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991.
Immunosuppressive therapy has been employed as the initial treatment for acquired chronic pure red cell aplasia (PRCA), such as idiopathic, thymoma‐associated, or large granular lymphocyte (LGL) leukaemia‐associated PRCA, which is thought to be immune‐mediated. To explore the overall long‐term outcome following immunosuppression and to identify the risk factors for death in these disorders, we conducted nationwide surveys in Japan 2004 and 2006, and identified a total of 185 patients with acquired chronic PRCA, including 72 idiopathic, 41 thymoma‐associated and 14 LGL leukaemia‐associated cases of PRCA for whom data was available. The present study evaluated 127 patients with these three subsets of PRCA. The median overall survival has not yet been reached in idiopathic PRCA. The estimated median overall survival times in patients with thymoma‐associated and LGL leukaemia‐associated PRCA were 142·1 and 147·8 months, respectively. Twenty‐two deaths were reported, and the response to induction therapy and relapse of anaemia were found to be associated with death. The major causes of death were infection in seven patients and organ failure in another seven patients. The results suggest that maintenance therapy and the management of infectious complications are crucial for improving the prognosis of chronic PRCA.  相似文献   
992.
993.
Programmed cell death, or apoptosis, is a tightly regulated, naturally occurring process by which damaged or unwanted cells are removed. Dysregulated apoptosis has been implicated in a variety of pathophysiological conditions, including degenerative diseases, tissue remodeling, and tumorigenesis. The decision to live or die results from integration of numerous environmental signals transmitted by specific classes of cell surface receptors that bind hormones, growth factors, or components of the extracellular matrix. Here we show that platelet endothelial cell adhesion molecule-1 (PECAM-1), a homophilic-binding member of the immunoreceptor tyrosine-based inhibitory motif (ITIM) family of inhibitory receptors, functions prominently to inhibit apoptosis in naturally occurring vascular cells subjected to apoptotic stimuli. Murine endothelial cells and human T lymphocytes lacking PECAM-1 were found to be far more sensitive than their PECAM-1-expressing counterparts to multiple death signals that stimulate Bax, a multidomain, proapoptotic member of the Bcl-2 family that plays a central role in mitochondrial dysfunction-dependent apoptosis. In addition, PECAM-1 markedly suppressed Bax overexpression-induced cytochrome c release, caspase activation, and nuclear fragmentation. Amino acid substitutions within PECAM-1's extracellular homophilic binding domain, or within its cytoplasmic ITIM, completely abolished PECAM-1-mediated cytoprotection. Taken together, these data implicate PECAM-1 as a novel and potent suppressor of Bax-mediated apoptosis and suggest that members of the immunoglobulin gene (Ig) superfamily, like cell surface integrins, may also transmit survival signals into blood and vascular cells.  相似文献   
994.
995.

Background:

Functional microRNAs (miRNAs) in exosomes have been recognised as potential stable biomarkers in cancers. The aim of this study is to identify specific miRNAs in exosome as serum biomarkers for the early detection of recurrence in human colorectal cancer (CRC).

Methods:

Serum samples were sequentially obtained from six patients with and without recurrent CRC. The miRNAs were purified from exosomes, and miRNA microarray analysis was performed. The miRNA expression profiles and copy number aberrations were explored using microarray and array CGH analyses in 124 CRC tissues. Then, we validated exosomal miRNAs in 2 serum sample sets (90 and 209 CRC patients) by quantitative real-time RT–PCR.

Results:

Exosomal miR-17-92a cluster expression level in serum was correlated with the recurrence of CRC. Exosomal miR-19a expression levels in serum were significantly increased in patients with CRC as compared with healthy individuals with gene amplification. The CRC patients with high exosomal miR-19a expression showed poorer prognoses than the low expression group (P<0.001).

Conclusions:

Abundant expression of exosomal miR-19a in serum was identified as a prognostic biomarker for recurrence in CRC patients.  相似文献   
996.
This study aimed to evaluate the impact of three types of block bone substitute material on bone formation and graft resorption in vivo. Standardized bone defects (n?=?4 defects/animal) were created in the calvaria of nine dogs. Block bone substitutes made of deproteinized bovine bone mineral (DBBM), beta-tricalcium phosphate (β-TCP) and a mixture alpha-TCP and hydroxyapatite (α-TCP/HA) were inserted into the bone defects. A fourth defect was left untreated (empty). All sites were covered with a collagenous membrane. Block biopsies were harvested at 3, 6 and 12 months post-implantation and analyzed by micro-CT and histology. Biomaterial absorption was minimal and incorporation within the defect margin was good for all biomaterials. However, β-TCP demonstrated a relatively greater volume of new bone formation and less residual material volume when compared with DBBM and α-TCP/HA. Conversely, α-TCP/HA showed higher osteoconductive potential and a greater new bone area compared with the other two biomaterials. The block bone substitutes used in the present in vivo study showed advantageous in terms of maintenance of their original form in bony defect. However, the positive impact of all biomaterials on new bone formation and replacement of bone was minor even at 12 months. These findings indicate that block bone substitutes are not well suited to vertical bone augmentation. Further investigations are required to improve the insufficient new bone volume for promising clinical results.  相似文献   
997.
Limited and inconsistent studies exist on the association between the intake of fish, n ? 3 polyunsaturated fatty acids (PUFA) and n ? 6 PUFA and breast cancer. Fish and n ? 3 PUFA support various body functions and are thought to reduce the carcinogenesis risk while n ? 6 PUFA may have a positive association with cancer risk. We examined the association between intake of fish, n ? 3 PUFA [including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha‐linolenic acid (ALA)] and n ? 6 PUFA and breast cancer with subanalyses on estrogen (ER) and progesterone receptor (PR) status. We investigated 38,234 Japanese women aged 45–74 years from the Japan Public Health Center‐based prospective study (JPHC study), and during 14.1 years of follow‐up time, 556 breast cancer cases were newly diagnosed. Breast cancer risk was not associated with the intake of total fish, n ? 3 PUFA and n ? 6 PUFA when analyzed in totality through multivariable Cox proportional hazards regression models with age as the time scale. Intake of total n ? 6 was positively associated with the development of ER+PR+ tumors [multivariable‐adjusted HR Q4 vs. Q1 = 2.94 (95% CI: 1.26–6.89; ptrend = 0.02)]. Intake of EPA was associated with a decreased breast cancer risk for ER+PR+ tumors [multivariable‐adjusted HR Q2 vs. Q1 = 0.47 (95% CI: 0.25–0.89; ptrend =0.47)]. While the overall association between the intake of total fish, n ? 3 PUFA and n ? 6 PUFA and breast cancer risk is null, for ER+PR+ tumors, a positive association was seen between n ? 6 intake and breast cancer, and a marginally significant inverse association was observed for EPA intake.  相似文献   
998.
999.

Purpose

The response of rectal cancer to preoperative chemoradiotherapy (PRT) varies widely among patients, and predictors of the response remain to be elucidated. The purpose of this study is to investigate whether radiation-induced apoptosis (RIA) of peripheral blood lymphocytes (PBLs) reflects the underlying intrinsic radiosensitivity of rectal cancer.

Methods

Forty-one patients with clinical T3-4, M0 low rectal cancers, treated with PRT and curative surgery, were retrospectively studied. PBLs were obtained from blood samples of the patients, irradiated at 0, 2, 8, and 16 Gy in vitro, and analyzed for RIA by flow cytometry using Annexin V (AV) and propidium iodide (PI). The correlation of the RIA of PBLs and histological regression of rectal cancer in response to PRT was examined.

Results

Both the proportions of AV+/PI? PBLs (early apoptosis) and AV+/PI + PBLs (late apoptosis) were significantly higher in patients with high histological regression than in those with low histological regression. Age, sex, tumor size, and clinical T and N stages did not affect the RIA of PBLs.

Conclusions

This study showed that the RIA of PBLs is correlated with the histological regression of rectal cancer in response to PRT and suggested that the radiosensitivity of rectal cancer might be estimated by the RIA of PBLs.  相似文献   
1000.
An intrahepatic arterioportal fistula is a rare cause of portal hypertension and variceal bleeding. We report on a patient with an intrahepatic arterioportal fistula following liver biopsy who was successfully treated by hepatectomy after unsuccessful arterial embolization. We also review the literature on symptomatic intrahepatic arterioportal fistulas after liver biopsy. A 48-year-old male with bleeding gastric varices and hepatitis B virus-associated liver cirrhosis was transferred to our hospital; this patient previously underwent percutaneous liver biopsies 3 and 6 years ago. Abdominal examination revealed a bruit over the liver, tenderness in the right upper quadrant, and splenomegaly. Ultrasonographic examination, computed tomography, and angiography confirmed an arterioportal fistula between the right hepatic artery and the right portal vein with portal hypertension. After admission, the patient suffered a large hematemesis and developed shock. He was treated with emergency transarterial embolization using microcoils. Since some collateral vessels bypassed the obstructive coils and still fed the fistulous area, embolization was performed again. Despite the second embolization, the collateral vessels could not be completely controlled. Radical treatment involving resection of his right hepatic lobe was performed. For nearly 6 years postoperatively, this patient has had no further episodes of variceal bleeding.  相似文献   
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