THE RELATION OF THYROID AUTO-IMMUNITY TO ROUND-CELLED INFILTRATION OF THE THYROID GLAND

The relationship between thyroid auto-immunity and the presence of lymphocytes in the thyroid gland has been analysed in patients with Graves' disease, toxic adenoma, and non-toxic nodular goitre. In all these conditions circulating antibody to thyroglobulin was significantly associated with lymphocytic infiltration. No similar correlation was established in the case of the complement-fixing antibody.     

Experimental reproduction of the runting-stunting syndrome of broiler chickens

A model for the reproduction of the runting-stunting syndrome (RSS) of broiler chickens is described. In this model, groups of at least 90 day-old broiler chickens were inoculated (per os) with various tissue homo-genates or virus preparations. During the first week post-inoculation, birds were examined for the development of histopathological changes in their intestines. At day 14 post-inoculation, the remaining birds were weighed and tested for elevations in plasma amylase activity and examined for the development of pancreatic atrophy. Bacteria-free intestinal and pancreatic homogenates from chickens of different ages, taken from flocks which developed RSS, regularly induced a lower mean live-weight in treated birds. Of these, only intestinal homogenates prepared from 5-day-old birds induced intestinal lesions, lowered mean live-weight and increased the incidence of both elevated plasma amylase activity and pancreatic atrophy. These changes were more marked in birds exposed to short periods of sub-optimal temperatures during the first week post-inoculation. An ultracentri-fuged pellet prepared from this intestinal homogehate, was also found to induce an increased incidence of pancreatic atrophy in treated birds. These studies suggest that the causative agent(s) of RSS is an as yet unidentified virus, and that the effects of this infection are greater in birds subjected to stress, such as sub-optimal temperature exposure, within the first week of hatch.     

Molecular determinants of glycine receptor αβ subunit sensitivities to Zn2+-mediated inhibition

Glycine receptors exhibit a biphasic sensitivity profile in response to Zn²⁺-mediated modulation, with low Zn²⁺ concentrations potentiating (< 10 μ m ), and higher Zn²⁺ concentrations inhibiting submaximal responses to glycine. Here, a substantial 30-fold increase in sensitivity to Zn²⁺-mediated inhibition was apparent for the homomeric glycine receptor (GlyR) α1 subunit compared to either GlyR α2 or α3 subtypes. Swapping the divergent histidine (H107) residue in GlyR α1, which together with the conserved H109 forms part of an intersubunit Zn²⁺-binding site, for the equivalent asparagine residue present in GlyR α2 and α3, reversed this phenotype. Co-expression of heteromeric GlyR α1 or α2 with the ancillary β subunit yielded receptors that maintained their distinctive sensitivities to Zn²⁺ inhibition. However, GlyR α2β heteromers were consistently 2-fold more sensitive to inhibition compared to the GlyR α2 homomer. Comparative studies to elucidate the specific residue in the β subunit responsible for this differential sensitivity revealed instead threonine 133 in the α1 subunit as a new vital component for Zn²⁺-mediated inhibition. Further studies on heteromeric receptors demonstrated that a mutated β subunit could indeed affect Zn²⁺-mediated inhibition but only from one side of the intersubunit Zn²⁺-binding site, equivalent to the GlyR α1 H107 face. This strongly suggests that the α subunit is responsible for Zn²⁺-mediated inhibition and that this is effectively transduced, asymmetrically, from the side of the Zn²⁺-binding site where H109 and T133 are located.     

Association of polymorphisms of the estrogen receptor gene with anxiety-related traits in children and adolescents: a longitudinal study

Anxiety problems and associated temperamental traits are multifactorial, determined by the interaction of genetic and environmental factors. Genetic effects may involve both neurotransmitters and hormones. A good candidate gene for association with anxiety-related traits is the estrogen receptor (ESRalpha). Estrogen exerts an effect on mood and behavior in humans through gene regulation on binding to estrogen receptor protein. Association between ESRalpha polymorphism and anxiety-related traits was investigated in a cohort of 680 Australian adolescents studied from 4-8 months to 15-16 years of age. Genotype frequencies were estimated for polymorphic PvuII and XbaI restriction sites in intron 1 and a microsatellite [(TA)(n)] locus 5' of ESRalpha. There was strong linkage disequilibrium between the three loci and a significant sex difference was observed in allele (for (TA)(n), PvuII) and genotype (for XbaI) frequencies. There were no significant allelic or genotypic differences in anxiety-related traits for the three loci tested. However, some significant associations were found for PvuII/(TA)(n) and XbaI/(TA)(n) two-locus genotypes and anxiety, accounting for between 1.6% and 2.8% of the total variance for anxiety in this population. The discordance in Hardy-Weinberg proportions at the XbaI locus between the sexes is an important finding, perhaps indicating a sex-specific role for ESRalpha in fetal survival.     

No interaction between the serotonin transporter polymorphism (5-HTTLPR) and childhood adversity or recent stressful life events on symptoms of depression: results from two community surveys.

In this study we investigated interactions between the 5-HTTLPR genotype and environmental risk factors (G x E) on symptoms of depression in two large Australian community samples of adolescents and young adults. We postulated that a significant interaction between the 5-HTTLPR genotype and environmental risk factors of childhood adversity or stressful life events on symptoms of depression would be observed in subjects with at least one short allele (s/l or s/s) compared with subjects with no short alleles (l/l). We did not find significant G x E interactions between the 5-HTTLPR genotype and recent stressful life events or childhood adversity on symptoms of depression in our sample populations. However, we did find adolescents aged 17-18 years homozygous for the long allele (l/l) and exposed to persistently high levels of family adversity over a 6-year period were at a greater risk of depression than subjects with the same genotype exposed to no or persistently low levels of family adversity. This interaction should be interpreted cautiously due to the small number of depressed subjects in the sample with persistently high levels of family adversity.     

Responses of antigen-specific long-term murine T cell lines to wheat gliadin fractions

Recent evidence suggests that the four electrophoretically defined gliadin subfractions (alpha, beta, gamma and omega) of wheat can induce the typical pathological finding of coeliac disease. We have prepared long-term murine T cell lines to gliadin and its four major subfractions. The cell lines were tested in proliferative assays with each homologous gliadin subfraction, and to the other gliadin subfractions. There was some cross-reactivity, with unfractionated gliadin and its alpha-subfraction being the most antigenic, while omega-gliadin was the least. These data demonstrate that gliadin components are effective stimuli for specific T cell responses, and further suggest that the alpha-gliadin subfraction generates the highest specific responses. This accords with observations in man that all four gliadin subfractions exacerbate coeliac mucosa, but that the alpha-subfraction is the most active.     

Civic responsibility among Australian adolescents: Testing two competing models

The development of civic responsibility is considered to be an important component of healthy adolescent development. However, the study of its development has been relatively neglected and few studies have attempted to ground understanding of its development in a theoretical framework. The present study operationalized civic responsibility as attitudes and behaviors relating to political and community issues that are beneficial to society and compared two theoretical causal models, the social development model (SDM) and a coping‐competency model for their predictive value. Gender differences were also assessed. A total of 500 subjects, drawn from a longitudinal study (the Australian Temperament Project), participated in the study, using questionnaire and interview data. Approximately 1 in 5 adolescents actively engaged in behaviors reflecting community civic responsibility and less than 1 in 10 actively participated in the political arena. However, positive levels of social awareness were evident. Hierarchical multiple regression analyses indicated that the SDM had the most predictive value for political and community civic responsibility. Peer encouragement and peer participation were the most significant predictors. Variables from the coping‐competency model played some role in the prediction of community, but not political, civic responsibility. Gender differences in community civic responsibility, but not political civic responsibility, were found. One in two adolescents indicated that they would participate in volunteer work or political activities if more opportunities existed. This suggests the need for greater availability of appropriate community‐oriented activities for adolescents. © 2004 Wiley Periodicals, Inc. J Comm Psychol 32: 229–255, 2004.     

Two cellular pathways regulate the response to TNP-Ficoll in Xenopus laevis

The initiation of the anti-TNP response to TNP-Ficoll in the amphibian Xenopus laevis has been studied. Although the response to this antigen is thymus independent in mammals, it is thymus dependent for the first three days following immunization in Xenopus. This thymus regulation is not MHC restricted, since it can be substituted for by thymus xenografts, and by prior or co-injection of heterologous red blood cells or Concanavalin A. The pathway which is activated by the Con A to substitute for the thymus is NMU sensitive, unlike the thymic pathway. The peripheralised alternative pathway is activated by particulate but not soluble TNP-Ficoll. The thymus-dependent and alternative pathways are discussed in terms of their possible nature, regulation and evolutionary significance.     

Interaction of 5-bromowillardiine with non-NMDA receptors expressed in Xenopus laevis oocytes injected with chick brain mRNA.

Excitatory amino acid (EAA) receptors were studied in Xenopus laevis oocytes microinjected with 1-day-old chick brain mRNA using a two-electrode voltage clamp technique. EAA agonists could be differentially characterised according to their current/voltage (I/V) relationships; I/V plots to kainate (KA) and domoate (Dom) inwardly rectified at positive membrane potentials whereas quisqualate (QA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and L-glutamate (L-Glu) produced linear I/V plots. Interestingly, the non-NMDA (N-methyl-D-aspartate) agonist, 5-bromowillardiine (BrW), displayed properties similar to KA and Dom. It is proposed that BrW acts as a KA-like agonist on chick EAA receptors expressed in Xenopus oocytes.     

Vulnerability of developing brain: IV. Passive avoidance behavior in young rats following maternal undernutrition

An investigation was carried out of the effect of undernourishing rats during much of gestation and throughout the whole suckling period on their behavior in a passive avoidance situation. All young were fed ad libitum from 21 days of age. Passive avoidance tests were done at 30 and 31 days in a two-compartment box. On the first test normal rats tended to cross between compartments more promptly than previously underfed rats. Cross-over latency was always greater on the second test than on the first. There were no significant differences in test 2 latency or in the ratio, test 2 latency/test 1 latency, between sexes, between normal and previously undernourished rats, between groups with 2-min and 24-hr interest intervals, or between master and yoked control rats. The last finding indicates that the apparent passive avoidance response may have been either nonspecific ‘freezing’ behavior following unpleasant stimulation, or inhibition specifically of movement, due to its association with shock.