Interactions of antisera to different <Emphasis Type="Italic">Chlamydia</Emphasis> and <Emphasis Type="Italic">Chlamydophila</Emphasis> species with the ribosomal protein RPS27a correlate with impaired protein synthesis in a human choroid plexus papilloma cell line

Chlamydia trachomatis (CT) and the Chlamydophila species (CS) Chlamydophila pneumoniae (CPn), and Chlamydophila psittaci (CPs) are suggested to induce autoantibodies causative of several human autoimmune disorders like rheumatoid arthritis and systemic lupus erythematosus (SLE). The aim of the present study was therefore to identify cellular protein interaction partners with antisera to CT (α-CT) or CS (α-CS) and to identify functional consequences of such interaction in vitro. As detected with a commercial first trimester human prenatal brain multiprotein array (hEXselect, Engine, Germany), the most frequent interaction partner with both α-CT and α-CS was the ribosomal small subunit protein RPS27a. This could be confirmed by Western blot analysis with a recombinant RPS27a sample. In addition, immunocytochemistry with both antisera in the human choroid plexus papilloma cell line HIBCPP revealed a granular cytoplasmic staining, and Western blot analysis with whole-cell protein samples of HIBCPP cells revealed both antisera to label protein bands of different molecular weights and intensity. By 2D Western blot analysis and mass spectrometry, one of the protein spots interacting with α-CT could be identified as the RPS27a. Finally, two different methods for the detection of protein synthesis activity, the SUnSET technique and an HPG fluorescence assay revealed both antisera to cause reduced translational activity in HIBCPP cells. Together with previous findings of RPS27a as an autoimmune target in a mouse model of systemic lupus erythematosus (SLE), these results suggest that infections with CT and/or CS could induce SLE-associated immune modifications. However, direct evidence for a pathogenic role of these interactions for SLE demands further investigations.     

Anterograde tracing of retinal afferents to the tree shrew hypothalamus and raphe

The anterograde neuronal transport of Cholera toxin B subunit (CTB) was used in this study to label the termination of retinal afferents in the hypothalamus of the tree shrew Tupaia belangeri. Upon pressure-injection of the substance into the vitrous body of one eye, a major projection of the retinohypothalamic tract (RHT) was found to the hypothalamic suprachiasmatic nuclei (SCN). Although the innervation pattern was bilateral, the ipsilateral SCN received a somewhat stronger projection. Labeling was also found in the supraoptic nucleus and its perinuclear zone, respectively, mainly ipsilaterally as well as in the bilateral para- and periventricular hypothalamic regions without lateral predominance. In the raphe region, scattered fibers and terminals were seen in the dorsal and median raphe nuclei. CTB-immunoreactive structures were observed neither in the locus ceruleus nor in vagal nuclei. Our results, partly in contradiction to earlier studies using different tracing techniques in another tree shrew species (Tupaia glis), reveal that hypothalamic nuclei, in particular the SCN, are contacted by retino-afferent fibers which are thought to mediate the effects of light to the endogenous ‘clock’ and to parts of the neuroendocrine system.     

Thyroxine values from newborn screening of 919 infants born before 29 weeks' gestation.

OBJECTIVES: Severe transient hypothyroxinemia in premature infants is associated with cerebral palsy and mental retardation: this study assessed its prevalence in very premature infants. METHODS: Congenital hypothyroidism screening programs in three states provided thyroxine values for 919 newborn infants younger than 29 weeks who were enrolled in a multicenter study. RESULTS: Thyroxine values were lower than 4.0 micrograms/dL in 21% of survivors and increased each week by 0.6 microgram/dL (95% confidence interval [CI] = 0.4, 0.7). At tests done 1 to 2 days after birth, levels were 2.5 micrograms/dL higher (95% CI = 1.8, 3.3) than at tests done at 8 to 14 days. In New York, levels were 1.0 microgram/dL higher (95% CI = 0.3, 1.6) than elsewhere. The levels of infants who died were 1.3 micrograms/dL lower (95% CI = 0.6, 2.0) than those of survivors. CONCLUSIONS: Severe transient hypothyroxinemia is common in very premature infants and deserves further study.     

Loss of connexin36 in rat hippocampus and cerebellar cortex in persistent Borna disease virus infection

Neonatal Borna disease virus (BDV) infection of the Lewis rat leads to progressive degeneration of dentate gyrus granule cells, and cerebellar Purkinje neurons. Our aim here was to clarify whether BDV interfered with the formation of electrical synapses, and we, therefore, analysed expression of the neuronal gap junction protein connexin36 (Cx36) in the Lewis rat hippocampal formation, and cerebellar cortex, 4 and 8 weeks after neonatal infection. Semiquantitative RT-PCR, revealed a BDV-dependent decrease in Cx36 mRNA in the hippocampal formation 4 and 8 weeks post-infection (p.i.), and in the cerebellar cortex 8 weeks p.i. Correspondingly, immunofluorescent staining revealed reduced Cx36 immunoreactivity in both dentate gyrus, and ammons horn CA3 region, 4 and 8 weeks post-infection. In the cerebellar cortex, Cx36 immunoreactivity was detected only 8 weeks post-infection in the molecular layer, where it was down regulated by BDV. Our findings demonstrate, for the first time, distinct BDV-dependent reductions in Cx36 mRNA and protein in the rat hippocampal formation and cerebellar cortex, suggesting altered neuronal network properties to be an important feature of persistent viral brain infections.     

Hypothyroxinemia of prematurity and the risk of cerebral white matter damage.

OBJECTIVE: Infants with hypothyroxinemia of prematurity (HOP) are at increased risk for neurodevelopmental dysfunction. Infants born near the end of the middle trimester are also at increased risk for an echolucency (EL) in the cerebral white matter, which reflects white matter damage and is the cranial ultrasound abnormality that best predicts neurodevelopmental dysfunction. We postulated that some of the increased risk of neurodevelopmental problems associated with HOP reflects an increased risk of EL. STUDY DESIGN: We studied 1414 infants weighing 500 to 1500 g who were born at 4 medical centers between 1991 and 1993. The infants had thyroxine blood levels measured during the first weeks of life, at least 1 of 3 cranial ultrasound scans performed at specified postnatal intervals, and their own and their mother's hospital charts reviewed. Infants were classified by whether or not their first thyroxine level placed them in the lowest quartile among all infants in this sample (ie, <67.8 nmol/L, our definition of HOP, equivalent to <5.3 micrograms/dL). RESULTS: After adjusting for such potential confounders as low gestational age and measures of illness severity, infants with HOP had twice the risk of EL as their peers with higher thyroxine levels. CONCLUSION: Our findings are consistent with the hypothesis that a "normal" blood thyroxine level protects infants born near the end of the middle trimester against the risk of cerebral white matter damage.