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51.
Involvement of the programmed death-1/programmed death-1 ligand pathway in CD4+CD25+ regulatory T-cell activity to suppress alloimmune responses 总被引:4,自引:0,他引:4
BACKGROUND: Immune regulatory CD4+CD25+ T (regulatory T; Treg) cells play a vital role in the induction and maintenance of self-tolerance. They are essential for the homeostasis of T cells, the prevention of autoimmunity, and the induction of tolerance to allogeneic donor grafts. However, the underlying mechanism of their functions remains mostly elusive. Therefore, we investigated here a crucial role of Treg cells in their response to alloantigen via the programmed death (PD)-1/PD-1 ligand (PD-L1) pathway. METHODS: In vitro mixed lymphocyte reaction (MLR) assay, graft-versus-host disease (GvHD) and a skin transplantation model were used to evaluate the mechanisms of PD-1/PD-L1 pathway. RESULTS: Blockade of the PD-1/PD-L1 pathway using anti-PD-L1 monoclonal antibodies (mAb) is found to inhibit Treg cell's ability to suppress and restore CD4+CD25-T-cell proliferation in vitro. GvHD was lethal after adoptive transfer of allogeneic C57BL/6 (H-2K) spleen cells to NOD/SCID (H-2K) mice unless CD25+ T cells were also included. Strikingly, the suppression of GvHD by CD25+ cells was abrogated by anti-PD-L1 mAb administration. The abrogation of Treg-cell-mediated suppression could also be demonstrated in a Balb/c (H-2K) to B6/Rag-2KO (H-2K) skin-allograft model. CONCLUSIONS: The blockade of the PD-1/PD-L1 pathway abrogates Treg-mediated immunoregulation, thus suggesting that the PD-1/PD-L1 pathway is required for Treg suppression of the alloreactive responses of CD4+CD25-T cells. This finding has important implications for clarifying the mechanisms of allograft rejection and GvHD. 相似文献
52.
Takagawa R Fujii S Ohta M Nagano Y Kunisaki C Yamagishi S Osada S Ichikawa Y Shimada H 《Annals of surgical oncology》2008,15(12):3433-3439
Background We evaluated the prognostic value of the preoperative serum carcinoembryonic antigen (CEA) level in patients with colorectal
cancer (CRC).
Patients and Methods The study group comprised 638 patients. The optimal cutoff value for the preoperative serum CEA level was determined. Predictive
factors of recurrence were evaluated using multivariate analyses. The relapse-free time was investigated according to the
CEA level.
Results All patients underwent potentially curative resection for CRC without distant metastasis, classified as stage I, II, or III.
The optimal cutoff value for preoperative serum CEA level was 10 ng/ml. Elevated preoperative serum CEA level was observed
in 92 patients. Multivariate analysis identified tumor–node–metastasis (TNM) stage and preoperative serum CEA level as independent
predictive factors of recurrence. The relapse-free survival between CEA levels >10 ng/ml and <10 ng/ml significantly differed
in patients with stage II and III. However, there was no significant difference in relapse-free survival between CEA levels
>10 ng/ml and <10 ng/ml in patients with stage I.
Conclusion Preoperative serum CEA is a reliable predictive factor of recurrence after curative surgery in CRC patients and a useful indicator
of the optimal treatment after resection, particularly for cases classified as stage II or stage III. 相似文献
53.
Chikara Kunisaki Hirochika Makino Ryo Takagawa Kei Sato Mayumi Kawamata Amane Kanazawa Naoto Yamamoto Yasuhiko Nagano Shoichi Fujii Hidetaka A. Ono Hirotoshi Akiyama Hiroshi Shimada 《Surgical endoscopy》2009,23(9):2085-2093
Background Some studies have found high incidences of intraoperative and postoperative complications for patients with gastric cancer.
To determine the predictive factors for the surgical complications of laparoscopic gastric surgery, surgical outcomes were
evaluated.
Methods Between April 2002 and December 2007, 152 patients with preoperatively diagnosed early gastric cancer who underwent laparoscopy-assisted
distal gastrectomy (LADG) were enrolled. Visceral (VFA) and subcutaneous fat areas (SFA) were assessed by Fat Scan software.
The predictive factors for surgical complications of LADG were evaluated by univariate and logistic regression analyses.
Results Of 152 patients, conversion to open surgery due to uncontrollable bleeding was observed in nine male patients, and postoperative
complications were detected in seven male and one female patient (four anastomotic leakage, two intraabdominal abscess, one
pancreatic fistula, and one lymphorrhea). High body mass index (BMI) and high VFA independently predicted conversion to open
surgery and postoperative complications. VFA was significantly higher, operation time was longer, blood loss was greater,
and SFA was lower in male than in female patients, whereas no significant difference was observed in BMI between male and
female patients.
Conclusions High BMI and high VFA can predict technical difficulties during laparoscopic gastric surgery and postoperative complications.
Particularly, LADG should be performed cautiously to prevent surgical complications for male patients with high VFA. Predictive
impact of VFA should be further determined in a larger set of patients. 相似文献
54.
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56.
Hiroi H Momoeda M Nakazawa F Koizumi M Tsutsumi R Hosokawa Y Osuga Y Yano T Tsutsumi O Taketani Y 《Endocrine journal》2008,55(1):183-189
Periostin/OSF2 is a ligand for alphavbeta3 and alphavbeta5 integrins and activates the Akt/PKB pathway. Recent reports of periostin/OSF2 gene disrupted mice indicate that periostin/OSF-2 plays an important role in implantation. Quantitative RT-PCR revealed that the expression of periostin/OSF-2 mRNA in rat uteri was reduced to approximately 10% at 12 h after 17beta-estradiol (E2) injection, but was not changed after progesterone (P) injection. RT-PCR revealed the expression of periostin/OSF-2 in human endometrium, cultured human endometrial stromal cells (ESCs), and cultured human endometrial epithelial cells. In ESCs, the expression of periostin/OSF-2 mRNA was reduced to approximately 50% at 6 h after E2 treatment. The amount of periostin/OSF2 mRNA in human endometrium significantly increased during mid-proliferative and early secretory phases of menstrual cycle, and decreased during late-proliferative, mid-secretory and late secretory phases. The expression of periostin/OSF2 mRNA significantly decreased in ESCs decidualized by treatment with E2 and P for 7 and 11 days. By immunohistochemistry, the expression of periostin/OSF-2 was strongly detected in endometrial stromal cells during early proliferative, mid-proliferative and early secretory phases, and was strongly detected in endometrial epithelial cells during late secretory phase. This study demonstrated that the expression of periostin/OSF-2 is regulated by ovarian steroid hormones in rat uterus and human endometrium. 相似文献
57.
Shiratori Y Kato N Yoshida H Nakata R Ihori M Imazeki F Yokosuka O Kawase T Katamoto T Unuma T Nakamura A Ikegami F Hirota K Omata M 《Digestive diseases and sciences》2000,45(3):565-574
Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50–94% of patients with 2 × 104 copies/ml (competitive RT-PCR) or <100 × 103 copies/ml (Amplicor monitor) of HCV RNA by 468–1206 MU of IFN, but response was only 0–25% of the patients with 2 × 105.5 copies/ml (competitive RT-PCR) or >200 × 103 copies/ml (Amplicor monitor), even with 468–1206 MU of IFN. A high sustained rate was demonstrated in patients with 100–200 × 103 copies/ml of HCV RNA by 901–1206 MU of IFN, in comparison to that with 900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100–200 × 103 copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000–227,000 for one person-viral eradication in the patients with <100, 100–200, and >200 × 103 copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with <200 × 103 copies/ml of HCV RNA. 相似文献
58.
59.
Kentaro Matsuo Sang-Woong Lee Ryo Tanaka Yoshiro Imai Kotaro Honda Kazuhiro Yamamoto Kazuhisa Uchiyama 《Medicine》2021,100(16)
Introduction:Gastric varices can be present in up to 20% of patients with portal hypertension. However, a varix of the left gastroepiploic vein (LGV) is extremely rare. Surgery is required if bleeding occurs; thus, precise diagnosis is crucial. We present a successful case of preoperative diagnosis intraabdominal varix of the LGV using three-dimensional-computed tomography angiography (3D-CTA) followed by laparoscopic resection. This is the first report of a case with variant LGV. Our study demonstrates the efficacies of 3D-CTA and laparoscopic surgery for the diagnosis and safe resection of the intraabdominal varix, respectively.Patient concerns:A 74-year-old woman was referred to our department with a tumor in the abdominal cavity. On physical examination, no lumps were palpable in the upper abdomen.Diagnosis:The enhanced CT was revealed that the tumor was not enhanced in the early phase, but in the equilibrium phase. Moreover, 3D-CTA clearly revealed that the tumor was being supplied by the LGV. Thus, it was diagnosed as a variant of the LGV.Interventions:Surgical resection was performed laparoscopically as per the guidance of preoperative 3D-CTA findings. During surgery, a dark tumor was found along the gastroepiploic vessels, supplied by the LGV. The tumor was resected safely based on the preoperative information.Outcomes:Histopathological examination of the tumor showed accumulation of various vessels, but no malignant cells. Therefore, we made a final diagnosis of the tumor as an LGV varix. For follow-up, an annual CT examination was performed and after 3 years postoperation, no recurrence was observed.Conclusions:In the present case, we have achieved a successful preoperative diagnosis using 3D-CTA, and resection was safely accomplished using laparoscopy guided by preoperative anatomical information. This is the first report of an LGV variant. Appropriate management is crucial because bleeding is a catastrophic event. Therefore, imaging procedures such as 3D-CTA for diagnosis, followed by safe resection by laparoscopic surgery, are effective tools for the treatment of epiploic vein varices. 相似文献
60.
Humic acid induces the endothelial nitric oxide synthase phosphorylation at Ser1177 and Thr495 Via Hsp90α and Hsp90β upregulation in human umbilical vein endothelial cells 下载免费PDF全文
Masato Tanaka Miki Miyajima Naoko Hishioka Ryo Nishimura Yusuke Kihara Toshiyuki Hosokawa Masaaki Kurasaki Shunitz Tanaka Takeshi Saito 《Environmental toxicology》2015,30(2):223-231
Humic acid (HA) has been implicated as a contributory factor for blackfoot disease, which is an endemic peripheral vascular disease. We investigated the effect of HA on the regulation of endothelial nitric oxide (NO) synthase (eNOS) in human umbilical vein endothelial cells (HUVECs) to evaluate the involvement of eNOS and related factors in peripheral vascular impairment with HA exposure. Treatment of HUVECs with HA induced upregulation of eNOS. This result coincides with those of previous studies. Furthermore this is the first study to report that HA induces upregulation of heat shock protein (Hsp)90α, Hsp90β, eNOS phosphorylation at Ser1177, and eNOS phosphorylation at Thr495, as compared to that in the control. In contrast, treatment with BAPTA, an intracellular Ca2+ chelator, inhibited upregulation of these proteins induced by HA. This study demonstrates that HA treatment leads to increases in both Hsp90α and Hsp90β proteins and indicates that Hsp90α leads to eNOS phosphorylation at Ser1177 and that Hsp90β leads to eNOS phosphorylation at Thr495, respectively. Upregulation of eNOS, Hsp90α, and Hsp90β in HUVECs is regulated by intracellular Ca2+ accumulation induced by HA. These results suggest that upregulation of eNOS phosphorylation at Ser1177 and eNOS phosphorylation at Thr495 produce NO and superoxide anions, respectively, resulting in generation of peroxynitrite, which causes impairment of vascular endothelial cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 223–231, 2015. 相似文献