GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside GD3

The gangliosides of melanoma and other tumours of neuroectodermal origin are suitable targets for immune intervention with tumour vaccines. The optimal vaccines in current use contain ganglioside plus bacillus Calmette-Guérin and induce considerable morbidity. We have screened a variety of new adjuvants in the mouse, and describe one antigen-delivery system, proteosomes, which is especially effective. Highly hydrophobic Neisserial outer membrane proteins (OMP) form multimolecular liposome-like vesicular structures termed proteosomes which can readily incorporate amphiphilic molecules such as GD3 ganglioside. The optimal GD3/proteosome vaccine formulation for induction of GD3 antibodies in the mouse is determined. Interestingly, the use of potent immunological adjuvants in addition to proteosomes augments the IgM and IgG antibody titres against OMP in these vaccines but GD3 antibody titres are unaffected. The application of proteosomes to enhance the immune response to GD3 extends the concept of the proteosome immunopotentiating system from lipopeptides to amphipathic carbohydrate epitopes such as cell-surface gangliosides. The demonstrated safety of meningococcal OMP in humans and the data in mice presented here suggest that proteosome vaccines have potential for augmenting the immunogenicity of amphipathic tumour antigens in humans.     

Cholesterol and lipoprotein(a) as risk factors for coronary heart disease in elderly subjects

The changes in lipoprotein(a) concentration that occur with age as a result of its association with an increased risk of coronary artery disease were investigated. Lipoprotein(a) concentrations were measured in serum samples from healthy volunteers, individuals with premature coronary artery disease, individuals with hyperlipidaemia but without evidence of premature coronary artery disease, and also in elderly men and women who had hyperlipidaemia. Concentrations in individuals with premature coronary artery disease were the same as those of the healthy volunteers, while in both these groups they were lower than those found in hyperlipidaemic elderly men and women, and those found in hyperlipidaemic women aged 36-68 years. No association between raised lipoprotein(a) concentration and mortality as a result of premature coronary artery disease was demonstrated. Raised lipoprotein(a) levels found in the hyperlipidaemic individuals also suggested that it may not be an independent risk factor.     

Cerebral protection by intermittent reperfusion during temporary focal ischemia in the rat

Temporary arterial occlusion has been routinely used as an adjunct in intracranial aneurysm surgery. This has commonly been performed using a protocol of multiple short periods of occlusion alternating with periods of restoration of normal circulation. Recently, the logical basis of this method has come under scrutiny. There is extensive experimental evidence to suggest that repetitive, brief periods of global ischemia may cause more severe cerebral injury than an equivalent single period of global ischemia. Only recently has this issue begun to be addressed with regard to focal ischemia. Hence, despite the common use of temporary clipping, little experimental data are available regarding the ischemic consequences of temporary arterial occlusion with periods of reperfusion versus uninterrupted temporary occlusion. To investigate this issue, a protocol of occlusion/reperfusion that simulates the temporal profile that occurs during surgery was performed in a rat model of focal ischemia. Sixteen anesthetized Sprague-Dawley rats were divided into two groups. The animals in Group I underwent 60 minutes of uninterrupted middle cerebral artery occlusion and the animals in Group II were subjected to six separate 10-minute occlusion periods with 5 minutes of reperfusion between occlusions. Histopathological analysis was performed 72 hours postischemia. Group I had significantly increased mean infarction volumes (50.0 +/- 12.1 mm3) compared to Group II (8.7 +/- 3.1 mm3) (p = 0.008). Injuries in Group I occurred in both the cortex and striatum, whereas Group II showed only striatal injuries. Furthermore, the extent of the injuries in Group II was less severe, characterized by ischemic neuronal injury rather than frank infarction. The results indicate that intermittent reperfusion is neuroprotective during temporary focal ischemia and support the hypothesis that intermittent reperfusion is beneficial if temporary clipping is required during aneurysm repair.     

Rapid screening of doping agents in human urine by vacuum MALDI-linear ion trap mass spectrometry

Detection of doping agents in urine frequently requires extensive separation prior to chemical analyses. Gas or liquid chromatography coupled to mass spectrometry has produced accurate and sensitive assays, but chromatographic separations require time and, sometimes, chemical derivatization. To avoid such tedious and lengthy procedures, vacuum matrix-assisted laser desorption ionization (vMALDI) coupled with the linear ion trap mass spectrometry (LIT/MS) technique is tested for its applicability as a rapid screening technique. Commonly used doping agents like nandrolone, boldenone, trenbolone, testosterone, and betamethasone were chosen as study compounds. Different MALDI matrixes like alpha-cyano-4-hydroxycinnamic acid (CHCA), dihyroxy benzoic acid (DHB) with and without cetyl trimethyl ammonium bromide (CTAB), a surfactant, and meso-tetrakis(pentafluorophenyl) porphyrin (F20TPP) were tested. Among them, F20TPP (MW 974.57 Da) was selected as the preferred matrix owing to the lack of interfering matrix peaks at the lower mass range (m/z 100-700). Urine samples spiked with study compounds were processed by solid-phase extraction (SPE) and consistently detected through a linear range of 0.1-100 ng/mL. The limit of detection and lower limit of quantification for all five analytes have been determined to be 0.03 and 0.1 ng/mL, respectively, in urine samples. Testosterone-d3 was used as an internal standard, and the quantitative measurements were achieved by the selective reaction monitoring (SRM) mode. The method was validated and showed consistency in the results. Hence, vMALDI-LIT/MS can be used as a rapid screening method to complement the traditional GC/MS and LC/MS techniques for simultaneous identification, confirmation, and quantification of doping agents in urine.     

Effect of temperature and pH on the post-mortem degradation of myofibrillar proteins

Incubation of bovine muscle at 37°C promoted a more drastic proteolytic change in myofibrillar proteins, as determined from sodium dodecyl sulphate polyacrylamide gels of isolated myofibrils, than incubation at 4°C. Degradation of myosin and troponin-T were the most noticeable changes at 37°C. Loss of α-actinin was observed in the 4°C incubated muscle. Ground bovine muscle incubated at pH 5·4 and 7 revealed that alterations in myosin and troponin-T were the most noticeable changes at ph 5·4 while troponin-T and α-actinin were altered at pH7. More troponin-T degradation occurred at pH 5·4 and 37°C than at pH7 and 4°C (similar to the degradation of myosin), indicating that troponin-T degradation in post-mortem muscle may be an indicator of overall myofibrillar proteolysis and not responsible for post-mortem tenderisation per se. Myosin degradation in the ground samples incubated at pH 5·4 and in whole samples incubated at 37°C was compared with the digestion of myofibrillar myosin by papain. Both pyrophosphate and Guba-Straub extracts of the 37°C and pH 5·4 treated samples confirmed that myosin degradation did occur to a much greater extent at this temperature and pH than at 4°C and pH7, and, in addition, at pH 5·4 frequent cleavage occurred near the papain sensitive site of myosin.     

The effect of fly ash on fluid dynamics of CO2 scrubber in coal-fired power plant

Uncaptured fly ash and/or suspended solids from wet flue gas desulfurization (WFGD) scrubbing solutions are one of several factors that will influence the performance and robustness of carbon dioxide capture systems in coal-fired power plants which will be installed prior to the exhaust stack. In this study, a 100 mm ID packed column scrubber was tested with different concentrations of ash in various chemical solutions to evaluate the influence of solids on the fluid dynamics of the packing material. Data reported here are collected from three solutions including water, 30 wt% MEA (monoethanolamine), and 20 wt% potassium carbonate. The packing selected for this study was a 16 mm polypropylene pall rings. Compressed air was used to simulate flue gas at near ambient temperature and pressure.     

The North Carolina High School Athletic Injury Study: design and methodology

PURPOSE: Organized interscholastic athletics are an integral part of the educational program at almost every school level. With this growing popularity of sports and their inclusion in more public school programs, it becomes increasingly apparent that additional consideration must be given to the injury problem associated with sport. The North Carolina High School Athletic Injury Study (NCHSAIS) was undertaken to identify patterns of injury among male and female athletes in North Carolina high schools participating in any of 12 sports. Specific aims are to measure the incidence, severity and etiology of injuries; to determine the relationship of demographic factors and protective equipment, exposure to play, and school characteristics to injuries; to study the relationship of coaches' training and experience to injury occurrence; and to compare the incidence and severity of injury among female and male athletes in the same or comparable sports. METHODS: A two-stage cluster sample of 100 high schools in North Carolina was selected for this 4-yr prospective study. RESULTS: Participation by the initial sample or a random replacement was achieved for 91 of the 100 schools. Nonresponse occurred at multiple levels of the sample for this study, and the weekly participation form posed the greatest respondent burden. CONCLUSIONS: The NCHSIAS offers a successful methodology for addressing sports injuries. In this paper we describe the design, methodology, and implementation issues that emerge in conducting a large scale epidemiological study in a population of high school athletes.     

Long-term outcome in acute myocardial infarction patients admitted to hospitals with and without on-site cardiac catheterization facilities. MITI Investigators. Myocardial Infarction Triage and Intervention

BACKGROUND: Previous studies have documented the strong association between availability of on-site cardiac catheterization facilities and increased use of coronary angiography in patients with acute myocardial infarction (AMI). Although these studies have shown little influence of the availability of catheterization labs on hospital mortality, no long-term follow-up has been reported. METHODS AND RESULTS: From a cohort of 12,331 AMI patients admitted to 19 Seattle area hospitals, we compared long-term outcome in 7985 patients admitted to hospitals with and 4346 patients admitted to hospitals without on-site catheterization labs. During the index hospitalization, patients admitted to hospitals with on-site catheterization were more likely to undergo coronary angiography (67.1% versus 39.3%, P<.0001), coronary angioplasty (32.5% versus 13.2%, P<.0001), or coronary bypass surgery (12.5% versus 9.5%, P<.0001). At 3-year follow-up, patients admitted to hospitals with on-site catheterization labs were more likely to undergo postdischarge angiography (19.2% versus 15.2%, P=.0001) and coronary angioplasty (11.6% versus 8.2%, P<.0001). This was associated with approximately $2500.00 per patient in higher cumulative costs. Despite this higher rate of procedure use, there was no association between admission to a hospital with on-site catheterization facilities and lower long-term mortality (multivariate hazard ratio, 1.0; 95% CI, 0.93 to 1.1., the hazard being associated with admission to hospitals with on-site catheterization facilities). CONCLUSIONS: In an urban area with unconstrained patient transfer mechanisms and high overall cardiac procedure use rates, AMI patients admitted to hospitals without on-site catheterization facilities were managed with fewer procedures during hospitalization and follow-up. This more conservative treatment approach was not associated with any observed increase in long-term mortality.