Biocompatibility of cardiopulmonary bypass circuit with new polymer Senko E-Ternal Coating™.

OBJECTIVE: The aim of this study was to compare the biocompatibility of a new Senko E-Ternal coating (SEC) for cardiopulmonary bypass (CPB) circuits with the well-established poly-2-methoxyethyl acrylate (PMEA) coating. METHODS: Forty patients undergoing aortic valve replacement were randomly assigned to either an SEC-coated group (n = 20) or a PMEA-coated group (n = 20). Clinical data and the following markers were analyzed: platelet count, platelet factor (PF) 4, fibrinogen, fibrinogen degradation products (FDPs), antithrombin III (AT III), thrombin-antithrombin complex (TAT), plasminogen, complement hemolytic activity (CH50), complement 3 (C3) and interleukin-6 (IL-6). Blood samples were obtained at five time points in both groups. RESULTS: CPB time, aortic cross-clamp time and blood loss and transfusion were similar in both groups. There were no significant differences between the groups in terms of platelet count, PF4 and all coagulation and fibrinolytic parameters (FDP, AT III, TAT, and plasminogen) at any time points. Inflammatory markers (CH50, C3 and IL-6) were also similar in both groups at all time points. CONCLUSIONS: The SEC-coated circuit demonstrated equivalent biocompatibility to the PMEA-coated circuit. SEC-coated circuits are, therefore, favorably comparable to PMEA-coated circuits for clinical use in CPB.

Metformin suppresses progression of muscle aging via activation of the AMP kinase-mediated pathways in Drosophila adults.

OBJECTIVE: Metformin, a medicine used for the treatment of type 2 diabetes, was previously reported to suppress age-dependent hyperproliferation of intestinal stem cells in Drosophila. Here, we aimed to investigate its anti-aging effects on other tissues, such as adult muscle and elucidate the mechanisms underlying the anti-ageing effect. MATERIALS AND METHODS: To evaluate the anti-muscle ageing effect of Metformin, we visualized ubiquitinated protein aggregates accumulated in adult muscle as the flies age by immunostaining and measured the total pixel size of the aggregates. We altered gene expression in the muscle by induction of dsRNA against the relevant mRNAs or mRNAs encoding the constitutively active mutant proteins using the Gal4/UAS system. We determined the mRNA levels by quantitative Real Time-Polymerase Chain Reaction (QRT-PCR). RESULTS: Continuous metformin feeding significantly extended the lifespan of Drosophila adults. Furthermore, the feeding suppressed the aging-dependent accumulation of ubiquitinated aggregates in adult muscle. To delineate the mechanism through which metformin influences the muscle aging phenotype, we induced the constitutively active AMPK specifically in the muscles and found that the activation of the AMPK-mediated pathway was sufficient for the anti-aging effect of Metformin. Furthermore, the AMPK-mediated downregulation of Tor-mediated pathways, subsequent induction of an eIF-4E inhibitor were involved in the effect. These genetic data suggested that the metformin effect is related to the partial suppression of protein synthesis in ribosomes. Furthermore, metformin stimulated autophagy induction in adult muscles. CONCLUSIONS: Our results suggest that metformin can be regarded as an anti-aging compound in Drosophila muscle. The stimulation of autophagy was also involved in the anti-aging effect, which delayed the progression of muscle aging in Drosophila adults.

The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism.

OBJECTIVE: Autism appears to have a strong genetic component. The product of the NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene is included in the mitochondrial electron transport chain. METHOD: We performed a case-control study of 235 patients with autism and 214 controls and examined three single-nucleotide polymorphisms (SNPs) within this gene in a Japanese population. We then conducted a transmission disequilibrium test (TDT) analysis in 148 autistic trios. RESULTS: In the case-control study, two SNPs (rs12666974 and rs3779262) showed a significant association with autism (P=0.00064 and 0.00046 respectively). Furthermore, a haplotype containing these two SNPs showed a significant association (P-global=0.0013, individual haplotype A-A: P=0.010). In TDT analysis, the global and A-A haplotype P-values also indicated significant associations. Minor allele and genotype frequencies were decreased in the autistic subjects. CONCLUSION: We found significant association between the NDFA5 gene and autism.

Associations of PD-L1, PD-L2, and HLA class I expression with responses to immunotherapy in patients with advanced sarcoma: post hoc analysis of a phase 1/2 trial.

BACKGROUND: Although immunotherapy is thought to be a promising cancer treatment, most patients do not respond to immunotherapy. In this post hoc analysis of a phase 1/2 study, associations of programmed death ligand 1 (PD-L1), PD-L2, and HLA class I expressions with responses to dendritic cells (DCs)-based immunotherapy were investigated in patients with advanced sarcoma. METHODS: This study enrolled 35 patients with metastatic and/or recurrent sarcomas who underwent DC-based immunotherapy. The associations of PD-L1, PD-L2, and HLA class I expressions in tumor specimens, which were resected before immunotherapy, with immune responses (increases of IFN-γ and IL-12) and oncological outcomes were evaluated. RESULTS: Patients who were PD-L2 (+) showed lower increases of IFN-γ and IL-12 after DC-based immunotherapy than patients who were PD-L2 (-). The disease control (partial response or stable disease) rates of patients who were PD-L1 (+) and PD-L1 (-) were 0% and 22%, respectively. Disease control rates of patients who were PD-L2 (+) and PD-L2 (-) were 13% and 22%, respectively. Patients who were PD-L1 (+) tumors had significantly poorer overall survival compared with patients who were PD-L1 (-). No associations of HLA class I expression with the immune response or oncological outcomes were observed. CONCLUSIONS: This study suggests that PD-L1 and PD-L2 are promising biomarkers of DC-based immunotherapy, and that addition of immune checkpoint inhibitors to DC-based immunotherapy may improve the outcomes of DC-based immunotherapy.

Canine oocyte maturation in culture: significance of estrogen and EGF receptor gene expression in cumulus cells.

We examined the role of cumulus cells regarding in vitro maturation of canine oocytes, and investigated estrogen and epidermal growth factor (EGF) receptor gene expression and action on nuclear maturation. Canine cumulus-oocyte complexes (COC) were collected from anestrous and diestrous bitches; only COC with vitelline diameter >100 microm were used. In Experiment 1, expression of estrogen receptor (ER) alpha, ERbeta and EGF-receptor (EGF-R) were determined by reverse transcription-polymerase chain reaction (RT-PCR), using mRNA from the oocyte or cumulus cell. Transcripts for the ERbeta and EGF-R were detected in oocytes and cumulus cells, but no message was detected for ERalpha. In Experiment 2, intact COC and the denuded oocytes were cultured in TCM199 medium supplemented with various concentrations of estradiol-17beta (E(2); 0-10 microg/mL) or EGF (0-100 ng/mL) for 72 h; nuclear maturation was then evaluated. In oocytes cultured within intact COC, the rate of germinal vesicle breakdown (GVBD) was higher in the 1 microg/mL E(2) supplemented group (P<0.05), and the rate of metaphase I (MI) was higher in the 10 ng/mL EGF supplemented group, than in the non-supplemented group (P<0.05). However, supplementation of E(2) or EGF to denuded oocytes failed to promote nuclear maturation. In Experiment 3, intact COC were cultured in TCM199 supplemented with 1 microg/mL E(2), 10 ng/mL EGF, and 10% fetal bovine serum (FBS) for 72 h, and nuclear maturation was evaluated. There was no significant difference in the rate of metaphase II (MII) between the medium only, E(2)+EGF, and FBS supplement groups. When E(2) and EGF in combination with FBS were supplemented, the rate of MII was higher than in other groups (P<0.05). We inferred that cumulus cells were involved in mediating the stimulatory effects of E(2) and EGF on nuclear maturation of canine oocytes, and that E(2) and EGF in combination with FBS promoted the completion of oocyte meiotic maturation.

Immunopathophysiological aspects of an emerging neonatal infectious disease induced by a bacterial superantigen.

We recently discovered an emerging neonatal infectious disease, neonatal toxic shock syndrome-like (TSS-like) exanthematous disease (NTED), which is induced by a superantigen, TSS toxin-1 (TSST-1), produced by methicillin-resistant Staphylococcus aureus (MRSA). Here, we analyzed the activation and the response of TSST-1-reactive Vss2(+) T cells in NTED patients during the acute and recovery phases and in asymptomatic infants exposed to MRSA. In the acute phase, Vss2(+) T cells were anergic to stimulation with TSST-1 and underwent marked expansion, but by 2 months after disease onset, their numbers had declined to about 10% of the control level. Although the percentage of Vss2(+) T cells in the ten asymptomatic neonatal MRSA carriers was within the control range, these individuals could be divided into two groups on the basis of Vss2(+) T-cell activation. Vss2(+)CD4(+) T cells from three of these infants (Group 1) highly expressed CD45RO and were anergic to TSST-1, whereas in the other seven asymptomatic neonatal MRSA carriers (Group 2), these cells expressed CD45RO at the control level and were highly responsive to stimulation with TSST-1. The serum anti-TSST-1 IgG Ab titer was negligible in the four NTED patients in the acute phase and the three asymptomatic neonatal MRSA carriers in Group 1, but it was high in the seven asymptomatic carriers in Group 2. We suggest that maternally derived anti-TSST-1 IgGs helps to suppress T-cell activation by TSST-1 and protects infants from developing NTED.

Automated PET-only quantification of amyloid deposition with adaptive template and empirically pre-defined ROI.

Amyloid PET is useful for early and/or differential diagnosis of Alzheimer's disease (AD). Quantification of amyloid deposition using PET has been employed to improve diagnosis and to monitor AD therapy, particularly in research. Although MRI is often used for segmentation of gray matter and for spatial normalization into standard Montreal Neurological Institute (MNI) space where region-of-interest (ROI) template is defined, 3D MRI is not always available in clinical practice. The purpose of this study was to examine the feasibility of PET-only amyloid quantification with an adaptive template and a pre-defined standard ROI template that has been empirically generated from typical cases. A total of 68 subjects who underwent brain (11)C-PiB PET were examined. The (11)C-PiB images were non-linearly spatially normalized to the standard MNI T1 atlas using the same transformation parameters of MRI-based normalization. The automatic-anatomical-labeling-ROI (AAL-ROI) template was applied to the PET images. All voxel values were normalized by the mean value of cerebellar cortex to generate the SUVR-scaled images. Eleven typical positive images and eight typical negative images were normalized and averaged, respectively, and were used as the positive and negative template. Positive and negative masks which consist of voxels with SUVR ⩾1.7 were extracted from both templates. Empirical PiB-prone ROI (EPP-ROI) was generated by subtracting the negative mask from the positive mask. The (11)C-PiB image of each subject was non-rigidly normalized to the positive and negative template, respectively, and the one with higher cross-correlation was adopted. The EPP-ROI was then inversely transformed to individual PET images. We evaluated differences of SUVR between standard MRI-based method and PET-only method. We additionally evaluated whether the PET-only method would correctly categorize (11)C-PiB scans as positive or negative. Significant correlation was observed between the SUVRs obtained with AAL-ROI and those with EPP-ROI when MRI-based normalization was used, the latter providing higher SUVR. When EPP-ROI was used, MRI-based method and PET-only method provided almost identical SUVR. All (11)C-PiB scans were correctly categorized into positive and negative using a cutoff value of 1.7 as compared to visual interpretation. The (11)C-PiB SUVR were 2.30 ± 0.24 and 1.25 ± 0.11 for the positive and negative images. PET-only amyloid quantification method with adaptive templates and EPP-ROI can provide accurate, robust and simple amyloid quantification without MRI.

15-Hydroperoxyeicosapentaenoic acid inhibits arachidonic acid metabolism in rabbit platelets more potently than eicosapentaenoic acid.

The effect of 15-hydroperoxy-5,8,11,13,15-eicosapentaenoic acid (15-HPEPE), a hydroperoxy adduct of eicosapentaenoic acid (EPA), on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), thromboxane (TX) B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) from exogenous arachidonic acid in washed rabbit platelets was examined. 15-HPEPE inhibited 12-HETE, TXB2 and HHT formation at concentrations ranging from 2 to 8 microM. The inhibitory effect of 15-HPEPE was dose-dependent (12-HETE, 16.0-82.9% inhibition; TXB2, 16.7-57.2% inhibition; HHT, 4.6-52.0% inhibition). EPA inhibited the production of these three metabolites, but the inhibitory effect was kept low (20-100 microM: 12-HETE, 8.3-31.1% inhibition; TXB2, 18.9-49.5% inhibition; HHT, 12.5-41.7% inhibition) as compared with 15-HPEPE. Experiments utilizing 15-hydroxy-5,8,11,13,15-eicosapentaenoic acid and hydroxyl radical scavengers (dimethyl sulfoxide and mannitol) revealed that 15-HPEPE exerted its effect in the form of the hydroperoxy adduct. These results suggest that 15-HPEPE has the potential to modulate the activities of the cyclo-oxygenase and 12-lipoxygenase in platelets. This may also be one convincing mechanism for the anti-thrombotic and anti-atherosclerotic actions of EPA.

Inhibitory effect of Mg2+ on the protonophoric activity of palmitic acid.

To discriminate whether fatty acids are uncouplers that cause acceleration of State-4 respiration, associated with a decrease in the protonmotive force, or decouplers that increase respiration without associated decrease in the protonmotive force, we examined the effect of palmitate on functions of rat-liver mitochondria under various conditions. We found that palmitate itself increases State-4 respiration, releases oligomycin-inhibited State-3 respiration, inhibits ATP synthesis and ATP<->Pi exchange reaction, and increases H+ permeability in mitochondrial and model bilayer phospholipid membranes. Thus, palmitate is a classical uncoupler of oxidative phosphorylation. However, these effects were inhibited by Mg2+, due to rapid formation of a stable complex between palmitate and Mg2+.

Phospholipid transfer protein can transform reconstituted discoidal HDL into vesicular structures.

The present study investigated the effect of phospholipid transfer protein (PLTP) on transformation of discoidal HDL (d-HDL) to vesicular structures by using primarily KBr density gradient centrifugation, non-denaturing gradient gel electrophoresis, and electron microscopy. The incubation of reconstituted d-HDL preparations containing apo-AI with PLTP resulted in the formation of vesicular structures differing in hydrated densities and sizes. The extents of transformation were dependent upon PLTP concentrations and incubation times. Substantial transformations occurred, even with plasma concentrations of PLTP, within 4 h of incubation at 37 degrees C. After 8 h of incubation, almost 80% of d-HDL was converted to vesicular structures with a hydrated density of 1.07 g ml-1. The d-HDL-vesicle transformation appeared to be triggered by the PLTP-mediated displacement of apo-AI. This apo-AI displacement might have led to the fusion of transiently produced apo-AI deficient particles, producing thermodynamically stable vesicular structures. The cross-linking of apo-AI in d-HDL almost completely prevented d-HDL-vesicle transformation. The addition of free apo-AI to the PLTP/d-HDL incubation mixtures also greatly reduced the transformation. The conversion of smaller vesicles of density 1.07 g ml-1 to larger vesicles of density 1.05 g ml-1 also seemed to have been affected by PLTP-mediated apo-AI displacement. We described the possible implications of the transformation of d-HDL into vesicular structures in lipid and lipoprotein transport processes under physiological and pathological conditions.

Benefit of bilateral over single internal mammary artery grafts for multiple coronary artery bypass grafting.

BACKGROUND: The aim of this study was to evaluate the performance of bilateral internal mammary artery (BIMA) grafts in isolated CABG. METHODS AND RESULTS: Beginning in April 1985, elective primary multiple CABG for multivessel disease was performed in 1131 patients. The early and late results of 688 patients who received single internal mammary artery (SIMA) grafts and 443 patients who received BIMA grafts were compared (median follow-up, 6.15 years). Hospital mortality was not significantly different in the SIMA (0.9%) and BIMA (0.9%) groups. Graft patency was 97.3% in the BIMA group and 94.3% in the SIMA group (P<0.0001). The 7-year repeated CABG-free rate was significantly higher in the BIMA group (P=0.026). The 7-year new myocardial infarction-free rate in all patients tended to be higher in the BIMA group (P=0.06). The hazard ratio for all death or repeated CABG in patients with ejection fractions >0.4 and age <71 years was lower in the BIMA group (P=0.0499). CONCLUSIONS: Our data suggest that the use of BIMA grafts in patients with in situ coronary artery anastomoses achieves a significantly higher repeated CABG-free rate in all patients compared with the use of SIMA.

Coronary artery bypass with only in situ bilateral internal thoracic arteries and right gastroepiploic artery.

BACKGROUND: With the rapid advance of catheter intervention, the direction taken by surgeons is not only to make conventional CABG less invasive but also to pursue better long-term results by using more arterial conduits. METHODS AND RESULTS: Between July 1989 and April 2000, 239 patients (218 men, 21 women) with a mean age of 59.7 (range 39 to 79) years underwent CABG with exclusive use of both internal thoracic arteries (ITAs) and the right gastroepiploic artery (RGEA). ITA grafts were harvested by using the skeletonization technique. Most patients (96%) had either triple-vessel or left main disease. Fifty percent of the patients were diabetic, and 16 were being treated with insulin. The left ventricular ejection fraction was

Cell fate specification by localized cytoplasmic determinants and cell interactions in ascidian embryos.

Tadpole larvae of ascidians show the basic body plan of chordates. An ascidian larva consists of only a few types of cells and has a relatively small number of cells. Cell lineages are invariant among individuals and have been described in detail. These advantages facilitate the analysis of how the fate of each blastomere becomes specified during development. Over a century of research on ascidian embryogenesis has uncovered many interesting features concerning cellular mechanisms responsible for the fate specification. During embryogenesis, the developmental fate of a blastomere is specified by one of three different mechanisms: localized maternal cytoplasmic determinants, inductive interactions, or lateral inhibition in an equivalence cell group.

Crystallization and preliminary X-ray diffraction studies of photolyase (photoreactivating enzyme) from the cyanobacterium Anacystis nidulans.

Photolyase (photoreactivating enzyme) from the cyanobacterium Anacystis nidulans was crystallized by the hanging drop vapor diffusion procedure using ammonium sulfate as a precipitant. The pale-yellow crystals were grown to a size of 0.4 mm in length and 0.1 mm in diameter. They belong to the tetragonal space group P4(1)2(1)2 or P4(3)2(1)2 with unit cell dimensions of a = b = 90.7 A and c = 135 A. Assuming that the asymmetric unit contains one molecule, the Vm value is calculated as 2.6 A3/dalton. The crystals are stable towards X-ray exposure and diffract beyond 2.5 A resolution.

Ras is an essential component for notochord formation during ascidian embryogenesis.

In ascidian embryos, inductive interactions are necessary for the fate specification of notochord cells. Previous studies have shown that notochord induction occurs at the 32-cell stage and that basic fibroblast growth factor (bFGF) has notochord-inducing activity in ascidian embryos. In vertebrate, it is known that bFGF receptors have tyrosine kinase domain and the signaling pathway is mediated by the small-GTP binding protein, Ras. To study the role of Ras in ascidian embryos, we injected dominant negative Ras (RasN17) into fertilized eggs. RasN17 inhibited the formation of notochord, suggesting that the Ras signaling pathway is involved in signal transduction in the induction of notochord cells. When the presumptive-notochord (A6.2) blastomere was co-isolated with the inducer (A6.1) blastomere and then RasN17 was injected into the A6.2 blastomere, notochord differentiation was suppressed. The presumptive-notochord blastomeres injected with RasN17 were treated with bFGF. Many of them failed to develop notochord-specific features. Next, we examined the effect of injecting constitutively active Ras (RasV12) into the A6.2 blastomeres. However, microinjection of RasV12 into these cells did not bypass notochord induction. These results suggest that the Ras signaling pathway is essential for the formation of notochord and that another signaling pathway also must be activated simultaneously in notochord formation during ascidian embryogenesis.

Reconstruction using an autograft containing tumour treated by liquid nitrogen.

We describe a method of reconstruction using tumour-bearing autograft treated by liquid nitrogen in 28 patients. The operative technique consisted of en bloc excision of the tumour, removal of soft tissue, curettage of the tumour, drilling and preparation for internal fixation or prosthetic replacement before incubation for 20 minutes in liquid nitrogen, thawing at room temperature for 15 minutes, thawing in distilled water for ten minutes, and internal fixation with an intramedullary nail, plate or composite use of prosthetic replacement. Bone graft or cement was used to augment bone strength when necessary. The limb function was rated as excellent in 20 patients (71.4%), good in three (10.7%), fair in three (10.7%), and poor in two (7.1%). At the final follow-up six patients had died at a mean of 19.8 months after the operation, while 21 remained free from disease with a mean follow-up of 28.1 months (10 to 54). One patient is alive with disease. Bony union was seen at a mean of 6.7 months after the operation in 26 patients. Complications were encountered in seven patients, including three deep infections, two fractures, and two local recurrences. All were managed successfully. Our results suggest that this is a simple and effective method of biological reconstruction.

Apnea, glial apoptosis and neuronal plasticity in the arousal pathway of victims of SIDS.

Of 27,000 infants whose sleep-wake characteristics were studied under the age of 6 months, 38 died unexpectedly 2-12 weeks after the sleep recording in a pediatric sleep laboratory. Of these infants, 26 died of sudden infant death syndrome (SIDS), and 12 of definitely identified causes. The frequency and duration of sleep apneas were analysed. Sleep recordings and brainstem histopathology were studied to elucidate the possible relationship between sleep apnea and neuropathological changes within the arousal system. Immunohistochemical analyses were conducted using tryptophan hydroxylase (TrypH), a serotonin synthesizing enzyme, and growth-associated phosphoprotein 43 (GAP43), a marker of synaptic plasticity. The terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used for apoptosis. The pathological and physiological data were correlated for each infant. In the SIDS victims, statistically significant positive correlations were seen between the number of TrypH-positive neurons in the dorsal raphe nucleus of the midbrain and the duration of central apneas (p = 0.03), between the number of TUNEL-positive glial cells in the pedunculopontine tegmental nucleus (PPTN) and the average number of spines in GAP43-positive neurons in the PPTN (p = 0.04). These findings in the dorsal raphe nucleus of the midbrain and PPTN, that play important roles in the arousal pathway suggest a possible link between changes in arousal and SIDS.

Salvage living-donor liver transplantation for liver failure following definitive radiation therapy for recurrent hepatocellular carcinoma: a case report.

A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases.

Serum N-acetyl-beta-D-glucosaminidase activity in predicting the development of hypertension.

We conducted a prospective study in residents of a small farming community in southwestern Japan to determine whether elevated serum N-acetyl-beta-D-glucosaminidase (NAG) activity would predict future hypertension. The 505 normotensive subjects (blood pressure, < 140/90 mm Hg; mean age, 52 +/- 12 years) were reexamined after 7 years; 111 (22%) had become hypertensive (defined as blood pressure > or = 140/90 mm Hg and/or taking antihypertensive medication at follow-up). After adjustment for age and sex, the development of hypertension was significantly related to body mass index (P < .002), the sum of skinfolds (P < .001), baseline blood pressure (P < .0001), serum cholesterol (P < .01), serum uric acid level (P < .0001), and serum NAG activity (P < .005). Elevated NAG activity showed an independent relationship to future hypertension (P < .005) after adjustments for age, sex, baseline blood pressure (systolic, diastolic, or mean), uric acid level, and the sum of skinfolds. Therefore, elevated serum NAG activity was an effective indicator of future hypertension, and it might therefore be related to functional and/or structural changes in the cardiovascular system.