Jan Aten

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We searched for the presence of apoptotic cell death and studied the distribution of bcl-2, an oncoprotein that counteracts apoptosis, in amyotrophic lateral sclerosis (ALS). Brain and spinal cord specimens from 12 ALS patients were compared with those from six non-neurological controls. ALS brain tissue was pre-selected by the presence of reactive cortical(More)
Aphasic patients who met stringent selection criteria were assigned randomly to three groups: clinic treatment by a speech pathologist for 12 weeks, followed by 12 weeks of no treatment; home treatment by a trained volunteer for 12 weeks, followed by 12 weeks of no treatment; or deferred treatment for 12 weeks, followed by 12 weeks of treatment by a speech(More)
A growing body of evidence implicates ceramide and/or its glycosphingolipid metabolites in the pathogenesis of insulin resistance. We have developed a highly specific small molecule inhibitor of glucosylceramide synthase, an enzyme that catalyzes a necessary step in the conversion of ceramide to glycosphingolipids. In cultured 3T3-L1 adipocytes, the(More)
1) Gene expression profiles of podocyte-associated molecules as molecular diagnostic markers in acquired proteinuric diseases 2) Co-culture of podocytes and glomerular endothelial cells induces podocyte differentiation in vitro 7) Antibody induced focal segmental glomerulosclerosis in the Thy-1.1 transgenic mouse
Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation and class switch recombination of the immunoglobulin (IG) genes in B cells. It has recently been proposed that AID, as the newly identified DNA mutator in man, may be instrumental in initiation and progression of B-cell non-Hodgkin's lymphomas (B-NHL). We quantitatively(More)
Connective tissue growth factor (CTGF) is a secreted protein involved in a variety of cellular events such as survival, proliferation, and extracellular matrix production. Recent studies suggest a role for this protein also in the repair processes of the central nervous system. The distribution and significance of CTGF in human brain is, however, poorly(More)
Adipose tissue is a critical mediator in obesity-induced insulin resistance. Previously we have demonstrated that pharmacological lowering of glycosphingolipids and subsequently GM3 by using the iminosugar AMP-DNM, strikingly improves glycemic control. Here we studied the effects of AMP-DNM on adipose tissue function and inflammation in detail to provide an(More)
Lysosomal integral membrane protein-2 (LIMP2) mediates trafficking of glucocerebrosidase (GBA) to lysosomes. Deficiency of LIMP2 causes action myoclonus-renal failure syndrome (AMRF). LIMP2-deficient fibroblasts virtually lack GBA like the cells of patients with Gaucher disease (GD), a lysosomal storage disorder caused by mutations in the GBA gene. While GD(More)
The iminosugar N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynoijirimycin (AMP-DNM), an inhibitor of glycosphingolipid (GSL) biosynthesis is known to ameliorate diabetes, insulin sensitivity and to prevent liver steatosis in ob/ob mice. Thus far the effect of GSL synthesis inhibition on pre-existing NASH has not yet been assessed. To investigate it,(More)
Connective tissue growth factor (CTGF; CCN2) plays a role in the development of diabetic nephropathy (DN). Urinary CTGF (uCTGF) is elevated in DN patients and has been proposed as a biomarker for disease progression, but it is unknown which pathophysiological factors contribute to elevated uCTGF. We studied renal handling of CTGF by infusion of recombinant(More)