This study analyzed data from the 1995 National College Health Risk Behavior Survey (NCHRBS) to assess the prevalence of lifetime rape among female college students and to examine the association between rape and health-risk behaviors. The NCHRBS used a mail questionnaire to assess health-risk behaviors among a nationally representative sample of undergraduate students. Twenty percent of female students reported ever having been forced to have sexual intercourse, most often during adolescence. When analyses controlled for demographic characteristics, female students who had ever been raped were significantly more likely than those who had not to report a wide range of health-risk behaviors. These results highlight a need to improve rape prevention and treatment programs for female adolescents.

Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near (rs9942471, = 4.5 × 10) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at and, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.

During a search for benzodiazepine receptor modulators, a highly potent adenosine antagonist (CGS 15943) was discovered. The compound was defined as a resonance-stabilized hybrid of the canonical structures 9-chloro-2-(2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (2a) and 9-chloro-2-(2-furyl)-5,6-dihydro[1,2,4]triazolo[1,5-c]-quinazolin- 5-imine (2b). Spectroscopic evidence and chemical reactivity in polar media favor the amine form 2a as the major contributor of the two canonical structures. The synthesis of 2 and some of its analogues and the structure-activity relationships in four biological test systems are described. Replacement of the 9-chloro group by hydrogen, hydroxyl, or methoxyl gave compounds with comparable binding potency at the A1 and A2 receptors but much less activity as antagonists of 2-chloroadenosine in guinea pig tracheal strips. Alkylation of the 5-amino group caused, in general, a loss of binding activity, particularly at the A2 receptor, as well as complete loss of activity in the tracheal model. Modification of the 2-furyl group caused a pronounced loss of activity in all of the test systems.

The iminodihydroquinoline WIN 17317-3 was previously shown to inhibit selectively the voltage-gated potassium channels, K(v)1.3 and K(v)1.4 [Hill, R. J., et al. (1995) Mol. Pharmacol. 48, 98-104; Nguyen, A., et al. (1996) Mol. Pharmacol. 50, 1672-1679]. Since these channels are found in brain, radiolabeled WIN 17317-3 was synthesized to probe neuronal K(v)1 channels. In rat brain synaptic membranes, [(3)H]WIN 17317-3 binds reversibly and saturably to a single class of high-affinity sites (K(d) 2.2 +/- 0.3 nM; B(max) 5.4 +/- 0.2 pmol/mg of protein). However, the interaction of [(3)H]WIN 17317-3 with brain membranes is not sensitive to any of several well-characterized potassium channel ligands. Rather, binding is modulated by numerous structurally unrelated sodium channel effectors (e.g., channel toxins, local anesthetics, antiarrhythmics, and cardiotonics). The potency and rank order of effectiveness of these agents in affecting [(3)H]WIN 17317-3 binding is consistent with their known abilities to modify sodium channel activity. Autoradiograms of rat brain sections indicate that the distribution of [(3)H]WIN 17317-3 binding sites is in excellent agreement with that of sodium channels. Furthermore, WIN 17317-3 inhibits sodium currents in CHO cells stably transfected with the rat brain IIA sodium channel with high affinity (K(i) 9 nM), as well as agonist-stimulated (22)Na uptake in this cell line. WIN 17317-3 interacts similarly with skeletal muscle sodium channels but is a weaker inhibitor of the cardiac sodium channel. Together, these results demonstrate that WIN 17317-3 is a new, high-affinity, subtype-selective ligand for sodium channels and is a potent blocker of brain IIA sodium channels.

This study examines antibiotic usage and associated infections in infants and young children in Iowa. Longitudinal data were collected using a cohort recruited at birth from eight hospitals in eastern Iowa. Parents of recruited children were mailed questionnaires at 6 weeks, and 3, 6, 9, 12, 16, and 20 months of age. The cumulative incidence of antibiotic use and associated infections was determined using Kaplan-Meier survival analysis. There were data on 1,368 children. Antibiotic use was common in our cohort and increased with age. Beginning at age 3 months, approximately 50% of the cohort was exposed to an antibiotic during each reporting period. Otitis media was the most common indication and was responsible for 67.3% of antibiotic use. Children were most frequently treated with amoxicillin, followed by the cephalosporins and sulphonamides. By 12 and 20 months of age 79.0% and 92.5% of the children, respectively, had been treated with at least one course of antibiotics. Children received antibiotics for a median of 43 days by 20 months of age. Males were more likely to experience any antibiotic exposure than females (hazard ratio = 1.18) and showed a trend for more days of use (P = 0.052). There was a small but significant variation in antibiotic usage in the different recruitment communities (P = 0.02).

No abstract

Detection of acute myocardial ischaemia using electrocardiographic methods is generally based on assessment of the ST segments in the standard 12-lead electrocardiogram (ECG). Several studies have also shown changes in high-frequency QRS components during acute ischaemia. The purpose of the present study was to determine the changes in high-frequency QRS components during prolonged percutaneous transluminal coronary angioplasty (PTCA) and to compare these changes with ST-segment deviations in the standard 12-lead ECG. The study population consisted of 19 patients receiving prolonged PTCA. Standard and high-resolution signal-averaged ECGs were recorded before and during balloon inflation. The high-resolution recordings were performed using bipolar X, Y and Z leads. The QRS complexes in the high-resolution signal-averaged ECGs were analysed within a bandwidth of 150-250 Hz. During inflation, significant reductions in high-frequency QRS components were observed (12-72%). Changes in the high-frequency QRS components were seen in four of the patients without ST-segments deviation in the standard ECG. The correlation between the ST-segment deviation and the reduction in high-frequency QRS components was weak (r = 0.27). Acute coronary artery occlusion produces changes in high-frequency QRS components, even in the absence of ST-segment deviation in the standard ECG. Further studies need to be carried out to evaluate whether analysis of high-frequency QRS components could provide a method for detecting myocardial ischaemia and give additional information to that available in the ST segment in the standard ECG.

The denaturation of staphylococcal enterotoxin B at 23 I : :1" by aqueous guanidine hydrochloride, urea, or dilute HCI was studied by measuring change in the intrinsic viscosity and near-ultraviolet difference spectrum of the protein. Prolonged exposure (hours to days, depending on denaturant concentration) of enterotoxin B to guanidine up to 6 M or urea up to 9 M was required for unfolding to reach equilibrium. Refolding of denatured toxin to native protein after dilution of denaturant was complete within minutes to a few hours. Thus, the native conformation of enterotoxin B C ertain strains of Sfup/zj,lococcirs uurrus elaborate watersoluble exoproteins which are capable of inducing an acute gastroenteritis in nian (Casman e f d., 1963). One of these exoproteins, staphylococcal enterotoxin B, can be obtained in high purity from the culture supernatants of appropriate staphylococcal strains (Schantz ef a / . . 1965). SEB' is also ii nonspecific mitogen. stimulating lymphocytes in riri'o to undergo blastoid transformation with increased mitotic activity (Peavy er a/., 1970) and to release macrophage migration inhibition factor (Kaplan: 1972). SEB. a globular protein with a molecular weight of 28,500, i s composed of one peptide chain containing 239 amino acid residues (Huang and Bergdoll. 1970; Schantz er ([/.. 1Y65). The single intramolecular disulfide bond of SEB spans a stretch of 21 amino acids b2-tween residues 92 and 112; 32 of the 34 aromatic residues in thy toxin niolecule are located outside of the closed disulfide loop. The basic and acidic residues are distributed along the entire length of the SEB chain. Our laboratory is presently investigating structural features of the native or modified SEB molecule requisite for in cico enterotoxic or immunogenic (Warrcn i'r d., 1973) and in i'ifro mitogenic activity, An iniportant part of this effort has been a study of the stability of SEB under various solvent conditions. Detailed information on the denaturation of other protein enterotoxins or mitogens is presently not available in the literature. Characteristics of the isothermal denaturation of a protein give important insights into structural features of thc protein in its native state . The native conformation of SEB in 0.15 hi KCI was found to be stable toward disruption by Gdn'HCI and urea in that unfolding of the protein in aqueous solutions of these denaturants showed a large time dependency. However, the protein was relatively susceptible to acid denaturation. drastic alteration in SEB structure having occurred helow pH 3.5.is favored by a large activation energy of denaturation and a comparatively small activation energy of renaturation. These isothermal denaturation experiments indicate a very stable core of structure in native enterotoxin B. However, toxin in 0.15 M KCI was rapidly denatured following addition of HCI to a p H of below 3.5. Below p H 2.3 slow association of acid-denatured toxin into a 7.6s aggregate was detected. The lability of enterotoxin to acid pH suggests stabilization of stru...