Stabilization of juvenile metachromatic leukodystrophy after bone marrow transplantation: a 13-year follow-up.

A 29-year-old female patient with juvenile metachromatic leukodystrophy diagnosed at age 14 years received a bone marrow transplant at age 16 years. A report was published 6 years after bone marrow transplantation concluding that the disease had slowly progressed in the 2 years following bone marrow transplantation. We now report on a further 7-year follow-up, typified by a steady state of spastic paraplegia and mild dementia. Neurophysiological, neuroradiological, and psychological status also remained stable. In the patient's leukocytes, the activity of arylsulfatase A, the enzyme deficient in untreated metachromatic leukodystrophy, was within the normal range whereas urinary sulfatides remained elevated. Data on the natural course of juvenile metachromatic leukodystrophy are rare, so in the present case it is difficult to establish whether the rather favorable course can be attributed with certainty to bone marrow transplantation. The long-term stabilization in this patient, however, suggested that bone marrow transplantation may halt the progression of juvenile metachromatic leukodystrophy.

Normal brain maturation characterized with age-related T2 relaxation times: an attempt to develop a quantitative imaging measure for clinical use.

OBJECTIVES: We studied age-related changes in T2 relaxation times from the normal maturating human brain under routine clinical MR examination conditions. MATERIALS AND METHODS: In 70 healthy subjects aged between 3 weeks and 39 years, T2 maps of the brain in which the intensity of each pixel corresponded to T2 relaxation times were generated based on magnetic resonance imaging data collected with a triple spin echo sequence. T2 relaxation times in white matter (WM) and gray matter (GM) were measured in 6 distinctive regions of interest of the T2 maps. The age dependence of the T2 values was mathematically simulated using a biexponential function. RESULTS: T2 values were largest at the age of 3 weeks (maximum: approximately 400 milliseconds for WM and 200 milliseconds for GM) and decreased continuously with increasing age, faster in the first few months and slower thereafter, until values achieved between 95 and 110 milliseconds for WM and 88 and 95 milliseconds for GM in adults. The relationship between T2 values and age could be well simulated using a biexponential function (R > 0.92). CONCLUSIONS: T2 relaxation time correlates well with the progress of brain maturation. The used biexponential function reflects the dynamic development of myelination in newborns and young children as well as the maturation of myelination during adolescence and could be used to develop a "normal" reference for neuroradiological diagnoses.

Oxidized LDL and its compound lysophosphatidylcholine potentiate AngII-induced vasoconstriction by stimulation of RhoA.

RhoA stimulates vascular tone by increasing smooth muscle Ca(2+) sensitivity, e.g., in atherosclerosis. This study was an investigation of the influence of oxidized LDL (OxLDL), which accumulates in atherosclerotic plaques, on vascular tone induced by angiotensin II (AngII), with particular emphasis on the RhoA pathway. OxLDL had no influence on unstimulated vascular tone of isolated rabbit aorta, but it potentiated contractile responses induced by AngII. The Ca(2+)-antagonist felodipin partially prevented potentiation of contractile responses, whereas the AT(1) receptor antagonist losartan blunted AngII responses in presence and in absence of OxLDL. Rho-kinase inhibition by Y27632 abolished potentiation of contractile responses, and RhoA inhibition by C3-like transferase partially prevented it, suggesting that OxLDL activated RhoA. Activation of RhoA was further analyzed by detection of its translocation to the cell membrane after stimulation with OxLDL. Western blot analysis of aorta homogenates, as well as direct visualization in cultured smooth muscle cells using confocal laser scan microscopy, revealed that OxLDL potently activated RhoA. The effect of OxLDL was mimicked by its compound lysophosphatidylcholine, and C3 inhibited both lysophosphatidylcholine and OxLDL-induced RhoA stimulation. In conclusion, OxLDL stimulates the RhoA pathway, resulting in potentiation of AngII-induced vasoconstriction. Lysophosphatidylcholine mimics the OxLDL effect, consistent with a causal role of this OxLDL compound. Stimulation of RhoA by OxLDL may contribute to vasospasm in atherosclerotic arteries.