Congenital dyserythropoietic anaemia, type I, in a Caucasian patient with retinal angioid streaks (homozygous Arg1042Trp mutation in codanin-1).

A congenital dyserythropoietic anaemia (CDA) was recognised in a French Caucasian male patient. Blood smears showed a pronounced aniso-poikilocytosis. Bone marrow light microscopy showed signs of dyserythropoesis, but no internuclear chromatin bridges. Electron microscopy disclosed erythroblast nuclei with the Swiss cheese aspect and the presence of cytoplasmic organelles, assessing the diagnosis of CDA I. The presence of internuclear chromatin bridges may thus be missing in CDA I. The patient proved to be homozygous for the Arg1042Trp mutation in codanin-1 (the 'Bedouin mutation'). By the age of 25, the patient's vision started to deteriorate as a result of retinal angioid streaks and macular abnormalities. Evolution was controlled and the patient, being nearly 50 yr old now, still has a partial use of his eyes. This second case of retinal angioid streaks reported in CDA I adds to the non-haematological features likely to be associated with this condition.

Interleukin-1 beta-induced changes in the kinetic constants of L-proline uptake in human skin fibroblasts.

The effects of interleukin-1 beta (IL-1) on L-proline uptake in human skin fibroblasts were investigated. Exposure of the fibroblasts to IL-1 (5, 10 or 50 pg/ml) for 2 h did not change L-proline uptake. In contrast, inhibition was observed after 6 h of IL-1 treatment, and only 60% of the control uptake remained after incubation for 24 h with 10 pg of IL-1/ml. IL-1 depressed the activity of both transfer systems; the low-affinity system inhibited by alpha-(methylamino)isobutyric acid (Me-AIB), corresponding to system A, and a high-affinity transfer system which is unaffected by Me-AIB. The inhibitory effect increased as the L-proline concentration decreased. To determine whether IL-1-induced prostaglandin release influences proline uptake, indomethacin (14 microM) was added as a cyclo-oxygenase inhibitor. Indomethacin itself decreased L-proline uptake but to a lesser extent than did IL-1. When IL-1 was tested in the presence of indomethacin, the inhibition of L-proline uptake was still observed, with values between those obtained with each substance in isolation. This suggests that the inhibitory effect of IL-1 on proline uptake by skin fibroblast does not only involve the prostaglandins that accumulate in the medium, but no firm conclusion can be drawn, due to the fact that the inhibition by the two agents was not statistically independent. Kinetic analyses for 1 min combined with inhibition experiments showed that IL-1 induced a decrease in the Km and Vmax, values of the high-affinity transport system, whereas it increased the Km of system A. Therefore the two systems of proline uptake in skin fibroblasts are probably inhibited by IL-1 via different mechanisms.

Effect of vitamin E on 2-deoxy-D-glucose uptake in human fibroblast cultures.

2-Deoxy-D-glucose (2-DOG) uptake was tested in human fibroblast cultures in the presence and absence of vitamin E. Addition of 10 micrograms/ml vitamin E to the culture medium significantly reduced this uptake for 2-DOG concentrations of 0.005 to 10 mmol/liter (P less than or equal to 0.01). The decrease of 2-DOG uptake was inversely proportional to the rise in 2-DOG concentration (P less than or equal to 0.01). The presence of vitamin E reduced by 71% the average cellular level of lipid peroxides (expressed as thiobarbituric acid reactive substances) and caused a small but significant decrease in the cholesterol concentration (P less than or equal to 0.01). These last results might explain the decrease in 2-DOG uptake observed in the presence of vitamin E.

L-proline uptake in human fibroblasts: evidence for a high-affinity system in addition to system A.

Proline uptake was studied in human skin fibroblasts by simultaneous running of kinetic and inhibition experiments on the same cell lines. Two systems for proline uptake were shown: a high-affinity system not inhibited by alpha-(methylamino)isobutyric acid and a low affinity system inhibited by this amino acid (i.e. system A). These results appear to be of interest, firstly because up till now, system A was considered preferable for proline uptake in human fibroblasts, and secondly because they illustrate the need for combined inhibition and kinetic studies of amino acid uptake, especially when the substrate concentration range used and the respective Km of the systems do not allow their detection by kinetic analysis alone. Furthermore, this high-affinity system may have major physiological implications.

Isolation and characterization of an abnormal alpha slow-moving high-density lipoprotein subfraction in serum from children with long-standing cholestasis.

An abnormal high-density lipoprotein (HDL) subfraction, detected during periods of mild jaundice in the serum of seven children with chronic cholestasis from birth, was isolated and characterized. This fraction, identified by its slow alpha electrophoretic migration, is present in addition to normal HDL and differs from the abnormal HDL previously described in cholestatic syndromes. It is devoid of apolipoprotein B but is precipitated by phosphotungstate-MgCl2. These properties allowed its isolation by double selective precipitation. This subfraction is undetectable with this procedure in the serum of healthy subjects, is rich in cholesterol, and contains a large amount of apolipoprotein E, which may explain its precipitation by phosphotungstate-MgCl2. These apo E-containing HDL may play a major role in the lipid metabolism of patients with long-standing cholestasis during periods of mild jaundice.