Expression of leukocyte fucosyltransferases regulates binding to E-selectin: relationship to previously implicated carbohydrate epitopes

E-selectin is a carbohydrate-binding endothelial cell adhesion molecule that reportedly interacts with several related sialylated and fucosylated carbohydrates. The activity of leukocyte alpha1,3-fucosyltransferases (FucT-IV or FucT-VII) is an essential step in the synthesis of E-selectin ligands. Using a panel of stably transfected hemopoietic cell lines, we have investigated the role of alpha1,3-fucosyltransferases in generating E-selectin ligands, and the relationship between adhesion to E-selectin and expression of mAb-defined carbohydrates. Expression of FucT-VII was always sufficient for binding to E- and P-selectin, while the ability of FucT-IV to construct E-selectin ligands varied among different cell types. Furthermore, FucT-IV was unable to support any binding to P-selectin in a lymphoid cell line, even when expressed at levels equivalent to those in myeloid cells. FucT-IV expression generated high levels of surface Le(x)/CD15 and CDw65, whereas expression of FucT-VII correlated with a subset of mAb-defined sialyl Lewis X (sLex)-like structures. FucT-IV-associated epitopes were present on both binding and nonbinding cells, whereas all cells that expressed FucT-VII-associated epitopes bound E-selectin. However, treatment of HL60 cells with neuraminidase destroyed FucT-VII-associated epitopes at a faster rate than E-selectin binding sites. Surface expression of a subset of mAb-defined sLex-like carbohydrates is therefore a good marker for high levels of FucT-VII activity, but these carbohydrates are not themselves required for recognition of E-selectin.     

Association between serum amyloid A proteins and coronary artery disease: evidence from two distinct arteriosclerotic processes

BACKGROUND: Serum amyloid A (SAA) proteins are a family of inflammatory apolipoproteins that may modify high-density lipoprotein structure and function. Elevations of SAA have been reported in unstable coronary syndromes, but the levels and types of SAA protein in humans with spontaneous or transplant-associated coronary artery disease are not known. METHODS AND RESULTS: SAA levels were analyzed using an ELISA in 76 sera from 36 patients after cardiac transplantation and in 346 other individuals, 85 patients with atherosclerotic coronary disease plus 261 of their relatives. The mean SAA level was 5-fold higher in transplant patients (203+/-181 microg/mL [23 to 934 microg/mL]) compared with normal subjects without coronary disease (36+/-16 microg/mL [2.8 to 193 microg/mL], P<.005). The mean SAA level was significantly elevated in patients with transplant coronary disease (206+/-160 microg/mL, n=23) compared with those without (140+/-104 microg/mL, n=12, P=.02). Elevated SAA levels were associated with increased mortality after transplantation. On multiple regression analysis, SAA levels were predicted by corticosteroid dose, pretransplant diagnosis of atherosclerotic coronary artery disease, and the presence of transplant coronary disease. SAA levels were elevated in patients with spontaneous atherosclerotic coronary disease (49+/-31 microg/mL) compared with unaffected relatives (39+/-36 microg/mL, mean+/-SD, P=.02). There was no evidence for a genetic contribution to SAA levels. All inducible human SAA protein types were documented by immunoblotting in both spontaneous and transplant coronary disease. CONCLUSIONS: Environmentally determined elevations in SAA levels in patients with both spontaneous and transplant coronary artery disease provide further evidence for a potential pathophysiological link between inflammation, lipoprotein metabolism, and the development of atherosclerosis.     

Low dietary fiber and high protein intakes associated with newly diagnosed diabetes in a remote aboriginal community

The high prevalence of diabetes mellitus in North American aboriginal populations may be due to recent changes in lifestyle, including the adoption of a high-fat, low-fiber diet. To determine whether fat or fiber intakes were associated with new cases of diabetes, we studied 72% (728/1018) of residents aged > 9 y from a remote aboriginal community in northern Ontario using the 75-g oral-glucose-tolerance test and 24-h dietary recall. The mean fat intake of this population (36% of energy) was typical for North America, but fiber intake (1.2 g/MJ) was very low. Logistic-regression analysis, adjusted for age, sex, and body mass index, showed that a 1-SD increase in fiber intake reduced the risk of having diabetes by 39% (P = 0.026) whereas the same increase in protein intake increased the risk by 38% (P = 0.027). There was no significant effect of energy, fat, starch, or simple sugars. These data support Trowell's original dietary-fiber hypothesis that "... dietary fiber depleted starchy foods are conducive to the development of diabetes mellitus in susceptible human genotypes."     

Sensitivity of computed tomography in detecting local recurrence of prostatic carcinoma following radical prostatectomy

The aim of this study was to evaluate CT imaging in the post-operative follow-up and in the detection of recurrence after radical prostatectomy in cases of prostatic carcinoma. In over 500 patients undergoing radical prostatectomy for prostatic carcinoma, 22 cases with local recurrence were found. CT examinations of the pelvis were retrospectively evaluated in these patients. Local recurrence was detected by PSA uptake and confirmed by transrectal ultrasound (TRUS) in combination with guided biopsy. In 22 cases of confirmed local recurrence, positive results on CT were found in eight patients (36%) and negative results in nine patients (41%). In the remaining five cases (23%), no distinction could be made between scar and local recurrence. All cases definitively classified as recurrent tumour disease showed a soft tissue mass of 2 cm or more. CT sensitivity in local recurrence of prostatic carcinoma after surgery is low. Even in a very careful follow-up, the understaging would be up to 41%. In comparison, PSA, TRUS and needle biopsy are the methods of choice and are superior to CT imaging. Based on these results, there would be no reason for including pelvic CT examinations in the follow-up of prostatic carcinoma after radical prostatectomy.     

Chest pain centers

Conceptually, the Chest Pain Center model is nothing more than a system of delivering health care. It is a model that all hospitals can embrace as a framework for organizational decision making in meeting the heart-care needs of their communities. It also provides a framework for clinical decision making. By adopting some or all of the common features of the model, hospitals develop a common language, similar to what took place when CCUs first opened in the 1960s. Application of evidence-based clinical practice is promoted. Approaches that account for both clinical outcomes and financial outcomes will be further refined. One result will be simultaneous improvement in clinical outcomes and a decrease in costs, but the most important aspect of the Chest Pain Center model is that it puts the patient first.     

Further evidence for elevated human minisatellite mutation rate in Belarus eight years after the Chernobyl accident

Analysis of germline mutation rate at human minisatellites among children born in areas of the Mogilev district of Belarus heavily polluted after the Chernobyl accident has been extended, both by recruiting more families from the affected region and by using five additional minisatellite probes, including multi-locus probe 33.6 and four hypervariable single-locus probes. These additional data confirmed a twofold higher mutation rate in exposed families compared with non-irradiated families from the United Kingdom. An elevated rate was seen at all three independent sets of minisatellites (detected separately by multi-locus probes 33.15, 33.6 and six single-locus probes), indicating a generalised increase in minisatellite germline mutation rate in the Belarus families. Within the Belarus cohort, mutation rate was significantly greater in families with higher parental radiation dose estimated for chronic external and internal exposure to caesium-137, consistent with radiation induction of germline mutation. The spectra of mutation seen in the unexposed and exposed families were indistinguishable, suggesting that increased mutation observed over multiple loci arises indirectly by some mechanism that enhances spontaneous minisatellite mutation.     

Limiting amino acids in meat and bone and poultry by-product meals

In situ, digestion, and growth studies were conducted to evaluate four meat and bone meals and six poultry by-product meals as sources of escape protein and to predict the first-limiting amino acid for growing calves. Escape protein values, determined by 12-h in situ incubation, ranged from 41.7 to 51.0% of CP for meat and bone meals; poultry by-product meals ranged from 32.0 to 39.8%. True protein digestion in the gastrointestinal tract of lambs differed among protein sources (P < .05), ranging from 79 to 95%. In each of three growth trials, 60 steers (258 +/- 24, 241 +/- 23, and 230 +/- 16 kg for Trials 1, 2, and 3, respectively) were supplemented with 4 of the 10 protein sources along with a urea supplement. Protein sources were fed at 30, 40, 50, and 60% of the supplemental CP, with urea supplying the remainder. Protein efficiency differed among treatments ( P < .10), ranging from .61 to 1.55. Amino acid composition was determined for each protein source, and the individual metabolizable amino acids were regressed on the protein efficiency values. Escape protein values were correlated (R2 = .75) with protein efficiency but had a negative slope. Metabolizable methionine was the only amino acid moderately correlated (R2 = .40, slope = 1.9) to protein efficiency, whereas other amino acids either correlated poorly or had negative slopes. These data indicate that the protein value of meat and bone meal and poultry by-product meal is limited by the amount of metabolizable methionine they contain.