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31.
BACKGROUND: Recently there have appeared on the market many external dressings for wound management. They all use water-sealing materials to maintain wounds in a moist state. However, in our daily clinical observations, a water-sealing material sometimes results in poor wound healing. Although a water-sealing material does in fact keep the wound moist, the quality of the water is far from that of the optimum extracellular fluid. METHODS: A second-degree burn wound was made in the rat by contact with a metal stick. Experiment 1 was to evaluate the influence of delayed primary wound treatment on burn-wound depth progression. We used a time lag procedure. Each group was treated with a water-sealing application (hydrocolloid sheet). Experiment 2 was to investigate the progression-preventing effect of normal saline on a burn allowed to dry for 3 hours, we compared a group that received a water sealing (non-moistening and incomplete moisture) dressing with one that received a water-supplying (moistening) dressing with using chi-square test. RESULTS: In the Experiment 1 (time lag and water sealing test), the early group showed quite normal wound healing at 7 days after onset. The slough was thin (about 10-20% of full dermal thickness). The delayed groups showed the poor healing characteristic. The slough was relatively thick (about 30-60% of full dermal thickness). Three hours' delay seemed to bring about poor healing. In the Experiment 2 (water application test), the moistening (water application) group showed relatively good healing after seven days. The slough was as thin as in the early group in the Experiment 1. The non-moistening group showed a poor healing process like the delayed group in the Experiment 1. For the moistening group, the healing percentage of 77.8% was significantly greater than the 41.3% observed in the non-moistening group (chi-square test, p < 0.05). CONCLUSIONS: All the materials in wound dressing are water-sealing. When the component water under the sheet is far from the extracellular fluid, these applications bring about poor healing. Delayed application and incomplete moisture should be corrected by external water-application. 相似文献
32.
Nakashima K Kokubo T Shichijo M Li YF Yura T Yamamoto N 《European journal of pharmacology》2004,505(1-3):223-228
The initiation of antigen presentation by dendritic cells requires proper internalization of antigens through various mechanisms. Internalization of immune complexes via Fc receptors has been shown to be around 100 times more efficient than the internalization of non-complexed antigens. Spleen tyrosine kinase (Syk) plays an essential role in the signaling cascade initiated by immunoglobulin receptors. We used a selective Syk inhibitor, 7-(3,4-dimethoxyphenyl)-N-1H-indazol-6-ylimidazo[1,2-c]pyrimidin-5-amine dihydrochloride (compound-D), to evaluate the role of Syk in antigen presentation by mouse bone marrow-derived dendritic cells. In line with our expectation, compound-D concentration-dependently inhibited the internalization of immune complexes but not that of antigen itself. Furthermore, when dendritic cells were pretreated with compound-D, the ability of dendritic cells to present immune complex antigens to Th2 cells was attenuated, parallel by a reduced release of interleukin-4 production in Th2 cells. Therefore, Syk kinase activity is a critical component in the process of Fcgamma receptor-mediated internalization of immune complex antigens in dendritic cells, and Syk kinase inhibitors may be beneficial in selectively suppressing antibody-mediated antigen presentation in allergic diseases. 相似文献
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Takedatsu H Shichijo S Azuma K Takedatsu H Sata M Itoh K 《International journal of oncology》2004,24(2):337-347
The molecular basis of host-tumor interaction in HLA-A31+ cancer patients has not been well understood. This lack of clarification is hampering the development of specific immunotherapies for these patients. This study aimed to identify a set of CTL-epitope peptides applicable for the specific immunotherapy of cancer patients with HLA-A31 allele. HLA-A31 allele is expressed in 5-10% of the world population, with the highest expression among Brazilian Amerinds (65%), and the lowest in the Eskimo population (0%). We report herein four cDNAs encoding CTL-epitopes and 7 epitope peptides with the ability to induce HLA-A31-restricted CTLs cytotoxic to tumor cell lines in the peripheral blood mononuclear cells of HLA-A31+ cancer patients. These peptides might be useful for the development of a peptide-based immunotherapy for HLA-A31+ cancer patients. 相似文献
35.
Sahara N Takeshita A Kobayashi M Shigeno K Nakamura S Shinjo K Naito K Maekawa M Horii T Ohnishi K Kitamura K Naoe T Hayash H Ohno R 《Leukemia & lymphoma》2004,45(5):987-995
We studied the cytotoxic effect of an organic arsenical compound, phenylarsine oxide (PAO) on an acute promyelocytic leukemia (APL) cell line (NB4) and an As2O3-resistant NB4 subline (NB4/As). Cell growth was inhibited by 50% (IC50) upon 2-day treatment with As2O3 or PAO at 0.54 and 0.06 μM, respectively in NB4 cells (P = 0.025), and 2.80 and 0.08 μM, respectively in NB4/As (P = 0.030). 0.1 μM PAO increased the proportion of hypodiploid cells (50.3%) by a greater degree than the same dose of As2O3 (3.8%) in NB4 cells. In NB4 cells, 0.1 μM PAO reduced the mitochondrial transmembrane potential (20.5% in a PInegative-Rhodamine123low fraction) by a greater degree than 1 μM As2O3 (7.1%). Western blotting showed that 0.1 μM PAO downregulated the expression of both Bcl-2 and Bcl-XL proteins, whereas I μM As2O3 downregulated only Bcl-2 expression. These results suggest that the cytotoxic effect of PAO on an APL cell line and As2O3-resistant subline is significantly higher than that of As2O3. PAO-induced apoptosis seems to be related to the activation of the mitochondrial pathway and downregulation of both Bcl-2 and Bcl-XL. PAO is a considerable agent for relapsed/refractory APL and for purging APL cells following stem cell transplantation. 相似文献
36.
Long-term assessment of hind limb motor function and neuronal injury following spinal cord ischemia in rats 总被引:1,自引:0,他引:1
Sakamoto T Kawaguchi M Kurita N Horiuchi T Kakimoto M Inoue S Furuya H Nakamura M Konishi N 《Journal of neurosurgical anesthesiology》2003,15(2):104-109
Recent evidence suggests that brain injury caused by ischemia is a dynamic process characterized by ongoing neuronal loss for at least 14 days after ischemia. However, long-term outcome following spinal cord ischemia has not been extensively examined. Therefore, we investigated the changes of hind limb motor function and neuronal injury during a 14-day recovery period after spinal cord ischemia. Male Sprague-Dawley rats received spinal cord ischemia (n = 64) or sham operation (n = 21). Spinal cord ischemia was induced by inflation of a 2F Fogarty catheter placed into the thoracic aorta for 6, 8, or 10 minutes. The rats were killed 2, 7, or 14 days after reperfusion. Hind limb motor function was assessed with the 21-point Basso, Beattie, and Bresnahan (BBB) scale during the recovery period. The number of normal and necrotic neurons was counted in spinal cord sections stained with hematoxylin/eosin. Longer duration of spinal cord ischemia produced severer hind limb motor dysfunction at each time point. However, BBB scores gradually improved during the 14-day recovery period. Neurologic deterioration was not observed between 7 and 14 days after reperfusion. The number of necrotic neurons peaked 2 days after reperfusion and then decreased. A small number of necrotic neurons were still observed 7 and 14 days after reperfusion in some of the animals. These results indicate that, although hind limb motor function may gradually recover, neuronal loss can be ongoing for 14 days after spinal cord ischemia. 相似文献
37.
Shichijo M Yamamoto N Tsujishita H Kimata M Nagai H Kokubo T 《Biological & pharmaceutical bulletin》2003,26(12):1685-1690
To investigate the effect of flavonoids on the activation of p72(syk) (Syk) protein tyrosine kinase which plays a pivotal role in the high affinity IgE receptor-mediated degranulation of mast cells, we picked out 10 flavonoids, classified them into 4 series, and examined their effects on the activation of Syk and on the degranulation of human mast cells. Flavones and flavonols showed clear inhibition, whereas flavanones and isoflavones had either weak or no effect on Syk enzymatic activity induced by amino acid peptide corresponding to the activation loop domain and on IgE-dependent degranulation of human cultured mast cells (HCMC). On the basis of calculated logP (ClogP) values as a prediction of compound lipophilicity, some flavonoids were speculated to have low lipophilicity, the reason for poor cell permeability. A significant relationship was observed between the inhibition of Syk activity and HCMC degranulation attributable to flavonoids when the ClogP values of the compounds were taken into account (r(2)=0.89). These results suggested that the impairment of mast cell degranulation by several flavonoids classified into flavones and flavonols might be mediated via inhibition of the intracellular activation of Syk. 相似文献
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40.
Yamamoto N Takeshita K Shichijo M Kokubo T Sato M Nakashima K Ishimori M Nagai H Li YF Yura T Bacon KB 《The Journal of pharmacology and experimental therapeutics》2003,306(3):1174-1181
Spleen tyrosine kinase (Syk) tyrosine kinase plays essential roles in receptors for Fc portion of immunoglobulins and B cell receptor complex signaling in various inflammatory cells; therefore, inhibitors of Syk kinase may show potential as antiasthmatic/allergic therapeutics. We identified 2-[7-(3,4-dimethoxyphenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-nicotinamide dihydrochloride (BAY 61-3606), a potent (Ki = 7.5 nM) and selective inhibitor of Syk kinase. BAY 61-3606 inhibited not only degranulation (IC50 values between 5 and 46 nM) but also lipid mediator and cytokine synthesis in mast cells. BAY 61-3606 was highly efficacious in basophils obtained from healthy human subjects (IC50 = 10 nM) and seems to be at least as potent in basophils obtained from atopic (high serum IgE) subjects (IC50 = 8.1 nM). B cell receptor activation and receptors for Fc portion of IgG signaling in eosinophils and monocytes were also potently suppressed by BAY 61-3606. Oral administration of BAY 61-3606 to rats significantly suppressed antigen-induced passive cutaneous anaphylactic reaction, bronchoconstriction, and bronchial edema at 3 mg/kg. Furthermore, BAY 61-3606 attenuated antigen-induced airway inflammation in rats. Based on these anti-inflammatory effects of BAY 61-3606 both in vitro and in vivo, it was demonstrated that Syk may play a very critical role in the pathogenesis of allergic reactions. 相似文献