Epstein–Barr virus antibodies mark systemic lupus erythematosus and scleroderma patients negative for anti‐DNA

Systemic lupus erythematosus (SLE) is an autoimmune disease that can attack many different body organs; the triggering event is unknown. SLE has been associated with more than 100 different autoantibody reactivities – anti‐dsDNA is prominent. Nevertheless, autoantibodies to dsDNA occur in only two‐thirds of SLE patients. We previously reported the use of an antigen microarray to characterize SLE serology. We now report the results of an expanded study of serology in SLE patients and scleroderma (SSc) patients compared with healthy controls. The analysis validated and extended previous findings: two‐thirds of SLE patients reacted to a large spectrum of self‐molecules that overlapped with their reactivity to dsDNA; moreover, some SLE patients manifested a deficiency of natural IgM autoantibodies. Most significant was the finding that many SLE patients who were negative for autoantibodies to dsDNA manifested abnormal antibody responses to Epstein–Barr virus (EBV): these subjects made IgG antibodies to EBV antigens to which healthy subjects did not respond or they failed to make antibodies to EBV antigens to which healthy subjects did respond. This observation suggests that SLE may be associated with a defective immune response to EBV. The SSc patients shared many of these serological abnormalities with SLE patients, but differed from them in increased IgG autoantibodies to topoisomerase and centromere B; 84% of SLE patients and 58% of SSc patients could be detected by their abnormal antibodies to EBV. Hence an aberrant immune response to a ubiquitous viral infection such as EBV might set the stage for an autoimmune disease.     

Apolipoprotein-E Genotype and the Risk of Developing Cholelithiasis following Bariatric Surgery: a Clue to Prevention of Routine Prophylactic Cholecystectomy

Background: Obesity and especially rapid weight loss following bariatric surgery are known risk factors for cholelithiasis. Since the risk may be high, prophylactic cholecystectomy has been advocated. Apolipoprotein (Apo) E, an important carrier protein in cholesterol metabolism and trafficking, is believed to play a role in gallstone pathogenesis. In particular, the Apo E4 allele has been suggested to be associated with cholesterol cholelithiasis. The aim of this study was to assess the incidence of postoperative cholelithiasis in our patient population and to determine a possible correlation with the Apo-E genotype. Methods: 134 morbidly obese patients undergoing gastric restrictive surgery [laparoscopic assisted gastric banding (LAGB) or silastic ring vertical gastroplasty (SRVG)] had abdominal ultrasound before and 6 to 12 months after operation, to determine the presence of gallstones. None of the patients enrolled in the study had gallstones before surgery.They did not have a prophylactic cholecystectomy or receive bile salt treatment. Apo-E genotypes were determined by Polymerase Chain Reaction restriction enzyme analysis. Results: 10 patients (7.5%) developed postoperative cholelithiasis. The incidence of cholelithiasis in each ApoE genotype was: E2/E3 - 1/20 (5%), E3/E3 - 3/91 (3%), E3/E4 - 6/21 (29%), and E4/E4 - 0/2. ApoE allele frequencies in the study population were identical to those of a healthy control population. The mean BMI dropped from 43.6 to 29.4 kg/m². Conclusions: The occurrence of postoperative gallstones was low in our population. However, in subjects with the Apo-E3/E4 genotype, the incidence is of practical significance. These data suggest that Apo-E genotyping may be useful in selecting patients for gallstone prevention (surgical or medical) when undergoing bariatric surgery.Further testing in larger patient populations may be able to give more definite guidelines in the future.     

Deficits in temporal-order judgments in dyslexia: evidence from diotic stimuli differing spectrally and from dichotic stimuli differing only by perceived location

The main debate concerning dyslexia focuses on the question of whether dyslexia is a language-specific disorder or a general nervous system dysfunction manifested in deficits of temporal processing. According to the temporal-order deficit hypothesis, dyslexia manifests difficulty in discriminating the temporal order of stimuli. Evidence has usually involved testing the ability to discriminate series of phonemes or pure tones whose components are separated by very short intervals. One of the difficulties in interpreting the data is the confound of changes in the spectrum with changes in temporal order. Two experiments are reported. In the first experiment, we verified the difficulty by adult dyslexics in judging the temporal order of two tones differing in frequency and presented diotically. The second experiment was designed to isolate temporal-order judgment (TOJ) from holistic frequency-based pattern discrimination processes. We tested temporal-order judgments with 15 ms duration tones of equal frequency presented dichotically (left-right, right-left) with ISI intervals ranging from 8 to 400 ms. Dichotic temporal threshold was significantly lower for adult normal readers than for the adult dyslexics. The results support the claim that adult dyslexics have difficulty in discriminating temporal order even when no spectral changes are involved.     

Posttraumatic Growth and Shattered World Assumptions Among Ex-POWs: The Role of Dissociation

Objective: The controversy regarding the nature of posttraumatic growth (PTG) includes two main competing claims: one which argues that PTG reflects authentic positive changes and the other which argues that PTG reflects illusionary defenses. The former also suggests that PTG evolves from shattered world assumptions (WAs) and that the co-occurrence of high PTG and negative WAs among trauma survivors reflects reconstruction of an integrative belief system. The present study aimed to test these claims by investigating, for the first time, the mediating role of dissociation in the relation between PTG and WAs. Method: Former prisoners of war (ex-POWs; n = 158) and comparable controls (n = 106) were assessed 38 years after the Yom Kippur War. Results: Ex-POWs endorsed more negative WAs and higher PTG and dissociation compared to controls. Ex-POWs with posttraumatic stress disorder (PTSD) endorsed negative WAs and a higher magnitude of PTG and dissociation, compared to both ex-POWs without PTSD and controls. WAs were negatively correlated with dissociation and positively correlated with PTG. PTG was positively correlated with dissociation. Moreover, dissociation fully mediated the association between WAs and PTG. Conclusion: These findings imply that PTG might reflect illusory defenses and raise questions regarding the integration between the co-occurrence of high PTG and negative WAs among trauma survivors.     

Quality of care after early childhood trauma and well-being in later life: child Holocaust survivors reaching old age

The link between deprivation and trauma during earliest childhood and psychosocial functioning and health in later life was investigated in a group of child Holocaust survivors. In a nonconvenience sample 203 survivors, born between 1935 and 1944, completed questionnaires on Holocaust survival experience and several inventories on current health, depression, posttraumatic stress, loneliness, and attachment style. Quality of postwar care arrangements and current physical health independently predicted lack of well-being in old age. Loss of parents during the persecution, year of birth of the survivors (being born before or during the war), and memories of the Holocaust did not significantly affect present well-being. Lack of adequate care after the end of World War II is associated with lower well-being of the youngest Holocaust child survivors, even after an intervening period of 60 years. Our study validates Keilson's (1992) concept of "sequential traumatization," and points to the importance of aftertrauma care in decreasing the impact of early childhood trauma.     

Cross-modal interactions in auditory and visual discrimination.

Three experiments examined auditory-visual interactions using two sensory discrimination paradigms. Experiments 1 and 2 used a one-interval confidence-rating procedure and found modest effects of concurrent visual stimulation on auditory pitch and loudness discrimination, but little effect of auditory stimulation on visual brightness discrimination. The cross-modal interactions could have either a sensory or decisional basis. Experiment 3 used a two-interval same-different procedure and found no effect of visual stimulation on auditory sensitivity in pitch discrimination, and very little effect of auditory stimulation on visual sensitivity in brightness discrimination. Although the ensemble of results could be explained by sensory facilitation and/or inhibition that varies with the behavioral task, the pattern of these and related findings suggests instead that the cross-modal interactions result primarily from relatively late decisional processes (e.g. shifts in response criterion or 'bias').     

Guanine polynucleotides are self‐antigens for human natural autoantibodies and are significantly reduced in the human genome

In the course of investigating anti‐DNA autoantibodies, we examined IgM and IgG antibodies to poly‐G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20‐mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo‐nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti‐G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170 000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain‐associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti‐G20 antibodies; so natural anti‐G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti‐G20 antibodies in human health and disease and of runs of G20 in the human genome.     

Retinitis pigmentosa associated with rhodopsin mutations: Correlation between phenotypic variability and molecular effects

Similar retinitis pigmentosa (RP) phenotypes can result from mutations affecting different rhodopsin regions, and distinct amino acid substitutions can cause different RP severity and progression rates. Specifically, both the R135L and R135W mutations (cytoplasmic end of H3) result in diffuse, severe disease (class A), but R135W causes more severe and more rapidly progressive RP than R135L. The P180A and G188R mutations (second intradiscal loop) exhibit a mild phenotype with regional variability (class B1) and diffuse disease of moderate severity (class B2), respectively. Computational and in vitro studies of these mutants provide molecular insights into this phenotypic variability.