Ornithine decarboxylase transformation of NIH/3T3 cells is mediated by altered epidermal growth factor receptor activity

Ornithine decarboxylase (ODC) has been shown to be oncogenic in transfected NIH/3T3 cells overexpressing the enzyme from a heterologous promoter. These cells, designated as NODC-2 cells, acquire proliferative properties associated with tumorigenic transformation such as loss of contact inhibition, decreased population doubling time, anchorage-independent growth, and tumor production in nude mice. At least one of these parameters, loss of contact inhibition, remains dependent on elevated ODC levels. We have used these cells to investigate the molecular mechanisms by which ODC overexpression drives cell transformation and to examine the involvement of other proto-oncogene products in this process. An interaction between ODC overexpression and the epidermal growth factor receptor (EGF-R) was suggested initially by the elevation of both basal (300%) and ligand-induced (457%) EGF-R tyrosine kinase activities in NODC-2 cells compared to similarly treated control NLK cells. Disruption of EGF-R mediated signal transduction in NODC-2 cells both by treatment with tyrphostin-25 or by transfection with a vector expressing a dominant negative EGF-R mutant resulted in reacquisition of contact-inhibited growth and suppression of anchorage-independent, clonogenic growth in soft agar. We conclude that ODC-induced transformation of NIH/3T3 cells is mediated, at least partly, by alterations in EGF-R signal transduction activity.     

Study of the use of vitamin K in neonates in France

Our objective was to assess flow velocity waveforms of the portal venous system of the anemic fetus prior to and immediately following intravascular transfusion. Color-guided pulsed Doppler was used to obtain flow velocity waveforms from the fetal portal vein in 14 anemic fetuses that were transfused in utero for rhesus alloimmunization The portal vein velocity pattern was defined as continuous when no change in velocity during the cardiac cycle was noted. It was defined as pulsatile when a deflection of the wave was present. The flow velocity waveforms were quantified by using the ratio between the peak (highest, H) and the nadir (lowest, L) velocities (H/L ratio). Fourteen intravascular transfusions were performed. Gestational age ranged from 19.5 to 35 weeks (mean +/- SD, 26.7 +/- 5.3 weeks). The hematocrit ranged from 5.9 to 31.2% (mean +/- SD, 20.3 +/- 9%) prior to transfusion; after transfusion it was between 24.8 and 56.7% (mean +/- SD, 42 +/- 10.4%). In six cases (43%) the waveforms were pulsatile prior to transfusion; in the other eight (57%) they were continuous. The pulsatile pattern was present following transfusion in 13 cases (93%, p < 0.05). The mean of the H/L ratio was 1.3 +/- 0.38 prior to transfusion and 2.0 +/- 0.86 after transfusion (p < 0.05). Because the portal vein has continuous non-pulsatile flow in the normal fetus, the presence of pulsatility in the waves of six anemic fetuses (43%) may suggest portal hypertension. Compared to normal fetuses, there was an increased number of cases with pulsation, and even more so after transfusion. The pattern corresponds to findings in children with portal hypertension.     

Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy

Based on successful results in animal models, it has been proposed that high-dose myeloablative therapy followed by autologous bone marrow or stem cell transplantation (ABMT/ASCT) may cure autoimmune disease. The coexistence of autoimmune disease and hematologic malignancy provides an opportunity to examine the response of autoimmune disease to ABMT or ASCT. We describe 4 patients with autoimmune disease (3 with psoriasis and 1 with rheumatoid arthritis) and hematologic malignancy. In each patient, the autoimmune disease remitted posttransplantation, but, in 4 patients with long-term followup, it recurred at 8-24 months. The earliest relapse occurred in a patient treated with interferon-alpha. Our experience suggests that a single autograft with unpurged stem cells is unlikely to cure autoimmune disease, but that other strategies building on this approach are worthy of investigation.     

Biomechanical regularities in the distribution of tension in various topographic zones of the eyelids in children in health and myopia of different degree

The authors assessed the method for life-time study of the biomechanical characteristics of ocular tissues in 281 children (562 eyes) aged 7 to 14 years. The method for assessing the biomechanics of the eyelids is described. In detail. The rates of propagation of acoustic waves in normal tissue and in 1.0 to 6.0 diopters myopia are presented. A correlation has been revealed between the increase of the velocity of acoustic surface waves, propagating in the horizontal direction in the internal segment of the orbital area of the upper eyelids, and the value of clinical refraction in myopia. The authors consider clinical signs of myopia-screwing up one's eyes and a wider lid slit-from a biomechanical viewpoint.     

Exit of the pre-TCR from the ER/cis-Golgi is necessary for signaling differentiation, proliferation, and allelic exclusion in immature thymocytes

A major issue is whether surface expression of the pre-TCR is necessary for signaling the development of immature thymocytes. To address this question, we generated transgenic mice expressing a TCRbeta chain that had a strong endoplasmic reticulum (ER) retrieval signal (TCRbetaER) and that was expressed intracellularly but failed to reach the cell surface. In TCRbetaER transgenic mice, there was a failure of allelic exclusion. Also, the transgene failed to rescue the developmental defects observed in TCRbeta-null mice. In contrast, TCRbeta transgenes with a mutant ER retrieval sequence or lacking this sequence signaled efficient allelic exclusion and suppressed the TCRbeta-/- defect. These data show that exit of the pre-TCR from the ER/cis-Golgi is required for progression through the double-negative thymocyte checkpoint.