Effects of neutron radiation generated in deep space-like environments on food resources.

The impact of deep space cosmic rays on food resources is as important as the risks of cosmic rays to the human body. This study demonstrates the potential for neutrons as secondary radiation in deep space spacecraft to cause meat activation and oxidative modification of proteins and lipids. We conducted a series of experiments such as the neutron irradiation experiment, the radioactivation analysis and the biochemical analysis. Neutrons with energies from 1 to 5 MeV with doses from 0.01 Gy to 4 Gy were irradiated by the RIKEN accelerated-driven neutron source (RANS). Radioactive nuclei, 24Na, 42K, and 38Cl, were detected in the neutron-irradiated meat. The modification products of the proteins by oxidative nitration, 6-nitrotryptophan (6NO2Trp), and by a lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE), were detected in several proteins with neutron dose dependent. The proteome analysis showed that many oxidative modifications were detected in actin and myosin which are major proteins of myofibrils. This study is of crucial importance not only as risk factors for human space exploration, but also as fundamental effects of radiation on the components of the human body.

Optimization study of chlorine detection sensitivity in concrete based on prompt gamma analysis using 252Cf neutron source.

Chloride attack is a serious problem that decreases the durability of concrete structures of bridges and highways. A compact neutron salt meter with a252Cf neutron source and germanium (Ge) gamma-ray detector based on prompt gamma-ray neutron activation analysis (PGNAA) has been proposed to determine the chlorine concentration in concrete structures. The Optimization of the dimensions of its components, such as polyethylene (PE) moderator, graphite reflector, and lead shield, as well as the positions of the 252Cf source and the Ge detector has been performed to make it highly sensitive for the detection of gamma-rays of chlorine, in addition to lightweight and small volume for in situ use. The results demonstrated that gain factors of 2.5 and 2.2 were obtained for gamma-ray intensity of chlorine and chlorine-to-hydrogen ratio (CHR), respectively, whereas the weight and volume became 19.1% and 23.4%, respectively, compared with the reference setup. The effectiveness of optimization was confirmed by preliminary experiments.

Neutron flat-panel detector using In-Ga-Zn-O thin-film transistor.

Neutron imaging is a powerful tool for observing the internal structure of an object without destroying the object. Neutron imaging (neutron radiography) is a prominent application of neutrons but still requires significant improvements, for example, in sensitivity, resolution, radiation hardness, and handling of neutron imaging detectors. This paper presents the development and the first neutron imaging results of a neutron flat-panel detector (nFPD) based on an In-Ga-Zn-O (IGZO) thin-film transistor (TFT)/photodiode array coupled with a LiF/ZnS scintillator sheet. Direct photo-coupling to the scintillator increases the light collection efficiency. Moreover, unlike lens-coupled neutron cameras, the proposed detector is compact and easy to handle. Owing to the high off-state resistance of IGZO TFTs, their leakage current is lower than that of conventional TFTs, enabling the IGZO TFTs to hold an accumulated charge for a longer period of time and allowing longer exposure times for imaging. This would be a powerful feature for imaging at compact neutron sources with limited flux. This paper reports on the first neutron imaging results with an IGZO nFPD, its performance evaluation, and a demonstration of three-dimensional computed tomography with neutrons.

[A Case of Pseudopancreatic Cyst Development during Bevacizumab plus Paclitaxel Therapy for Pancreatic Metastasis of Breast Cancer].

A 70s woman with pancreatic metastases of HER2-negative breast cancer was being treated with bevacizumab plus paclitaxel. Tumor markers decreased after treatment initiation. After 8 months of treatment, the patient developed abdominal pain and distention, along with loss of appetite. Contrast-enhanced abdominal CT scan images showed the presence of a large 25 cm pseudopancreatic cyst and disappearance of the pancreatic metastatic lesions. Endoscopic ultrasound-guided cystogastrostomy was performed and an AXIOS stent was placed in the lower part of the gastric body. Subsequently, the cyst disappeared and her abdominal symptoms improved. The patient was able to resume treatment with other drugs and did not experience any recurrence of pancreatitis. Four months later, the AXIOS stent was removed. Bevacizumab plus paclitaxel is reportedly effective against HER2-negative metastatic breast cancer. Bevacizumab is a molecular targeted therapy against vascular endothelial growth factor, and the mechanism of its antitumor effect and complications are different from those of conventional drugs. Paclitaxel has also been reported to cause pancreatitis in rare cases. In this case, the mechanism of response to bevacizumab plus paclitaxel for metastatic pancreatic lesions or the development of drug-induced pancreatitis was considered to be the cause of pseudopancreatic cyst formation.

[Complete Response with Neoadjuvant Chemotherapy and Curative Resection in a Case of Locally Advanced Gastric Cancer That Was Strongly Positive for HER2 with Multiple Liver Metastases].

As a part of community screening, a 64-year-old man underwent gastric fluoroscopy, which revealed abnormalities indicative of a type 3 tumor. Contrast-enhanced abdominal computed tomography showed advanced gastric cancer with multiple regional lymph nodes and liver metastases. Chemotherapy was initiated, and after completion of 2 courses of capecitabine (Cape)and oxaliplatin(OHP)therapy, a distalgastrectomy was performed. The response to chemotherapy was Grade 2, and the lymph node status was pN1(1/17). The patient was strongly positive for HER2; thus, 4 courses of Cape, OHP, and trastuzumab(T-mab)therapy were administered for the metastatic liver lesions, and the liver metastases shrank markedly. S5 subsegmentectomy and S7 partial resection were performed subsequently, and pathological analysis showed completely necrotic tissue. Remarkable progress has been made in chemotherapy for gastric cancer, and the use of T-mab in combination is extremely effective for gastric cancer that is strongly positive for HER2. In our patient, we resected the primary lesion and liver metastatic lesions after neoadjuvant chemotherapy. The metastatic lesion showed complete response(CR). Metastases and recurrences can even occur in patients with primary and/or metastatic lesions who show a CR. Furthermore, whether cancers that are strongly positive for HER2 are recurrent remains unknown. The patient is alive and recurrence-free after having undergone a hepatectomy.

Mechanism of neutrophil accumulation in sinusoids after extrahepatic biliary obstruction.

BACKGROUND/AIMS: Polymorphonuclear neutrophil (PMN) infiltration represents a potential source of liver injury, but the precise mechanisms of PMN infiltration in cholestatic liver are not fully understood. METHODOLOGY: This study investigated hepatic expression of cytokine-induced neutrophil chemoattractant (CINC) 14 days after bile duct ligation, as well as the number of infiltrated PMNs in livers. Portal venous endotoxin levels were also evaluated. Furthermore, in vitro CINC production by isolated liver cells from obstructive jaundice (OJ) liver or sham-treated liver was evaluated after stimulation with tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta) or LPS. RESULTS: The number of infiltrated PMNs in sinusoids significantly increased in OJ liver, as compared to sham-treated liver. CINC mRNA expression was also increased in OJ liver. Immunohistochemical study revealed that the majority of the CINC-positive cells were hepatocytes. In vitro study proved that CINC production by isolated hepatocytes was markedly enhanced by IL-1beta stimulation in OJ liver. Furthermore, IL-1beta production by LPS-stimulated Kupffer cells isolated from OJ liver was significantly increased, compared to those from sham-treated liver. Portal venous endotoxin was detectable only in OJ rats. CONCLUSIONS: Excessive production of IL-1beta by activated Kupffer cells, as a result of portal endotoxemia, may play an important role for increased CINC release from hepatocytes in cholestatic liver, leading to PMN infiltration.

Orotic aciduria and plasma urea cycle-related amino acid alterations in short bowel syndrome, evoked by an arginine-free diet.

BACKGROUND: The small bowel is believed to play a crucial role in endogenous arginine synthesis. Therefore, an insufficient arginine supply in the situation of massive intestinal resection might impede normal arginine metabolism. This study sought to determine the clinical and metabolic effects of an arginine-free diet in stable short-bowel patients. METHODS: Four patients, mean age 49 years (range: 26-67), mean time from intestinal resection 46 m (range: 15-97), and remnant small bowel of 30 to 100 cm consumed an L-amino acid arginine-free diet (egg pattern) for 5 days (0.9 g protein equivalent/kg/d plus malabsorption adjustments). Fasting plasma amino acids, ammonium, and blood chemistries were assessed at days 0, 3, and 5. Urinary orotate, orotidine, uric acid, urea, creatinine, and total nitrogen were evaluated daily. RESULTS: Significant decreases in plasma levels of arginine, ornithine, and hydroxyproline occurred at day 5. A decreasing trend in plasma citrulline and a significant plasma glutamine increase were also observed in the same period. Conversely, ammonium concentrations remained normal. Regarding urine compounds, striking orotic aciduria with a peak at day 4 (14-fold vs baseline) and significant decreases in uric acid and urea excretion were found. There were no relevant clinical events. CONCLUSIONS: Despite the limited number of patients in our work and their relative heterogeneity, our results support the idea of the indispensability of an exogenous arginine supply in humans under short bowel syndrome conditions. Studies in larger series are needed to further investigate these findings.

Effects of ethanol on the induction of uncoupling protein-1 (UCP1) mRNA in the mouse brown adipose tissue.

Expression of uncoupling protein-1 (UCP1) is increased by cold acclimation and overfeeding, and reduced in fasting and genetic obesity. It is known that the mitochondrial UCP1 in the brown adipose tissue (BAT) is an important key molecule for non-shivering thermogenesis. On the other hand, ethanol (EtOH) alters thermoregulation in humans and laboratory animals. However, the relationship between EtOH intake and UCP1 expression is not yet clear. Accordingly, the present study employed the technique of real-time quantitative polymerase-chain reaction (PCR) to investigate the effects of EtOH (0.5 or 2.0 g/kg) on the expression of UCP1 mRNA in the mouse BAT. Control mice were injected with the same volume of physiological saline intraperitoneally (IP). IP injection of EtOH (0.5 g/kg) caused a decrease and an increase of the expression of BAT UCP1 mRNA at 1 and 4 hours, respectively. Treatment with EtOH (2.0 g/kg) caused an increases of the expression of BAT UCP1 mRNA at both 2 and 4 hours. BAT UCP1 mRNA levels in both groups increased at 4 hours after EtOH administration. The levels of UCP1 mRNA returned to the control levels by 8 hours after EtOH administration. The expression of BAT UCP1 mRNA was upregulated following EtOH administration, although a lower dose of EtOH initially reduced the expression of UCP1 mRNA in BAT. These findings suggest that EtOH-induced UCP1 mRNA expression in BAT reflects an alteration of the set point of thermogenesis.

Angiopoietins and Tie-2 expression in angiogenesis and proliferation of human hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) is a hypervascular tumor but the mechanisms underlying the process of angiogenesis are not fully understood. Angiopoietins (Ang) have been recently identified as ligands for Tie-2 receptor and are thought to be important factors in vascular maturation and stability during angiogenesis. In this study, we investigated the expression of Ang-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in surgically resected specimens from 46 patients with HCC to determine their potential role in tumor angiogenesis and its progression. VEGF messenger RNA (mRNA) was significantly up-regulated in HCC compared to normal liver tissue from patients with hepatic metastases. No differences were found between HCC and adjacent liver tissue. Meanwhile, Ang-2 mRNA expression in HCC was significantly increased when compared to adjacent liver tissue. On the other hand, Ang-1 and Tie-2 mRNA expression in HCC was not different from that in adjacent liver tissue. Immunohistochemical staining also showed increased Ang-2 protein in HCC. Furthermore, a high Ang-2/1 mRNA ratio in HCC was closely associated with tumor portal vein invasion, tumor diameter, and the microvessel density level as assessed by CD34 immunostaining. With regard to prognosis, the survival time for patients in the high Ang-2/1 mRNA ratio group was significantly poorer when compared with the low Ang-2/1 mRNA ratio group. In conclusion, an increased expression of Ang-2/1 in the presence of VEGF may play a critical role in promoting tumor angiogenesis and progression in human HCC.

Effect of cold-ischemia time on C-X-C chemokine expression and neutrophil accumulation in the graft liver after orthotopic liver transplantation in rats.

BACKGROUND: The precise mechanisms leading to polymorphonuclear neutrophil (PMN) recruitment and activation in the extended cold-preserved liver after transplantation are not yet fully understood. METHODS: We histologically evaluated the number of accumulated PMNs in graft livers, with varying time periods of cold ischemia (1, 6, and 24 hr in University of Wisconsin solution at 4 degrees C), after liver transplantation in rats. Intragraft expression of macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) mRNA, as well as immunohistochemical expression of MIP-2 and CINC in the graft liver, were investigated after reperfusion. The levels of MIP-2 and CINC in the hepatic vein, and tumor necrosis factor (TNF)-alpha, which stimulates these chemokine production, were also monitored. RESULTS: The number of accumulated PMNs in sinusoids significantly increased in the 24-hr cold-ischemia group within 3 hr after reperfusion, compared with the 1-hr and 6-hr groups. Serum MIP-2 levels in the 24-hr group significantly increased at 3, 6, and 12 hr after reperfusion, compared with the other groups. Intragraft MIP-2 mRNA was also up-regulated to a greater extent in the 24-hr group. Similarly, serum CINC levels in the 24-hr group significantly increased at 3 hr, compared with the 1-hr group. CINC mRNA also increased as cold-ischemia time was prolonged. Immunohistochemical staining revealed that hepatocytes were the main source of both MIP-2 and CINC protein. In addition, TNF-alpha in the hepatic vein was detected only in the 24-hr group after reperfusion. CONCLUSION: Extended cold preservation of the graft liver might up-regulate MIP-2 and CINC expression of hepatocytes, most probably through elevated TNF-alpha, and might contribute to PMN recruitment and activation after reperfusion.