Close phenotypic and functional similarities between human and murine alphabeta T cells expressing invariant TCR alpha-chains

Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expressing V alpha14+ TCR alpha-chains with highly conserved invariant junctional sequences and able to secrete Th2 cytokines when exposed to CD1+ stimulator cells. In humans, alphabeta T cells carrying invariant V alpha24+ TCR alpha-chains highly homologous to those expressed by murine NK1.1 cells have been recently described. Here we show that these cells (referred to as V alpha24inv T cells) and murine NK1.1+ alphabeta T cells resemble each other in several ways. First, like their murine counterparts, T cells expressing high levels of V alpha24inv TCRs can be either CD4- CD8- double negative (DN) or CD4+, but they never express heterodimeric CD8 molecules. Second, most V alpha24inv T cells are brightly stained by NKRP1-specific mAb but not by mAb directed against other type II transmembrane proteins of the NK complex. Third, DN and particularly CD4+ V alpha24inv T cells are greatly enriched for IL-4 producers. The concomitant expression of highly conserved TCRs of a particular set of NK markers and of Th2 cytokines in human and murine alphabeta T cells suggests a coordinate acquisition of these phenotypic and functional properties. Furthermore, the relatively high frequency of human V alpha24inv T cells, which are presently shown to represent on average 1/500 PBL, and the high interindividual variations of the size of this cell subset under physiologic conditions go for a major role played by alphabeta T cells carrying invariant TCR in a large array of immune responses.     

An isolated ZVS/ZCS flyback converter using the leakage inductanceof the coupled inductor

This paper describes a simple and effective way to modify an existing hard-switched flyback power converter into a circuit with zero-voltage switching (ZVS) and zero-current switching (ZCS). The key improvement is to turn the unattractive features of the coupled inductor leakage inductance and snubber capacitor into attractive ones. The coupled inductor leakage inductance and snubber are used to form a quasi-resonant circuit to facilitate ZVS/ZCS of all power devices. The operating principles of the power converter and experimental results are presented     

Pulmonary sequestration receiving arterial supply from the right coronary artery. A case report

Pulmonary sequestration is a relatively rare anomaly. The arterial supply usually is derived from the aorta or its major branches. We present a 65-year-old female patient with pulmonary sequestration receiving arterial supply from the right coronary artery, complicated with sick sinus syndrome.     

Cloning, functional expression and tissue distribution of rabbit alpha 1d-adrenoceptor

We attempt to determine the utility of CERAD in detecting early Alzheimer's disease (AD). CERAD battery was administered to a group of 14 control subjects, 12 patients with possible dementia prodromes and to patients with Alzheimer's disease stratified according to severity (16 mild, 8 moderate). Other measures as some subtest of the Wechsler memory scale and the Rey Complex Figure Test were also applied. Delayed recall as well as logical memory of Wechsler memory scale were found to be the best discriminators for detecting very mild cases of AD (Prodromes) (p < 0.05). None of the memory test proved of value in staging the disorder. Visuospatial functions are better determinants of the progression of the illness. Fluency also distinguish between control subjects and very mild cases. These findings suggest that delayed recall memory and probably executive function are the most useful and sensitive indicators of Alzheimer's disease.     

Changes in extracellular nitrite and nitrate levels after inhibition of glial metabolism with fluorocitrate

The role of glial cells in nitric oxide production in the cerebellum of conscious rats was investigated with a glial selective metabolic inhibitor, fluorocitrate. The levels of nitric oxide metabolites (nitrite plus nitrate) in the dialysate following in vivo microdialysis progressively increased to more than 2-fold the basal levels during a 2-h infusion of fluorocitrate (1 mM), and the increase persisted for more than 2 h after the treatment. Pretreatment with N(G)-nitro-L-arginine methyl ester attenuated the fluorocitrate-induced increase in nitric oxide metabolite levels. None of the glutamate receptor antagonists, including D(-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione, and (+/-)-alpha-methyl-4-carboxyphenylglycine, inhibited the fluorocitrate-induced increase. The L-arginine-induced increase was significantly reduced by fluorocitrate treatment, while N-methyl-D-aspartate, (+)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and trans-(+/-)-1-amino-(1S,3R)-cyclopentane-dicarboxylic acid increased nitric oxide metabolites levels in the fluorocitrate-treated rats, as much as in control animals. These results suggest that glial cells play an important role in modulating nitric oxide production in the cerebellum by regulating L-arginine availability.     

Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor

Chronic bone infection, as attends periodontitis, is often complicated by severe osteolysis. While LPS is believed to be central to the pathogenesis of the osteolytic lesion, the mechanisms by which this bacteria-derived molecule promotes bone resorption are unknown. We find that LPS induces bone marrow macrophages (BMMs) to express c-src, a protooncogene product that we demonstrate is a specific marker of commitment to the osteoclast phenotype. We next turned to possible soluble mediators of LPS-induced c-src. Of a number of osteoclastogenic cytokines tested, only TNF-alpha mirrors the c-src-enhancing effect of LPS. Suggesting that LPS augmentation of c-src is TNF-mediated, endotoxin sequentially induces BMM expression of TNF, followed by c-src. TNF and c-src expression, by cultured BMMs derived from LPS-injected mice, reflects duration of exposure to circulating endotoxin, intimating that endotoxin's effect in vivo is also mediated by TNF. Consistent with these findings, thalidomide (which antagonizes TNF action) attenuates c-src induction by LPS. An anti-TNF antibody blocks LPS enhancement of c-src mRNA, validating the cytokine's modulating role in vitro. Using BMMs of TNF receptor-deleted mice, we demonstrate that TNF induction of c-src is transmitted through the cytokine's p55, but not p75, receptor. Most importantly, LPS administered to wild-type mice prompts osteoclast precursor differentiation, manifest by profound osteoclastogenesis in marrow cultured ex vivo, and by a profusion of marrow-residing cells expressing the osteoclast marker tartrate resistant acid phosphatase, in vivo. In contrast, LPS does not substantially enhance osteoclast proliferation in mice lacking the p55TNF receptor, confirming that LPS-induced osteoclastogenesis is mediated by TNF in vivo via this receptor. Thus, therapy targeting TNF and/or its p55 receptor presents itself as a means of preventing the osteolysis of chronic bacterial infection.     

Contribution of IL-1 beta to the enhancement of Campylobacter rectus lipopolysaccharide-stimulated PGE2 production in old gingival fibroblasts in vitro

Campylobacter rectus is associated with adult periodontitis. We previously reported that C. rectus lipopolysaccharide (LPS)-stimulated prostaglandin E2 (PGE2) production in old cells of human gingival fibroblasts (HGFs) is higher than that in young cells. The present study examined whether an enhancement of C. rectus LPS-stimulated interleukin (IL)-1 beta production in old HGFs contributed to the increased production of PGE2. LPS was prepared from C. rectus ATCC33238. HGFs were established from healthy gingiva in three patients, aged 10-12 years. Cellular aging in culture was determined with increasing doubling. The cultured cells were treated with LPS (0.01-10 micrograms/ml), and the amount of IL-1 beta in the medium was measured after a 24 h incubation. The LPS-stimulated IL-1 beta production in each old cell (corresponding to 57-67% of complete life-span) was increased (1.6-2.6 times) compared to that in the young cells (corresponding to 17-20% of the life-span). The IL-1 beta mRNA synthesis in the presence of LPS in the old cells was higher than that in the young cells. The enhancement of LPS-stimulated PGE2 production was inhibited by anti-IL-1 beta antibody and by IL-1 receptor antagonist. These findings suggest that the greater ability of old cells to produce PGE2 in response to C. rectus LPS is due to their greater level of IL-1 beta.