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.

Autologous blood stem cell transplantation (ABSCT) is a new technique which has been increasingly used in recent years. It is now well established that ABSCT can be performed as safely as autologous bone marrow transplantation (ABMT) when high numbers of hemopoietic precursors are infused. Multiple leukophoreses are performed during marrow regeneration following chemotherapy-induced aplasia. Hemopoietic recovery (predominantly the granulocytic series) is probably faster after ABSCT than after ABMT. Among other advantages there may be minimal contamination by residual tumor cells in buffy-coats; however, this has not been fully investigated.

Interleukin-3 induces an increase in histamine synthesis, in the murine hematopoietic system. Evidence is given here that this biological activity also exists in the human hematopoietic system (fetal liver, bone marrow and cord blood), and is already detectable after 3 days of culture in the presence of interleukin-3.

Microinjections of antibodies directed against the protein encoded by the c-myc protooncogene strongly inhibit or arrest the early cell cleavage stage of Xenopus laevis embryos. Injections in one blastomere of a two cell stage embryo inhibit the segmentation of this blastomere. The cleavage of the uninjected blastomere behaves normally. Injections of control rabbit immunoglobulins do not alter the embryonic development.

Cytokinins are biological proteins which permit the transmission of signals from one cell to another. These proteins are secreted by groups of specialized cells and are fixed on specific receptors on the surface of responding cells. However, since receptors may be widely distributed, and since the activation of a cell usually permits the release of other cytokinins and a succession of reactions, cytokinins have pleiotropic effects. Cloning of the genes encoding for these cytokinins and their obtention on a large scale by genetic recombination techniques have allowed a better understanding of their biological characteristics and their use in therapy. This cytokinin network is particularly wide in the hematopoietic and in the immune systems. In the present study, we describe the biological properties of the main interleukins and hematopoietic cell growth factors, together with their therapeutic applications, particularly in hemato-oncology.

The hematologic immediate toxicity during radiotherapy for Hodgkin's disease was studied from a series of 72 patients with stage IIB or III who received 3 courses or more of chemotherapy before radiotherapy. The toxicity in the group of 36 of them who received total nodal irradiation (TNI) was the most important. Sixteen of the 28 TNI had irradiation interrupted, 12 of them began with inverted Y type. The blood cells count at the beginning of the treatment was crucial; only 16% of the patients had interruption of irradiation when the blood cells count was normal; on the other side, 63% had interruption when the blood cells count was abnormal (P less than 0.05). Toxicity was due to the daily destruction of the dividing bone marrow stem cells located in the irradiated area, from the first day of treatment; there was a progressive decrease in the pool of these stem cells within a late resaturation. The absence of resaturation of this pool after initial chemotherapy and after the first part of irradiation explained the immediate and durable toxicity; in the same way, inverted Y irradiation destroyed a great part of active bone marrow (40%) and the pool of remaining stem cells with high mitotic index would be located in areas irradiated subsequently. So, waiting for the absolute normalisation of blood cells count before beginning irradiation and start irradiation by mantle field (rather than inverted Y) seem to be the 2 measures able to reduce the number of interruptions of irradiation due to hematotoxicity.

Six patients with acute non-lymphocytic leukemia underwent autologous transplantation of circulating stem cells collected during remission. They were given cyclophosphamide (120 mg/kg) and total body irradiation (1,000-1,200 rads) (five patients) or busulfan (16 mg/kg) and melphalan (140 mg/m2) before the transfusion of 6.7 X 10(8) nucleated cells/kg corresponding to 19.7 X 10(4) CFU-GM/kg. Granulopoietic engraftment was observed in every case and was influenced by the number of CFU-GM injected. Megakaryocytic recovery was obtained in four cases.

A 48 year-old patient with a myelosclerosis was operated from a cauda equina compression which had been revealed by bilateral sciatica. The epidural space was filled with extra-medullary hematopoietic tissue. The mechanism of epidural hematopoiesis is discussed.

A preliminary study of the culture of leukemic progenitor cells (CFU-L) from acute non-T lymphoblastic leukemia was undertaken for 25 patients (19 were considered in complete remission and 6 in the acute phase of the disease). Two culture systems were tested; a double layer agar-liquid phase and a single layer of methylcellulose. The major problem was the characterization of the colonies: immunological labelling coupled with cytofluorometry, as well as cytomorphology, cytogenetic and more recently molecular biology may allow the characterization of the CFU-L. The culture of CFU-L appears to be an efficient method for detecting residual leukemic cells which can be used to evaluate the quality of both the remission obtained and that of autologous bone marrow after purging.

Limiting dilution analysis, a technique which measures the ability of cells to form colonies in liquid media has been used to quantitative residual cells subsequent to treatment. The reliability of this in vitro test as a tool in the selection of process of bone marrow purging was examined. With conventional methods like release of 51Chrome a 2 log reduction could be evaluated, while a reduction of 4 log was assessed by limiting dilution analysis for a same treatment. However the sensibility of this method depends of several factors which we have been examined in this study.