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71.
Tung TC Oshima K Cui G Laks H Sen L 《American journal of physiology. Heart and circulatory physiology》2003,285(3):H964-H973
Activation-induced cell death and cytokine deprivation are demonstrated by peripheral T cell populations at the conclusion of natural immune responses, and each of these processes is modulated by the immunosuppressive cytokine interleukin (IL)-10 in vitro. This study employs a clinically relevant in vivo model of IL-10 gene transfer with heterotopically transplanted cardiac allografts to determine the mechanisms of the effects of IL-10 on T cell survival. IL-10 protein overexpression within allografts 4-5 days after gene transfer augments apoptosis of CD4+ and CD8+ graft-infiltrating lymphocytes by 7.1-fold (P < 0.001) and 6.0-fold (P < 0.001), respectively. Graft-infiltrating T cells express 10-fold more proapoptotic Fas (P < 0.01) and 30-fold more Bax (P < 0.01) than controls. The fractions of activated caspase-8 (FADD-like IL-1beta-converting enzyme) and activated caspase-9 were increased 7- and 2.3-fold, respectively, in IL-10 gene-treated allografts at postoperative day 4-5. These changes in the Fas-Fas ligand pathway and Bcl-2 mitochondrial apoptosis regulation are enhanced by complete suppression of antiapoptotic FADD-like IL-1beta-converting enzyme inhibitory protein (FLIP) (from 30.5 to 0.0%, P < 0.01) and Bcl-xL (from 22.5 to 0.1%, P = 0.03) expression among these cells from the earliest days after gene transfer. Although changes in proteins of Fas- and Bcl-2-mediated apoptosis signaling occur, only the levels of Fas and FLIP correlate to the rate of apoptosis of graft-infiltrating CD3 lymphocytes and histological rejection scores. These results indicate that dichotomous apoptosis-regulatory pathways are affected by IL-10 gene therapy, but Fas-mediated mechanisms of activation-induced cell death more substantially contribute to the greater cell death of graft-infiltrating T cells after ex vivo IL-10 gene transfer. 相似文献
72.
The physiological significance of the position and shape of the oxygen equilibrium curve (OEC) of horse hemoglobin (Hb) is considered from the viewpoint of oxygen (O2) transport efficiency and the effectiveness of the Bohr effect. In horse fetal and maternal bloods, their physiological O2 affinities are nearly optimized with respect to the effectiveness of the Bohr shift occurring at the O2 release site, when it is measured by the change in O2 saturation per unit change in P50. With relatively low cooperativity (n=2.69) of horse Hb under physiological conditions, the effectiveness of the Bohr shift for fetal blood at O2 uptake site and maternal blood at O2 release site is high. These facts imply that the position and the cooperativity of horse Hb OEC are optimized to receive maximal benefit from the double Bohr shift. Before exercise, the position of the OEC for adult mares is nearly optimized for the effectiveness of the Bohr shift occurring at the O2 release site, whereas, at maximal exercise, the position of the OEC tends to become advantageous for O2 transport efficiency. 相似文献
73.
The physiological significance of the cooperativity of human hemoglobin (Hb) is considered from the viewpoint of the effectiveness of the Bohr shift at the sites of O(2) release and uptake across the placental membrane. The effects of the Bohr shift was examined by changing the O(2) saturation of Hb (S(pO2)) per unit change in P(50), -dS(PO2)/d P(50), where P(50) is partial pressure of O(2) at half saturation. The Bohr shift at the sites of O(2) uptake and release was found to be highly effective in both fetal and maternal bloods at physiological degree of cooperativity (Hill's coefficient, n=2.65). From the results obtained in this paper, it is concluded that the positions of OECs of fetal and maternal Hbs are regulated to receive a maximal benefit from the Bohr shift, and that a relatively low n value of human tetrameric Hb is adequate for the O(2) and CO(2) exchange across the placental membrane. 相似文献
74.
We undertook this project to clarify whether hemoglobin (Hb) dimers have a high affinity for oxygen and cooperativity. For this, we prepared stable Hb dimers by introducing the mutation Trp-->Glu at beta37 using our Escherichia coli expression system at the alpha1beta2 interface of Hb, and analyzed their molecular properties. The mutant hybrid Hbs with a single oxygen binding site were prepared by substituting Mg(II) protoporphyrin for ferrous heme in either the alpha or beta subunit, and the oxygen binding properties of the free dimers were investigated. Molecular weight determination of both the deoxy and CO forms showed all these molecules to be dimers in the absence of IHP at different protein concentrations. Oxygen equilibrium measurements showed high affinity and non-cooperative oxygen binding for all mutant Hb and hybrid Hb dimers. However, EPR results on the [alpha(N)(Fe-NO)beta(M)(Mg)] hybrid showed some alpha1beta1 interactions. These results provide some clues as to the properties of Hb dimers, which have not been studied extensively owing to practical difficulties in their preparation. 相似文献
75.
Ozaki H Nakajima K Kuwahara M Sawai H 《Bioorganic & medicinal chemistry letters》2004,14(5):1115-1118
An oligodeoxyribonucleotide (ODN) containing three C5-substituted arabinofuranosyluracils was synthesized by the post-synthetic modification method from the ODN containing three C5-substituted 2,2'-anhydrouridines. The stability of the modified ODN/DNA duplex was lower than that of the corresponding normal duplex but that of the modified ODN/RNA duplex showed little change. The modified ODN could induce RNase H activity and was resistant against nuclease. 相似文献
76.
Minami T Shimane M Tanaka H Namikawa K Ichida S 《Biological trace element research》2001,84(1-3):169-179
The aim of this study was to observe whether a low dosage of zinc induced mouse pancreatic injury. Dosages of zinc from 0.1
to 50 mg/kg were injected subcutaneously in mice, and plasma and pancreatic clinical parameters were observed 3–24 h after
the injection. Plasma α-amylase activity increased 10 and 24 h after the injection of 25 or 50 mg/kg of zinc, whereas pancreatic
α-amylase activity decreased 3 h after more than 5 mg/kg of zinc was injected. The activity recovered after 24 h except in
the group injected with 50 mg/kg of zinc. The plasma glucose level did not change when less than 25 mg/kg of zinc was injected.
The pancreatic zinc contents increased 3 h after more than 1 mg/kg of zinc was injected. The pancreatic metallothionein (MT)
contents increased 6 h after the injection of 1 mg/kg of zinc. In addition, when more than 5 mg/kg of zinc was injected, the
MT content increased at 3 h. In histochemical observations, cell damages such as fibrosis and necrosis were observed in pancreatic
exocrine cells, but not in cells of Langerhans islets. From the present study, a single injection of a low dosage of zinc
induces injury in pancreatic exocrine cells, but not endocrine cells. 相似文献
77.
Kiyohiro Hamatani Hidetaka Eguchi Keiko Takahashi Kazuaki Koyama Mayumi Mukai Reiko Ito Masataka Taga Wataru Yasui Kei Nakachi 《The journal of histochemistry and cytochemistry》2006,54(7):773-780
Recently, in addition to DNA, RNA extracted from archival tissue specimens has become an invaluable source of material for molecular biological analysis. Successful amplification with PCR/RT-PCR is problematic when using amplicons of short size due to degradation of DNA or RNA. We established an improved method for efficient RT-PCR amplification of RNA extracted from archival formalin-fixed, paraffin-embedded tissue by the elimination of RNA modification and the restoration of RNA template activity. Namely, the preheating in citrate buffer (pH 4.0) of RNA extracted from long-term preserved tissue specimens resulted in significantly increased efficiency of RT-PCR. 相似文献
78.
Misato Aizawa Kiyohiro Nakai Takeo Watanabe Akemi Kumano Kumie Tamagaki Shoji Sonoda 《Applied Entomology and Zoology》2018,53(1):165-170
A simple plant-free method to monitor for cypermethrin resistance of Thrips tabaci Lindeman at 24 h after insect collection was developed, which utilizes an agar-coated glass pipette. In the laboratory, when cypermethrin-resistant and -susceptible insects were mixed in various ratios and subjected to the method, only resistant insects were detected as survivors. All survivors in the field bioassay were found to have a particular amino acid mutation (T929I) in the sodium channel. Results obtained in this study also showed that the method is affected by temperature, possibly because pyrethroid toxicity increases as the temperature decreases. This method could be used for the on-site monitoring of T. tabaci for cypermethrin resistance with careful temperature management after insect collection. 相似文献
79.
Tomoko Yamazaki Mayumi Mori Satoko Arai Ryosuke Tateishi Masanori Abe Mihoko Ban Akemi Nishijima Maki Maeda Takeharu Asano Toshihiro Kai Kiyohiro Izumino Jun Takahashi Kayo Aoyama Sei Harada Toru Takebayashi Toshiaki Gunji Shin Ohnishi Shinji Seto Yukio Yoshida Yoichi Hiasa Kazuhiko Koike Ken-ichi Yamamura Ken-ichiro Inoue Toru Miyazaki 《PloS one》2014,9(10)
Background
Hepatocellular carcinoma (HCC), the fifth most common cancer type and the third highest cause of cancer death worldwide, develops in different types of liver injuries, and is mostly associated with cirrhosis. However, non-alcoholic fatty liver disease often causes HCC with less fibrosis, and the number of patients with this disease is rapidly increasing. The high mortality rate and the pathological complexity of liver diseases and HCC require blood biomarkers that accurately reflect the state of liver damage and presence of HCC.Methods and Findings
Here we demonstrate that a circulating protein, apoptosis inhibitor of macrophage (AIM) may meet this requirement. A large-scale analysis of healthy individuals across a wide age range revealed a mean blood AIM of 4.99±1.8 µg/ml in men and 6.06±2.1 µg/ml in women. AIM levels were significantly augmented in the younger generation (20s–40s), particularly in women. Interestingly, AIM levels were markedly higher in patients with advanced liver damage, regardless of disease type, and correlated significantly with multiple parameters representing liver function. In mice, AIM levels increased in response to carbon tetrachloride, confirming that the high AIM observed in humans is the result of liver damage. In addition, carbon tetrachloride caused comparable states of liver damage in AIM-deficient and wild-type mice, indicating no influence of AIM levels on liver injury progression. Intriguingly, certain combinations of AIM indexes normalized to liver marker score significantly distinguished HCC patients from non-HCC patients and thus could be applicable for HCC diagnosis.Conclusion
AIM potently reveals both liver damage and HCC. Thus, our results may provide the basis for novel diagnostic strategies for this widespread and fatal disease. 相似文献80.
Yutaka Kamura Minoru Iwata Shiro Maeda Satomi Shinmura Yukiko Koshimizu Hisae Honoki Kazuhito Fukuda Manabu Ishiki Isao Usui Yasuo Fukushima Atsuko Takano Hiromi Kato Shihou Murakami Kiyohiro Higuchi Chikaaki Kobashi Kazuyuki Tobe 《PloS one》2016,11(11)
AimSeveral studies have demonstrated that polymorphisms within the fat-mass and obesity-associated gene (FTO) are associated with type 2 diabetes (T2D). However, whether the effects of the FTO locus on T2D susceptibility are independent of fat-mass increases remains controversial. To investigate this issue, we examined the association of FTO variants with T2D and various aspects of BMI history during adult life in a Japanese population.MethodsWe genotyped SNPs within FTO (rs1121980 and rs1558902) in 760 Japanese patients with T2D who had reached a lifetime maximum BMI (BMImax) before or at the time of diagnosis and 693 control individuals with information regarding their BMImax.ResultsThe BMImax showed the strongest association with T2D risk among the BMIs evaluated in this study. In the sex-combined analysis, FTO SNPs were not associated with any of the BMI variables or with T2D, but in sex-stratified analyses, both SNPs were significantly associated with the BMImax and rs1558902 was associated with T2D in men. The association of the SNPs with T2D remained significant after adjustments for the current BMI and age, whereas the T2D association of the SNP was no longer significant after adjustments for BMImax and age.ConclusionsThese results suggest that the effects of FTO polymorphisms on T2D susceptibility in Japanese men are mediated through their effect on increasing the BMImax before or at the time of diagnosis. 相似文献