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We show that Nras is transiently localized in the Golgi prior to the plasma membrane (PM). Moreover, green fluorescent protein (GFP)-tagged Nras illuminated motile, peri-Golgi vesicles, and prolonged BFA treatment blocked PM expression. GFP-Hras colocalized with GFP-Nras, but GFP-Kras4B revealed less Golgi and no vesicular fluorescence. Whereas a secondary membrane targeting signal was required for PM expression, the CAAX motif alone was necessary and sufficient to target proteins to the endomembrane where they were methylated, a modification required for efficient membrane association. Thus, prenylated CAAX proteins do not associate directly with the PM but instead associate with the endomembrane and are subsequently transported to the PM, a process that requires a secondary targeting motif.

We have identified and cloned the cDNA for a 912-aa protein, rab11BP, that interacts with the GTP-containing active form of rab11, a GTP-binding protein that plays a critical role in receptor recycling. Although rab11BP is primarily cytosolic, a significant fraction colocalizes with rab11 in endosomal membranes of both the sorting and recycling subcompartments. In vitro binding of rab11 to native rab11BP requires partial denaturation of the latter to expose an internal binding site located between residues 334 and 504 that is apparently masked by the C-terminal portion of the protein, which includes six repeats known as WD40 domains. Within the cell, rab11BP must undergo a conformational change in which the rab11-binding site becomes exposed, because when coexpressed with rab11 in transfected cells the two proteins formed abundant complexes in association with membranes. Furthermore, although overexpression of rab11BP did not affect transferrin recycling, overexpression of a truncated form of the protein, rab11BP(1–504), that includes the rab11-binding site but lacks the WD40 domains inhibited recycling as strongly as does a dominant negative rab11 mutant protein that does not bind GTP. Strikingly, the inhibition caused by the truncated rab11BP was prevented completely when the cells also expressed a C-terminally deleted, nonprenylatable form of rab11 that, by itself, has no effect on recycling. We propose that rab11BP is an effector for rab11, whose association with this GTP-binding protein is dependent on the action of another membrane-associated factor that promotes the unmasking of the rab11-binding site in rab11BP.

The catalytic decomposition conditions of O 2 , N 2 O and NO were investigated to avoid oxidization of heated tungsten filaments. It was confirmed that no oxidization takes place in the presence of an excess amount of H 2 or NH 3 : for example, when the catalyzer temperature is 1990 K and the H 2 /O 2 flow rate ratio is more than 18. These results are consistent with the recent results that no oxidization is observed in the SiH 4 / NH 3 /H 2 /O 2 /He system to deposit SiO x N y films as long as the O 2 flow rate is low. In addition, it was revealed that in this SiH 4 /NH 3 /H 2 /O 2 /He system, O 2 is not only decomposed on the catalyzer surfaces but also is consumed in homogeneous and/or heterogeneous reactions. One of the consumption paths in the gas phase should be the reaction with SiH 3 to produce SiO.

Malignancy is a common and dreaded complication following organ transplantation. The high incidence of neoplasm and its aggressive progression, which are associated with immunosuppressive therapy, are thought to be due to the resulting impairment of the organ recipient's immune-surveillance system. Here we report a mechanism for the heightened malignancy that is independent of host immunity. We show that cyclosporine (cyclosporin A), an immunosuppressant that has had a major impact on improving patient outcome following organ transplantation, induces phenotypic changes, including invasiveness of non-transformed cells, by a cell-autonomous mechanism. Our studies show that cyclosporine treatment of adenocarcinoma cells results in striking morphological alterations, including membrane ruffling and numerous pseudopodial protrusions, increased cell motility, and anchorage-independent (invasive) growth. These changes are prevented by treatment with monoclonal antibodies directed at transforming growth factor-beta (TGF-beta). In vivo, cyclosporine enhances tumour growth in immunodeficient SCID-beige mice; anti-TGF-beta monoclonal antibodies but not control antibodies prevent the cyclosporine-induced increase in the number of metastases. Our findings suggest that immunosuppressants like cyclosporine can promote cancer progression by a direct cellular effect that is independent of its effect on the host's immune cells, and that cyclosporine-induced TGF-beta production is involved in this.

A 21-year-old woman was seen at the hospital because of lower abdominal pain. A soft mass was palpable with the fingertip on the posterior wall of the rectum. CT, magnetic resonance imaging and transrectal ultrasonographic examination showed a presacral cystic tumor. The tumor was resected by using a sacral approach. Histological examination showed that the tumor wall was made of squamous epithelium without any adnexal structure, and hence it was diagnosed as epidermoid cyst. In a review of the Japanese literature, 31 cases of presacral epidermoid cyst are seen. Complete excision of those presacral cysts is advised because of possible complications including infection and malignancy.

The route of nutrient delivery may alter the production of albumin and induce changes at the molecular level. Donryu rats ( n = 75) were divided into the following three groups. The oral feeding (OR) group received a non-purified solid diet ad libitum, the parenteral nutrition (PN) group received a total parenteral nutrition (TPN) solution intravenously, and the enteral nutrition (EN) group received intragastric infusions of the TPN solution for 7 d. Serum albumin and glucocorticoid levels were measured and messenger RNA (mRNA) levels of albumin and hepatic specific transcription factors in the liver were analyzed. Serum albumin and albumin mRNA levels in the PN group became significantly decreased compared to those in the OR group, whereas the EN group did not show a significant difference compared to the OR group. mRNA levels of DBP, D-site binding transcription factor for the albumin gene, showed a circadian rhythm in the OR and EN groups, but not in the PN group, as indicated by a DBP mRNA level at 2200 h in the PN group that was significantly lower than that in the OR group. mRNA levels of C/EBP α, CCAAT-enhancer binding protein α, were highest in the OR group and lowest in the PN group. In contrast, mRNA levels of C/EBP β were highest in the PN group and lowest in the OR group. Serum glucocorticoid level showed a circadian rhythm in the OR group, highest at 2200 h and lowest at 1000 h, whereas such a rhythm was not found in either the PN or the EN group. Albumin synthesis was down-regulated in PN in association with changes in transcription factors. A loss of circadian rhythm reflected in changes of DBP mRNA and serum glucocorticoid level may play a role. Down-regulation of albumin was improved by enteral feeding, indicating that EN is more advantageous for albumin synthesis than PN.

A broad range of aliphatic, alicyclic, and aromatic ketones and aldehydes underwent smooth reduction with a combination of common, inexpensive laboratory reagents, sodium borohydride and chromatographic neutral alumina, in hexane to afford the corresponding alcohols in a selective and high-yielding manner under mild and neutral conditions. The NaBH4-based biphasic system can also successfully be used for the reduction of unsaturated substrates as well as steroidal and highly hindered ketones.

A new type of strapped down ship’s inertial navigation system having rapid settling time for alignment and calibration is proposed. This system furnishes with a Kaiman filter to estimate precise velocity error and a pre-Filter to reject the effect of ship’s motion from observed velocity through accelerometers and a gyro system.

(1998). SYNTHESIS OF DISULFIDES BY THE OXIDATIVE COUPLING OF THIOLS WITH CALCIUM HYPOCHLORITE AND SILICA GEL IN HEXANE. Organic Preparations and Procedures International: Vol. 30, No. 3, pp. 360-363.

Ten sulfated and three phosphorylated β-D-galactopyranoside dimers and one sulfated β-D-galactopyranoside trimer containing fatty alkyl residues in place of ceramide have been synthesized. The coupling of 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide (2) with branched fatty alkyl diols and a triol (1a-1j) using mercury bromide as an activating agent gave the corresponding parent glycolipids (4a-4j) in good yields. Regioselective sulfation of these parent glycolipids through the dibutylstannylene acetals produced the target sulfated glycolipids, 3-sulfate (5a-5j) while stepwise phosphorylation with dibenzyloxy(diisopropylamino) phosphine gave the phosphorylated glycolipids, 3,4-bisphosphate (9e, g, i). The synthetic glycolipids were assayed for their ability to block the adhesion of HL-60 cells to immobilized P-, L- and E-selectin. 1. Dedicated to the memory of Professor Akira Hasagawa. 2. Synthetic studies on sialoglycoconjugates, Part 102. For Part 101, see Y. Makimura, H. Ishida, A. Kondo...

Aliphatic, alicyclic, and aromatic alkenes underwent smooth vic-dichlorination upon treatment with a reagent combination of NaClO2, Mn(acac)3 catalyst, and chromatographic neutral alumina preloaded with a small amount of water in dichloromethane under mild conditions.

(1998). A SIMPLE REGIOSELECTIVE NUCLEAR BROMINATION OF ALKYL PHENYL ETHERS. Organic Preparations and Procedures International: Vol. 30, No. 2, pp. 218-222.

Nuclear monobromination of aromatic ethers can be achieved with a NaClO2/NaBr/Mn(acac)3 catalyst/silica gel system in dichloromethane in regioselective and high-yielding manner under mild conditions.

Background: Regulation of perioperative albumin synthesis under parenteral (PN) and enteral (EN) nutrition was investigated. Methods: Rats were divided into PN and EN groups. Both groups received the same regimen of artificial nutrition for 7 days and then underwent 70% hepatectomy. Serum albumin and mRNA levels of albumin and its promoter-binding nuclear factors (C/EBPα, β, and DBP) were measured. Results: Serum albumin and albumin mRNA in the PN group were significantly lower than those in the EN group at 72 hours after hepatectomy. Preoperative and postoperative DBP and C/EBPα mRNA levels in the EN group were significantly higher than those in the PN group. Conclusion: Serum albumin was well maintained by EN after hepatectomy owing to an early recovery of albumin mRNA level and its nuclear factor mRNA levels (C/EBPα and DBP). Compared with PN, EN is a more advantageous from of perioperative nutrition as pertains to albumin synthesis.

Regioselective and high-yielding nuclear monobromination of aromatic ethers can be accomplished with a combination of NaClO2, NaBr, and Mn(acac)3 catalyst in dichloromethane under mild and neutral conditions with the aid of Montmorillonite K10.

Oxidation of α,ω-diols with sodium bromite can be readily performed in dichloromethane to afford lactones in fair good yield under mild and neutral conditions with the aid of chromatographic acidic alumina.

Chlorination of a variety of aliphatic, alicyclic, and aromatic ketones with a reagent combination of NaClO2 and Mn(acac)3 catalyst can be readily performed in dichloromethane to afford α-chloroket...

A man in his 30s visited our hospital after a local doctor diagnosed him with a rectal submucosal tumor. Colonoscopy and fine needle biopsy revealed a lower rectal gastrointestinal tumor (GIST). Pelvic MRI examination revealed apparent tumor invasion of the left levator ani muscle. Curative abdominoperineal resection( APR) of the tumor was required. Our strategy involved the initiation of neoadjuvant imatinib therapy to facilitate subsequent sphincter-preserving resection. Neoadjuvant chemotherapy for 11 months reduced the tumor size and permitted the R0 laparoscopic sphincter-preserving resection. He was discharged without any postoperative complications. The pathological findings revealed semi-curative effects and pR0 resection. Thus, neoadjuvant chemotherapy for advanced rectal GIST was a useful strategy for this function- preserving operation.

A 75-year-old man with a complaint of right hypochondrial pain consulted our hospital, and was diagnosed as having acute cholecystitis. We performed percutaneous transhepatic gallbladder drainage (PTGBD), and the cholecystitis resolved. However, obstructive jaundice occurred 2 weeks later. Thus, we performed an in-depth investigation and detected duodenal papilla cancer (cT3N1M0, Stage III). Pancreatoduodenectomy was performed. As postoperative histological diagnosis yielded positive and strongly positive immunostaining for synaptophysin and Ki-67, respectively, we diagnosed the patient as having neuroendocrine carcinoma (NEC) of the duodenal papilla. Three months after surgery, computed tomography (CT) scan showed multiple liver metastases and lymph node metastasis. Chemotherapy with carboplatin and etoposide was administered, but severe neutropenia developed, and therefore, the chemotherapy was discontinued. Subsequently, we decided on a policy of best supportive care (BSC). The patient died 11 months after surgery. NEC of the duodenal papilla is reported to be a rare and rapidly progressing disease and is associated with a very poor prognosis. Herein, we report a case of a patient in whom NEC of the duodenal papilla was resected.

We report a case of undifferentiated carcinoma of the duodenum. A 40-year-old man was referred to our hospital as he experienced upper abdominal pain that had persisted for half a year. Gastrointestinal endoscopy revealed a semicircular tumor in the duodenum. Enhanced computed tomography( CT) revealed that the tumor had not invaded the adjacent tissues, and lymph node metastases were not detected. Biopsy indicated a diagnosis of Group V cancer. Because the tumor was diagnosed as primary duodenal cancer, pancreatoduodenectomy and lymphadenectomy were performed. Histopathological examination revealed the presence of variant cells with irregular cores; we then diagnosed the tumor as undifferentiated cancer of the duodenum. No lymph node metastasis was detected microscopically. This patient has remained well without recurrence for 17 months since the operation. Undifferentiated carcinoma of the duodenum is rare, as only 9 cases have been reported in the Japanese literature.

Chemotherapy followed by surgery for Stage IV gastric cancer with passage obstruction poses a problem in terms of poor postoperative nutritional status. By maintaining an adequate postoperative nutrition status with jejunostomy catheter feeding, chemotherapy may possibly be continued. We treated 40 cases of Stage IV gastric cancer with passage obstruction from January 2008 to December 2011. In every case, jejunostomy catheter feeding tubes were placed during gastric cancer surgery. We performed 13 total gastrectomies, 20 distal gastrectomies, and 7 gastrojejunal bypass surgeries. Tube obstruction in 4 cases( 10%) and tube deviation in 1 case( 2.5%) occurred during the tube feeding period. Chemotherapy could be resumed in 37 cases( 92.5%), and the duration of chemotherapy was 330 days( range, 41-721). In cases of Stage IV gastric cancer, patients are obliged to start postoperative chemotherapy at an unstable period. By starting jejunal catheter feeding at an early stage after surgery, improved results could be expected in terms of shortening of the hospital stay or continuation of chemotherapy.

The patient was a 50-year-old woman who had undergone pancreaticoduodenectomy for bile duct carcinoma in April 2010. In August 2011, abdominal computed tomography (CT) revealed a solitary tumor (30×17 mm in diameter) behind the anastomosis of gastrojejunostomy. Gastrointestinal endoscopy revealed gastrojejunal ulceration (biopsy: Group V adenocarcinoma). Positron emission tomography (PET)-CT revealed a solitary tumor without any recurrence. We diagnosed the patient as having solitary recurrence of peritoneal dissemination of bile duct carcinoma. In September 2011, we performed resection of the peritoneal dissemination. The patient was discharged from the hospital 12 days after the operation and had a good postoperative course. Histologically, the tumor was diagnosed as peritoneal dissemination of bile duct carcinoma. Subsequently, the patient received postoperative chemotherapy. The patient remains alive with recurrence of peritoneal dissemination 37 months after pancreaticoduodenectomy and 20 months after resection of the peritoneal dissemination.

The reaction of alkyl phenyl ethers with sodium chlorite in dichloromethane in the presence of a (salen)manganese(III) complex and alumina preloaded with a small amount of water afforded monochlorination products with unusually high para selectivities under mild conditions. The NaClO2-based biphasic system can also be successfully used for the regioselective monochlorination of substituted anisoles and polymethoxybenzenes. Keywords: aromatic chlorination, alkyl aryl ethers, sodium chlorite, (salen)manganese(III) complex, alumina.

A combination of sodium chlorite, (salen)manganese(III) catalyst, and chromatographic neutral alumina in dichloromethane can be successfully utilized for the aromatic monochlorination of a variety of alkyl phenyl ethers in excellent to quantitative yields under mild and anhydrous conditions.

— Aromatic, aliphatic, and alicyclic thiols can be readily oxidized to the disulfides quantitatively by calcium hypochlorite and moist Montmorillonite K10 under mild and neutral conditions.

(1997). DETHIOACETALIZATION OF DITHIOLANES WITH FERRIC NITRATE AND SILICA GEL IN HEXANE. Organic Preparations and Procedures International: Vol. 29, No. 4, pp. 480-484.

1,3-Dithianes derived from aromatic, aliphatic, and alicyclic ketones or aldehydes can be conveniently converted to the parent carbonyl compounds with a combination of ferric nitrate and silica gel in hexane in excellent to quantitative yields.

Background We have previously reported that the addition of nucleosides and a nucleotide mixture (OG-VI) to total parenteral nutrition (TPN) prevents TPN-induced intestinal mucosal atrophy and results in increased intestinal cathepsin activities under TPN. The aims of the present study are to examine the effects of OG-VI on mucosal barrier functions and to clarify whether the intestinal cathepsins can be used as a new marker of mucosal barrier function. Methods Male Wistar rats were divided into three groups: FED (food ad libitum), TPN (a standard TPN solution), and OG (OG-VI in addition to the TPN solution). Mucosal barrier functions were analyzed by the lactulose/mannitol (L/M) test, mucosal ZO-1 messenger RNA level, and electron micrographs in the gut. Intestinal cathepsin B, H, and L activities were also measured. Results The L/M ratio for TPN was much higher than that for FED. Only lactulose excretion was significantly reduced by OG-VI. The intercellular spaces of the mucosal cells for TPN were significantly wider than those for FED, but were reduced in size by the addition of OG-VI. All cathepsin activities of the ileum were higher for TPN than for FED, whereas OG showed no increase. Conclusion OG-VI contributes to the improvement of gut mucosal barrier function. Intestinal cathepsin activities can be used as a new marker of mucosal barrier function.

A solid–liquid biphasic system (dichloromethane and chromatographic neutral alumina) has been tested for the aromatic chlorination of various alkyl aryl ethers using a reagent combination of sodium chlorite and manganese(III) acetylacetonate catalyst. Efficient incorporation of a chlorine atom into the benzene ring with high para-selectivity results. This catalytic system is also applicable to the regiocontrolled chlorination of polyether substrates.

S-1+cisplatin (CDDP) is the standard treatment for advanced gastric cancer (AGC) in Japan and Korea. However, the usefulness of S-1 based chemotherapy for elderly patients is unclear. Therefore, we conducted a multicenter phase II study of S-1 monotherapy for AGC in elderly patients.Chemotherapy-naïve patients aged over 75 years with AGC were enrolled. The starting dose of S-1 was determined on the basis of body surface area and modified according to the creatinine clearance value. S-1 was administered twice a day during a 4-week period followed by a 2-week rest period.Thirty-five patients were enrolled. The response rate (RR) was 14.3% and the median overall survival was 14.6 months. Grade 3 or more severe adverse events consisted of anaemia (3%), neutropaenia (3%), anorexia (3%), and fatigue (6%). There were no treatment-related deaths.Our study indicates that S-1 monotherapy is safe and well tolerated in chemotherapy-naïve elderly patients with AGC, but exerts limited activity when given using a tailor-made dosing strategy based on renal function.

A variety of unsubstituted and mono- or di-substituted cycloalkanones can be oxidised with modest excess of magnesium monoperoxyphthalate hexahydrate in acetonitrile to produce the corresponding lactones in a facile, selective, and high yielding manner.

The effect of temperature on protein metabolism of C2C12 myotubes was investigated in order to estimate the potential effect of fever on muscle catabolism. The half-life of long-lived proteins in C2C12 myotubes was significantly (13%) shorter when incubated at 40 degrees C than at 37 degrees. The activities of cathepsins B and L were not significantly different at 37 and 40 degrees C, nor were the levels of the protein and mRNA of the two cathepsins. In contrast, the chymotrypsin-like activity of 26S proteasome was elevated by 53% at 40 degrees C, compared to that at 37 degrees C, although it was not associated with an increase in the levels of the protein and mRNA of proteasome subunits. mRNA levels of calpain and ubiquitin were not affected by temperature. It is concluded that temperature-dependent enhancement of proteolysis in C2C12 myotubes is associated with an increase in 26S proteasome activity.

A wide variety of sulphides can be readily converted to the corresponding sulphoxides in good to excellent yields by treatment with a combination of sodium chlorite, (salen)manganese(III) complex, and chromatographic alumina in dichloromethane under mild and neutral conditions.

We studied the topogenic properties of five hydrophobic segments (H5-H9) in the COOH-terminal third of Na,K-ATPase alpha subunit using in vitro insertion of fusion proteins into endoplasmic reticulum membranes. These fusion proteins consisted of several different lengths of truncated alpha subunit starting at Met729 and a reporter protein, chloramphenicol acetyltransferase, that was linked in frame after each hydrophobic segment. We found that membrane insertion of the newly synthesized COOH-terminal third was initiated by H5 and terminated by H9, indicating that here only H5 and H9 have topogenic function. The other three, H6-H8, did not have topogenic function in the native context and were translocated into the endoplasmic reticulum lumen. These results were in striking contrast to the previous models in which four or six hydrophobic segments were proposed to cross the membrane. Furthermore, the findings suggest a novel mechanism for achieving the final membrane topology of the COOH-terminal third of the alpha subunit.

(1995). OXIDATION OF VARIOUS ALCOHOLS WITH IN SITU GENERATED MONTMORILLONITE K10-SUPPORTED FERRIC NITRATE REAGENT IN AN APROTIC SOLVENT. Organic Preparations and Procedures International: Vol. 27, No. 6, pp. 703-706.

Magnesium monoperoxyphthalate oxidation of unsubstituted and substituted cyclohexanones has been carried out in acetonitrile in the presence of bentonite clay, affording the corresponding e-caprolactones in fairly good yields.

Two new monogalactosyl diacylglycerols were isolated from the freshwater green alga, Chlorella vulgaris, as anti-tumour promoters, together with three monogalactosyl diacylglycerols and two digalactosyl diacylglycerols. The new monogalactosyl diacylglycerol containing (7Z,10Z)-hexadecadienoic acid showed a more potent inhibitory effect toward tumour promotion than the other glycerolipids isolated.

1. A cell culture system of C2C12 myotubes was established as a model of the muscle. With the aid of this model, the half-lives of intracellular proteins as well as the activities and mRNA levels of proteasomes (26S and 20S) and cathepsins (B, L, and H) were examined in the presence of various amounts of cytokines. 2. It was found that 100 units/ml recombinant human interleukin-6 somewhat shortened the half-life of long-lived proteins to 23.79 ± 1.55 h (control: 25.60 ± 1.87 h). When 1% fetal bovine serum contained in the culture medium was replaced by 0.5 mg/ml bovine serum albumin, interleukin-6 was more effective since 10 units/ml of interleukin-6 shortened the half-life to 19.09 ± 2.87 h (control: 22.26 ± 321 h). Interleukin-6 (100 units/ml) increased the activity of 26S proteasome by 31.5%, of cathepsin B by 53.5% and of cathepsin B + L by 21.3%. These increases occurred in association with an increase in their transcription. 3. On the other hand, 1000 units/ml of recombinant human tumour necrosis factor α prolonged the half-life of long-lived proteins while reducing the protease activities of 20S proteasome (−27.1%), cathepsins B (−64.6%) and B + L (−54.9%). 4. These results suggest that interleukin-6 induces degradation of long-lived intracellular proteins by activating both the non-lysosomal (proteasomes) and lysosomal (cathepsins) proteolytic pathways. It is therefore concluded that interleukin-6 is a candidate for a proteolysis-inducing factor in myotubes and may play an important role in the progression of muscle degradation in systemic inflammatory responses induced by sepsis or severe injury.

Hepatic albumin synthesis is down-regulated after both inflammation and hepatectomy. The transcriptional control of albumin synthesis was investigated in models of both conditions to differentiate the underlying mechanisms. Male Donryu rats underwent 70% hepatectomy or turpentine injection. Serum albumin and mRNA levels of albumin and promoter binding proteins (D site binding protein [DBP] CCAAT/enhancer binding protein-α[ C EBP -α], -β , and hepatocyte nuclear factor-1 [HNF-1]) in the liver were measured from 0 to 96 hr. After hepatectomy, the albumin mRNA level decreased to 0.6 at 36 hr and then recovered. After turpentine injection, it decreased to 0.4 at 36 hr and then recovered. The serum level of albumin decreased in a time-dependent manner in both models. The C EBP -α mRNA level decreased to 0.5 at 6 and 12 hr after hepatectomy and to 0.6 at 24 hr after turpentine injection. The DBP mRNA level decreased to 0.3 at 6 hr, to 0.2 at 24 hr after hepatectomy, and to 0.3 at 30 hr after turpentine injection. The C EBP -β mRNA level increased to 1.7 at 3 hr after hepatectomy and to 1.5 at 12 hr after turpentine injection. On the other hand, HNF-1 mRNA levels showed no consistent change in either model. The change in mRNA of the nuclear factors ( C EBP -α, C EBP -β , and DBP) thus precedes that of albumin. In conclusion, transcriptional regulation of albumin synthesis in the regenerating and the acute inflammation phase of the liver can be assessed by monitoring the mRNA levels of nuclear factors. The mechanisms for down-regulation of albumin in both conditions share substantial similarities.

The title oxidation has been investigated in acetonitrile. The substrates examined include alkyl aryl, diaryl, dialkyl, and cyclic sulphides, which afforded the corresponding sulphoxides in good to excellent yields under neutral and mild conditions.

Convenient synthesis of 1-O-acyl-3-O-(6'-O-acyl-β-D-galactopyranosyl-sn-glycerol was studied. The lipase from Achromobacter sp. catalyzed acylation of 3-O-β-D-galactopyranosyl-sn-glycerol, which contains two primary hydroxyl functions, proceeded regioselectively to furnish 1-O-acyl-3-O-β-D-galactopyranosyl-sn-glycerol.

To elucidate the basis of innate immune responses against insoluble compounds (such as silica and alum) through the inflammasome activation pathway in fish, biological assays and expression analysis of immune-related genes were conducted in the Japanese pufferfish (Takifugu rubripes) head kidney (HK) cells. At first, the Japanese pufferfish was stimulated by intraperitoneal injection of alum (4 mg/fish). After 0, 6, 12, 24 and 48 h post-injection, HK cells were prepared from the injected fish. To understand functionality of activated inflammatory response, phagocytic activity and superoxide anion production (NBT assay) in the HK cells were assessed. As results, the phagocytic and NBT reduction activities were significantly increased in alum-stimulation. To further clarify the immune response through transcriptomic analysis, expression of 19 cytokine genes was checked by the multiplex reverse transcription (RT)-PCR method. Results showed that expression of IL-6 and type I-IFN genes was significantly elevated in the alum-stimulated fish. Furthermore, expression of NLR-C9 and NLR-C12 genes [i.e., NOD-like receptor (NLR) family genes as sensor molecules of inflammasome], ASC and caspase-1 genes (inflammasome associated molecules) were examined by qPCR. Results indicated an increased expression of four different inflammasome associated genes in the HK cells of fish injected with alum. The results suggested activation of inflammatory response to the alum with a likely involvement of inflammasome components in the Japanese pufferfish.

2527Background: Whether participation in a randomized-controlled trial provides benefits to patients is controversial. Some studies have showed that participants have longer prognosis than non-part...

Interleukin(IL)-6 transgenic mice were produced by microinjection of human IL-6 cDNA fused with H-2Ld promoter into the pronucleus of fertilized eggs from C57BL/6J mice. At 16 weeks old, the gastrocnemius muscles of the IL-6 transgenic mice became atrophic as compared to those of the normal mice, while the body weights increased significantly. The activities and mRNA levels of lysosomal cathepsins B and L were increased in the muscles of the transgenic mice. Immunohistochemical study on the muscles showed increased staining of both cathepsins B and L in the transgenic mice. IL-6 is responsible for enhanced muscle catabolism by activating the lysosomal cathepsin (B and L) system.

Our previous study demonstrated that reticuloendothelial system function can be monitored by in vivo clearance of chondroitin sulfate iron colloid [Ishida, H. et al. (1991): J. Biochem. Biophys. Methods; Ishida, H. et al (1992): J. Biochem. Biophys. Methods; Tsujinaka, T. et al. (1993): JPEN]. In the present study hepatic clearance of radiolabeled chondroitin sulfate iron colloid (CS59Fe) was investigated in detail. When administered intravenously, CS59Fe was taken up by not only Kupffer cells but also liver endothelial cells and liver parenchymal cells. Radioactivity per 106 cells was highest in Kupffer cells. When binding of CS59Fe to isolated liver cells was examined at 4°C, the association of CS59Fe showed a good linearity on a double-reciprocal plot, giving Nr (number of receptors) and Kp (membrane-particle constant). Nr was greatest of all for Kupffer cells. When CS59Fe was pretreated with plasma, the Nr increased and Kp decreased in Kupffer cells and liver endothelial cells, whereas Kp increased in liver parenchymal cells. However, no influence was found as a result of pre-treatment of CS59Fe with fibronectin or heated plasma. The addition of mannan had no effect. This in vitro chondroitin sulfate iron colloid binding assay may be useful to evaluate effects of various mediators on phagocytosis of hepatic cells.

A 57-year-old woman was discovered to have a cystic tumor, 8 cm in diameter, at the pancreas tail, during routine screening with ultrasonography. The patient did not complain of tenderness, and no abdominal mass was palpable at physical examination. Enhanced computed tomography(CT) revealed that the tumor had mural nodules in the cyst wall, and we suspected it to be a malignant tumor that had occurred in the mucinous cystic neoplasm(MCN). Therefore, surgical resection was attempted, upon which the tumor was found to be hard and the surrounding tissue adhered widely to the stomach. We separated it carefully from the stomach and then performed a distal pancreatectomy. The cut surface revealed that the posterior wall of the cystic tumor was partly thickened, and microscopic examination revealed it to be invasive ductal carcinoma. No ovarian-like stroma was involved and some degree of dysplasia(PanIN 1-3) was found in the neighboring tissues. Therefore, we re-diagnosed it to be invasive ductal carcinoma of the pancreas derived from intraductal papillary mucinous tumor(IPMT), not from MCN. The patient received adjuvant chemotherapy, although 5 months later multiple lung metastases had appeared. The international consensus guidelines for management of IPMN and MCN of the pancreas suggest that they can usually be distinguished preoperatively, if there is a complete understanding of their clinical and imaging features. However, we sometimes find it difficult to distinguish the 2, because some IPMN or MCN cases have shared preoperative features. Herein, we report the case of invasive ductal carcinoma of the pancreas derived from IPMT that was originally misdiagnosed as a MCN.

Our patient was a 67-year-old man, with a chief complaint of brown urine. He subsequently underwent medical examination in June. Because the results of his blood examination revealed liver dysfunction, he was admitted to our hospital for further careful examination. An abdominal computed tomography(CT) scan showed the presence of a pancreas tumor, with a diameter of 2 cm, at the pancreas head, as well as common biliary duct dilatation and main pancreatic duct dilation from the head to the tail of the pancreas. The patient was diagnosed with pancreatic cancer[cT3( CH+, DU+), cN0, cM0, cStage III], with obstructive jaundice. After biliary drainage, we performed laparotomy in August. During the operation, other than the tumor on the pancreas head, identified at the preoperative diagnosis, we found 2 white nodules on the pancreas surface. One nodule was located at the body of the pancreas and the other, at its tail. On intraoperative pathological examination of the nodules, they were found to be invasive ductal carcinomas. On the basis of these findings, we suspected multiple cancers or overall pancreatic cancer; therefore, we performed total pancreatectomy, not pancreaticoduodenectomy (PD). We choose pancreatectomy over PD because it was impossible to confirm the cancerous area. Pathological examination of the resected specimen did not reveal any malignant lesion. Thus, if we had not performed pancreatectomy, assuming that the pancreas body or tail had no cancer lesion, based on the pathological examination result, the cancer would have persisted. Further, careful examination involving inspection and palpation is considered to be essential before resection of the pancreas tumor.