Role of the common cytokine receptor gamma chain (gammac) in thymocyte selection

During thymocyte development, T-cell receptor (TCR) alphabeta-mediated intracellular signals can elicit two entirely different cellular responses: positive selection (resulting in rescue from death and maturation or differentiation) and negative selection (induction of apoptosis). Here, Hiroshi Nakajima and colleagues discuss how survival signals that are dependent on the common cytokine receptor gamma chain (gammac) might affect the TCR-driven selection process in thymocytes, underscoring the potential role of cytokines in this process.     

A patient homozygous for the SCA6 gene with retinitis pigmentosa

The present authors studied a 55-year-old-patient homozygous for the SCA6 gene who experienced frequent attacks of positional vertigo at 37 years of age with subsequent staggering gait and night blindness. Retinitis pigmentosa (RP), as well as cerebellar ataxia and vertical antidirectional nystagmus, were detected. The subject's parents were first cousins, and two of his three male cousins, whose parents were also first cousins, had RP without ataxia or nystagmus. The numbers of CAG repeats in the expanded alleles of the SCA6 gene found by molecular analysis were 21 and 21. The genetic results were negative for SCA1, SCA2, SCA3, SCA7 and dentatorubral pallidoluysian atrophy. The retinal degeneration in this patient is most likely to be secondary to a genetic disorder of autosomal or X-linked recessive inheritance rather than SCA6. Other reported cases of patients homozygous for the SCA6 gene are also reviewed.     

Characterization of IL-4 and IL-13 signals dependent on the human IL-13 receptor alpha chain 1: redundancy of requirement of tyrosine residue for STAT3 activation

IL-4 and IL-13 are pleiotropic cytokines whose biological activities overlap with each other. IL-13 receptor alpha chain 1 (IL-13R alpha 1) is necessary for binding to IL-13, and the heterodimer composed of IL-13R alpha 1 and IL-4R alpha chain transduces IL-13 and IL-4 signals; however, the functional mapping of the intracellular domain of IL-13R alpha 1 is not fully understood. In this study, we constructed wild and mutated types of human IL-13R alpha 1, and analyzed IL-4 and IL-13 signals using an IL-13R alpha 1-transfected human B cell line. Expression of IL-13R alpha 1 evoked STAT3 activation by IL-4 and IL-13, and in stimulated human B cells, on which IL-13R alpha 1 was highly expressed, IL-4 and IL-13 induced STAT3 activation. Replacement of the two tyrosine residues completely abolished STAT3 activation, although replacing either tyrosine residue alone retained it. Furthermore, we found that the Box1 region and the C-terminal tail of IL-13R alpha 1 were critical for binding to Tyk2, and activation of Jak1, Tyk2, the insulin receptor substrate-1 and STAT6 respectively. These results suggest that STAT3 activation is involved with IL-4 and IL-13 signals in human B cells along with the activation of STAT6, and that there is a unique sequence in IL-13R alpha 1 to activate STAT3.     

Elemental distributions and microtensile bond strength of the adhesive interface to normal and caries-affected dentin

The aim of this study was to evaluate the microtensile bond strength (microTBS) and the elemental contents of the adhesive interface created to normal versus caries-affected dentin. Extracted human molars with coronal carious lesions were used in this study. A self-etching primer/adhesive system (Clearfil Protect Bond) was applied to flat dentin surfaces with normal and caries-affected dentin according to the manufacturer's instructions. After 24 h water storage, the bonded specimens were cross-sectioned and subjected to a microTBS test and electron probe microanalysis for the elemental distributions [calcium (Ca), phosphorus (P), magnesium (Mg), and nitrogen (N)] of the resin-dentin interface after gold sputter-coating. The microTBS to caries-affected dentin was lower than that of normal dentin. The demineralized zone of the caries-affected dentin-resin interface was thicker than that of normal dentin (approximately 3 microm thick in normal dentin; 8 microm thick in caries-affected dentin), and Ca and P in both types of dentin gradually increased from the interface to the underlying dentin. The caries-affected dentin had lost most of its Mg content. The distributions of the minerals, Ca, P, and Mg, at the adhesive interface to caries-affected dentin were different from normal dentin. Moreover, a N peak, which was considered to be the collagen-rich zone resulting from incomplete resin infiltration of exposed collagen, was observed to be thicker within the demineralized zone of caries-affected dentin compared with normal dentin.     

Dependence of the anterior olfactory area self-stimulation upon the lateral hypothalamic area

The functional relation between the anterior olfactory area (AO) and the lateral hypothalamic area (LH) was examined in a self-stimulation situation. Bar-pressing responses for AO sitmulation were suppressed by unilateral injection of procaine, and enhanced by glutamate, into LH. Neither procaine nor glutamate injected into AO had any influence upon LH self-stimulation. It is unlikely that the procaine effect was due to motor disturbance because similar injection of procaine into LH did not disturb the performance of a one-way avoidance task. It appears that the rewarding effect of AO stimulation is dependent upon the excitation of the more caudal structures including LH.     

The inhibitory effect of oxatomide, an anti-allergic agent, on eosinophil-mediated and eosinophilic cell line-mediated natural cytotoxicity against bronchial epithelial cells

Recently, eosinophils have been implicated as inflammatory effector cells in allergic and inflammatory reactions such as bronchial asthma. In this study eosinophil-mediated and eosinophilic cell line-mediated natural cytotoxicity against bronchial epithelial cells and the effects of oxatomide, an anti-allergic agent, on their cytotoxicity were investigated. Treatment with oxatomide diminished both eosinophil-mediated and eosinophilic cell line-mediated natural cytotoxicity in vitro. We concluded from these results that oxatomide not only has anti-allergic activity but also anti-inflammatory properties for eosinophils. In addition this method for isolating eosinophils seems to well serve the purpose of evaluating eosinophil function as in this investigation, as we have reported previously.     

Studies on the behavior of peritoneal cells against soluble immune complexes using the “agar-bullet” method

The results of our previous investigation indicated that the reaction of intraperitoneal cells against foreign materials depended on the heterogenicity and the molecular weight of the substance (Takeuchi, 1973). Substances tested for cellular reaction in this agar-bullet method were (1) bovine serum albumin, (2) soluble antigen-antibody complexes, (3) mixtures of bovine serum albumin and rabbit gamma globulin, (4) precipitated complexes, and (5) bovine gamma globulin. The soluble complex prepared with excess antigen in vitro showed a marked cellular reaction, which was considered to be due to its heterogenicity and molecular weight.