Citations

We investigated the relationship of aortic pulse wave velocity (aPWV), a measure of central arterial stiffness, with the presence and quantity of coronary artery calcium (CAC) in a community-based sample of adults without prior history of heart attack or stroke (n=401, mean age 59.8 years, 53% men). ECG-gated waveforms of the right carotid and right femoral artery were obtained by applanation tonometry, and aPWV was calculated using established methods. CAC was measured noninvasively by electron beam computed tomography, and CAC score was calculated. aPWV was significantly correlated with log(CAC +1; r =0.41; P <0.0001) and pulse pressure ( r =0.47; P <0.0001). Multivariable logistic and linear regression models were used to identify independent predictors of the presence and quantity of CAC, respectively. In multivariable logistic regression analyses, aPWV was associated with the presence of CAC ( P =0.011) after adjustment for age, male sex, total cholesterol, high-density lipoprotein cholesterol, diabetes, history of smoking, systolic blood pressure, body mass index, and use of hypertension and statin medications. In multivariable linear regression analyses, aPWV was significantly associated with log(CAC +1) after adjustment for the covariates enumerated above ( P <0.0001). aPWV remained significantly associated with both the presence and quantity of CAC even after the additional adjustment for diastolic blood pressure. We conclude that aPWV is related to subclinical coronary atherosclerosis independent of conventional risk factors (including indices of blood pressure) and may be a biomarker of cardiovascular risk in asymptomatic individuals.

AbstractB-lymphocyte homeostasis and function are regulated by complementary actions of the TNFR family members TACI, BCMA, and BAFF-R, which are expressed by mature B cells. How these receptors are differentially activated is not entirely understood, because the primary ligand BAFF binds to all three. We searched for alternative ligands for TACI using recombinant TACI-Fc fusion protein as a probe and identified syndecan-2 as a new binding partner. TACI binding appears to require heparan sulfate posttranslational modifications of syndecan-2, because free heparin or pretreatment with heparitinase blocked the interaction. Syndecan-2 bound TACI but bound neither BAFF-R nor BCMA. Transfected cells expressing syndecan-2 activated signaling through TACI, as indicated by an NFAT-specific reporter. Syndecan-1 and syndecan-4 were also able to induce TACI signaling in a similar manner. This is the first identification of ligands that selectively activate TACI without simultaneously triggering BCMA or BAFF-R. This finding may help explain the alternative outcomes of signaling from this family of receptors in B cells.

The current study attempts to clarify the multi‐faceted nature of impulsivity through the use of the four‐factor UPPS Impulsive Behaviour scale. In order to build the nomological network surrounding this scale, the UPPS was administered to individuals with borderline personality disorder (BPD), pathological gamblers (PG), alcohol abusers (divided into two groups based on the presence of antisocial features), and a control group. Several of the UPPS scales (e.g. Urgency, lack of Premeditation, and Sensation Seeking) differentiated the BPD, PG, and alcohol abusers with antisocial features from a group of non‐antisocial alcohol abusers and a control group. Overall, the UPPS scales accounted for between 7% (pathological gambling) and 64% (borderline personality disorder features) of the overall variance in the psychopathology measures. Individual UPPS scales also made unique contributions to several of these disorders, which may provide insight into which of these personality traits may predispose individuals to behave in maladaptive or problematic ways. The results provide support for the differentiation of impulsivity‐related constructs into the current four‐factor model. Copyright © 2005 John Wiley & Sons, Ltd.

AbstractWaldenström macroglobulinemia (WM) is a serious and frequently fatal B-cell malignancy associated with an elevated monoclonal IgM protein in the serum. Many of the mechanisms leading to this disease are not yet known. B-lymphocyte stimulator (BLyS) is a TNF family member that is critical for maintenance of normal B-cell development and homeostasis. BLyS is overexpressed in a variety of B-cell malignancies and has been shown to inhibit apoptosis in malignant B cells. It also regulates immunoglobulin secretion by normal B cells. To determine the relevance of BLyS in WM, we examined the role of BLyS in WM patient samples. Malignant B cells were found to bind soluble BLyS and variably express the receptors BAFF-R, TACI, and BCMA. We also found expression of BLyS in bone marrow specimens by immunohistochemistry and elevated serum BLyS levels in patients with WM. BLyS, alone or in combination with cytokines that induce immunoglobulin production, was found to increase IgM secretion by malignant B cells. Furthermore, BLyS was found to increase the viability and proliferation of malignant B cells from WM patients. Due to the role of BLyS in WM, strategies to inhibit BLyS may potentially have therapeutic efficacy in these patients.

Pulse pressure, the difference between systolic and diastolic blood pressure, is an independent risk factor for cardiovascular disease. Increased pulse pressure reflects reduced compliance of arteries and is a marker of atherosclerosis. To locate genes that affect pulse pressure, a genome-wide linkage scan for quantitative trait loci influencing pulse pressure was performed using variance components methods as implemented in sequential oligogenic linkage analysis routines. The analysis sample included 10 798 participants in 3320 families who were recruited as part of the Family Blood Pressure Program and were phenotyped with an oscillometric blood pressure measurement device using a consistent protocol across centers. Pulse pressure was adjusted for the effects of sex, age, age 2 , age-by-sex interaction, age 2 -by-sex interaction, body mass index, and field center to remove sources of variation other than the genetic effects related to pulse pressure. Significant linkage was observed on chromosome 18 (logarithm of odds [LOD]=3.2) in a combined racial sample, chromosome 20 (LOD=4.4), and 17 (LOD=3.6) in Hispanics, chromosome 21 (LOD=4.3) in whites, chromosome 19 (LOD=3.1) in a combined sample of blacks and whites, and chromosome 7 (logarithm of odds [LOD]=3.1) in blacks from the GenNet Network. Our genome scan shows significant evidence for linkage for pulse pressure in multiple areas of the genome, supporting previous published linkage studies. The identification of these loci for pulse pressure and the apparent congruence with other blood pressure phenotypes provide increased support that these regions contain genes influencing blood pressure phenotypes.

Distortion product otoacoustic emission (DPOAE) input/output functions were measured at nine f2 frequencies ranging from 500 to 8000 Hz in 210 normal-hearing and hearing-impaired subjects. In a companion paper [Stover et al., J. Acoust. Soc. Am. 100, 956–967 (1996)], L1−L2 was held constant at 10 dB, and L2 was varied from 65 to 10 dB SPL in 5-dB steps. Based upon analyses using clinical decision theory, it was demonstrated that DPOAE amplitudes for 65/55 dB SPL primaries (L1/L2) and DPOAE thresholds resulted in the greatest separation between normal and impaired ears. In this paper, the data for these two conditions were recast as cumulative distributions, which not only describe the extent of overlap between normal and impaired distributions, but also provide the measured value (i.e., the specific DPOAE amplitude or threshold) for any combination of hit and false alarm rates. From these distributions, confidence limits were constructed for both DPOAE amplitude and threshold to determine the degree of certainty with which any measured response could be assigned to either the normal or impaired population. For these analyses, DPOAE measurements were divided into three categories (a) response properties that would be unlikely to come from normal ears, (b) response properties that would be unlikely to come from impaired ears, and (c) response properties for which hearing status was uncertain. Based upon DPOAE amplitude measurements, the region of uncertainty, defined between the 95 percentile for impaired ears and the 5 percentile for normal ears, was relatively narrow for f2 frequencies ranging from 707 to 4000 Hz. For DPOAE thresholds, this region was relatively narrow for f2 frequencies ranging from 1414 to 4000 Hz.

This study examined the effect of primary stimulus level on the ability of distortion product otoacoustic emission (DPOAE) measurements to separate normal-hearing from hearing-impaired ears. Complete I/O functions were obtained for nine f2 frequencies on 210 people approximately evenly divided between normal hearing and hearing impaired. Clinical decision theory was used to assess both DPOAE amplitudes and DPOAE threshold as diagnostic indicators of hearing status. Moderate level primary stimuli elicited responses that separated normal from impaired better than either lower level or higher level stimuli. The two populations were differentiated for all frequencies above 500 Hz by DPOAE amplitude, given primary levels, L1 and L2, of 65 and 55 dB SPL. DPOAE threshold performed equally well, but threshold ambiguity in noise and longer testing times make it a less suitable DPOAE measure to use diagnostically.

Background and Purpose— With the changes in management of atrial fibrillation (AF) over time, it is possible that the time trends of post-AF stroke incidence and mortality have changed. We sought to determine whether the incidence and survival of ischemic stroke after AF diagnosis have improved. Methods— We identified the Olmsted County, Minn, residents who developed first AF from 1980 to 2000 and followed them in medical records to 2004. The outcomes were first ischemic stroke and death. Results— Of the 4117 subjects diagnosed with first AF and without previous stroke, 446 (11%) sustained a first ischemic stroke during a mean follow-up time of 5.5±5.0 years. The age- and sex-adjusted incidence of stroke decreased, on average, by 3.4% per year ( P =0.0001), concurrent with an increase in warfarin and aspirin use (both P <0.0001) and reduction of systolic blood pressure ( P <0.001). The age-adjusted ischemic stroke incidence was higher in women ( P =0.039), but not after adjusting for systolic blood pressure ( P =0.41). Compared with the general Minnesota white population, the relative mortality hazard ratio was 1.88 for men and 1.84 for women without stroke and 3.03 for men and 3.80 for women ( P <0.05) with stroke. The relative mortality hazard did not vary by age or calendar year of AF diagnosis. Conclusions— Post-AF ischemic stroke incidence decreased significantly from 1980 to 2000, during which time a substantial increase in the use of antithrombotic therapy and reduction of systolic blood pressure was evident. The relative mortality risk of stroke, however, had not improved over time.