Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle

OBJECT: Ependymomas in children continue to generate controversy regarding their histological diagnosis and grading. optimal management, and possible prognostic factors. To increase our knowledge of these tumors the authors addressed these issues in a cohort of children with prospectively staged ependymomas treated with radiotherapy and chemotherapy. METHODS: Children between the ages of 2 and 17.3 years harboring an intracranial ependymoma confirmed by a central review of the tumor's pathological characteristics were treated according to Children's Cancer Group Protocol 921 from 1986 to 1992. Treatment following surgery and postoperative tumor staging (including brain computerized tomography or magnetic resonance [MR] imaging, spinal MR imaging or myelography, and cerebrospinal fluid cytological investigation) included craniospinal irradiation with a local boost to the primary tumor and patient randomization to receive adjuvant chemotherapy with either 1) CCNU, vincristine, and prednisone, or 2) the eight-drugs-in-1-day regimen. Centralized review of the tumor pathological characteristics revealed 20 ependymomas and 12 anaplastic ependymomas in the 32 children included in the study. Diagnoses made at the individual institutions included anaplastic (malignant) ependymoma (15 patients), ependymoma (four patients), ependymoblastoma (nine patients), ependymoastrocytoma (one patient), and primitive neuroectodermal tumor (three patients), which were discordant with the centralized review diagnosis in 22 of 32 cases. Only three of the 32 patients had metastatic disease (two with M and one with M3 stages). At surgery, 47% of tumors were estimated to be totally resected. Among the 14 of 17 patients who suffered a relapse and were evaluated for site of relapse, 10 (71%) had an isolated local relapse, three (21%) had concurrent local and metastatic relapse, and only one (7%) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year progression-free survival (PFS) and overall survival rates were 50 +/- 10% and 64 +/- 9%, respectively. CONCLUSIONS: Predictors of PFS duration included an estimate of the extent of resection made at surgery (total compared with less than total, p = 0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiological review (< or = 1.5 cm2 compared with > 1.5 cm2, p < 0.0001). No other factors, including centrally reviewed tumor histopathological type, location, metastasis and tumor (M and T) stages, patient age, race, gender, or chemotherapy treatment regimen significantly correlated with PFS duration. The pattern of predominantly local relapse and the important influence of residual tumor or the extent of resection on PFS duration confirms a prevailing impression that local disease control is the major factor in the prediction of outcome of ependymoma. Survival rates were comparable with those reported by other investigators who have treated patients with similar doses of radiation and no chemotherapy.     

Does 'intestinal angina' exist? A critical study of obstructed visceral arteries

A study of the mesenteric arteries was carried out in 203 unselected autopsies. Although mild degrees of stenosis were common, the incidence of a 'critical stenosis' was rare and no correlation between degrees of stenosis and previous gastrointestinal symptoms could be found. Radiological demonstration of stenosed or blocked visceral arteries remains therefore of doubtful clinical significance.     

Dendritic cell-based immunotherapy of prostate cancer

The protective effect of catechins, major components of green tea, was studied in cultured human umbilical vein endothelial cells exposed to toxicity induced by linoleic acid hydroperoxide (LOOH). In the case where cells were incubated in medium containing both LOOH and catechins, (+)-catechin (C) was effective in suppressing of LOOH-induced cytotoxicity, but (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG) had no effect. EGCG monoglucoside (EGCG-G1) and EGCG diglucoside (EGCG-G2), apophilic derivatives of EGCG, show a protective effect on LOOH-induced cytotoxicity when present at the time of treatment with LOOH. On the other hand, when cells were incubated with catechins for 24 h before treatment with LOOH there was no protection against the oxidative damage by LOOH. Furthermore, the interaction between catechins and alpha-tocopherol was examined under these culture conditions. C showed a synergistic effect with alpha-tocopherol in protecting against LOOH-induced damage. These results suggest that catechins interact with LOOH present in the medium or near the surface of membranes, but not with LOOH incorporated into cellular membranes and that catechins are able to interact with alpha-tocopherol to provide synergistic protection against the cytotoxicity of LOOH.     

Fc epsilon receptor I on dendritic cells delivers IgE-bound multivalent antigens into a cathepsin S-dependent pathway of MHC class II presentation

In this study, we elucidate the Fc epsilon RI-mediated Ag uptake and presentation mechanisms of dendritic cells (DC). We found that Fc epsilon RI-bound IgE, after polyvalent but not after monovalent ligation, is efficiently internalized into acidic, proteolytic compartments, degraded, and delivered into organelles containing MHC class II, HLA-DM, and lysosomal proteins. To follow the fate of the fragmented ligand, we sought to interfere with invariant chain (Ii) degradation, a process critical for peptide loading of nascent MHC class II molecules. We found DC to express cathepsin (Cat) S, a cysteine protease involved in Ii processing by B cells. Exposure of DC to a specific, active-site inhibitor of Cat S resulted in the loss of anti-Cat S immunoreactivity, led to the appearance of an N-terminal Ii remnant, and decreased the export of newly synthesized MHC class II to the DC surface. Furthermore, inactivation of Cat S as well as blockade of protein neosynthesis by cycloheximide strongly reduced IgE/Fc epsilon RI-mediated Ag presentation by DC. Thus, multimeric ligands of Fc epsilon RI, instead of being delivered into a recycling MHC class H pathway, are channeled efficiently into MIIC (MHC class II compartment)-like organelles of DC, in which Cat S-dependent Ii processing and peptide loading of newly synthesized MHC class II molecules occur. This IgE/Fc epsilon RI-dependent signaling pathway in DC may be a particularly effective route for immunization and a promising target for interfering with the early steps of allergen presentation.     

Changes in myocardial A1 adenosine receptor and message levels during fetal development and postnatal maturation

Dysembryoplastic neuroepithelial tumor (DNT) is a recently described rare brain neoplasm with characteristic clinical and morphological features and favorable prognosis. We report here two cases of DNT. The first concerned a 12 years old girl who presented complex seizures preceded by acoustic aura (melodies). Computed tomography revealed a hypodense tumor measuring 2 x 2.5 cm in diameter, located paracortically in the left temporal lobe. The second tumor was removed from a 21-year-old man with partial complex seizures. Nine years earlier patient underwent neurosurgery with partial removal of the tumor The tumor's histopathologic diagnosis is unfortunately lacking. Computed and magnetic resonance imaging showed a mass occupying the cortex and paracortical areas of the anterior pole of the temporal lobe. Histologically, both tumors consisted of small, S-100 protein immunopositive oligodendrocyte-like cells (OLCs) arranged between synaptophysin- and, to a lesser degree, NFP-immunopositive axons (glioneuronal element). In the second case, an area of pilocytic astrocytoma-like appearance was also found, these cells were immunopositive for GFAP. The present study provides clinical, radiological and histological data, which may be helpful in differential diagnosis of this newly recognised brain tumor.     

Pharmacologic adjuncts to mechanical ventilation in acute respiratory distress syndrome

This article reviews pharmacologic approaches to treating acute respiratory distress syndrome (ARDS). The authors discuss the therapeutic effects of ketoconazole, antioxidants, corticosteroids, surfactant, ketanserin, pentoxifylline, bronchodilators, and almitrine in ARDS. Current animal data and proposed mechanics which may foster future pharmacologic therapies are also examined.