Analysis of serum soluble CD40 ligand (sCD40L) in the patients undergoing allogeneic stem cell transplantation: platelet is a major source of serum sCD40L

CD40 ligand (CD40L) is expressed not only on activated T cells but also on activated platelets. A soluble CD40 ligand (sCD40L) is released from the activated T cells and platelets by ill-defined proteolytic process in vitro. It has been reported that sCD40L is elevated in the serum of patients with systemic lupus erythematosus, unstable angina, essential thrombocythemia, and autoimmune thrombocytopenic purupura. However, source of sCD40L in vivo remains to be elucidated. We investigated the serial sCD40L in the serum in patients undergoing allogeneic stem cell transplantation and compared with the platelets number and soluble IL2R, which is a marker of activated T cells. The value of sCD40L was well correlated with platelet number or thrombopoiesis. In cases of severe graft vs. host disease with markedly increased sIL2R, sCD40L was not increased in vivo. These results indicate that sCD40L in vivo is released mainly from the platelets or in the process of platelet production but not from the activated T cells.     

Improvement of liver function parameters in patients with type 2 diabetes treated with thiazolidinediones

To increase our understanding of the effect of thiazolidinediones, a new class of antidiabetic drugs, on liver function as well as glycemic control, we investigated liver function before, during, and after treatment with troglitazone and pioglitazone. A total of 32 patients with type 2 diabetes were studied. Glycemic control and liver function were measured before, during, and after 4 to 12 weeks of treatment with troglitazone or pioglitazone. Glycemic control was assessed by fasting levels of plasma glucose, hemoglobin A 1c , and serum insulin, and liver function was assessed by asparatate aminotransferase (AST), alanine aminotransferase (ALT), and gamma -glutamyl transpeptidase ( gamma-GTP). Homeostasis model assessment for insulin resistance was used as an index of insulin resistance. During treatment with troglitazone, fasting plasma glucose and hemoglobin A 1c levels and homeostasis model assessment for insulin resistance were significantly decreased. Serum AST, ALT, and gamma-GTP levels were significantly decreased during treatment (AST, -17.4%; ALT, -27.2%; gamma-GTP, -47.9%) and returned to pretreatment levels after 4 weeks of withdrawal of the drug. A similar tendency was observed during treatment with pioglitazone (AST, -4.7%; ALT, -16.4%; gamma-GTP, -30.8%). These data suggest that, in contrast to the deterioration of liver function reported in a small subset of patients treated with troglitazone, treatment with thiazolidinediones was associated with a decrease in serum transaminases in most patients. The improvement in liver function parameters known to be associated with fatty liver in the present study, together with an improvement in fatty liver reported for another class of insulin sensitizers, biguanides, suggests that thiazolidinediones may have a beneficial effect on fatty liver.     

Terminal stage cardiac findings in patients with cardiac Fabry disease: an electrocardiographic, echocardiographic, and autopsy study

OBJECTIVES: Fabry disease is caused by deficiency of alpha-galactosidase A, and typically causes multi-organ dysfunction. Patients with manifestations limited to the heart, mainly left ventricular hypertrophy (LVH), have been reported as a disease variation. We have reported a 3% prevalence of this cardiac variant in men with LVH, which we designated 'cardiac Fabry disease'. The purposes of this study were to evaluate the terminal stage cardiac manifestations and autopsy findings in patients with cardiac Fabry disease. METHODS: We examined seven terminal stage patients with cardiac Fabry disease. During hospitalization, standard 12-lead electrocardiograms, Holter electrocardiograms, and echocardiograms were obtained. Autopsies were performed and macroscopic along with microscopic findings were evaluated. RESULTS: Six patients died of heart failure and one of ventricular fibrillation. Electrocardiograms revealed the presence of conduction abnormalities and nonsustained ventricular tachycardia. Echocardiograms and autopsy findings revealed LVH in all patients. Localized basal posterior wall thinning of the left ventricle was detected in the six patients who died of heart failure. All patients had severe left ventricular dysfunction. Histologically, myocardial cells, but not cardiac vascular endothelial cells, showed glycosphingolipid accumulation. No accumulation was observed in other organs or in systemic vascular endothelial cells. CONCLUSIONS: Severe left ventricular dysfunction with associated conduction disturbances and ventricular arrhythmias occur in patients with terminal stage cardiac Fabry disease. Furthermore, LVH is present and associated with thinning of the base of the left ventricular posterior wall. In contrast to typical Fabry disease, accumulation of glycosphingolipids was observed in myocardial cells but not in other organs.     

Memory impairment following right cerebellar infarction: a case study

We reported a patient with a right cerebellar infarction who showed anterograde amnesia. Cognitive dysfunction caused by cerebellar lesions was called cerebellar cognitive affective syndrome, and deactivation of the contralateral prefrontal cortex function due to disconnections of cerebello-cerebral fiber tracts have been hypothesized as mechanism underlying the syndrome. The episodic memory impairment, however, could not be supported by the same mechanism because the prefrontal lesions cannot cause amnesia syndrome. The feature of the impairment of our patient was similar to that of diencephalic amnesia, and a single photon emission computed tomography study showed a relative hypoperfusion in the right cerebellar hemisphere and left anterior thalamus. We considered that the memory deficit was caused by the dysfunction of the thalamus, which is a relay center of the cerebello-cerebral connectivity network.