Caudate nucleus volumes in stroke and vascular dementia

We aimed to assess the volume of the nucleus caudatus as a neuroanatomical substrate of fronto-subcortical circuits, in stroke patients with/without dementia, and the relationship to potential determinants of neural circuit integrity such as white matter hyperintensities (WMH) and stroke volume. Stroke only (Stroke) (n = 19) and stroke with Vascular Dementia (VaD) (n = 16) and healthy control (n = 20) subjects, matched on demographic variables, underwent extensive neuropsychiatric assessments and manual MRI-based volumetric measurements for intracranial area (ICA), stroke volume, and bilateral caudate volume. WMH on MRI were quantified using an automated algorithm. Multivariate analysis of covariance (controlling for age and ICA), revealed that across the three groups, caudate volumes were significantly different. There was a significant difference in bilateral caudate nucleus volume between subjects by diagnosis (Stroke, VaD, control). The control group was largest in overall mean volume of the diagnostic groups, followed by the Stroke group (86% of controls), and finally, the VaD group (72%). There was a partial correlation between total caudate volume and the total volume of deep WMH including periventricular regions and brainstem, controlling for ICA; and for total stroke volume. Stroke patients with VaD have smaller caudate nuclei compared to those without dementia and healthy controls, with the stroke-only patients being intermediate in their caudate volume status. There was preliminary evidence of negative correlation of caudate volume with volume of deep WMH and total stroke volume, suggesting cerebrovascular disease contributes to caudate atrophy,which, in turn may disrupt fronto-subcortical circuits.     

Abnormal assembly of membrane proteins in erythroid progenitors of patients with beta-thalassemia major

The life threatening anemia in beta-thalassemia major (Cooley's anemia) is characterized by profound intramedullary lysis, the cause of which is incompletely understood. Using marrow obtained from beta thalassemia major patients undergoing allogeneic bone marrow transplantation in Pesaro Italy, it became possible to directly study the mechanism of the intramedullary hemolysis. Based on our previous studies, we hypothesized that the unmatched alpha globin chains would interfere with normal assembly of erythroid precursor membrane proteins. Patient and control erythroid precursors were reacted with monospecific polyclonal rabbit antibodies directed against spectrin, band 3, and band 4.1 and with a monoclonal anti-alpha globin chain antibody. Using laser confocal fluorescence microscopy, normal erythroid precursors show no alpha globin chain accumulation and exhibited uniformly smooth rim fluorescence of the three membrane proteins. In some thalassemic precursors, spectrin appeared to interact with large alpha globin accumulations, and in many of these cells the spectin appeared clumped and discontinuous. Band 4.1 interacted strongly with accumulations of alpha globin in thalassemic precursors to produce bizarrely clumped zones of abnormal band 4.1 distribution. Band 3 was incorporated smoothly into thalassemic erythroblast membranes. However, the proerythroblasts and basophilic erythroblasts were significantly deficient in band 3. Thus, accumulations of alpha globin in beta- thalassemia major colocalized with and disrupt band 4.1 and spectrin assembly into the membrane. The cause of deficient band 3 incorporation into thalassemic proerythroblast membranes remains unknown. These profound membrane alterations would likely contribute to the intramedullary lysis seen in Cooley's anemia.