Celiac artery dissection in polycystic kidney disease

Autosomal‐dominant polycystic kidney disease (ADPKD) is rarely complicated by celiac artery dissection. Dissection of the aorta and its major branches should be carefully differentiated in ADPKD patients with acute‐onset abdominal pain.     

Downregulation of Tie2 gene by a novel antitumor sulfolipid, 3'-sulfoquinovosyl-1'-monoacylglycerol, targeting angiogenesis

We previously reported that 3'-sulfoquinovosyl-1'-monoacylglycerol (SQMG) was effective in suppressing the growth of solid tumors due to hemorrhagic necrosis in vivo . In the present study, we investigated the antiangiogenic effect of SQMG. In vivo assessment of antitumor assays showed that some tumor cell lines, but not others, were sensitive to SQMG. Microscopic study suggested that in SQMG-sensitive tumors, but not SQMG-resistant tumors, angiogenesis was reduced. We next investigated gene expression relating to angiogenesis in tumor tissues by quantitative real-time polymerase chain reaction. Consequently, although vascular endothelial growth factor gene expression was not detected with significant differences among the cases, significant downregulation of Tie2 gene expression was observed in all SQMG-sensitive tumors as compared with controls, but not in SQMG-resistant tumors. These data suggested that the antitumor effects of SQMG could be attributed to antiangiogenic effects, possibly via the downregulation of Tie2 gene expression in SQMG-sensitive tumors. ( Cancer Sci 2008; 99: 1063–1070)     

High serum values of soluble CD154, IL-2 receptor, RANKL and osteoprotegerin in Langerhans cell histiocytosis

BACKGROUND: To determine useful biochemical markers in Langerhans cell histiocytosis (LCH), we analyzed the serum levels of soluble CD154 (sCD154), IL2 receptor (sIL2-R), receptor activator of NF-kappaB ligand (sRANKL), and osteoprotegerin (OPG). PROCEDURE: Our study included 46 newly diagnosed LCH patients (single-system multi-site (SM type): n = 20, and multi-system multi-site (MM type): n = 26) who were treated with the JLSG-02 protocol between 2002 and 2004. The median age of the patients was 3.8 years old (range 0-18). sCD154, sIL2-R, sRANKL, and OPG were measured by ELISA at diagnosis (n = 46) and after 6-weeks of induction therapy (n = 14). RESULTS: The values of sCD154, sIL-2R, sRANKL, and OPG, and the sRANKL/OPG ratio in sera were significantly higher in patients with LCH compared with controls (1.83 +/- 1.38 vs. 0.22 +/- 0.16 ng/ml, P < 0.001; 1,600 +/- 1,060 vs. 420 +/- 160 pg/ml, P < 0.001; 1.72 +/- 1.20 vs. 1.04 +/- 1.09 pmol/L, P = 0.019; 6.34 +/- 2.94 vs. 3.71 +/- 2.03 pmol/L, P < 0.001; and 0.40 +/- 0.45 vs. 0.16 +/- 0.17, P = 0.023, respectively). Serum levels of sIL-2R were significantly elevated in the MM type compared with the SM type (2,050 +/- 1,060 vs. 870 +/- 340 pg/ml, P < 0.001). Serum OPG levels were also significantly elevated in the MM type compared with the SM type (7.58 +/- 2.72 vs. 5.13 +/- 2.69 pmol/L, P = 0.008) and negatively correlated with the number of bone lesions (r = -0.56, P = 0.007). In contrast, the sRANKL/OPG ratios were significantly higher in the SM type than the MM type (0.57 +/- 0.54 vs. 0.19 +/- 0.14, P = 0.002) and positively correlated with the number of bone lesions (r = 0.34, P = 0.040). In patients who responded to the induction therapy, serum levels of sIL-2R, sRANKL, and OPG, and the sRANKL/OPG ratio decreased significantly after the therapy (1,170 +/- 600 vs. 730 +/- 290 pg/ml, P = 0.029; 2.19 +/- 1.06 vs. 1.24 +/- 0.66 pmol/L, P < 0.001; 6.13 +/- 2.40 vs. 4.72 +/- 2.03 pmol/L, P = 0.040; and 0.57 +/- 0.52 vs. 0.41 +/- 0.37, P = 0.02, respectively). In the three patients who did not respond to the induction therapy, the serum levels of sCD154 increased significantly after the therapy (1.3 +/- 1.1 vs. 2.7 +/- 1.2, P = 0.004). CONCLUSIONS: Serum levels of sIL-2R and sCD154 could be useful as indicators of inflammation and sRANKL/OPG ratios as markers of osteolytic activity in LCH patients.     

Does prolonged biliary obstructive jaundice sensitize the liver to endotoxemia?

Biliary obstructive jaundice (OJ) is an important clinical consideration concerning high bacteremic risk. Hepatocyte apoptosis is one of the causes of cholestatic liver injury. The aim of the current study was to examine the precise pathway and time course of hepatocyte apoptosis during OJ with LPS administration and to determine if OJ sensitizes the liver to endotoxemia. Male C57BL/6 mice were subjected to bile duct ligation and division and were administered with LPS at 3 (OJ3) or 14 (OJ14) days after surgery. Fas ligand expression, poly (adenosine diphosphate-ribose) polymerase p85 fragment immunohistochemistry, activation of caspases 3, 8, and 9, serum alanine aminotransferase levels, and hepatic adenosine triphosphate (ATP) contents were examined. Survival after LPS administration in male C57BL/6 or gld/gld (Fas ligand-deficient) mice was determined. The expression of Fas ligand increased during OJ. After LPS administration, the expression of cleaved caspases 3 and 8 increased in Sham3, Sham14, OJ3, and OJ14 mice, and it significantly increased in OJ14 compared with other mice. Poly (adenosine diphosphate-ribose) polymerase p85 immunohistochemistry showed significant hepatocyte apoptosis after LPS administration in OJ14 mice relative to OJ3. In OJ14 with LPS administration, ATP contents significantly decreased and alanine aminotransferase levels increased. Hepatocyte apoptosis was decreased in gld/gld OJ14 mice compared with C57BL/6 OJ14. All C57BL/6 OJ14 mice with LPS died, but survival in gld/gld OJ14 significantly ameliorated. In prolonged OJ with LPS administration, hepatocyte apoptosis depending on Fas ligand expression significantly increased in association with a decrease in ATP contents, thus resulting in liver necrapoptosis.     

Improved Accuracy Of Cardiac Output Estimation By The Partial CO2 Rebreathing Method

Objective  This study investigated the accuracy of the NICO monitor equipped with the newer software. Additionally, the effects of the increased dead space produced by the NICO monitor on ventilatory settings were investi- gated. Methods  Forty-two patients undergoing elective aortic reconstruction participated in this prospective, obser- vational study at a university hospital. Cardiac output was continuously monitored using both the NICO monitor and continuous cardiac output (CCO) measured by a pulmonary artery catheter. A NICO monitor equipped with ver. 4.2 software was used for the first 21 patients while a NICO monitor equipped with ver. 5.0 software was used for the rest of␣the patients. Cardiac output measured by bolus thermo- dilution (BCO) at 30 min intervals was used as a reference. Results  The bias ± precision of the NICO monitor was 0.18 ± 0.88 l/min with ver. 4.2 software (n = 182) and 0.18 ± 0.83 l/min with 5.0 software (n = 194). The accuracy of the NICO monitor is comparable to CCO, whose bias ± &!hairsp;precision against BCO is 0.19 ± 0.81 l/min (n = 376). At the␣same level of CO₂ production and minute ventilation, PaCO₂ was lower in the patients monitored by NICO with ver. 5.0 software than patients with ver. 4.2 software. Conclusions  This study demonstrated the improved perfor- mance of the NICO monitor with updated software. The performance of the NICO monitor with ver. 4.2 or later software is similar to CCO. However, the cardiac output measurement did not fulfill the criteria of interchangeability to the cardiac output measurement by bolus thermodilution. Updates to ver. 5.0 attenuated the effects of rebreathing introduced by the NICO monitor without compromising the accuracy of the cardiac output measurement. This study was presented at the Annual Meeting of the American Society of Anesthesiologists, 2004.10.26, Las Vegas, NV, USA. Kotake Y, Yamada T, Nagata H, Suzuki T, Serita R, Katori N, Takeda J, Shimizu H. Improved accuracy of cardiac output estimation by the partial CO₂ rebreathing method.     

Comparison of the protein composition of breast milk and the nutrient intake between Thai and Japanese mothers

This study compared the protein composition of breast milk and the nutrient intake between Thai and Japanese lactating mothers. The breast milk was collected from 15 Thai and 14 Japanese mothers at the fifth day post-partum. Twenty-four-hour dietary records were performed from the second-to-the-fourth day post-partum. The nutrient intake was calculated by using the nutrient content of a food table. The protein composition of the whey was separated by gel electrophoresis and was identified by mass spectrometry and two-dimensional electrophoresis. The results showed that the concentrations of the major protein types in the breast milk were not significantly different between the two groups. The concentrations of the minor protein types varied markedly with the individuals, with higher concentrations in the breast milk of the Thai mothers. There were no significant differences in terms of the energy and protein intake; however, the sources of energy were different. The results indicate that the total protein and lactoferrin concentrations in the breast milk could be predicted by the maternal daily energy and fat intake.     

Aspiration biopsy-nucleic acid diagnosis of thyroid malignant lymphoma by vectorette PCR: experience of eight cases

The usefulness of a new method to detect B-cell monoclonality named VR, which is a combination of the digestion with restriction enzymes and vectorette PCR, in aspiration biopsy-nucleic acid diagnosis (ABND) of thyroid malignant lymphoma was investigated. ABND was performed in 12 patients in whom malignant lymphoma was suspected. Among the patients who underwent open surgery, monoclonality was detected in the aspirates in four (50%) of eight patients with malignant lymphoma, but was not detected in one patient with Hashimoto disease. ABND using VR is a useful adjunct of aspiration biopsy cytology in the diagnosis of thyroid malignant lymphoma.     

The effect of p53 gene expression on the inhibition of cell proliferation by paclitaxel

BACKGROUND/AIMS: We evaluated the relationship between p53 status and paclitaxel (PTX)-induced inhibition of the growth of human stomach cancer cells. MATERIALS AND METHODS: We made use of two human stomach cancer cell lines, MKN45 and MKN28. Growth inhibition in response to PTX was evaluated by MTT method. We used flow cytometry to monitor the cell cycle and western blot analysis to evaluate the expression of signaling molecules. RESULTS: PTX inhibited the proliferation of both stomach cancer cell lines in a dose-dependent manner. However, PTX cytotoxicity was stronger in MKN28 cells. Flow cytometric analysis showed that 1 muM PTX enhanced the percentage of MKN 45 cells in the sub-G1 phase of the cell cycle, whereas it increased the percentage of MKN 28 cells arrested at G2/M phase. 1 muM PTX was found to increase cyclin B1 production in MKN28 cells, but not in MKN 45 cells. In contrast, PTX-treatment led to an increase in the cleaved form of caspase-3 in MKN45, but not MKN28 cells. An inhibitor of p53, pifithrin-alpha, antagonized the expression of the cleaved form of caspase-3 in MKN45 cells. CONCLUSION: Both p53 status and cyclin-B1 expression might be useful for predicting the therapeutic response of stomach cancer to PTX.     

Marked regression of liver metastasis by combined therapy of ultrasound-mediated NF kappaB-decoy transfer and transportal injection of paclitaxel, in mouse

Nuclear factor-kappaB (NF kappaB) plays a pivotal role in cancer progression. In this study, we developed a decoy cis-element oligo-deoxyribonucleic acid against NF kappaB-binding site (NF kappaB-decoy), which effectively inhibits NF kappaB activity, and tested the effect of combined therapy comprising local transfection of NF kappaB-decoy into the liver and transportal injection of paclitaxel on cancer growth and metastasis using an orthotopic murine model of colon cancer liver metastasis. For NF kappaB-decoy transfection, we employed a novel approach using ultrasound exposure with an echocardiographic contrast agent, Optison. We examined the influence of NF kappaB-decoy transfer on susceptibility to paclitaxel in cancer cells and the mechanism involved using several in vitro analysis systems. We then studied the in vivo effect of combined NF kappaB-decoy transfer and paclitaxel in preventing cancer progression using a murine model of liver metastasis created by splenic injection of a human colon cancer cell line, HT29. In vitro experiments, including MTT-assay, fluorescence-activated cell sorter and cDNA array analysis, revealed that NF kappaB-decoy transfer significantly increased the susceptibility of cancer cells to paclitaxel, and that decreased expression of anti-apoptotic genes along with increased expression of genes relevant to the apoptosis-promotor may be involved. In vivo experiments showed that local transfection of NF kappaB-decoy into the liver followed by portal injection of paclitaxel effectively induced cancer cell apoptosis in the liver metastasis, and significantly prolonged animal survival compared to controls, without notable side effects. In conclusion, a combination of local NF kappaB-decoy transfer into the liver and transportal injection of paclitaxel may be a safe and effective new therapy for liver metastasis.