Tumor induction by ras and myc oncogenes in fetal and neonatal brain: modulating effects of developmental stage and retroviral dose

Introduction into fetal rat brain cells of a replication-defective retroviral vector harboring v-Ha-ras and v-gag-myc rapidly causes the induction of highly malignant undifferentiated neuroectodermal tumors following transplantation into the brains of syngeneic hosts [Wiestler, et al. (1992) Cancer Res. 52: 3760–3767]. In the present study, we have investigated the modulating effect of the developmental stage of neural target cells and of the dose of the retroviral vector used in the grafting experiments. Exposure of fetal cells from embryonic day (E)12 or E14 produced a 100% incidence of malignant neuroectodermal tumors which led to the death of recipient animals after a median latency period of 32 days. A 100-fold reduction of the virus dose from 2.062×10⁶ to 2.062×10⁴ focus-forming units/ml resulted in a lower tumor incidence of 25%. Of six neural grafts exposed to v-Ha-ras and v-myc at E16, only one showed evidence of tumorigenesis (low-grade astrocytoma and hemangioma). All other transplants were morphologically normal for observation periods of 26 weeks, indicating a marked loss of transforming activity of ras and myc in more advanced stages of brain development. In retrovirus-exposed donor cells which caused the development of neural tumors in recipient rats, malignant transformation was also evident during culture in vitro, usually after 9–12 days. Oncogene complementation was also studied in the newborn rat brain. After microinjection of the retroviral vector into the brain at postnatal day (P)0, P1 and P3, 5 out of 20 animals (25%) developed a total of seven brain tumors. Histopathologically, three of these neoplasms were malignant neuroectodermal tumors which, in contrast to those induced in fetal brain transplants showed evidence of focal glial and/or neuronal differentiation. In addition, we observed one oligodendroglioma, two hemangiomas and a malignant hemangioendothelioma. These data indicate that neural precursor cells and endothelia of the rat brain represent the major target cells for the complementary action of ras and myc and that the use of target cells from later developmental stages (E16 and postnatal) leads to the induction of both primitive and more differentiated neoplasms.These studies were supported by the Fonds zur Förderung der wissenschaftlichen Forschung in Österreich (Erwin Schrödinger fellowship, JO501-MED), by the Swiss National Science Foundation and by the Cancer League of the Kanton of Zürich     

Functional diagnosis of early arthroses of the extremities

Patient history and clinical examination are important for the diagnosis of degenerative joint disease. Here the typical statements of a patient suffering from early osteoarthritis are described and, as far as possible, explained. The joint in question must be systematically examined. Furthermore, the neighboring joints and soft-tissue structures, i.e., muscles, tendons etc., should be examined and evaluated with respect to their importance in hindering the functional chain. The neuroreflectory mechanisms involved herein are described.     

Some central effects of brofaromine given repeatedly are phase-dependent

Effects of the MAO-A-inhibitor brofaromine (BRO), 10 mg/kg po after repeated (twice daily for 14 days) administration on the spontaneous behavior (exploratory and basal locomotor activities) and the exploratory activity modified by methoxamine, clonidine and d-amphetamine in male Wistar rats were studied in both light and dark phases of a diurnal cycle (L: 0700-1900 h). After single administration BRO in the light phase had no effects. In the dark phase BRO decreased the exploration (62% of control, p less than 0.01), increased the clonidine-evoked hypoactivity and amphetamine-evoked hyperactivity. The L-D differences occurred also after repeated administration. BRO in the light phase did not influence the exploration, decreased basal locomotor activity, did not change methoxamine and clonidine action and potentiated the action of amphetamine. In the dark phase, however, it did not influence the exploration and basal locomotor activity, intensified the methoxamine effect, and did not change the clonidine and amphetamine actions. The results demonstrate that the effects of BRO on behavior in rats: 1) differ from the effects caused by other antidepressants which are not MAO inhibitors; 2) are phase-dependent after both single and repeated administration.     

New stand magnifiers do not meet rated levels of performance

A new range of stand magnifiers has been released by the COIL company in the United Kingdom. Examination of these magnifiers reveals that they fail to deliver the rated magnifications labelled prominently on the appliances, as a result of the manufacturer's conformance with the requirements of the German DIN standard and the use of back vertex power (F'_v) rather than equivalent dioptric power (F_m) of the magnifier. In this study we provide information on the optometric parameters of these new stand magnifiers that will assist the more accurate specification of improvements in vision expected from their use.     

Echocontrast agent-enhanced color flow imaging of the breast.

An ultrasound contrast agent which survives transit through the pulmonary circulation after injection into a peripheral vein can also be used for the demonstration of flow characteristics in the peripheral organs. Such a substance (SH U 508 A, Schering AG, Berlin) was tested in the Gynecological Department of the University of Marburg for its suitability for enhancing color-coded Doppler signals in mammary diagnosis in a group of ten women with breast tumors. The observations made are compared with the histologically confirmed diagnoses. The very distinct enhancement of the color-coded Doppler signals allows reliable demonstration of the vascularization characteristics, not only of the malignant, but also of all benign solid tumors examined. Color signals were even recorded from normal mammary tissue, which means that the demonstration of perfusion can no longer be used on its own as a diagnostic criterion. Observation of the characteristics of the blood supply to a tumor might, on the other hand, be an advantage, not only in respect of tumor typing, but also as regards the prognosis of a tumor. In this connection, the registration of the arrival, retention and wash-out phases specific to a contrast agent appears to furnish particularly interesting information about the growth dynamics of a tumor.