Detection of Tyrosinase Autoantibodies in Patients With Vitiligo Using 35S-Labeled Recombinant Human Tyrosinase in a Radioimmunoassay

Tyrosinase antibodies recently have been reported to occur frequently in patients with vitligo. We describe the detection of tyrosinase antibodies in vitiligo patients using in vitro 35S-labeled human tyrosinase in a radioimmunoassay. Of 46 vitiligo sera examined in the assay, five (10.9%) were found to be positive for tyrosinase antibodies. In contrast, 20 control sera and sera from 10 patients with Hashimoto's thyroiditis were negative. Four of the sera positive in the radioimmunoassay were also positive in an ELISA using mushroom tyrosinase as antigen. Absorption studies indicated that pre-incubation with mushroom tyrosinase absorbed out the immunoreactivity of the positive sera in the radioimmunoassay, suggesting cross-reactivity, but this absorption was never complete, indicating that there are tyrosinase antibodies in human sera that do not react with the mushroom protein. There was no obvious association between the presence of tyrosinase antibodies and the age of the patients (range: 22–62 y), their duration of disease (range: 5–20 y), or the type of vitiligo (one segmental, one symmetricallperiorificial, three symmetrical), although the three patients with the highest antibody levels also had an associated autoimmune disorder (one with Graves' disease; two with autoimmune hypothyroidism). The results confirm that tyrosinase autoantibodies are present in the sera of vitiligo patients but at a low frequency. The technique described is sensitive and quantitative and allows the detection of confirmational epitopes. It will be useful in longitudinal studies to determine the relation between the clinical features of vitiligo and tyrosinase antibody levels

Antidepressant exposure in pregnancy and child sensorimotor and visuospatial development

Motor development underlies many aspects of education and learning. There has been uncertainty about the impact of exposure of antidepressant medication in pregnancy on child motor outcomes. This paper examines whether exposure to antidepressants in utero increases the risk of poorer motor development in two areas: sensorimotor and visuospatial processing. Data were obtained from 195 women and children across 3 groups: women with untreated depression in pregnancy, women treated with antidepressants and control women. Data were collected across pregnancy, postpartum and until 4 years for mother and child. Maternal depression was established at baseline with the Structured Clinical Interview for DSM-IV. Antidepressant exposure, including type, dose and timing, was measured through repeated self-report across pregnancy and the postpartum, medical records at delivery and in cord blood samples collected at delivery. Child sensorimotor and visuospatial outcomes were assessed at 4 years of age with four subtests from the NEPSY-II. Our study found for sensorimotor development, visuomotor precision completion time was associated with better performance for antidepressant exposed children compared to those with mothers with untreated depression. Yet another measure of sensorimotor development, motor manual sequences, was poorer in those exposed to antidepressants. One subtest for visuospatial processing, block construction, was associated with poorer performance in antidepressant-exposed children who had poor neonatal adaptation and those exposed to a higher dose of antidepressant. These findings suggest an inconsistent association between sensorimotor development and antidepressant use in pregnancy. However, the findings for visuospatial processing would support further exploration of antidepressant associated poor neonatal adaption and later motor development

Autoantigens in Vitiligo Identified by the Serological Selection of a Phage-Displayed Melanocyte cDNA Expression Library

Vitiligo is an acquired idiopathic hypomelanotic disorder characterized by circumscribed depigmented macules resulting from the loss of cutaneous melanocytes. Although the exact cause of vitiligo remains obscure, autoimmunity may play a role in the development of the disease. The present study was undertaken to investigate the applicability of phage display technology to identify B-cell autoantigens in vitiligo. A melanocyte cDNA phage display library was subjected to rounds of enrichment with vitiligo patient IgG. Subsequently, enriched IgG-binding peptides representing putative autoantigens were identified by sequencing their encoding cDNAs. Radioimmunoassays were used to confirm the immunoreactivity of vitiligo patient (n=61) and control (n=28) sera to several of the putative autoantigens. Non-segmental vitiligo patient sera (n=53) were positive for antibody (Ab) reactivity to gamma-enolase (8%); alpha-enolase (9%); heat-shock protein 90 (13%); osteopontin (4%); ubiquitin-conjugating enzyme (15%); translation-initiation factor 2 (6%); and GTP-binding protein, Rab38 (15%). Ab reactivity to at least one of the previously unknown autoantigens was detected in 51% of patients with non-segmental vitiligo. In contrast, Ab reactivity in a group of patients with segmental vitiligo (n=8) was not demonstrated. Overall, the study indicated that the targets of autoantibodies in vitiligo patients can be revealed by employing the methodology of phage display

Mismatch negativity/P3a complex in young people with psychiatric disorders : a cluster analysis

Background: We have recently shown that the event-related potential biomarkers, mismatch negativity (MMN) and P3a, are similarly impaired in young patients with schizophrenia- and affective-spectrum psychoses as well as those with bipolar disorder. A data driven approach may help to further elucidate novel patterns of MMN/P3a amplitudes that characterise distinct subgroups in patients with emerging psychiatric disorders. Methods: Eighty seven outpatients (16 to 30 years) were assessed: 19 diagnosed with a depressive disorder; 26 with a bipolar disorder; and 42 with a psychotic disorder. The MMN/P3a complex was elicited using a two-tone passive auditory oddball paradigm with duration deviant tones. Hierarchical cluster analysis utilising frontal, central and temporal neurophysiological variables was conducted. Results: Three clusters were determined: the 'globally impaired' cluster (n = 53) displayed reduced frontal and temporal MMN as well as reduced central P3a amplitudes; the 'largest frontal MMN' cluster (n = 17) were distinguished by increased frontal MMN amplitudes and the 'largest temporal MMN' cluster (n = 17) was characterised by increases in temporal MMN only. Notably, 55% of those in the globally impaired cluster were diagnosed with schizophrenia-spectrum disorder, whereas the three patient subgroups were equally represented in the remaining two clusters. The three cluster-groups did not differ in their current symptomatology; however, the globally impaired cluster was the most neuropsychologically impaired, compared with controls. Conclusions: These findings suggest that in emerging psychiatric disorders there are distinct MMN/P3a profiles of patient subgroups independent of current symptomatology. Schizophrenia-spectrum patients tended to show the most global impairments in this neurophysiological complex. Two other subgroups of patients were found to have neurophysiological profiles suggestive of quite different neurobiological (and hence, treatment) implications

Black hole formation via hypercritical accretion during common envelope evolution

Neutron stars inspiralling into a stellar envelope can accrete at rates vastly exceeding the Eddington limit if the flow develops pressures high enough to allow neutrinos to radiate the released gravitational energy. It has been suggested that this hypercritical mode of accretion leads inevitably to the formation of stellar mass black holes during common envelope evolution. We study the hydrodynamics of this flow at large radii (R >> R_ns), and show that for low Mach number flows, in two dimensions, modest density gradients in the stellar envelope suffice to produce a hot, advection dominated accretion disk around the accreting object. The formation of outflows from such a disk is highly probable, and we discuss the impact of the resultant mass loss and feedback of energy into the envelope for the survival of the neutron star. Unless outflows are weaker than those inferred for well observed accreting systems, we argue that in most cases insufficient accretion occurs to force collapse to a black hole before the envelope has been ejected. This conclusions is of interest for black hole formation in general, for some models of gamma ray bursts, and for predictions of the event rate in future LIGO observations.Comment: ApJ, submitte

Polyunsaturated fatty acid status and methylmercury exposure are not associated with leukocyte telomere length in mothers or their children in the Seychelles Child Development Study

Background: Leukocyte telomere length (TL) is associated with age-related diseases and early mortality, but there is a lack of data on the determinants of TL in early life. Evidence suggests that dietary intake ofmarine n-3 (v-3) polyunsaturated fatty acids (PUFAs) is protective of telomere attrition, yet the effect of methylmercury exposure, also found in fish, on TL is unknown. Objective: The aim of this study was to investigate the associations between prenatal PUFA status, methylmercury exposure, and TL in mothers and children in the SCDS (Seychelles Child Development Study), for whom fish consumption is high. Methods: Blood samples collected from 229 mothers (at 28 wk gestation and delivery) and children (at 5 y of age) in the SCDS first nutrition cohort were analyzed for PUFA concentrations. Prenatal mercury was measured in maternal hair collected at delivery. Postnatalmercury was alsomeasured in children's hair samples with the use of a cumulativemetric derived from values obtained at 3-5 y of age. Relative TL wasmeasured in blood obtained from mothers at delivery, in cord blood, and in children at 5 y of age by quantitative polymerase chain reaction. Linear regression models were used to investigate the associations between PUFA status, methylmercury exposure, and TL. Results: Neither prenatal PUFA status or methylmercury exposure was associated with TL of the mother or child or with TL attrition rate. However, a higher prenatal n-6:n-3 PUFA ratiowas significantly associated with longer TLs in the mothers (β = 0.001, P = 0.048). Child PUFA status andmethylmercury exposurewere not associated with child TL. However, higher family Hollingshead socioeconomic status (SES) scores at 9 mo of agewere significantly associatedwith longer TLs in cord blood (β = 0.005, P=0.03). Conclusions: We found no evidence that PUFA status or methylmercury exposure are determinants of TL in either the mother or child. However, our results support the hypothesis that family SES may be associated with child TL

Seasonally stable temperature gradients through supraglacial debris in the Everest region of Nepal, Central Himalaya

Rock debris covers about 30% of glacier ablation areas in the Central Himalaya and modifies the impact of atmospheric conditions on mass balance. The thermal properties of supraglacial debris are diurnally variable but remain poorly constrained for monsoon-influenced glaciers over the timescale of the ablation season. We measured vertical debris profile temperatures at 12 sites on four glaciers in the Everest region with debris thickness ranging from 0.08–2.8 m. Typically, the length of the ice ablation season beneath supraglacial debris was 160 days (15 May to 22 October)—a month longer than the monsoon season. Debris temperature gradients were approximately linear (r2 > 0.83), measured as –40°C m–1 where debris was up to 0.1 m thick, –20°C m–1 for debris 0.1–0.5 m thick, and –4°C m–1 for debris greater than 0.5 m thick. Our results demonstrate that the influence of supraglacial debris on the temperature of the underlying ice surface, and therefore melt, is stable at a seasonal timescale and can be estimated from near-surface temperature. These results have the potential to greatly improve the representation of ablation in calculations of debris-covered glacier mass balance and projections of their response to climate change.Peer reviewe

The planetary system host HR\,8799: On its λ\lambda Bootis nature

HR\,8799 is a $\lambda$ Bootis, $\gamma$ Doradus star hosting a planetary system and a debris disk with two rings. This makes this system a very interesting target for asteroseismic studies. This work is devoted to the determination of the internal metallicity of this star, linked with its $\lambda$ Bootis nature (i.e., solar surface abundances of light elements, and subsolar surface abundances of heavy elements), taking advantage of its $\gamma$ Doradus pulsations. This is the most accurate way to obtain this information, and this is the first time such a study is performed for a planetary-system-host star. We have used the equilibrium code CESAM and the non-adiabatic pulsational code GraCo. We have applied the Frequency Ratio Method (FRM) and the Time Dependent Convection theory (TDC) to estimate the mode identification, the Brunt-Va\"is\"al\"a frequency integral and the mode instability, making the selection of the possible models. When the non-seismological constraints (i.e its position in the HR diagram) are used, the solar abundance models are discarded. This result contradicts one of the main hypothesis for explaining the $\lambda$ Bootis nature, namely the accretion/diffusion of gas by a star with solar abundance. Therefore, according to these results, a revision of this hypothesis is needed. The inclusion of accurate internal chemical mixing processes seems to be necessary to explain the peculiar abundances observed in the surface of stars with internal subsolar metallicities. The use of the asteroseismological constraints, like those provided by the FRM or the instability analysis, provides a very accurate determination of the physical characteristics of HR 8799. However, a dependence of the results on the inclination angle $i$ still remains. The determination of this angle, more accurate multicolour photometric observations, and high resolution spectroscopy can definitively fix the mass and metallicity of this star.Comment: 11 pages, 10 figures. Accepted for publication in MNRA

Genetic variation in FADS genes is associated with maternal long-chain PUFA status but not with cognitive development of infants in a high fish-eating observational study

AbstractLong-chain n-6 and n-3 PUFA (LC-PUFA), arachidonic acid (AA) (20:4n-6) and DHA (22:6n-3), are critical for optimal brain development. These fatty acids can be consumed directly from the diet, or synthesized endogenously from precursor PUFA by Δ-5 (encoded by FADS1) and Δ-6 desaturases (encoded by FADS2). The aim of this study was to determine the potential importance of maternal genetic variability in FADS1 and FADS2 genes to maternal LC-PUFA status and infant neurodevelopment in populations with high fish intakes. The Nutrition Cohorts 1 (NC1) and 2 (NC2) are longitudinal observational mother-child cohorts in the Republic of Seychelles. Maternal serum LC-PUFA was measured at 28 weeks gestation and genotyping for rs174537 (FADS1), rs174561 (FADS1), rs3834458 (FADS1-FADS2) and rs174575 (FADS2) was performed in both cohorts. The children completed the Bayley Scales of Infant Development II (BSID-II) at 30 months in NC1 and at 20 months in NC2. Complete data were available for 221 and 1310 mothers from NC1 and NC2 respectively. With increasing number of rs3834458 minor alleles, maternal concentrations of AA were significantly decreased (NC1 p=0.004; NC2 p<0.001) and precursor:product ratios for linoleic acid (LA) (18:2n-6)-to-AA (NC1 p<0.001; NC2 p<0.001) and α-linolenic acid (ALA) (18:3n-3)-to-DHA were increased (NC2 p=0.028). There were no significant associations between maternal FADS genotype and BSID-II scores in either cohort. A trend for improved PDI was found among infants born to mothers with the minor rs3834458 allele.In these high fish-eating cohorts, genetic variability in FADS genes was associated with maternal AA status measured in serum and a subtle association of the FADS genotype was found with neurodevelopment