Benign solitary fibrous tumour of the pre-sacral space: MRI findings

Benign solitary fibrous tumour, a rare mesenchymal tumour of adults, usually arises from the pleura. Only a few cases have been reported in the retroperitoneum and, to our knowledge, there has been no report of its imaging features. We describe the MRI features of benign solitary fibrous tumour arising from the pre-sacral space.     

Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial

PURPOSE: The purpose of this study was to investigate the prognostic value of time to relapse in 188 adult patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) included on the Parma trial at the time of their first relapse. PATIENTS AND METHODS: The median follow-up of these patients is 102 months after registration onto the Parma study. Time to relapse was calculated from initial diagnosis, and a cutoff of 12 months was used to separate 77 patients defined as early relapse from 111 patients defined as late relapse. RESULTS: Patients with early and late relapses had significantly different overall response rates to salvage therapy with two courses of dexamethasone, high-dose cytarabine, and cisplatin (DHAP; 40% v 69%; P=.00007) and different 8-year survival rates (13% v 29%; P=.00001). Features at relapse with a negative prognostic value in univariate analysis were higher than normal lactic dehydrogenase (LDH) levels, tumor size greater than 5 cm, Ann Arbor stages III to IV, and Karnofsky score less than 80%. Therefore, multivariate analyses were performed. Time to relapse (P=.001) and LDH levels at relapse (P=.003) had independent prognostic value, whereas tumor size did not reach statistical significance in the logistic model that predicted overall response after two courses of DHAP. The study of prognostic factors for overall survival (OS) and progression-free survival (PFS) confirmed the prognostic value of time to relapse (P < .0001 for OS and P=.005 for PFS) independent of response or treatment after two courses of DHAP. CONCLUSION: Time to relapse may be used to stratify patients at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma.     

Inhibition of in vitro replication of the oyster parasite Perkinsus marinus by the natural iron chelators transferrin, lactoferrin, and desferrioxamine

The mammalian iron-binding proteins transferrin and lactoferrin, the bactericidal peptide lactoferricin B, and the bacterial siderophore desferrioxamine were tested for their ability to inhibit the in vitro replication of the oyster parasite Perkinsus marinus. All three chelators were effective in reducing the parasite proliferation in a dose-dependent manner. Lactoferricin B, a peptide of lactoferrin that exhibits bactericidal properties unrelated to iron chelation, had no inhibitory activity on the parasite. When the chelators were partially or completely saturated with the appropriate iron equivalents, their inhibitory effects on the parasite proliferation were diminished or abolished accordingly, confirming that this activity was related to the chelator's capacity for iron sequestration. Our results indicate that the parasite has a strong requirement for soluble iron and its growth rates are correlated with iron availability. We propose that excess iron accumulation in the host Crassostrea virginica promotes parasite proliferation. P. marinus may avoid oxidative damage that would compromise its intracellular survival by exhaustion the host's intracellular selected iron pools required for superoxide and hydroxyl radical production.     

Efficient expression of CFTR function with adeno-associated virus vectors that carry shortened CFTR genes

Adeno-associated virus (AAV)-based vectors have been shown to be effective in transferring the cystic fibrosis gene (CFTR) into airway epithelial cells in animal models and in patients. However, the level of CFTR gene expression has been low because the vector cannot accommodate the CFTR gene together with a promoter. In this study, we described a strategy to reduce the size of the CFTR cDNA to allow the incorporation of an effective promoter with the CFTR gene into AAV vectors. We engineered and tested 20 CFTR mini-genes containing deletions that were targeted to regions that may contain nonessential sequences. Functional analyses showed that four of the shortened CFTRs (one with combined deletions) retained the function and the characteristics of a wild-type CFTR, as measured by open probability, time voltage dependence, and regulation by cAMP. By using an AAV vector with a P5 promoter, we transduced these short forms of CFTR genes into target cells and demonstrated high levels of CFTR expression. We also demonstrated that smaller AAV/CFTR vectors with a P5 promoter expressed the CFTR gene more efficiently than larger vectors or a vector in which CFTR gene was expressed from the AAV inverted terminal repeat sequence. The CFTR mini-gene with combined deletions was packaged into AAV virions more efficiently, generated higher titers of transducing virions, and more effectively transferred CFTR function into target cells. These new vectors should circumvent the limitations of AAV vector for CFTR expression. Our strategy also may be applicable to other genes, the sizes of which exceed the packaging limit of an AAV vector.     

Cerebrospinal fluid fistula: detection with MR cisternography

PURPOSE: Our goal was to assess the role of MR cisternography in the examination of patients with suspected CSF rhinorrhea. METHODS: MR cisternography was performed as a heavily T2-weighted fast spin-echo study with fat suppression and video reversal of the images in 37 patients over a 3-year interval. Twenty-four of the patients subsequently had exploratory surgery for fistula. Statistical analysis of the surgical results was compared with the findings at MR cisternography. RESULTS: MR cisternography showed significant correlation with surgical findings, with sensitivity, specificity, and accuracy of 0.87, 0.57, and 0.78, respectively. CONCLUSION: MR cisternography proved to be an accurate diagnostic imaging technique in the evaluation of suspected CSF rhinorrhea.     

Effects of intravenous medium-chain triglycerides on pulmonary gas exchanges in mechanically ventilated patients

OBJECTIVE: In mechanically ventilated patients, pulmonary gas exchange was investigated during the administration of total parenteral nutrition containing medium-chain triglycerides or long-chain triglycerides as fat emulsions. DESIGN: Prospective, randomized, crossover trial (two lipid infusion periods of 8 hrs). SETTING: Intensive care unit in a university hospital. PATIENTS: Six mechanically ventilated patients, using the pressure-support mode. INTERVENTIONS: Total caloric intake was adapted according to measured energy expenditure. Fat emulsion provided 50% of the energy expenditure. Patients were infused with 50% medium-chain/50% long-chain triglycerides or 100% long-chain triglycerides in a random sequence. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption, CO2 production, and minute ventilation were measured by indirect calorimetry. PaO2 and PaCO2 were determined in blood samples. Medium-chain triglycerides increased oxygen consumption by 27.8% and minute ventilation by 14.3% at the end of the protocol. CO2 production, PaO2, and PaCO2 were not different between groups. CONCLUSIONS: Medium-chain triglycerides cause an increase in metabolic demand in mechanically ventilated patients when they are infused over a short period. Postoperative or intensive care unit patients with a low pulmonary reserve should receive infusions of medium-chain triglycerides over a more prolonged period than long-chain triglycerides.     

Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells

The aim of this study was to test the hypothesis that oxidative stress induces apoptosis in the H9c2 cardiac muscle cell line, and that signaling via mitogen-activated protein kinase (MAPK) pathways is involved. Three forms of oxidative stress were utilized: the superoxide generator menadione; hydrogen peroxide; or simulated ischemia followed by reperfusion. Relatively low concentrations of menadione (10 micrometer) or H2O2 (250 micrometer) caused maximal DNA fragmentation and caspase activation, both markers for apoptotic cell death, and preferential activation of the c-Jun NH 2-terminal kinase (JNK) and p38 MAPK pathways. In contrast, higher concentrations of menadione or H 2O2 caused less DNA fragmentation, more necrotic cell death and preferential activation of the extracellular signal-regulated kinase (ERK) pathway. Simulated ischemia alone did not induce DNA fragmentation or caspase activation and activated only the p38 MAPK pathway. However, ischemia plus reperfusion resulted in DNA fragmentation, caspase activation, necrotic cell death and activation of all three MAPK pathways. Selective inhibition of the ERK or p38 MAPK pathways (by PD98059 or SB-203580, respectively) had no effect on the extent of oxidative stress-induced DNA fragmentation or caspase activation. In contrast, inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK markedly reduced the extent of DNA fragmentation and caspase activation induced by oxidative stress. In conclusion, these data suggest that the JNK pathway plays an important role in signaling oxidative stress-induced apoptosis of H9c2 cardiac muscle cells.     

Nitrogen-regulated ubiquitination of the Gap1 permease of Saccharomyces cerevisiae

Addition of ammonium ions to yeast cells growing on proline as the sole nitrogen source induces rapid inactivation and degradation of the general amino acid permease Gap1 through a process requiring the Npi1/Rsp5 ubiquitin (Ub) ligase. In this study, we show that NH4+ induces endocytosis of Gap1, which is then delivered into the vacuole where it is degraded. This down-regulation is accompanied by increased conversion of Gap1 to ubiquitinated forms. Ubiquitination and subsequent degradation of Gap1 are impaired in the npi1 strain. In this mutant, the amount of Npi1/Rsp5 Ub ligase is reduced >10-fold compared with wild-type cells. The C-terminal tail of Gap1 contains sequences, including a di-leucine motif, which are required for NH4+-induced internalization and degradation of the permease. We show here that mutant Gap1 permeases affected in these sequences still bind Ub. Furthermore, we provide evidence that only a small fraction of Gap1 is modified by Ub after addition of NH4+ to mutants defective in endocytosis.