An in vitro model for toxin-mediated vascular leak syndrome: ricin toxin A chain increases the permeability of human endothelial cell monolayers

Vascular leak syndrome (VLS) is the dose-limiting toxicity observed in clinical trials of immunotoxins containing ricin toxin A chain (RTA). RTA itself is thought to cause VLS by damaging vascular endothelial cells, but the exact mechanism remains unclear. This is partially due to the paucity of appropriate models. To study VLS, we developed an in vitro model in which human umbilical vein-derived endothelial cells were first grown to confluence on microporous supports and then cultured under low pressure in the presence or absence of RTA. Endothelial cell barrier function was assessed by measuring the volume of fluid that passed through each monolayer per unit time. We found that RTA significantly increased monolayer permeability at times and concentrations consistent with the onset of VLS in patients treated with RTA-based immunotoxins. Scanning electron microscopy showed that intercellular gaps formed in endothelial monolayers exposed to RTA. Intercellular gap formation followed endothelial cell death caused by the enzymatic activity of RTA. We conclude that RTA is directly toxic to endothelial cells in vitro and speculate that this contributes to VLS in vivo.     

The interaction of peripheral blood leukocytes with alpha1-acid glycoprotein, its carbohydrate chains and neoglycoconjugates

The interaction of human peripheral blood leukocytes with alpha 1-acid glycoprotein (AGP), its glycoforms as well as neoglyco-conjugates representing carbohydrate chains of AGP or its fragments was studied by flow cytometry. It was shown that the main target cells for AGP as well as for conjugates of its carbohydrate chains with polyacrylamide (PAA) are monocytes and polymorphonuclear leukocytes but not lymphocytes. The interaction of AGP with monocytes and granulocytes are mediated by its carbohydrate chains: the binding of AGP with cells was inhibited by AGP, AGP oligosaccharides as well as conjugates of oligosaccharides and its fragments with PAA. The data obtained show the existence of monocyte (and granulocyte) receptors which interact with complex type sialooligosaccharides of AGP.     

Executing algorithms with hypercube topology on torusmulticomputers

Many parallel algorithms use hypercubes as the communication topology among their processes. When such algorithms are executed on hypercube multicomputers the communication cost is kept minimum since processes can be allocated to processors in such a way that only communication between neighbor processors is required. However, the scalability of hypercube multicomputers is constrained by the fact that the interconnection cost-per-node increases with the total number of nodes. From scalability point of view, meshes and toruses are more interesting classes of interconnection topologies. This paper focuses on the execution of algorithms with hypercube communication topology on multicomputers with mesh or torus interconnection topologies. The proposed approach is based on looking at different embeddings of hypercube graphs onto mesh or torus graphs. The paper concentrates on toruses since an already known embedding, which is called standard embedding, is optimal for meshes. In this paper, an embedding of hypercubes onto toruses of any given dimension is proposed. This novel embedding is called xor embedding. The paper presents a set of performance figures for both the standard and the xor embeddings and shows that the latter outperforms the former for any torus. In addition, it is proven that for a one-dimensional torus (a ring) the xor embedding is optimal in the sense that it minimizes the execution time of a class of parallel algorithms with hypercube topology. This class of algorithms is frequently found in real applications, such as FFT and some class of sorting algorithms     

Large-bandwidth frequency conversion in high-NA step index opticalfibers

Using high-NA step index optical fibers, we show, theoretically, that large-bandwidth second-harmonic generation and sum frequency generation can be achieved at conversion frequencies in the visible region of the spectrum     

Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.     

Qualitative approach: a contribution to nursing

This paper focus on some characteristics of the qualitative methodology. Some of these methods are explored such as: participatory research, phenomenology, grounded theory and ethnography critical theory Perspectives of their utilization in nursing research are examined.     

Heterochromatin effects on the frequency and duration of LCR-mediated gene transcription

Organ transplantation is associated with an early bone loss that subsequently increases the risk of osteopenia and bone fractures. It is not known whether bone loss continues in long-term survivors, but persistent bone demineralization could further jeopardize an already diminished bone mass. To better define long-term bone status of kidney transplant recipients (KTR), we conducted cross-sectional and longitudinal evaluations of bone mineral density (BMD) in 70 KTR with a mean posttransplantation time of 8.1 years. BMD was determined by dual-energy X-ray absorptiometry and was repeated in 55 of the patients after a mean follow-up period of 22 +/- 5 months. Lumbar and femoral osteopenia, defined as a BMD lower than 2 standard deviations from mean value of sex- and age-matched controls, was present in 28.6% and 10.5% of patients, respectively. There was a significant negative correlation between cumulative prednisone dose and adjusted lumbar as well as femoral BMD (R = 0.45, P < 0.001 and R = 0.29, P < 0.05, respectively). Five patients had a vertebral BMD below a fracture threshold of 0.777 g/cm2. Vertebral fractures (VF) were found in four men and were associated with higher prednisone dosage (P < 0.05), larger cumulative prednisone dose (P < 0.05), and significantly lower BMD values. According to World Health Organization recent criteria for women, prevalences of lumbar and femoral osteopenia and lumbar and femoral osteoporosis in female patients reach 75%, 65%, 33%, and 10%, respectively. The longitudinal part of the study showed a persistent pathological lumbar demineralization process. Over the study period, BMD, expressed as a percentage of that of controls, decreased from 89 +/- 14% to 86 +/- 14% (P < 0.001). Annual change of bone mass was -1.7 +/- 2.8% per year. Accelerated vertebral bone loss (defined as a decrease of BMD, expressed as a percentage of that of controls, of more than 1% per year) was present in 56% of patients and was associated with higher prednisone dosage (P < 0.01). In conclusion, although VF are relatively infrequent in long-term survivors of renal transplantation, osteopenia is a frequent finding, and a substantial proportion of women present lumbar osteoporosis. An ongoing demineralization process of the spine is also demonstrated and probably contributes to long-term spinal osteoporosis incidence. Prednisone dosage remains the most constantly isolated risk factor.     

In-laboratory removal of femoral sheath following protamine administration in patients having intracoronary stent implantation

Two hundred twenty-eight patients with successful coronary stent implantation were randomized either to protamine administration and femoral sheath removal (group I, n = 117) or no heparin neutralization and delayed sheath removal (group II, n = 111). The hospital stay after treatment was shorter in patients receiving protamine; therefore, protamine use for neutralizing circulating heparin may be safely administered immediately after stent implantation.     

Solution conformation of the Pseudomonas syringae MSU 16H phytotoxic lipodepsipeptide Pseudomycin A determined by computer simulations using distance geometry and molecular dynamics from NMR data

Pseudomycin A is a cyclic lipodepsinonapeptide phytotoxin produced by a strain of the plant pathogenic bacterium Pseudomonas syringae. Like other members of this family of bacterial metabolites, it is characterised by a fatty acylated cyclic peptide with mixed chirality and lactonic closure. Several biological activities of Pseudomycin A are lower than those found for some of its congeners, a difference which might depend on the diverse number and distribution of charged residues in the peptide moiety. Hence, it was of interest to investigate its conformation in solution. After the complete interpretation of the two-dimensional NMR spectra, NOE data were obtained and the structure was determined by computer simulations, applying distance geometry and molecular dynamics procedures. The conformation of the large ring of Pseudomycin A in solution includes three rigid structural regions interrupted by three short flexible regions that act as hinges. The overall three-dimensional structure of the cyclic moiety is similar to that of previously studied bioactive lipodepsinonapeptides produced by other pseudomonads.