Quantitative determination of anti-dsDNA antibodies and antibody/dsDNA stoichiometries in prepared,soluble complement-fixing antibody/dsDNA immune complexes

We have investigated quantitatively the complement-mediated binding of prepared, soluble ¹²⁵I-7S IgG antibody/³H-dsDNA immune complexes to human red blood cells (RBCs). We have performed these studies by using a detailed modification of the RBC-CF assay [Pedersen et al., J. Immun. Meth. 38, 2692–2280 (1980)] which now allows for the simultaneous measurement of both ³H-DNA and ¹²⁵I-binding to the cells. Our results indicate that, in the case of three SLE patients, their anti-dsDNA antibody titers are sufficiently high that a small fraction of their ¹²⁵I-7S IgG antibodies (ca 0.1–0.2%) can be identified as specifically anti-dsDNA. We have also used an indirect method (with ¹²⁵I-labelled rabbit anti-human IgG) for the determination of IgG anti-dsDNA antibodies in complement-fixing antibody/dsDNA immune complexes that bind to RBCs, and the results of these measurements are in reasonable agreement with the direct binding experiments. These studies have also allowed us to estimate the antibody/DNA stoichiometries in complement-fixing immune complexes. The results of these experiments may provide a useful standard for the analysis of monoclonal anti-dsDNA antibodies.     

Impact of pediatric epilepsy on sleep patterns and behaviors in children and parents

Purpose: Disrupted sleep patterns in children with epilepsy and their parents are commonly described clinically. A number of studies have shown increased frequency of sleep disorders among pediatric epilepsy patients; however, few have characterized the association between epilepsy and parental sleep quality and household sleeping arrangements. The purpose of this study was to explore the effect of pediatric epilepsy on child sleep, parental sleep and fatigue, and parent‐child sleeping arrangements, including room sharing and cosleeping. Methods: Parents of children 2 to 10 years of age with and without epilepsy completed written questionnaires assessing seizure history, child and parent sleep, and household sleeping arrangements. Children’s Sleep Habits Questionnaire (CSHQ) scores were used to evaluate sleep disturbances for the child. The Pittsburgh Sleep Quality Index (PSQI) and the Iowa Fatigue Scale (IFS) were used to evaluate parental sleep and fatigue, respectively. The Early Childhood Epilepsy Severity Scale (E‐Chess) was used to assess epilepsy severity. Key Findings: One hundred five households with a child with epilepsy and 79 controls participated in this study. Households with a child with epilepsy reported increased rates of both parent–child room sharing (p < 0.001) and cosleeping (p = 0.005) compared to controls. Children with epilepsy were found to have greater sleep disturbance by total CSHQ score (p < 0.001) and the following subscores: parasomnias (p < 0.001), night wakings (p < 0.001), sleep duration (p < 0.001), daytime sleepiness (<0.001), sleep onset delay (p = 0.009), and bedtime resistance (p = 0.023). Parents of children with epilepsy had increased sleep dysfunction (p = 0.005) and were more fatigued (p < 0.001). Severity of epilepsy correlated positively with degree of child sleep dysfunction (0.192, p = 0.049), parental sleep dysfunction (0.273, p = 0.005), and parental fatigue (0.324, p = 0.001). Antiepileptic drug polytherapy was predictive of greater childhood sleep disturbances. Nocturnal seizures were associated with parental sleep problems, whereas room sharing and cosleeping behavior were associated with child sleep problems. Within the epilepsy cohort, 69% of parents felt concerned about night seizures and 44% reported feeling rested rarely or never. Finally, 62% of parents described decreased sleep quality and/or quantity with cosleeping. Significance: Pediatric epilepsy can significantly affect sleep patterns for both the affected child and his or her parents. Parents frequently room share or cosleep with their child, adaptations which may have detrimental effects for many households. Clinicians must not only be attentive to the sleep issues occurring in pediatric patients with epilepsy, but also for the household as a whole. These data provide evidence of a profound clinical need for improved epilepsy therapeutics and the development of nocturnal seizure monitoring technologies.     

Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[(11)C]PK11195 brain PET studies

Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[¹¹C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer''s disease were analyzed using various kinetic models including plasma input, the simplified reference tissue model (RPM) and RPM with vascular correction (RPMV_b). In all subject groups, SVCA-based reference tissue curves showed lower blood volume fractions (V_b) and volume of distributions than those based on cerebellum time-activity curve. Probably resulting from the presence of specific signal from the vessel walls that contains in normal condition a significant concentration of the 18 kDa translocation protein. Best contrast between subject groups was seen using SVCA4-based reference tissues as the result of a lower number of kinetic classes and the prior removal of extracerebral tissues. In addition, incorporation of V_b in RPM improved both parametric images and binding potential contrast between groups. Incorporation of V_b within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[¹¹C]PK11195 neurodegeneration studies.     

Epstein-Barr virus reactivation during pregnancy and postpartum: Effects of race and racial discrimination

ObjectiveAdverse pregnancy outcomes, including preterm birth, are markedly higher among African–Americans versus Whites. Stress-induced immune dysregulation may contribute to these effects. Epstein-Barr virus (EBV) reactivation provides a robust model for examining cellular immune competence. This study examined associations of EBV virus capsid antigen immunoglobulin G (VCA IgG) with gestational stage, race, and racial discrimination in women during pregnancy and postpartum.MethodsFifty-six women (38 African–American, 18 White) were included. African–Americans and Whites did not differ in age, education, income, parity, or body mass index (ps ? .51). During the 1st, 2nd, and 3rd trimester and ～5 weeks postpartum, women completed measures of racial discrimination, perceived stress, anxiety, depressive symptoms and health behaviors. EBV VCA IgG antibody titers were measured via ELISA in serum collected at each visit.ResultsIn the overall sample, EBV VCA IgG antibody titers were lower in the 3rd versus 1st trimester (p = .002). At every timepoint (1st, 2nd, 3rd trimester and postpartum), African–American women exhibited higher serum EBV VCA IgG antibody titers than Whites (ps < .001). This effect was most pronounced among African–Americans reporting greater racial discrimination [p = .03 (1st), .04 (2nd), .12 (3rd), .06 (postpartum)]. Associations of race and racial discrimination with EBV VCA IgG antibody titers were not accounted for by other measures of stress or health behaviors.ConclusionsCompared to Whites, African–American women showed higher EBV VCA IgG antibody titers, indicative of impaired cellular immune competence, across pregnancy and postpartum. This effect was particularly pronounced among African–American women reporting greater racial discrimination, supporting a role for chronic stress in this association. In women overall, EBV antibody titers declined during late as compared to early pregnancy. This may be due to pregnancy-related changes in cell-mediated immune function, humoral immune function, and/or antibody transfer to the fetus in late gestation. As a possible marker of stress-induced immune dysregulation during pregnancy, the role of EBV reactivation in racial disparities in perinatal health warrants further attention.     

Computer-aided detection in diagnostic mammography: detection of clinically unsuspected cancers

OBJECTIVE: We had two objectives: to determine the percentage of women presenting with clinical findings whose diagnostic mammogram led to detection of a breast cancer at a site distant from the original clinical complaint and to assess the performance of computer-aided detection (CAD) on diagnostic mammography. MATERIALS AND METHODS: Three institutions contributed consecutive cases in which a mammogram was obtained to evaluate a clinical finding, after which a histologic diagnosis of breast cancer was made. Clinical data and the mammograms were reviewed to determine the nature of the clinical findings and to document the location and characteristics of 212 biopsy-proven cancers in 197 patients who met the study criteria. Standard four-view breast mammograms were then analyzed by a CAD system. RESULTS: The most common clinical finding was a palpable mass (90%, 177/197), with nipple discharge (5%, 9/197), focal tenderness or pain (2%, 5/197), and miscellaneous complaints (3%, 6/197) also noted. Two separate cancers were found in 7.6% (15/197) of the cases. In another 7.6% (15/197) of the cases, the single diagnosed cancer was not at the location of the specific clinical finding. The CAD system correctly marked 87% (26/30) of those cancers that were clinically unsuspected (i.e., not at the location of the clinical finding). CONCLUSION: Breast cancers occurred at locations other than the site of the presenting clinical finding in 15% (30/197) of patients undergoing diagnostic mammography in whom a cancer was detected. CAD identified 87% of these incidentally detected cancers and may therefore be useful as a detection aid to the radiologist when interpreting diagnostic mammograms.     

The relationship between avoidant personality disorder and social phobia

The main explanatory hypothesis for the distinction between social phobia (SP) and avoidant personality disorder (APD) has been the severity continuum hypothesis, stating that APD only differs from SP in terms of severity of dysfunction and symptomatic distress, that is, social anxiety and depressive symptoms. This study aimed at a comprehensive evaluation of this hypothesis in a large sample (n = 2192) of thoroughly assessed patients, most of whom had a diagnosis of personality disorder. Social phobia was stronger associated with APD than with other personality disorders, and APD was stronger associated with SP than with other symptom disorders. Social phobia-pure patients had a higher level of global functioning and lower levels of general symptom distress and interpersonal problems than APD-pure patients. The 2 groups were similar on domains that pertain to social anxiety and introversion, but APD was associated with a broader array of symptoms and interpersonal problems and was substantially lower on the personality domain of conscientiousness. Avoidant personality disorder was stronger associated with eating disorders, and SP was stronger associated with panic disorder. The APD diagnosis seems to capture a broader constellation of symptoms and personality features pointing toward more severe personality dysfunction. Our findings suggest that the severity continuum hypothesis lacks specificity and exploratory power to account for both similarities and differences between SP and APD.     

Demographic and social variables associated with psychiatric and school-related indicators for Asian/Pacific-Islander adolescents

BACKGROUND: Factors associated with Asian/Pacific-Islander adolescent adjustment is a greatly neglected research area. AIMS: The purpose of the present study was to investigate the relation between demographic, social and adjustment measures based on a large-scale investigation of Asian/Pacific-Islander youths. METHOD: A total of 2577 adolescents were surveyed across 4 public schools in Hawai'i during the 1992--1993 school year. RESULTS: Three social variables (number of relatives frequently seen, family support and friends' support) exhibited statistically significant but low correlations. Family support had the highest negative association with the four psychiatric symptoms (depression, anxiety, aggression, substance use). Friends' support was inconsistently associated with the adjustment measures, and the number of relatives frequently seen resulted in negligible effects. In contrast, demographic variables, especially ethnicity, played a much greater role in the association with the four school-related measures (grade-point average, absences, suspensions, conduct infractions). DISCUSSION: For Asian/Pacific-Islander youths, the quality of the social supports, including family relations, may be particularly important in the adolescents' adjustment. When examining school-related outcomes, demographic variables, with particular emphases on ethnicity and culture, must be considered. When developing and implementing prevention and intervention services and programs, consideration of family and ethnic-cultural influences should be taken into account, with further research needed in several related domains: other SES influences, life stressors, migration-generational effects, ethnic identity, self-concept indicators and socio-political aspects.     

A hypothalamic-pituitary system that stimulates the release of plasminogen activator in the rat

We have studied the possible role of the hypothalamic-pituitary system in the control of the release of plasminogen activator (PA) into peripheral blood of male rats. Plasminogen activator was measured by euglobulin lysis time. Desamino-D- arginine vasopressin (dDAVP) and adrenaline injected i.v. induced an increase in plasma PA as did electrical stimulation of the median eminence (ME), but dDAVP had no effect on plasma PA in hypophysectomized rats. The PA response to ME stimulation was similar in Brattleboro rats (deficient in vasopressin) and adrenalectomized Wistar rats compared with intact Wistar rats, but was abolished by section of the pituitary stalk and was negligible in hypophysectomized rats. The 41-residue corticotropin releasing factor (CRF) had no effect on PA release. Saline extracts of anterior pituitary gland from both normal Wistar and Brattleboro rats produced a dose-dependent increase in plasma PA when injected into normal Wistar rats. The activity of pituitary tissue was abolished by boiling, but not by di-isopropyl fluorophosphate which inactivates PA itself. Thus the anterior pituitary gland of the rat contains a heat-labile factor which stimulates the release of PA from peripheral stores into the circulation. This pituitary factor is released by a hypothalamic factor that is neither vasopressin nor CRF.     

Somatic Diseases and Conditions Before the First Diagnosis of Schizophrenia: A Nationwide Population-based Cohort Study in More Than 900 000 Individuals

Objective: Schizophrenia is associated with excess physical comorbidity. Yet, to our knowledge, large studies are lacking on the associations with somatic diseases before the onset of schizophrenia. The authors conducted a nationwide study of the full spectrum of treated somatic diseases before the first diagnosis of schizophrenia. Method: Nationwide sample of the Danish population consisting of singletons (n = 954351) born 1977–1993 and followed from birth to 2009, during which period 4371 developed schizophrenia. Somatic diagnoses at all general hospital contacts (admitted or outpatient care at a somatic hospital) from 1977 to 2009 were used as exposures. The incidence rate ratio (IRR) of schizophrenia was calculated using Poisson regression adjusted for confounders. Results: Among the 4371 persons who developed schizophrenia from 1992 to 2009, a total of 4180 (95.6%) persons had a previous somatic hospital contact. A history of any somatic hospital contact was associated with an elevated risk of schizophrenia (IRR = 2.04, 95% CI = 1.77–2.37). A wide range of somatic diseases and conditions were associated with an increased risk of schizophrenia, including epilepsy (IRR = 2.26, 95% CI = 1.93–2.62), nutritional or metabolic disorders (IRR = 1.57, 95% CI = 1.39–1.77), circulatory system diseases (IRR = 1.63, 95% CI= 1.38–1.92), and brain injury (IRR = 1.58, 95% CI = 1.45–1.72). Conclusions: A wide range of potential etiological factors could have contributed to the observed associations, including genetic or physiological overlaps between conditions, and interacting immunological, behavioral, and neurodevelopmental factors.Key words: schizophrenia, risk factors, physical illness     

Physiological consequences of U.S. Army Ranger training

PURPOSE: Soldiers are expected to maintain a high degree of physical readiness as operational demands can severely degrade performance capabilities. This study examined the physiological consequences of U.S. Army Ranger training on strength, power, body composition, and somatotrophic hormones. METHODS: In an intensive 8-wk military training course that included an average daily energy deficit of 1000 kcal.d, lower-body power output, maximal lifting strength, body composition, and serum concentrations of several somatotrophic hormones were measured in 50 male soldiers (24.6 +/- 4.4 y; 176.1 +/- 7.8 cm; 78.4 +/- 8.7 kg; 14.7 +/- 4.2% body fat) before and after the course. RESULTS: Vertical jump height (-16%), explosive power output (-21%), maximal lifting strength. (-20%), body mass (-13%), fat-free mass (-6%), and fat mass (-50%) declined (P < 0.05) after the training course. Circulating total testosterone and insulin-like growth factor-I (IGF-I) experienced significant (P < 0.05) declines, and cortisol was significantly increased. Lower-body power output, but not maximal lifting strength, correlated with changes in fat-free mass. IGF-I and cortisol, but not total testosterone, were correlated with losses of tissue mass. CONCLUSION: Lower-body power output, estimated from vertical jump height and body mass, is a sensitive and field expedient measure that can be used to assess the influence of caloric deficit on physical performance after 8 wk of U.S. Army Ranger training. With severe weight loss (>or=13% of body mass), IGF-I and cortisol correlate more closely with soft-tissue tissue adaptations than does testosterone.