Host Factors and susceptibility to rubella virus infection: The association of HLA antigens

To examine the role of host-dependent factors to natural rubella infection, the positive rates of HAI antibody according to HLA-A and -B antigens were studied in 93 children, aged 9 to 10, who were exposed only to a recent epidemic (single-exposure group), and in 199 adult females, aged 18 to 23, who were exposed also to a former epidemic (dual-exposure group). Furthermore, the phenotype frequencies of HLA antigens were investigated in seronegative subjects in both groups, as well as in 58 adult female vac-cinees, in comparison with those of the Japanese population. The seropositive rates by the HLA antigens, 38.7% and 73.4%, respectively, in each exposure group were found in subjects having some HLA antigens. Several of these candidate HLA antigens varied in phenotype frequencies in seronegative subjects of all three groups from those of the average Japanese. Although a few types were statistically significant, no contradictory findings in susceptibility were obtained among the groups during the study, which suggested strongly that subjects with HLA-Bw51 and -Bw16 are susceptible to rubella infection, and subjects with HLA-Aw33 are less susceptible. In addition, when the seropositive rates were compared in all combinations of HLA-A and -B antigens classified according to expected susceptibility, the positive rates were arranged in order of susceptibility with significant statistical differences in several groups.     

Serotonin and melatonin, neurohormones for homeostasis, as novel inhibitors of infections by the intracellular parasite chlamydia

OBJECTIVES: Chlamydiae are obligate intracellular bacteria, causing a variety of diseases, i.e. pneumonia, sexually transmitted disease, conjunctivitis and zoonosis. Tryptophan depletion by interferon-gamma (IFN-gamma) is the most important host defence system against chlamydial infection. Thus chlamydial tryptophan metabolism is thought to play key roles for IFN-gamma resistance, persistent infection and host/tissue tropisms. We tested tryptophan derivatives for activity against chlamydia-infected cells. METHODS: Rates of chlamydial infection and sizes of the inclusions were evaluated by in vitro infection using three Chlamydiaceae species, Chlamydia trachomatis, Chlamydophila pneumoniae and Chlamydophila felis, which show significant divergence of tryptophan synthesis genes and different susceptibilities to IFN-gamma. RESULTS: Melatonin and serotonin, which are recognized as neural hormones for maintenance of organism homeostasis, reduced chlamydial infection but not other bacterial growth tested here. Unlike IFN-gamma, melatonin limited infection of all three chlamydiae and the effects were not recovered by tryptophan supplementation. Melatonin treatment only of host cells could diminish infection and the infection reduction was neutralized by a pertussis toxin, an inhibitor of G proteins. Ligands of melatonin and serotonin receptors also hampered infection. CONCLUSIONS: Inhibition mechanisms of chlamydial infection by melatonin and serotonin appear to be different from those of IFN-gamma and involve specific G-protein-coupled receptors. Melatonin is deemed to inhibit early progression of the chlamydial development cycle, such as establishment of intracellular infection and/or conversion from elementary body to reticulate body. Utilization of melatonin, serotonin or their derivatives may be advantageous for harmless prevention of chlamydial infection.     

The effects of perceived chronic stress on the fMRI correlates of attentional control in women managers

Archives of Women's Mental Health - The aims of the current study were to examine differences in brain responses to cognitive control in stressed and non-stressed women managers. Stress...     

Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin

The autoimmune regulator Aire is expressed in a small proportion of medullary thymic epithelial cells (mTECs) and is crucial in the induction of central T cell tolerance. The origin and development of Aire(+) mTECs, however, are not well understood. Here we demonstrate that the tight-junction components claudin-3 and claudin-4 (Cld3,4) were 'preferentially' expressed in Aire(+) mTECs. In early ontogeny, Cld3,4(hi) TECs derived from the most apical layer of the stratified thymic anlage first expressed known mTEC markers such as UEA-1 ligand and MTS10. We provide evidence that such Cld3,4(hi) UEA-1(+) TECs represented the initial progenitors specified for Aire(+) mTECs, whose development crucially required NF-kappaB-inducing kinase and the adaptor molecule TRAF6. Our results suggest that Aire(+) mTECs represent terminally differentiated cells in a unique lineage arising during thymic organogenesis.     

Long-Term Stability and Reversible Thermal Unfolding of Antibody Structure at Low pH: Case Study

We have here observed that the differential scanning calorimetry profiles and melting temperatures of a humanized antibody were unchanged over a 10-year span when stored at 4°C and at different pH values, even at pH 2.7. This is somewhat surprising, as this particular antibody undergoes conformational changes below pH 4.0. Differential scanning calorimetry analysis showed that melting of the antibody at pH 2.7 was highly reversible, suggesting a possibility that the observed reversibility is at least in part responsible for a 10-year stability at low pH. Conversely, it showed thermal unfolding followed by aggregation at higher pH.     

Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiency

Carbamoylphosphate synthetase I deficiency (CPS1D) is a urea-cycle disorder characterized by episodes of life-threatening hyperammonemia. Correct diagnosis is crucial for patient management, but is difficult to make from clinical presentation and conventional laboratory tests alone. Enzymatic or genetic diagnoses have also been hampered by difficult access to the appropriate organ and the large size of the gene (38 exons). In this study, in order to address this diagnostic dilemma, we performed the largest mutational and clinical analyses of this disorder to date in Japan. Mutations in CPS1 were identified in 16 of 18 patients with a clinical diagnosis of CPS1D. In total, 25 different mutations were identified, of which 19 were novel. Interestingly, in contrast to previous reports suggesting an extremely diverse mutational spectrum, 31.8% of the mutations identified in Japanese were common to more than one family. We also identified two common polymorphisms that might be useful for simple linkage analysis in prenatal diagnosis. The accumulated clinical data will also help to reveal the clinical presentation of this rare disorder in Japan.     

Involvement of Toll-like receptors in the immune response of nasal polyp epithelial cells

Recognition systems employed by airway epithelial cells to respond to microbial exposure include the action of Toll-like receptors (TLRs). We investigated the presence and function of TLR2, 3, and 4 in primary cultures of human nasal polyp epithelial cells. dsRNA stimulation significantly enhanced the expression and secretion of RANTES, IP-10, IL-8, and GM-CSF. LPS also exhibited stimulatory action, but it was much weaker than dsRNA. Peptidoglycan had no significant stimulatory action on the genes. Flow cytometry showed that the nasal polyp epithelial cell mainly expressed TLR3 in an intracellular compartment, but expression of TLR2 and TLR4 was very low on both the cell surface and in the cell. The immune response of primary nasal polyp epithelial cells induced by TLR3 could not be blocked by anti-TLR3 antibody. Among the TLR ligands evaluated, dsRNA, the ligand for TLR3, mediated the strongest pro-inflammatory effects in primary nasal polyp epithelial cells.     

Stimulation of the nucleus basalis of Meynert produces an increase in the extracellular release of nerve growth factor in the rat cerebral cortex

Cerebral cortical extracellular NGF was collected and measured every 100 min using microdialysis and ELISA in anesthetized rats. The NGF level, which was stable at rest, increased in the ipsilateral cortex at 200-500 min after the end of focal electrical stimulation to the unilateral NBM for 100 min.     

Oral management of a child with mixed dentition affected by amelogenesis imperfecta

Amelogenesis Imperfecta (AI) is a hereditary developmental disorder affecting deposition, calcification or maturation of dental enamel in both the primary and permanent dentitions. Patients usually present tooth sensitivity as well as problems in chewing function and esthetics. In addition, dissatisfaction with the teeth appearance is often found, affecting the patient's social life. Oral rehabilitation of children with primary or mixed dentition is complex, since no definitive treatment can be done during periods of growth and until the end of eruption of the permanent dentition is accomplished. This clinical report describes the oral management of a 7-year-old girl with mixed dentition affected by AI. The patient showed accentuated teeth wear and root resorption, decreased occlusal vertical dimension, open bite and alteration in the sequence of eruption of permanent teeth. Most of the teeth were restored with resin modified glass ionomer cement. This approach markedly decreased the patient's dental hypersensitivity and improved functional chewing and esthetics. Positive psychological influence of the treatment on this patient was also observed.