The effects of chronic administration of phenytoin, a common anticonvulsive drug, on immune responses were studied in mice. Anti-keyhole limpet haemocyanin (KLH) IgE antibody response after KLH-immunization was enhanced in phenytoin-treated mice. Proliferative responses of spleen cells induced with KLH, concanavalin A (ConA), lipopolysaccharide and anti-CD3 antibody were reduced in phenytoin-treated mice. Accessory function of spleen adherent cells on ConA-induced T cell proliferative response was reduced in phenytoin-treated mice. KLH-induced IL-4 production of spleen cells was enhanced, while IFN-gamma production was reduced in phenytoin-treated mice. In addition, production of IL-1 alpha, but not IL-6 and IL-12 by spleen adherent cells from phenytoin-treated mice was reduced. Natural killer cell activity was reduced in phenytoin-treated mice. These results suggest that phenytoin treatment preferentially induces a Th2 type response. We also observed that plasma ACTH and corticosterone levels were increased in phenytoin-treated mice, and speculated that phenytoin might act directly and indirectly, through HPA axis activation, on the immune system to modulate Th1/Th2 balance. 相似文献
We found a glutamine/arginine polymorphism at codon 349 of the hBUBR1 gene, encoding a protein kinase required for spindle assembly checkpoint function. The observed heterozygosity was estimated
to be 45% in the Japanese population. This polymorphism may be helpful for genetic studies of many cancer types in which chromosomal
instability is observed.
Received: October 19, 1998 / Accepted: October 24, 1998 相似文献
α1-adrenoceptor sensitivity to noradrenaline has been studied in some arterial smooth muscles of rats and rabbits infected with T. brucei. In rabbits, a decrease in sensitivity of the arterial smooth muscles to noradrenaline was observed in the thoracic aorta, central ear but not renal arteries. No change in the sensitivity of the smooth muscles to histamine was observed. In rats, noradrenaline potency was reduced in the aorta, renal but not tail arteries. In both species, affinity of noradrenaline for a,-adrenoceptors was significantly (P < 0.05) reduced in arteries where the potency of noradrenaline was reduced. Prazosin KB values in infected animals were significantly (P < 0.05) lower than controls. These results are interpreted to suggest either an alteration in the structure of a,-adrenoceptors during an infection, or accumulation of some factor(s) in the receptor microenvironment that modulated binding of agonists and antagonists to the receptors during an infection with T. brucei. The possible role of reduced α1-adrenoceptor affinity in the hypotension observed during an infection with T. brucei is discussed. 相似文献
Summary Several clinical trials have shown that the duration of treatment of painful vertebral syndromes can be shortened by using a combination of vitamins B1, B6, B12 and diclofenac instead of diclofenac. In addition, a more efficient pain relief could be achieved by the combination therapy.In order to confirm these results, we compared the clinical efficacy of diclofenac (25 mg) and a combination preparation with diclofenac (25 mg) plus vitamins B1 (thiamine nitrate 50 mg), B6 (pyridoxine hydrochloride 50 mg) and B12 (cyanocobalamin 0.25 mg) in a multicentric randomized double-blind study including 418 patients. All patients received 3×2 capsules daily for a maximum of 2 weeks. In case of total pain relief, therapy should be discontinued after one week.Data of 376 patients could be evaluated. 53 out of 184 patients receiving the combination and 48 out of 192 patients treated with diclofenac alone could stop therapy due to sufficient pain relief after one week.The evaluation of the Hoppe Pain Questionnaire and the data concerning pain intensity also revealed better results for the combination preparation. The differences in favour of the B-vitamin-diclofenac-combination were statistically significant in patients with severe pain at the beginning of therapy.Considering undesirable side-effects (symptoms in 70 out of 418 patients) there were no significant differences between the two medications.This clinical trial provides further evidence that the combination therapy with diclofenac plus B-vitamins is more effective than diclofenac alone for the treatment of painful vertebral syndroms. 相似文献
Previous studies have shown that the induction of P450 cytochrome 2E1 (CYP2E1) is associated with the loss of proteasomal activities. To correlate the loss of proteasomal activity with CYP2E1 induction, ethanol was fed intragastrically for 1, 3, 7, and 15 days. The maximum induction of CYP2E1 (3.5-fold) occurred after 15 days of ethanol feeding. However, there was no significant decrease in the 26 S chymotrypsin-like and trypsin-like activity over this period of time. When ethanol was given to rats for 1 month, CYP2E1 was significantly induced, and the proteasomal activity was significantly decreased. These results indicate that proteasomal activity was not directly affected by ethanol or CYP2E1 induction. Since 4-hydroxynonenal (4-HNE) concentration was significantly increased at 1 month of ethanol feeding, it was suspected that 4-HNE adduct formation with proteasome subunits could be the mechanism of proteasome inhibition. Using an antibody to 4-HNE adducted proteins in Western blot analysis of the 26 S proteasome fraction isolated from the liver of alcohol fed rats, one extra band appeared around 44 kDa. When the antibody to an ATPase Rpt4 was used to stain the stripped membrane, the same band that was detected with the 4-HNE antibody was detected with the Rpt4 antibody. An adduct of 4-HNE formed with the Rpt4 subunit of 26 S could impede the association of 19 S and 20 S and thus account for the observed decrease of proteasomal activity. 相似文献
Summary: The polycondensation of 1‐ethynyl‐2,5‐dihexyl‐4‐iodobenzene in the presence of 1‐ethynyl‐2,5‐dihexyl‐4‐(2‐phenylethynyl)benzene proceeds according to the mechanism of initiated chain growth polycondensation. It has allowed the synthesis of oligomers with a desired molecular weight and a narrow molecular weight distribution. The reasons for the side reaction leading to the formation of diyne compounds are revealed and the presumed mechanism is given. This opens prospects for the preparation of defectless poly(p‐phenyleneethynylene)s with required molecular weights and narrow molecular weight distributions.
AIM: In restitution after superficial injury of the gastric mucosa, the epithelial continuity is restored by cellular migration. We have shown that heat shock preconditioning inhibits restitution after superficial injury. This study investigates the effect of heat shock preconditioning on tissue proliferation and apoptosis. EXPERIMENTAL DESIGN: Paired guinea pig gastric mucosae were mounted and perfused in Ussing chambers (37 degrees C). After heat shock preconditioning (42 degrees C) (30 min) and normothermic recovery (37 degrees C) (150 min) or normothermic perfusion, a superficial injury was induced by luminal exposure to 1.25 mol/L NaCl (5 min) followed by a 3 h restitution. During perfusion, the mucosa was exposed to 30 micromol/L arachidonic acid (AA) to enhance heat shock response, to 50 micromol/L quercetin (Q) to inhibit the metabolism of arachidonic acid via lipoxygenases, to 50 micromol/L indomethacin (In) to inhibit the metabolism of arachidonic acid via cyclo-oxygenases, or to 150 micromol/L cycloheximide (CHX) to inhibit de novo protein synthesis. After the experiment the mucosa was prepared for immunohistochemical analysis of the expression of Mib-1 proliferation antigen and pro-apoptotic protein Bax. RESULTS: Heat shock decreased Mib-1/Bax ratio and this effect was maintained after superficial injury and exposure to Q, to AA+CHX or to In+CHX. Exposure to CHX, to AA, to In+Q, to In+AA, In+AA+Q or to In+AA+CHX, however, blocked the effect of heat shock preconditioning. The decreasing effect of heat shock preconditioning on Mib-1/Bax ratio could be reversed by exposure to AA+Q or to In. CONCLUSION: The heat-preconditioning-induced effects on the mucosa are reversible and sensitive to exogenous pharmacological modulation. Heat shock preconditioning inhibits proliferation of superficially injured isolated gastric mucosa by a mechanism involving eicosanoid pathways and de novo protein synthesis. 相似文献
This special issue of the Journal of Immunological Methods brings together articles from some of the leaders in labelling antigen-specific T and NKT cells, describing recent technical advances and their impact on the study of immunology. Although tetramers, or tetrameric MHC class I/peptide complexes, are the best known reagents in the field, various forms of oligomeric complexes are now being successfully used to detect antigen-specific T cells, including cytotoxic T lymphocytes, MHC class II-restricted CD4+ T cells, and glycolipid-specific T cells restricted by CD1 isoforms. The articles presented here detail the breadth of the oligomeric structures being used to probe T, NK and NKT cell function, and cover both the technical and practical aspects of their use, as well as the new biology revealed. In addition to providing a summary of the current state of the art, these contributions also provide clear pointers to strategies likely to succeed in the future. In this introductory chapter, we summarise the work presented in the other articles of this issue, and provide an overarching view of this rapidly evolving field. We also provide a summary of the MHC class I molecules successfully refolded to date, and provide references to other relevant sources of technical information. 相似文献
The aim of this study was to elucidate the clinicopathological significance and prognostic role of loss of claudin-1 in colorectal cancer (CRC).
Methods
The correlations between claudin-1 expression and clinicopathological characteristics, including survival rates, were assessed using immunohistochemistry on 260 archival, paraffin-embedded CRC tissues. In addition, the correlations between cludin-1 and nuclear factor-kappa B (NF-κB), epithelial-mesenchymal transition markers and tumor-infiltrating lymphocytes were investigated.
Results
Claudin-1 expression was markedly lost in 42.7% of the 260 CRCs analyzed. Loss of claudin-1 expression significantly correlated with larger tumor size, vascular invasion, higher pT stage, and high metastatic lymph node ratio. In addition, loss of claudin-1 expression significantly correlated with NF-κB activation (P?<?0.001), high SNAI (P?<?0.001), and low E-cadherin (P?<?0.001) expressions. Patients with high immunoscores showed significantly lower rates of claudin-1 expression loss (P?=?0.020). In detail, loss of claudin-1 expression were frequently found in CRCs low CD3- and CD8-positive lymphocytes. There were significant correlations between claudin-1 expression loss and poor overall and recurrence-free survivals (P?<?0.001 and P?<?0.001, respectively).
Conclusion
Taken together, our results suggest that the loss of claudin-1 expression significantly correlates with aggressive tumor behaviors, high SNAI expression, lower immunoscore, and poor prognoses. 相似文献