are observed to colonize it. This phenomenon is more important with spleens from donors at early stages of development. When the spleen from a late larval stage or a metamorphosed animal is transplanted into another larva, the blood of the latter contains 66 or 72% erythrocytes originating from the graft. 3. Embryonic liver grafting is followed by a colonization of all haemopoietic organs by cells originating from the granulopoietic tissue of the graft. The proportion of grafted blood cells is then very high. A liver graft performed at a larval stage gives qualitatively similar results but the numbers of cells originating from the graft are lower. A survey of intra-cardiac erythropoiesis in these animals shows that it develops from stream blood cells and not from cardiac endothelial cells. 4. After thymus graft, the lymphoid part of the organ is replaced by the host cells. 5. From these results, it is suggested that the granulopoietic liver tissue contains one or several kinds of stem cells which could differentiate into all types of blood cells.

Irradiated chicken are injected with haemopoietic tissues from adult or 11-day-old embryos. Development of stem cells gives rise to well-defined erythrocytic colonies on the surface of the tibial marrow. Erythropoietic production appears to be similar from adult marrow and embryonic blood stem cells; production from injected vitelline stem cells seems to be between 3 and 4 times higher than that of adult marrow stem cells. Results are discussed on the basis of two hypotheses: -existence of an extramedullary erythropoietic site in the host after vitelline cells grafting; -development of vitelline stem cells in the host marrow with kinetic patterns different from those of grafted adult marrow or embryonic blood stem cells. Anyway, the 11-day-old embryo appears to contain at least two types of blood stem cells with distinctive properties. Developmental origin, relationship and future of these different stem cells remain to be analysed.

Bone marrow from a child with Chediak-Higashi-Steinbrinck disease was cultured. It was found that all cells with granulocytic colony forming ability were affected by the disease. Cytoplasmic vacuoles were identified as lysosomes by their cytochemical staining. The cloning rates suggest that granulopoiesis is largely ineffective.

The neutrophil granulocytes are derived, in the present state of our knowledge, from a hemocytoblast identical with that of the other blood cells, defined by its power to form in vivo clones of multiple composition, defining their characteristic of totipotential undifferentiated cell. The way in which the clone-forming cell evolves in vivo towards granulopoiesis, depends on a genetic factor, phenomena of derepression and an extrinsic factor, the origin of which is probably cellular. Differentiation of the hemocytoblast leads to a cell, the destiny of which is then fixed, which may then form clones in vitro in semi-solid medium (clone-forming cell in vitro or CFC). This cell is definitely a true entity. A humoral factor of macrophage origin intervenes to ensure granulopoiesis in vivo (clone-stimulating factor CSF3. The phenomena which regulate this granulopoiesis then cause to intervene various biochemical forms of this clone-stimulating factor and an inhibitor, the reality of which is not yet definitely demonstrated in vivo. Laboratory animals and cell culture of human normal and leukemic granular cells now supplies experimental models which permit studies of the granular differentiation of the hemocytoblast completed by kinetic studies in vivo to make rapid progress, especially in our knowledge of the human leukemic process.