Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults.

PURPOSE: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up. METHODS: A total of 255,170 participants aged 25-70 years were recruited in ten European countries (1992-2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC-MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. RESULTS: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087-0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041-0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. CONCLUSION: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

Barriers for progress in salt reduction in the general population. An international study.

Salt reduction is important for reducing hypertension and the risk of cardiovascular events, nevertheless worldwide salt intakes are above recommendations. Consequently strategies to reduce intake are required, however these require an understanding of salt intake behaviours to be effective. As limited information is available on this, an international study was conducted to derive knowledge on salt intake and associated behaviours in the general population. An online cohort was recruited consisting of a representative sample from Germany, Austria, United States of America, Hungary, India, China, South Africa, and Brazil (n=6987; aged 18-65 years; age and gender stratified). Participants completed a comprehensive web-based questionnaire on salt intake and associated behaviours. While salt reduction was seen to be healthy and important, over one third of participants were not interested in salt reduction and the majority were unaware of recommendations. Salt intake was largely underestimated and people were unaware of the main dietary sources of salt. Participants saw themselves as mainly responsible for their salt intake, but also acknowledged the roles of others. Additionally, they wanted to learn more about why salt was bad for health and what the main sources in the diet were. As such, strategies to reduce salt intake must raise interest in engaging in salt reduction through improving understanding of intake levels and dietary sources of salt. Moreover, while some aspects of salt reduction can be globally implemented, local tailoring is required to match level of interest in salt reduction. These findings provide unique insights into issues surrounding salt reduction and should be used to develop effective salt reduction strategies and/or policies.

Raw hulled shredded acorns from Downy Oak (Quercus pubescens) in the diet of pigs: effects on digestibility and faeces characteristics.

Faeces quality and composition are both of interest to veterinary practitioners dealing with pigs' health and disturbances in the alimentary tract, especially in free-range situations. In the Mediterranean basin, acorns are used as a starch source for fattening pigs, yet little information is available on how that affects faecal quality and digestibility. Therefore, a combined diet containing ripe hulled shredded acorns vs. a pelleted complete diet for finishers was evaluated for the digestibility and faecal consistency. The trial involved eight crossbred pigs, and a matched-pair approach was used to divide animals into two groups, which were fed with two different diets: acorns group (A): n = 4, 70% ripe hulled shredded acorns + 30% pelleted complete diet combined, as fed; control group (C): n = 4, 100% pelleted complete feed. The pigs were housed individually and fed the experimental diets for 8 days; daily feed intake and faeces amounts were recorded and faeces quality assessed. The digestibility of organic matter (OM) and starch of the two diets, as well as of pure acorns, were calculated and compared. Daily feed consumption was significantly higher in group A, but the mean dry matter intake (DMI) per pig was similar in both groups. Dark, firm and consistent faeces were reported for each pig from group A in comparison with group B, whose faeces were paler and softer. Digestibility of OM and starch were lower in group A than in group B (67.8 ± 3.4 vs. 83.9 ± 1.1 and 82.5 ± 3.4 vs. 92.3 ± 2.1 respectively): total tract digestibility of native starch from pure acorns was calculated at 77%. The peculiar consistency of faeces was related to macroscopic acorn hulls, constantly detected in the faeces of all animals sampled in group A.

Inequalities in education and national income are associated with poorer diet: Pooled analysis of individual participant data across 12 European countries.

BACKGROUND: Malnutrition linked to noncommunicable diseases presents major health problems across Europe. The World Health Organisation encourages countries to conduct national dietary surveys to obtain data to inform public health policies designed to prevent noncommunicable diseases. METHODS: Data on 27334 participants aged 19-64y were harmonised and pooled across national dietary survey datasets from 12 countries across the WHO European Region. Weighted mean nutrient intakes were age-standardised using the Eurostat 2013 European Standard Population. Associations between country-level Gross Domestic Product (GDP) and key nutrients and nutrient densities were investigated using linear regression. The potential mitigating influence of participant-level educational status was explored. FINDINGS: Higher GDP was positively associated with total sugar intake (5·0% energy for each 10% increase in GDP, 95% CI 0·6, 9·3). Scandinavian countries had the highest vitamin D intakes. Participants with higher educational status had better nutritional intakes, particularly within lower GDP countries. A 10% higher GDP was associated with lower total fat intakes (-0·2% energy, 95% CI -0·3, -0·1) and higher daily total folate intakes (14µg, 95% CI 12, 16) in higher educated individuals. INTERPRETATION: Lower income countries and lower education groups had poorer diet, particularly for micronutrients. We demonstrate for the first time that higher educational status appeared to have a mitigating effect on poorer diet in lower income countries. It illustrates the feasibility and value of harmonising national dietary survey data to inform European policy regarding access to healthy diets, particularly in disadvantaged groups. It specifically highlights the need for strong policies supporting nutritional intakes, prioritising lower education groups and lower income countries.

Evidence for renal kinins as mediators of amino acid-induced hyperperfusion and hyperfiltration in the rat.

This study examined the role of tissue kallikrein and kinins in renal vasodilation produced by infusion of amino acids (AA). In rats fed a 9% protein diet for 2 wk, intravenous infusion of a 10% AA solution over 60-90 min reduced total renal vascular resistance and increased glomerular filtration rate (GFR) by 25-40% and renal plasma flow (RPF) by 23-30% from baseline. This was associated with a two- to threefold increase in urinary kinin excretion rate. Acute treatment of rats with aprotinin, a kallikrein inhibitor, resulted in deposition of immunoreactive aprotinin in kallikrein-containing connecting tubule cells and inhibited renal kallikrein activity by 90%. A protinin pretreatment abolished the rise in urinary kinins and prevented significant increases in GFR and RPF in response to AA. In a second group of rats pretreated with a B2 kinin receptor antagonist, [DArg Hyp3, Thi5,8 D Phe7]bradykinin, AA infusion raised urinary kinins identically as in untreated controls, but GFR and RPF responses were absent. Aprotinin or the kinin antagonist produced no consistent change in renal function in rats that were not infused with AA.AA-induced increases in kinins were not associated with an increase in renal kallikrein activity. Notably, tissue active kallikrein level fell 50% in AA-infused rats. These studies provide evidence that kinins generated in the kidney participate in mediating renal vasodilation during acute infusion of AA.

Assessment of normal trapeziometacarpal joint alignment.

The purpose of this study was to determine the alignment of the normal trapeziometacarpal joint and any changes in its alignment with age. Radial, dorsal and dorsoradial subluxation were measured on computerized tomographic scans in 50 joints of 50 adults aged 18 to 62. There were statistically significant correlations between increasing age and dorsoradial subluxation but no significant correlation with dorsal and radial subluxation. Significant dorsoradial subluxation occurs after 46 years of age in the normal trapeziometacarpal joint. A mean dorsoradial subluxation of 21% (range 14%-30%) can be considered normal in this age group.

B-vitamin status and concentrations of homocysteine in Austrian omnivores, vegetarians and vegans.

BACKGROUND: A vegetarian diet is considered to promote health and longevity and reduce the risk of cardiovascular diseases and cancer. However, a vegetarian diet may be deficient in some nutrients. Exclusion of animal products in vegetarian diets may affect the status of certain B-vitamins, and further cause the rise of plasma homocysteine concentration. OBJECTIVE: The nutritional status of various B-vitamins (B(1), B(2), B(6), B(12), folic acid) and the concentration of homocysteine in blood plasma of omnivores (n = 40), vegetarians (n = 36) and vegans (n = 42) in Austria was evaluated. METHODS: The evaluation was done using the functional parameters erythrocyte transketolase (ETK), glutathione reductase (EGR) and glutamic oxaloacetic transaminase (EGOT) activation coefficients. Enzyme activity was measured photometrically. The quantity of vitamins B(1), B(2) and B(6) in urine and the concentrations of vitamin B(6) and homocysteine in plasma were determined by HPLC methods with fluorescence detection. Plasma concentration of vitamin B(12) and folic acid were measured with radioimmunoassay. RESULTS: Most of the subjects showed a satisfying vitamin B(1) status. Vegans presented a significantly lower mean plasma vitamin B(12) concentration than omnivores and vegetarians and deficiency in 2.4% of the volunteers but the highest mean value of plasma folate among the investigated groups. A deficient status of folate was found in 18% of omnivores and in approximately 10% of vegans and vegetarians. The status of riboflavin is considered to be deficient in about 10% of omnivores and vegetarians and in over 30% of vegans. According to the activation coefficient of GOT, approximately one third of all subjects showed vitamin B(6) deficiency. Elevated homocysteine concentration in plasma was observed in 66% of the vegans and about 45-50% of the omnivores and vegetarians. Vegan subjects had significantly higher mean plasma homocysteine levels than omnivores. CONCLUSION: Thiamin and folate need not be a problem in a well-planned vegan diet. Vitamins B(12) and B(2) may need attention in the strict vegan diet, especially regarding elevated homocysteine levels in plasma. Pyridoxine status appeared to be independent of the diet.

32nd International Austrian Winter Symposium : Zell am See, the Netherlands. 20-23 January 2016.

TABLE OF CONTENTS: A1 68Ga-PSMA PET/CT in staging and restaging of Prostate Cancer Patients: comparative study with 18F-Choline PET/CTW Langsteger, A Rezaee, W Loidl, HS Geinitz, F Fitz, M Steinmair, G Broinger, L Pallwien-Prettner, M BeheshtiA2 F18 Choline PET - CT: an accurate diagnostic tool for the detection of parathyroid adenoma?L Imamovic, M Beheshti, G Rendl, D Hackl, O Tsybrovsky, M Steinmair, K Emmanuel, F Moinfar, C Pirich, W LangstegerA3 [18F]Fluoro-DOPA-PET/CT in the primary diagnosis of medullary thyroid carcinomaA Bytyqi, G Karanikas, M Mayerhöfer, O Koperek, B Niederle, M HartenbachA4 Variations of clinical PET/MR operations: An international survey on the clinical utilization of PET/MRIT Beyer, K Herrmann, J CzerninA5 Standard Dixon-based attenuation correction in combined PET/MRI: Reproducibility and the possibility of Lean body mass estimationI Rausch, P Rust, MD DiFranco, M Lassen, A Stadlbauer, ME Mayerhöfer, M Hartenbach, M Hacker, T BeyerA6 High resolution digital FDG PET/MRI imaging for assessment of ACL graft viabilityK Binzel, R Magnussen, W Wei, MU Knopp, DC Flanigan, C Kaeding, MV KnoppA7 Using pre-existing hematotoxicity as predictor for severe side effects and number of treatment cycles of Xofigo therapyA Leisser, M Nejabat, M Hartenbach, G Kramer, M Krainer, M Hacker, A HaugA8 QDOSE - comprehensive software solution for internal dose assessmentWencke Lehnert, Karl Schmidt, Sharok Kimiaei, Marcus Bronzel, Andreas KlugeA9 Clinical impact of Time-of-Flight on next-generation digital PET imaging of Yttrium-90 radioactivity following liver radioembolizationCL Wright, K Binzel, J Zhang, Evan Wuthrick, Piotr Maniawski, MV KnoppA10 Snakes in patients! Lessons learned from programming active contours for automated organ segmentationM Blaickner, E Rados, A Huber, M Dulovits, H Kulkarni, S Wiessalla, C Schuchardt, RP Baum, B Knäusl, D GeorgA11 Influence of a genetic polymorphism on brain uptake of the dual ABCB1/ABCG2 substrate [11C]tariquidarM Bauer, B Wulkersdorfer, W Wadsak, C Philippe, H Haslacher, M Zeitlinger, O LangerA12 Outcome prediction of temporal lobe epilepsy surgery from P-glycoprotein activity. Pooled analysis of (R)-[11C]-verapamil PET data from two European centresM Bauer, M Feldmann, R Karch, W Wadsak, M Zeitlinger, MJ Koepp, M-C Asselin, E Pataraia, O LangerA13 In-vitro and in-vivo characterization of [18F]FE@SNAP and derivatives for the visualization of the melanin concentrating hormone receptor 1M Zeilinger, C Philippe, M Dumanic, F Pichler, J Pilz, M Hacker, W Wadsak, M MitterhauserA14 Reducing time in quality control leads to higher specific radioactivity of short-lived radiotracersL Nics, B Steiner, M Hacker, M Mitterhauser, W WadsakA15 In vitro 11C-erlotinib binding experiments in cancer cell lines with epidermal growth factor receptor mutationsA Traxl, Thomas Wanek, Kushtrim Kryeziu, Severin Mairinger, Johann Stanek, Walter Berger, Claudia Kuntner, Oliver LangerA16 7-[11C]methyl-6-bromopurine, a PET tracer to measure brain Mrp1 function: radiosynthesis and first PET evaluation in miceS Mairinger, T Wanek, A Traxl, M Krohn, J Stanek, T Filip, M Sauberer, C Kuntner, J Pahnke, O LangerA17 18F labeled azidoglucose derivatives as "click" agents for pretargeted PET imagingD Svatunek, C Denk, M Wilkovitsch, T Wanek, T Filip, C Kuntner-Hannes, J Fröhlich, H MikulaA18 Bioorthogonal tools for PET imaging: development of radiolabeled 1,2,4,5-TetrazinesC Denk, D Svatunek, T Wanek, S Mairinger, J Stanek, T Filip, J Fröhlich, H Mikula, C Kuntner-HannesA19 Preclinical evaluation of [18F]FE@SUPPY- a new PET-tracer for oncologyT Balber, J Singer, J Fazekas, C Rami-Mark, N Berroterán-Infante, E Jensen-Jarolim, W Wadsak, M Hacker, H Viernstein, M MitterhauserA20 Investigation of Small [18F]-Fluoroalkylazides for Rapid Radiolabeling and In Vivo Click ChemistryC Denk, D Svatunek, B Sohr, H Mikula, J Fröhlich, T Wanek, C Kuntner-Hannes, T FilipA21 Microfluidic 68Ga-radiolabeling of PSMA-HBED-CC using a flow-through reactorS Pfaff, C Philippe, M Mitterhauser, M Hartenbach, M Hacker, W WadsakA22 Influence of 24-nor-ursodeoxycholic acid on hepatic disposition of [18F]ciprofloxacin measured with positron emission tomographyT Wanek, E Halilbasic, M Visentin, S Mairinger, B Stieger, C Kuntner, M Trauner, O LangerA23 Automated 18F-flumazenil production using chemically resistant disposable cassettesP Lam, M Aistleitner, R Eichinger, C ArtnerA24 Similarities and differences in the synthesis and quality control of 177Lu-DOTA-TATE, 177Lu -HA-DOTA-TATE and 177Lu-DOTA-PSMA (PSMA-617)H Eidherr, C Vraka, A Haug, M Mitterhauser, L Nics, M Hartenbach, M Hacker, W WadsakA25 68Ga- and 177Lu-labelling of PSMA-617H Kvaternik, R Müller, D Hausberger, C Zink, RM AignerA26 Radiolabelling of liposomes with 67Ga and biodistribution studies after administration by an aerosol inhalation systemU Cossío, M Asensio, A Montes, S Akhtar, Y te Welscher, R van Nostrum, V Gómez-Vallejo, J LlopA27 Fully automated quantification of DaTscan SPECT: Integration of age and gender differencesF VandeVyver, T Barclay, N Lippens, M TrochA28 Lesion-to-background ratio in co-registered 18F-FET PET/MR imaging - is it a valuable tool to differentiate between low grade and high grade brain tumor?L Hehenwarter, B Egger, J Holzmannhofer, M Rodrigues-Radischat, C PirichA29 [11C]-methionine PET in gliomas - a retrospective data analysis of 166 patientsN Pötsch, I Rausch, D Wilhelm, M Weber, J Furtner, G Karanikas, A Wöhrer, M Mitterhauser, M Hacker, T Traub-WeidingerA30 18F-Fluorocholine versus 18F-Fluorodeoxyglucose for PET/CT imaging in patients with relapsed or progressive multiple myeloma: a pilot studyT Cassou-Mounat, S Balogova, V Nataf, M Calzada, V Huchet, K Kerrou, J-Y Devaux, M Mohty, L Garderet, J-N TalbotA31 Prognostic benefit of additional SPECT/CT in sentinel lymph node mapping of breast cancer patientsS Stanzel, G Pregartner, T Schwarz, V Bjelic-Radisic, B Liegl-Atzwanger, R AignerA32 Evaluation of diagnostic value of TOF-18F-FDG PET/CT in patients with suspected pancreatic cancerS Stanzel, F Quehenberger, RM AignerA33 New quantification method for diagnosis of primary hyperpatahyroidism lesions and differential diagnosis vs thyropid nodular disease in dynamic scintigraphyA Koljevic Markovic, Milica Jankovic, V Miler Jerkovic, M Paskas, G Pupic, R Dzodic, D PopovicA34 A rare case of diffuse pancreatic involvement in patient with merkel cell carcinoma detected by 18F-FDGMC Fornito, D FamiliariA35 TSH-stimulated 18F-FDG PET/CT in the diagnosis of recurrent/metastatic radioiodine-negative differentiated thyroid carcinomas in patients with various thyroglobuline levelsP Koranda, H Polzerová, I Metelková, L Henzlová, R Formánek, E Buriánková, M KamínekA36 Breast Dose from lactation following I131 treatmentWH Thomson, C LewisA37 A new concept for performing SeHCAT studies with the gamma cameraWH Thomson, J O'Brien, G James, A NotghiA38 Whole body F-18-FDG-PET and tuberculosis: sensitivity compared to x-ray-CTH Huber, I Stelzmüller, R Wunn, M Mandl, F Fellner, B Lamprecht, M GabrielA39 Emerging role 18F-FDG PET-CT in the diagnosis and follow-up of the infection in heartware ventricular assist system (HVAD)MC Fornito, G LeonardiA40 Validation of Poisson resampling softwareWH Thomson, J O'Brien, G JamesA41 Protection of PET nuclear medicine personnel: problems in satisfying dose limit requirementsJ Hudzietzová, J Sabol, M Fülöp.

Kinin, a mediator of diabetes-induced glomerular hyperfiltration.

Renal kallikrein is increased in diabetic patients and streptozotocin (STZ)-induced diabetic rats with hyperfiltration. Chronic inhibition of renal kallikrein reduces glomerular filtration rate (GFR) and renal plasma flow (RPF) in hyperfiltering STZ-induced diabetic rats. To investigate whether these actions of kallikrein and its inhibition are kinin-mediated, we used a B2-kinin receptor antagonist (BKA). In STZ-induced diabetic rats with hyperfiltration, renal kallikrein excretion rate was significantly increased (P < or = 0.01), and kinin excretion rate was increased 57%, as compared with control rats. Left kidney GFR and RPF were measured before and during a 40-min infusion of BKA (0.5 micrograms.kg-1.min-1) or vehicle. Infusion of the kinin receptor antagonist reduced the GFR and RPF significantly. GFR was reduced by 18%, from an average baseline value of 2.07 +/- 0.11 to 1.70 +/- 0.06 ml/min, P < or = 0.001 (means +/- SE). RPF was reduced by 25%, from 6.74 +/- 0.38 to 5.06 +/- 0.17 ml/min, P < or = 0.001. Total renal vascular resistance was significantly increased during BKA infusion, P < or = 0.001. Vehicle infusion for the same period had no significant effect on GFR, RPF, or renal vascular resistance. These findings further support the hypothesis that increased renal production of kinins contributes to the renal vasodilation of diabetes.

Bioinformatics and drug discovery.

Bioinformatics involves both the automatic processing of large amounts of existing data and the creation of new types of information resource. Both will be required if the data are to be transformed into information and used to help in the discovery of drugs.

Body mass index and body girths as predictors of mortality in black and white women.

BACKGROUND: The high prevalence of obesity in black women has been hypothesized to contribute to higher rates of coronary heart disease and total mortality. Investigators have recently refined the study of obesity by differentiating anatomic patterns of the physical location of adipose tissue on the body. We examined fat patterning as a predictor of mortality in black women. METHODS: Body mass index (BMI) and body girths were examined as predictors of all-cause and coronary heart disease mortality during 25 to 28 years of follow-up in black and white women in the Charleston Heart Study. RESULTS: The BMI was associated with all-cause and coronary heart disease mortality in white, but not black, women. After controlling for differences in BMI, the risk of all-cause mortality was greater in white women with larger chest and abdominal girths, while midarm girths were inversely associated with mortality. The hazard at the 85th percentile relative to the 15th percentile of abdomen/midarm ratio was 1.44 in models that included BMI, education, and smoking as covariates. In black women, the girths were not predictive of either all-cause or coronary heart disease mortality. CONCLUSIONS: The failure of BMI and fat patterning to predict mortality in black women challenges previously held assumptions regarding the role of overweight in the higher mortality experienced by black women.

Gut microbiota composition correlates with changes in body fat content due to weight loss.

Genetics, lifestyle, and dietary habits contribute to metabolic syndrome, but also an altered gut microbiota has been identified. Based on this knowledge it is suggested that host bacterial composition tends to change in response to dietary factors and weight loss. The aim of this study was to identify bacteria affecting host metabolism in obesity during weight loss and to correlate them with changes of the body composition obtained from bioelectrical impedance analysis (BIA). We recruited obese individuals receiving a dietary intervention according DACH (German, Austrian, and Swiss Society of Nutrition) reference values and guidelines for 'prevention and therapy of obesity' of DAG e.V., DDG, DGE e.V., and DGEM e.V. over three months. Faecal microbiota and BIA measurements were conducted at three time points, before, during, and after the intervention. Gut microbiota was analysed on the basis of 16S rDNA with quantitative real time PCR. Additionally, a food frequency questionnaire with questions to nutritional behaviour, lifestyle, and physical activity was administered before intervention. After weight reduction, obese individuals showed a significant increase of total bacterial abundance. The ratio of Firmicutes/Bacteroidetes significantly decreased during intervention. Lactobacilli significantly increased between the first and the second time point. These differences also correlated with differences in weight percentage. During the intervention period Clostridium cluster IV increased significantly between the second and the third time point. In contrast Clostridium cluster XIVa showed a decreased abundance. The dominant butyrate producer, Faecalibacterium prausnitzii, significantly increased as did the abundance of the butyryl-CoA: acetate CoA-transferase gene. Archaea and Akkermansia were significantly more prevalent after weight reduction. Our results show a clear difference in the gut bacterial composition before and after dietary intervention with a rapid change in gut microbial composition after a few weeks, but also indicate that a major shift requires long term dietary treatment.

Vascular compression of the rostral ventrolateral medulla in sympathetic mediated essential hypertension.

The pathophysiological factors of neurogenic or sympathetically mediated essential hypertension are unknown. Neurons close to the surface of the ventrolateral medulla (specifically, in the retro-olivary sulcus [ROS]) are integrally involved in the control of blood pressure by means of efferent connections to presympathetic neurons in the spinal cord. It is hypothesized that vascular contact with the ROS is pathogenically involved in neurogenically mediated hypertension. We evaluated that theory in 20 subjects with uncomplicated stage 1 to stage 2 essential hypertension (EHTN) (18 of whom completed the study). The baseline supine plasma norepinephrine level served as an index of central sympathetic outflow. The response of blood pressure to clonidine was used as a surrogate marker for neurogenically mediated hypertension. We also examined the relationship between those markers and evidence of anatomic abnormalities in the area of the ROS that was provided by magnetic resonance imaging. A vessel contacted the left ROS in 5 of the 18 subjects. Those 5 subjects had higher plasma norepinephrine concentrations than did the 13 subjects without this vascular contact (358+/-46 versus 76+/-43 pg/mL, P<0.001). These 5 subjects also exhibited a significant depressor response to clonidine that tended to be greater than that seen in the 13 subjects without vascular contact (-20.6+/-3.2 versus -13.6+/-9 mm Hg). Both race and baseline mean blood pressure had only an independent effect on the depressor response to clonidine. The findings are consistent with the theory that vascular contact with the left ROS may contribute to neurogenically mediated "essential" hypertension in some patients.

Association between fluorescent antinuclear antibodies, capillary patterns, and clinical features in scleroderma spectrum disorders.

Antinuclear antibody and in vivo capillary patterns were studied in 33 patients with Raynaud's phenomenon only and in 68 patients with scleroderma spectrum disorders; the results were correlated with clinical and laboratory findings. In addition, antinuclear antibody results in the groups with Raynaud's phenomenon only and scleroderma spectrum disorders were compared with those found in 70 patients with systemic lupus erythematosus (SLE). Distinct antinuclear antibody profiles were observed in the three diagnostic groups. Comparison of patients with anticentromere antibodies with others in the group with scleroderma spectrum disorders demonstrated that anticentromere antibody-positive patients tended to have a milder disease: less skin and visceral involvement, less frequent presence of hypertension, anemia, and elevated sedimentation rate. These differences did not, however, reach statistical significance. Comparison of patients with scleroderma spectrum disorders according to in vivo capillary patterns revealed that those with an "active" pattern had significantly more extensive skin involvement than those with a "slow" pattern. Visceral involvement tended to be greater in all organ systems in the group with an "active" pattern and reached statistical significance for muscle and kidney. Hypertension was also significantly more frequent in the group with an "active" pattern than in the group with a "slow" one. The latter was positively correlated with the presence of anticentromere antibody.

A series of penicillin-derived C2-symmetric inhibitors of HIV-1 proteinase: structural and modeling studies.

The binding modes of a series of penicillin-derived C2 symmetric dimer inhibitors of HIV-1 proteinase were investigated by NMR, protein crystallography, and molecular modeling. The compounds were found to bind in a symmetrical fashion, tracing and S-shaped course through the active site, with good hydrophobic interactions in the S1/S1' and S2/S2' pockets and hydrogen bonding of inhibitor amide groups. Interactions with the catalytic aspartates appeared poor and the protein conformation was very similar to that seen in complexes with peptidomimetics, in spite of the major differences in ligand structure.

Variability in islet cell antibody determination: a quantitative assessment.

The source of variability in the outcome of islet cell antibody (ICA) determinations due to pancreas and serum were independently assessed with a quantitative assay. The effect of choice of pancreatic substrate and serum specimen was assessed by testing for parallelism among twenty-five dilution curves of five sera from diabetic subjects and five pancreata. The five by five format allowed for five tests of pancreatic variability (one serum against five pancreata) and five tests of serum variability (one pancreas against five sera). Analyses of variance and covariance of these dilution curves indicate that test outcome is affected by both the sera (5 tests, p values 10(-6) to 10(-7) and the pancreas (5 tests, p values 10(-3) to 10(-5)). The data support heterogeneity among islet cell antibody isotypes and raise the possibility of diversity of islet cell antigens. Antigenic diversity of pancreatic substrates may interfere with inter- and intra-laboratory comparisons of islet cell antibody determinations. The strong effect of pancreas type on ICA outcome infers possible heterogeneity of the islet cell antigen(s) capable of reacting with human islet cell antibodies.

Levels of transferrin and alpha 2-HS glycoprotein in women with and without endometriosis.

The study objective was to test the hypothesis that elevated levels of transferrin and alpha 2-HS glycoprotein occur in the peritoneal environment of patients with endometriosis that may lead to the observed autoimmunity to these proteins. We set up a double sandwich enzyme-linked immunosorbent assay (ELISA) for measuring levels of transferrin and alpha 2-HS glycoprotein in the serum and peritoneal fluid samples from women with (n = 24-60) and without endometriosis (n = 35-49). Serum and peritoneal fluid levels of alpha 2-HS glycoprotein and peritoneal fluid levels of transferrin were significantly elevated in patients with endometriosis, in contrast to the controls. Serum levels of transferrin in patients, however, were significantly less in the patients than in controls. We conclude that transferrin and alpha 2-HS glycoprotein are present at high concentrations in the peritoneal fluids of patients with endometriosis. This may play a significant role in the autoimmune pathophysiology of endometriosis.

A comparison of the effects of cholesterol on CHD mortality in black and white women: twenty-eight years of follow-up in the Charleston Heart Study.

The relationship between cholesterol and 28-year CHD mortality in women was evaluated in the Charleston Heart Study. Linear, quadratic, and cubic models were investigated using Cox proportional hazards regression analysis. In white women, the linear, quadratic, and cubic terms for cholesterol were significant suggesting an asymmetric J-shaped relationship. In black women, only the linear term in all three models was statistically significant suggesting an increasing CHD mortality rate with increasing cholesterol level. The lack of consistency of results by different statistical analyses in black women make conclusions concerning the nature of the relationship between cholesterol and CHD mortality less strong in black women than in white women. Compared with women having a cholesterol value equal to the mean of the group (241 mg/dl), white women having a cholesterol value one standard deviation above the mean (s = 52.5 mg/dl) had a 60% higher CHD mortality rate (hazard ratio = 1.6, 95% CI: 1.2-2.1). In black women, the estimated hazard ratio for a one standard deviation (s = 47.8 mg/dl) increase in cholesterol is 1.4 (95% CI: 1.03-1.8). The results suggest that the relationship of cholesterol to CHD mortality is different in white and black women. The relationship in white women appears to be curvilinear and represented by an asymmetric curve while the relationship in black women is not curvilinear and the overall pattern of association, while possibly linear, is equivocal.

Black women have smaller abdominal girths than white women of the same relative weight.

Anthropometric measurements were compared in 312 white and 242 black women (mean age 54) who were participants in the Charleston Heart Study. Body mass index (BMI) was greater in black women (27.8 kg/m2) than in white women (24.7 kg/m2) as were body circumferences. However, when the girth measurements were adjusted for BMI, some racial differences were reversed. Age, smoking and BMI-adjusted abdominal girth was smaller in the black women than in the white women (88.9 cm vs 92.2 cm). The ratio of abdomen to midarm circumference was larger in white women than black women (3.24 vs 3.09), and could be interpreted to indicate a less central fat pattern in the black women. This conclusion should be viewed with caution since circumference measurements, though often used in epidemiologic research, do not differentiate between subcutaneous fat and visceral fat.

Predictors of physical disability in elderly blacks and whites of the Charleston Heart Study.

During the 1984/85 recall of the Charleston Heart Study Cohort, physical function data were obtained for 247 white males, 376 white females, 123 black males, 247 black females and 71 high socioeconomic status (SES) black males over 60 years of age. Black females had the highest prevalence of physical disability (55.8%), followed by white females (43.2%), black males (39.0%) and white males (25.8%) and high SES black males (22.3%). Physical disability was 1.5-2.5 times as prevalent among individuals with a history of cardiovascular disease (CVD) than those without such a history. Among individuals without a current history of CVD univariate analyses showed the following as significant (lower 95% CI greater than 1.0) predictors of physical disability: elevated systolic blood pressure in white females, black males, and black females; elevated cholesterol in black females; obesity in black females; and low educational level in white females. Regression analyses indicated that obesity in 1960 accounted for 10.9 and 2.9% respectively of the variability in physical disability scores in 1985 for black females and white females.