Caspase-dependent ceramide production in Fas- and HLA class I-mediated peripheral T cell apoptosis

We recently demonstrated that the engagement of HLA class I alpha1 domain induced Fas-independent apoptosis in human T and B lymphocytes. We analyzed the signaling pathway involved in HLA class I-mediated apoptosis in comparison with Fas (APO-1, CD95)-dependent apoptosis. The mouse mAb90 or the rat YTH862 monoclonal antibodies which bind the human HLA class I alpha1 domain induced the production of ceramide which was blocked by addition of the phosphatidylcholine-dependent phospholipase C inhibitor, D609. Furthermore, HLA class I-mediated apoptosis involved at least two different caspases, an interleukin-1 converting enzyme-like protease and another protease inhibited by the CPP32-like protease inhibitor Ac-DEVD-CHO. Despite similarity between Fas and HLA class I signaling pathways, we failed to demonstrate any physical association between these two molecules. We also report that the pan-caspase inhibitory peptide zVAD-fmk, but not Ac-DEVD-CHO and Ac-YVAD-CHO, inhibited decrease of mitochondrial transmembrane potential and generation of ceramide induced by anti-HLA class I and anti-Fas monoclonal antibodies, whereas all three peptides efficiently inhibited apoptosis. Altogether these results suggest that signaling through Fas and HLA class I involve caspase(s), targeted by zVAD-fmk, which act upstream of ceramide generation and mitochondrial events, whereas interleukin-1 converting enzyme-like and CPP32-like proteases act downstream of the mitochondria.     

The Palomo procedure in the treatment of boys with varicocele: a retrospective study of testicular growth and fertility

A 9-year-old male child had a IV ventricular medulloepithelioma of classical histology, showing tubulopapillary and undifferentiated areas. The unusual feature, however, was the presence of melanin pigmentation in the cells, which was further confirmed by electron microscopy. So far 28 cases of medulloepithelioma have been reported in the English literature. However, none of them showed melanin pigmentation. To the best of our knowledge this is the first case of pigmented medulloepithelioma in the English literature.     

The administration of fenamine into the rostral and caudal sections of the rat neostriatum disturbs the realization of conditioned reflex escape behavior

Daily injections of amphetamine during 3 weeks into the rat caudal and rostral neostriatum impaired avoidance conditioning of rats in shuttle box. The data obtained suggests involvement of both parts of the neostriatum's dopaminergic system in avoidance conditioning and complex behavioural actions in rats.     

Gene-for-gene disease resistance without the hypersensitive response in Arabidopsis dnd1 mutant

The cell death response known as the hypersensitive response (HR) is a central feature of gene-for-gene plant disease resistance. A mutant line of Arabidopsis thaliana was identified in which effective gene-for-gene resistance occurs despite the virtual absence of HR cell death. Plants mutated at the DND1 locus are defective in HR cell death but retain characteristic responses to avirulent Pseudomonas syringae such as induction of pathogenesis-related gene expression and strong restriction of pathogen growth. Mutant dnd1 plants also exhibit enhanced resistance against a broad spectrum of virulent fungal, bacterial, and viral pathogens. The resistance against virulent pathogens in dnd1 plants is quantitatively less strong and is differentiable from the gene-for-gene resistance mediated by resistance genes RPS2 and RPM1. Levels of salicylic acid compounds and mRNAs for pathogenesis-related genes are elevated constitutively in dnd1 plants. This constitutive induction of systemic acquired resistance may substitute for HR cell death in potentiating the stronger gene-for-gene defense response. Although cell death may contribute to defense signal transduction in wild-type plants, the dnd1 mutant demonstrates that strong restriction of pathogen growth can occur in the absence of extensive HR cell death in the gene-for-gene resistance response of Arabidopsis against P. syringae.     

Difference between the measured and ordered dose of catecholamine infusions

OBJECTIVE: To measure the actual concentrations of dopamine, dobutamine, and epinephrine in infusates prepared for patients, and to compare these concentrations with those of the dopamine HCl, dobutamine, and epinephrine HCl infusates that had been prescribed to evaluate drug preparation accuracy. DESIGN: Prospective, unblind study. SETTING: Pediatric intensive care unit in a tertiary-care teaching hospital. PARTICIPANTS: All dopamine, dobutamine, and epinephrine infusions ordered for patients during the 2-month study period were eligible for inclusion in the study. MEASUREMENTS: Daily samples of dopamine, dobutamine, and epinephrine infusates that were prepared for 41 pediatric patients were obtained; the infusate catecholamine concentration was measured by HPLC and compared with the ordered concentration. The concentration than was multiplied by the rate of infusion to determine the catecholamine dose. MAIN RESULTS: There were significant differences between the measured doses of dopamine, dobutamine, and epinephrine and the dopamine HCl, dobutamine, and epinephrine HCl doses (p = 0.0001, p = 0.039, and p = 0.0009, respectively) that had been ordered because of preparation inaccuracies. Failure to account for the HCl salt in the stock drug accounted for some, but not all, of the inaccuracy of the dopamine HCl and epinephrine HCl infusates. There was a wide interday variability in the measured catecholamine dosage in patients receiving the same dose for 3 days or more. CONCLUSIONS: There are daily fluctuations in the preparation of dopamine, dobutamine, and epinephrine infusates that could alter the amount of drug actually delivered to critically ill patients and potentially contribute to their hemodynamic instability.     

The role of scintigraphy in the evaluation of fever of unknown origin

Nuclear medicine imaging techniques are an important adjunct to other currently used modalities in the evaluation of patients with fever of unknown origin. Bone scanning performed with technetium-labeled phosphonate agents may identify osteomyelitis when plain radiography fails and may disclose sites of joint inflammation or unsuspected osseous tumor metastasis. Indium-labeled autologous leukocytes localize at sites of inflammation in the same manner as unlabeled leukocytes. Gallium citrate accumulates in areas of inflammation and in some tumors, most notably lymphomas. In most cases, scintigraphy is best used to determine the location of a lesion rather than to specifically identify the pathologic process.     

The incidence of dementia: a meta-analysis

OBJECTIVE: To carry out a meta-analysis of the age-specific incidence of all dementias, including AD and vascular dementia. BACKGROUND: Several meta-analyses have been carried out on dementia prevalence, but none on its incidence. METHODS: We used loess-curve fitting to analyze data from 23 published studies reporting age-specific incidence data. RESULTS: The incidence of both dementia and AD rose exponentially up to the age of 90 years, with no sign of leveling off. The incidence rates for vascular dementia varied greatly from study to study, but the trend was also for an exponential rise with age. There was no sex difference in dementia incidence (p = 0.21), but women tended to have a higher incidence of AD in very old age, and men tended to have a higher incidence of vascular dementia at younger ages. East Asian countries had a lower incidence of dementia than Europe (p = 0.0004), and also tended to have a lower incidence of AD. CONCLUSIONS: The incidence of dementia rises exponentially to the age of 90 years. Any sex differences are small, and incidence is lower in East Asia than in Europe.