Aicardi-Goutières Syndrome: Cutaneous, Laboratory, and Radiologic Findings: A Case Report

Abstract:  Aicardi-Goutières syndrome is a primarily autosomal recessive disorder characterized by congenital encephalopathy, basal ganglia calcifications, elevated interferon-α in blood and cerebral spinal fluid, and negative studies for intrauterine infections that can mimic the syndrome. Cutaneous manifestations include pernio, photosensitivity, and cutaneous vasculitis. We present a case of Aicardi-Goutières syndrome to increase awareness of the disorder and its possible relation to systemic lupus erythematosus.     

Are the effects of psychomotor stimulant drugs on hyperactive children really paradoxical?

The improved “attention” exhibited by hyperactive children treated with amphetamine-like compounds is postulated to be related to a normal action of these drugs in producing stereotyped behaviour. Such activity can be conceptualised as an increased “focusing” of attention, which would be expected to aid performance in tasks involving sustained concentration of attention, but impair performance on tasks involving reversals in cognitive strategy. These behavioural actions of the drugs can be linked to the functioning of central dopaminergic mechanisms.     

Rapid matching for transplantation: PHA primed lymphocytes

Human lymphocytes, 10 days after treatment with phytohemagglutinin P (PHA-P), show PLT (secondary in vitro restimulation) reaction patterns which correspond to their cellular (HLA-D) type. Lymphocytes with shared cellular type stimulate PHA primed cells to a lesser degree than the majority of lymphocytes with unshared HLA-D type, which stimulate a strong response. Using a standard 3H thymidine incorporation technique, it is possible to detect responses in as early as 12 hr total incubation time, although usually a 22-48 hr total incubation time is normally required. This method is simple, gives results that correspond to the primary mixed leukocyte response, and thus may be useful as a cross-matching technique for cadaveric renal transplantation.     

Cloning and molecular characterization of the myxoma virus genome

Restriction enzyme cleavage maps of the genomes of the Uriarra (Ur), Glenfield (GV), and Lausanne (Lu) strains of myxoma virus were deduced for the enzymes EcoRI, KpnI, BamHI, SalI, HindIII, BglI, PstI, and PvuII. Restriction maps for the three strains were indistinguishable with the exception of an additional KpnI site in the Lu genome at map position 38.8. Genomic DNA fragments were cloned into the plasmid vector pGEM-3 and the viral genome was determined to be 163.6 (+/- 0.2) kb in length. Covalently closed terminal fragments were identified by electrophoresis of "snapback" fragments and the 5.3 kb BglI end fragment was cloned after S1 nuclease digestion of the hairpin structure.     

Parcellation of the frontal cortex of the New World monkey Callithrix jacchus by eight neurotransmitter-binding sites

The most extensive development during primate brain evolution involves the cortex of the frontal lobe, especially its prefrontal region. The distribution of neurotransmitter receptors is unknown in this part of the cortex of New World monkeys. The respective distributions of eight different receptors for the transmitters l-glutamate (l-glu and NMDA), γ-amino-butyric acid (GABA_A), noradrenaline (α ₁), acetylcholine (M₁ and M₂) and serotonin (5-HT₁ and 5-HT₂) were therefore studied in cortical areas of the frontal lobe of the lissencephalic New World monkey, Callithrix jacchus. The results are compared to earlier data on Old World monkeys in order to obtain insight into evolutionary trends at the level of chemical neuroanatomy. Our results indicate that the density and laminar pattern of some receptors change precisely at the cytoarchitectonic boundaries between different cortical areas, while some other receptors do not exhibit measurable changes. For example, the premotor area 6 can be distinguished from prefrontal areas by its high concentration of adrenergic α₁ receptors as labelled with [³H] prazosin, with only the cingulate area 24 showing higher values. In other cases, the receptor distribution changes within a cytoarchitectonically homogeneous area. Thus, area 8 can be subdivided into dorsal and ventral regions on the basis of the distribution of GABA_A, muscarinic and serotonin receptors. Comparison of these results in a New World monkey with receptor distributions in other primate species reveals much larger interspecies differences in the areas of the frontal lobe than e.g. in the primary visual cortex. This is interpreted as an indication of extensive changes in the neuro-chemical organisation of this part of the brain during primate brain evolution.     

A new assay for rapid measurement of MIF levels by 3H-labelled cells in liquid scintillation counting vials: Statistical implications for the measurement of migration inhibition

A new quantitative assay for migration inhibitory factor (MIF) employs ³H-labelled cultured mouse or human lymphoid cells migrating from capillary tubes. Capillaries filled with labelled cells are placed in liquid scintillation counting vials, along with the MIF- containing sample and are removed at the end of a five-hour incubation period. The residual, labelled cells which have migrated out of the tubes are solubilized and counted in a liquid scintillation counter. While cultured lymphoblast cells are routinely used in the assay, the method was checked against mouse and guinea pig peritoneal exudate cells in both the labelled cell technique and the conventional chamber assay. The assay is technically simple to perform and a useful tool for laboratory research purposes because of the short span of time needed to obtain the results. These advantages indicate a potential for automation and use of this assay in a clinical immunology laboratory. Statistical analysis of data from both assays demonstrated that the relative variation among replicates is lower in the labelled cell assay. The new assay also measured a significant difference between controls and MIF-containing samples when the migration index (MI) was greater than 80%. Criteria for significant inhibition of migration are discussed in regard to the use of analysis variance (ANOVA) and other statistical procedures, and the inadequacy of a single measure, such as the MI, is discussed.     

Age-related autoantibody production in a nonhuman primate model

Autoantibody production increases with ageing. However, the pathological significance of this increase as well as the corresponding underlying mechanisms are poorly understood. To further our understanding of the role that ageing plays in the development of autoantibody responses, we used a novel nonhuman primate model consisting of healthy baboons of ages representing the entire lifespan of this animal species. Results from this study indicate that production of antinuclear antibodies, anticell extract antibodies and natural autoantibodies gradually and significantly increases from young age to old age without a corresponding increase in neither serum immunoglobulin concentration nor in levels of selected markers of immune dysregulation (sTNF-RI, sTNF-RII, IL-2 sR alpha and IFN-gamma). Therefore, in the baboon model, autoantibodies may be produced in absence of recognizable pathological conditions of the ageing immune system.     

Bronchial epithelial cells produce lung fibroblast chemotactic factor: fibronectin

The interaction between the epithelial cells and the subjacent mesenchymal cells in the airway is thought to play a major role during tissue repair after airway injury and lung morphogenesis. To evaluate this interaction, we cultured human lung fibroblasts, and bovine and human bronchial epithelial cells, and determined that bronchial epithelial cell-conditioned medium has a chemotactic activity for lung fibroblasts. This activity had the characteristics of protein: it was nondialyzable, heat-labile, pepsin-labile, acid-stable, and lipid-inextractable. Molecular sieve chromatography on Sephadex G-150 and affinity chromatography on gelatin-Sepharose revealed that there was one peak of chemotactic activity in high molecular weight range, which bound to gelatin, thus suggesting that the chemotactic factor might be fibronectin. Production and secretion of fibronectin into the culture media were demonstrated by biosynthetic incorporation of radioactive amino acid into fibronectin followed by immunoprecipitation on SDS-PAGE and autoradiography. Release into the culture medium was confirmed by ELISA. The identity of fibronectin as the chemotactic activity was confirmed by the addition of antifibronectin antibody to the conditioned medium, which inhibited chemotaxis in dose-dependent manner. Thus, bronchial epithelial cells produce fibronectin which can function as a chemotactic factor for lung fibroblasts. This production of fibronectin by bronchial epithelial cells may play an important role in regulating interaction between the bronchial epithelial cells that line the lumenal surface of the bronchial epithelial wall and the mesenchymal fibroblasts that underlie the bronchial epithelial basement membrane.