Osteoclast is derived from mononuclear hematopoietic stem cells, most likely within the granulocyte-macrophage lineage. The exact differentiation process of osteoclasts precurssors has only been partially uncovered. The authors isolated in vitro, from the medullary bone of hens a mononuclear precursor of the osteoclast. This cell expressed several characteristics of mature and multinucleated osteoclast including the capacity to resorb the extracellular bone matrix.

Autologous transplantation of hematopoietic stem cells (HSC) is an alternative therapeutic for patients with malignant hemopathies (acute leukemia, lymphoma...) especially when no HLA-identical sibling donor is available. Hsc harvesting (marrow or peripheral blood) is performed during complete remission and is cryo-preserved in liquid nitrogen. The HSC graft, infused after treatment intensification, results in a rapidly occurring hematopoietic reconstitution. As the graft is potentially contaminated by residual malignant cells, an ex-vivo treatment by chemical or immunological treatment can contribute to a reduction and maybe even a disappearance of the malignant population. The encouraging results seen after presently autologous transplantation concerns unfortunately only selected groups of patients (acute myeloid leukemia in particular). Progress in biotechnologies (hematopoietic growth factors, monoclonal antibodies, interleukin-2) now allow us to consider new therapeutic strategies and should contribute to improved clinical results after autologous transplantation.

Several studies have demonstrated that hematopoietic cells can be successfully cultured for several weeks in diffusion chambers (DC) implanted both in experimental animals and man. This technique is a useful assay of hematopoietic cell growth and a powerful tool for studying stem cell kinetics in vivo. The evaluation of the effects of humoral factors on hematopoietic cell proliferation and differentiation in this system has led to identification of both stimulators and inhibitors that may be different from the well characterized cytokines.

We have studied the effects of GM-CSF on cell growth in Dexter's type normal human long-term bone marrow cultures. Non adherent and adherent cells were weekly harvested and studied all over the time of culture up to 10 weeks: number, cytology, hematopoietic granulocyte-macrophage progenitors content (CFU-GM). Control consisted of cultures without growth factor. GM-CSF (100 ng/ml) induced a significant increase in the number of non adherent and adherent cells, mainly increasing the number of cells of the granulocytic lineage. GM-CSF also induced a transient increase in the number of CFU-GM in the non adherent fraction, but as from week 6 of culture, there were no more CFU-GM. At last GM-CSF inhibited completely or partially the adipocyte growth in the adherent stromal cell layers. In conclusion, at this concentration, GM-CSF might be responsible for the accelerated aging, maybe linked to the hematopoietic stem cells exhaustion and to the almost exclusive presence of monocyte-macrophage cell types in the culture supernatant.

Clonogenic cultures from 27 lung cancers were realised. For 68% of cases a clonogenic growth was observed, but no direct correlation could be done with the differentiation of the tumor or with the presence of ganglion metastases. EGF in medium increased the number of colonies obtained in 60% of cases.

Technical advances in molecular genetics have succeeded in elucidating the molecular basis of many hereditary diseases. The characterization of these abnormalities is currently giving rise to the concept of pharmacological treatment or, if possible, organ replacement (bone marrow grafting or liver transplantation). Genotherapy aims at replacing a single deficient gene by a functional gene introduced into an autologous, and therefore unrejectable, tissue. The haematopoietic stem cells are excellent targets for gene transfer, since the procurement, ex vivo, manipulation and reimplantation of these cells are easily performed. Several constitutional blood diseases would benefit from a causative treatment if a group of truly multipotent, self-renewing stem cells could integrate a transgene compensating for the hereditary deficit. The problems inherent in gene transfer, targeting on haematopoietic stem cells, mode of introduction of the transgene and its expression at a sufficiently high level are presented. Important progress has recently been made in this fields, and therapeutic applications to man can now be envisaged, although not all obstacles have been overcome. This concerns, in particular, the globin deficiency gene in beta thalassemia.

Many bilaterally profoundly deaf individuals cannot benefit from a cochlear implant because the eight nerve is not intact from the cochlea to the brain stem. For these individuals, electrical stimulation of the cochlear nuclear complex (CNC) may partially restore the sensation of hearing. Histological studies were done on 12 brain stems containing the region of the CNC and findings of this study seems important to accurate implantation of the prosthesis on the CNC for chronic electrical stimulation. Apparently the spheroid cells of the inferior ventral cochlear nucleus (IVCN) represents the site of the CNC for such stimulation.

We report herein the effect of soluble CD23 (sCD23) on the differentiation of early lymphoid and myeloid human precursors. CD23 is known as a low affinity receptor for IgE. In addition, our results show that sCD23 in synergy with IL1 has a potent activity on the maturation of prothymocytes and the proliferation of multipotential normal and leukemic myeloid precursors.

The control of tooth development by 1,25-Dihydroxyvitamin D3 is analyzed by light- and electron-microscope immunocytochemistry and Northern-blotting in vitamin D-deficient rats. The receptor for 1,25-Dihydroxyvitamin D3, immunostained at the light microscope in all stem-cells, became immunodetectable only at the ultrastructural level in the ameloblasts which elaborate enamel and odontoblasts which synthetize dentin. Moreover, 1,25-Dihydroxyvitamin D3 induces an up-regulation specifically in these cells. In parallel, the calbindins-D9k, -D28k and osteocalcin, in contrast to the phosphoprotein, appear sensitive to vitamin D-deficiency. A single injection of 1,25-Dihydroxyvitamin D3 led to the increase of steady-state levels of the corresponding calbindin mRNAs. These data show that tooth constitutes a target-organ for 1,25-Dihydroxyvitamin D3, as other components of the phospho-calcic metabolism.

Brain development in infants is characterized by growth and myelination. Myelin is a cell membrane devoid of MRI signal; the MRI images obtained at different stages of myelination result from changes in brain tissue water content, from the multiplication of glial cells which precedes myelination (the so-called myelination gliosis), and from the accumulation of lipid myelin precursors contained in cells. T1-weighted sequences are used for the "premyelination" process and T2-weighted sequences for myelination proper. The development of myelination in the white matter is sequential, precisely determined, identical in all individuals, and it has been well studied by histologists. In vivo, myelination in infants is shown at MRI as the same precise sequence but with some changes in time towards the end. The myelination process takes place at different times and different speeds in different brain regions, and for any given structure the speed of myelination varies in relation to time.

Rapid progress has occurred recently in characterizing the molecular structure of the glycoproteins controlling the growth, maturation and functional activities of hematopoietic cells. Several of these factors have been purified and cDNAs have been cloned, providing them in sufficient quantities for study and eventual clinical use. Both availability of these molecules and in vitro colony assays have revealed a large number of effects on erythroid differentiation. But, except erythropoietin (EPO), the physiological role of these hormones and their relative contributions to normal erythropoiesis remain to be specified. This paper attempts to review the most important data on this topic in 1990.

With the aim of immortalizing embryonic cells fixed at early embryonic stages, various plasmids carrying the SV40 early region were introduced into the mouse embryonal carcinomas (EC) F9 and 1003. Only the construction PK4, in which the SV40 oncogenes are placed under the control of the adenovirus E1A promoter, led to the immortalization of the cells at the onset of differentiation. Clones corresponding to committed precursors of each embryonic lineage (neuroectoderm, mesoderm and endoderm) were then selected with high efficiency according to the following strategy: selection of immature cells which: have lost EC cell markers, keep a stable phenotype, are immortalized by the expression of the SV40 oncogenes and are still able to differentiate along a restricted lineage in vitro or in vivo. Examples of an endodermal precursor (H7) which differentiates into extraembryonic and embryonic endoderm, of a neuroectodermic clone (ICII) committed to a serotoninergic differentiation, and of a mesodermal osteogenic clone (CI) which gives rise to bone in vivo and in vitro, are given.

To increase the number of HLA typed corneas a microlymphocytotoxicity assay on lymphocytes and PHA lymphoblasts was investigated. A double immunofluorescence technique using magnetic beads coated with anti-T8 (for class I) and anti-DR (for class II) monomorphic antibodies was applied. Blood samples from 50 non selected donors were obtained. HLA class I and class II typing was possible in 74% of the cases. Using PBL's (Peripheral Blood Lymphocytes) HLA class I could be defined in 29 out of 50 Cases and class II in 15 out of 50 cases. On PHA blasts HLA class I and class II antigens could be defined in 32 and 33 out of 50 cases respectively. Mean time of culture was 10 days (6-20). No influence of donor age and post partum time could be observed. By combination of both methods a significant proportion of eye donors could be reliably typed within a short time.

Oligodendrocytes are the myelin forming cells of the central nervous system. They are derived from a precursor cell, named O-2A. This precursor cell is bipotential, and can differentiate in vitro into either an oligodendrocyte or a certain type of astrocyte, named type 2 astrocyte, depending on the presence or absence of extracellular factors. The chronology of glial differentiation is now better understood. Some factors influencing the choice of the differentiation pathway have been described. Most of these factors seem to be secreted in vitro by an other type of astrocyte, type 1 astrocyte. The succession of events leading to myelination can now be analyzed at molecular level. These very recent results have mostly been obtained in vitro. Their significance in vivo has now to be ascertained.

In spite of the major advances in our knowledge of the cell biology of the osteoclast, many questions still remain to be answered: where does the osteoclast comes from, what is his fate and how it is activated. Bone resorption is considered in a global perspective as the resultant of two successive steps which are the formation of osteoclast progenitors in hematopoietic tissues, the generation of osteoclasts in bone and the activation of osteoclasts at the contact of mineralized bone. Activated osteoclasts resorb both the mineral and the organic of mineralized bone. All these steps are regulated by hormones and growth factors. Hormones have been studied extensively, but recent work has reveal that growth factors also have significant effects on bone function. The purpose of this article is to review current knowledge in the area of the biology of the osteoclast and to index all the growth factors that are known to act mainly on the formation and/or the activation of the osteoclasts.

Otoacoustic emissions are sounds emitted by the inner ear. Their genesis requires the outer hair cells of the organ of Corti to be intact. Analysis of these sounds provides a fine evaluation of cochlear function. Evoked otoacoustic emissions (in response to a sound) are constant in subjects with normal hearing, whereas they always have pathological characteristics in patients with endocochlear conduction or perceptive deafness. When the acoustic nerve or the central nervous system are affected, otoacoustic emissions are normal for as long as the pathological process has no repercussions on the inner ear. This new functional exploratory method is of particular interest, being simple, non-invasive, rapid and objective. One of its main uses in adults is early detection of a lesion of the organ of Corti by e.g. ototoxic drugs or acoustic trauma. In children, it might become a test for objective detection of deafness, being easier to perform than evoked potentials of the brain stem.

Synthetic antiestrogens are drugs commonly used in the endocrine therapy of breast cancer. Their pharmacology is complex, most of them presenting a partial estrogenic effect. Their action via the estrogen receptor (ER) has been better understood through the use of cellular models. The antihormone-ER complex binds to estrogen responsive elements on DNA, but is unable to mimic exactly the transcriptional activation induced by the estradiol-ER complex. The antiproliferative effect of these antihormones, mainly cystostatic but also cytotoxic, is the result of the competitive inhibition of estrogens, and might also involve interaction with other cellular mediators (stimulation of inhibitory factors, and growth factors inhibition). The term antiestrogen seems therefore to be too restrictive and it may be more accurate to name them estrogen-receptor mediated drugs inhibiting cell proliferation.