Comparison Between Total IgG, C1q, and C3d Single Antigen Bead Assays in Detecting Class I Complement-Binding Anti-HLA Antibodies.

BACKGROUND: Complement-binding donor-specific antibodies (DSAs) are associated with antibody-mediated rejection and allograft loss. Novel single antigen bead (SAB) assays-that is, complement component 1q (C1q) and complement component 3d (C3d) assays-have been developed to specifically detect complement-binding DSA, but it remains unclear whether these assays have an improved ability to detect complement-binding DSA as compared with using the total IgG SAB assay with a high mean fluorescence intensity (MFI) cutoff. The aim of this study was to compare the ability of the total IgG, C1q, and C3d SAB assays in detecting complement-binding anti-HLA antibodies. METHODS: Twenty sera known to have complement-binding anti-HLA antibodies (serologic class I HLA typing by complement-dependent cytotoxicity method) were tested with 3 different SAB assays: total IgG (undiluted and 1:8 dilution), C1q, and C3d. Serologic anti-HLA specificities were compared with those obtained by IgG, C1q, and C3d SAB assays. RESULTS: IgG SAB was more sensitive in detecting complement-binding antibodies (sensitivity 24 of 24 = 1, odds ratio infinity). Pearson correlation showed the association between (1) C1q and IgG SAB assays (cutoff C1q SAB 1000 MFI, cutoff IgG SAB 5000 MFI: r = 0.347, P < .0001) and (2) C3d and IgG SAB assays (cutoff 500 MFI C3d SAB, 5000 MFI for IgG SAB: r = -0.173, P = .279). CONCLUSIONS: For class I anti-HLA antibodies, IgG SAB (cutoff MFI > 5000) was more sensitive in detecting complement-binding antibodies when compared with C1q and C3d SAB assays.

SELDI-TOF proteomic analysis and cancer detection.

BACKGROUND: In recent years proteomic approaches have been widely used to diagnose disease and the new technology of surface enhanced laser-desorption and ionization time-of-flight mass spectrometry (SELDI-TOF MS) is very promising. METHODS: A review of English language literature was undertaken using Internet databases such as PubMed and Medline for studies using proteomic technologies for the early detection of cancer. RESULTS: SELDI-TOF is an array based mass spectrometric method in which proteins of interest are selectively absorbed onto a chemically modified surface and the mass and amount of each protein is measured by irradiating the surface with a laser and measuring the time-of-flight. The technology has revealed a large number of previously uncharacterized biomarkers for a wide variety of cancers. Its versatility has also been demonstrated by its application as a tool for mining a wide variety of biological tissues and fluids. CONCLUSIONS: The majority of these studies have discriminated between diseased and healthy controls with a high degree of sensitivity and specificity. The reproducibility, standardization and feasibility of this technology need to be addressed before these proteomic approaches to the discovery of novel, highly sensitive diagnostic tools can become routine clinical care.

Fruit consumption, fitness, and cardiovascular health in female adolescents: the Penn State Young Women's Health Study.

The objective of this study was to compare the relations among nutrient intake, fitness, serum antioxidants, and cardiolipoprotein profiles in female adolescents. The study design was a cross-sectional analysis of the Penn State Young Women's Health Study. The present study was performed with the entire cohort (n = 86) when they were 17.1+/-0.5 y (x+/-SD) of age. Primary measurements included cardiolipoprotein indexes, serum antioxidants, nutrient intakes, aerobic fitness, and percentage body fat. The cohort was stratified by estimated maximal oxygen uptake (VO2max) measurements and by percentage body fat. The fifth quintile by estimated VO2max had significantly lower percentage body fat, higher athletic scores, higher fruit intake, lower total serum cholesterol, and lower ratios of total serum cholesterol to HDL cholesterol than members of the first quintile. When the members of the first and fifth quintiles by percentage body fat were compared, the first quintile had significantly lower weight, lower body mass index, higher estimated VO2max, higher athletic scores, lower ratios of total serum cholesterol to HDL cholesterol, and higher fruit, carbohydrate, and fiber intakes. Correlation analyses performed with the data for the entire cohort showed fruit consumption to be positively correlated with estimated VO2max, and predicted VO2max to be positively correlated with circulating beta-carotene and alpha-tocopherol. This study provided evidence that the positive associations of exercise and fruit consumption with cardiovascular health apply to female adolescents as well as to adults.

Effects of PNU157706, a dual 5alpha-reductase inhibitor, on gene expression in the rat epididymis.

The epididymis is the site of sperm maturation and storage. 5alpha-Reductases (types 1 and 2) are key enzymes in this tissue because they convert testosterone to dihydrotestosterone (DHT), the main androgen regulating epididymal functions. Examining the consequences of inhibiting DHT formation is likely to provide important information regarding the regulation of epididymal functions, yet few inhibitor studies have focused on this tissue. To understand better DHT-mediated regulation of epididymal gene expression, we employed a dual 5alpha-reductase inhibitor and cDNA microarrays to examine the effects of 5alpha-reductase inhibition on gene expression in the initial segment, caput, corpus, and cauda epididymidis. Inhibition of epididymal 5alpha-reductase activity by PNU157706 was confirmed by in vitro enzyme assays. Rats were treated with 0, 0.1, 1.0 or 10 mg/kg per day PNU157706 for 28 days. The weights of DHT-dependent tissues, including the epididymis, were decreased following treatment. The effect of treatment on gene expression was dose-dependent and highly segment-specific. The initial segment responded uniquely in that a similar number of genes increased and decreased in expression compared with the other segments where the majority of affected genes decreased in expression. Some of the more dramatically affected genes were involved in signal transduction as well as fatty acid and lipid metabolism, regulation of ion and fluid transport, luminal acidification, oxidative defense and protein processing and degradation. These are essential processes contributing to the formation of an optimal luminal microenvironment required for proper sperm maturation. These results provide a novel insight into the DHT-dependent mechanisms that control epididymal functions.

Somatosensory cortical evoked potential changes after deformity correction.

The somatosensory cortical evoked potentials recorded during posterior spine fusion and instrumentation for 99 consecutive patients with idiopathic scoliosis, 18 years of age or younger, were retrospectively reviewed. The potentials were recorded from scalp electrodes while synchronously stimulating both tibial nerves near the ankles. Signal changes observed during consecutive 30-minute time intervals after deformity correction were analyzed. No changes in neurologic status were observed postoperatively. Latency values tended to remain constant on average. A small, but statistically significant, decrease in the first two interpeak amplitudes was observed during the first 30-minute interval after deformity correction. The first interpeak amplitude recovered, while the second remained statistically significantly decreased. No patient had a decrease of greater than 50% in both of the first two amplitudes, which persisted throughout the 60-minute interval immediately after deformity correction. This study demonstrated a tendency for somatosensory cortical evoked potential interpeak amplitudes to decrease during the first 30 minutes after deformity correction. There was a great deal of individual variation, including amplitude increases in many patients. There was no evidence supporting an association between dramatic, sustained amplitude decreases and uncomplicated deformity correction. The value of thoroughly evaluating somatosensory cortical evoked potential signal trends while making intraoperative decisions is emphasized.