Survival in lung reperfusion injury is improved by an antibody that binds and inhibits L- and E-selectin

The selectins are a three-member family of leukocyte, platelet, and endothelial cell adhesion proteins that mediate leukocyte traffic into normal and inflamed tissues. P-selectin is expressed by endothelial cells and platelets, E-selectin by endothelial cells, and L-selectin by circulating leukocytes. To determine if selectin-mediated leukocyte adhesion influences the development of lung reperfusion injury, we studied hemodynamics and respiratory and inert gas exchange in sheep subjected to 3-hour in situ left lung ischemia followed by 6-hour left lung reperfusion with the right lung excluded. Ten minutes before reperfusion, eight animals received EL-246 (1 mg/kg intravenously), a novel antihuman selectin antibody that recognizes and blocks both L- and E-selectin and cross-reacts in sheep. Eight control animals with ischemia received no treatment, whereas three received an isotype-matched antihuman L-selectin antibody that does not cross-react in sheep (DREG-56, 1 mg/kg intravenously). Eight sham control sheep underwent an identical operative procedure but were never subjected to ischemia. Volume-cycled, pressure-limited (20 cm H2O) mechanical ventilation was consistent in all animals throughout the experiment. Six-hour survival in EL-246 recipients (100%) was significantly higher than in either ischemic control sheep (37.5%) or DREG-56 recipients (33.3%), but gravimetric lung water was equivalent in EL-246 recipients (5.9 +/- 1.7 ml/kg), ischemic control sheep (8.3 +/- 3.0 ml/kg), and DREG-56 recipients (9.1 +/- 2.6 ml/kg).(ABSTRACT TRUNCATED AT 250 WORDS)     

The uptake of 3-deoxy-3-fluoro-D-glucose by synaptosomes from rat brain cortex

D-[3-3H]-3-deoxy-3-fluoroglucose was synthesized chemically and shown to be transported into rat brain synaptosomes by a saturable process with a Km 6.2 x 10(-4) M and a Vmax 2.8 nmole x mg protein-1. After an initial, rapid period of transport, further uptake of the fluorosugar is restricted by the rate of its phosphorylation. Both D-glucose and cytochalasin B are competitive inhibitors of 3-deoxy-3-fluoro-D-glucose transport with Ki values of 93 micron and 6.0 x 10(-7) M, respectively. Phloretin, N-ethylmaleimide and p-chloromercuribenzoate also inhibit the fluorosugar uptake, whereas ouabain and changes in K+, Na+, Mg2+ and Ca2+ ions have only a small effect. The recorded 3-deoxy-3-fluoro-D-glucose influx is slightly reduced by potassium cyanide, antimycin A, 2,4-dinitrophenol, and rotenone. The uptake reduction caused by these four reagents is relieved by the addition of exogenous ATP. The possible influence of hexokinse activity on the uptake process is discussed.     

Reforming the Israeli health care market

Israel's experience in attempting to implement a health system reform based in large measure on managed competition should provide important data to other countries considering reliance on competitive mechanisms for third-party purchase of health care. In this paper, current proposals for reform of the Israeli market for third-party purchase of health care are examined in light of ideal market structures, particularly the theory of managed competition. The relationship between the theory, the notion of a 'purchaser-provider split' and the Israeli case are explored. The current Israeli health care market, which features enrollment of 96% of the population in competing sick funds, is presented. The changes necessary to base third-party purchase of health-care on managed competition are discussed. Special conditions of the Israeli health care system likely to influence implementation of a managed competition strategy are considered. Beyond a 'purchaser-provider' split, the proposals call for other restructurings, such as a split between finance and insurance functions, which the standard theory of managed competition does not take into account. The implications of these proposals for smooth functioning of the health care market must be weighed against political and ethical considerations unique to the Israeli environment.     

Wound healing and complementary therapies: a review

A series of five innovative experiments conducted by Wirth et al. which examined the effect of various complementary healing interventions on the reepithelialization rate of full thickness human dermal wounds was assessed as to specific methodological and related factors. The treatment interventions utilized in the series included experimental derivatives of the Therapeutic Touch (TT), Reiki, LeShan, and Intercessory Prayer techniques. The results of the series indicated statistical significance for the initial two experiments and nonsignificance or reverse significance for the remaining three studies. This review article examines the methodological designs of the series of studies, along with the TT practitioners' phenomenologically based journal reports, to provide potential contributing correlative factors for the differential results obtained. These factors include: (1) methodological design restrictions, (2) a transference/inhibitory effect (3) the influence of experimental assistants, (4) healer visualization /imagery techniques, (5) variations in subject populations, and (6) a potential cancellation effect. While the placebo controlled double-blind methodological designs used in the series were as stringent as those used in other fields of scientific inquiry, the overall results of the experiments were inconclusive in establishing the efficacy of the treatment interventions for accelerating the rate of reepithelialization of full thickness dermal wounds.     

The NMR solution structure of intestinal fatty acid-binding protein complexed with palmitate: application of a novel distance geometry algorithm

The three-dimensional solution structure of rat intestinal fatty acid-binding protein (I-FABP) complexed with palmitate has been determined using multidimensional triple-resonance NMR methods. The structure is based on 3889 conformational restraints derived mostly from 3-D 13C- and 15N-resolved nuclear Overhauser (NOESY) experiments. The 3-D NOESY data for this 15.4 kDa complex contained an average of nine possible interpretations per cross-peak. To circumvent this ambiguity, an eight-stage iterative procedure was employed to gradually interpret and introduce unambiguous distance restraints during subsequent rounds of structure calculations. The first stage of this procedure relied critically upon an initial structural model based on the consensus 1H/13C chemical shift-derived secondary structure and a set of symmetry-checked restraints derived from the 3-D 13C-resolved NOESY spectrum. The structures were calculated using DISTGEOM, a program that implements a novel distance geometry algorithm with pairwise Gaussian metrization. A central feature of this algorithm is the use of an iteratively optimized Gaussian distribution for the selection of trial distances, which overcomes the tendency of metrization to produce crushed structures. In addition, this algorithm randomly selects pairwise elements of the distance matrix, which results in an improved sampling of conformational space for a given computational effort. The final family of 20 distance geometry/simulated annealing structures exhibited an average pairwise C(alpha) root-mean-square deviation of 0.98 A, and their stereochemical quality, as assessed by PROCHECK, was comparable to that of 2.5 A X-ray crystal structures. The NMR structure was compared with the X-ray crystal structure of the same ligand/protein complex and was found to be essentially identical within the precision of the results. The NMR structure was also compared with that of the palmitate complex with bovine heart FABP, which shares 30% sequence identity with rat I-FABP. The overall folds were the same, but differences were noted with respect to the presence or absence of apparent conformational heterogeneity and the location and conformation of the bound fatty acid.     

Sclerosing stromal tumour of the ovary

Two cases of sclerosing stromal tumour of the ovary in young Melanesian females are described and the differential diagnosis is discussed. Sclerosing stromal tumour of the ovary is a rare benign tumour of ovarian stromal origin which is associated with endocrine activity in a few cases. One of the patients presented with signs of precocious puberty and the tumour in this patient was considered as a functioning lesion.     

Epitope mapping using histidine-tagged protein fragments: application to Escherichia coli RNA polymerase sigma 70

The pathogenic Neisseria have exploited the processes of horizontal DNA transfer and genetic recombination as mechanisms for the generation of extensive protein variation and modulation of gene expression. Localized recombinations have been well documented in members of multigene families as have alterations in short repetitive sequences. Here we report an analysis of the chromosomal structure of a defined lineage of Neisseria gonorrhoeae strain MSl1 pilin variants. This study reveals the occurrence of large rearrangements, including the amplification of a 26 kb region and an inversion involving more than a third of the chromosome. Additionally, a restriction site polymorphism that correlates with pilin expression has been observed. These findings highlight the flexibility of the gonococcal genome.     

Infantile intestinal leiomyosarcoma: surgical resection (without adjuvant therapy) for cure

A 7-week-old boy presented with a 6-week history of failure to thrive, acute intestinal obstruction, and an apparently irreducible intussusception (noted on contrast enema). He underwent abdominal exploration, during which a cecal mass was identified and resected. The mass proved to be a leiomyosarcoma. Histologically, it was an intermediate-grade malignancy with a predicted 5-year survival rate of 16% to 23% based on data from the adult experience. Three years after resection and without having received adjuvant therapy, he is healthy and free of disease. A review of the literature showed that in infants these tumors are predominantly colonic, compared with the predilection for small intestinal lesions found in the older pediatric and adult populations. Infantile intestinal leiomyosarcomata are rare malignancies that do well if complete surgical excision of the disease can be accomplished. The histological prognostic indicators proposed for intestinal leiomyosarcomas in the adult population cannot be extrapolated to infants because when they occur in infants, they appear to be less aggressive, and these patients do well without adjuvant therapy.     

Immunologic dysfunction in cancer

The interactions between the tumor and its host are complex, and many aspects of the immune system appear to be adversely affected directly or indirectly by the presence of the tumor. Virtually all of the processes involved in immune induction and action have been implicated in the observed deficient response in tumor-bearing patients. Improved understanding and molecular analysis of the mechanisms underlying the escape of tumors from immune surveillance may lead to the development of novel strategies for the prevention of T-cell immunosuppression in cancer patients, the development of novel immunotherapeutic strategies, and potentially prevention of tumor progression or development.