The Origin of High Stereoselectivity in Di-tert-butylsilylene-Directed α-Galactosylation.

The origin of the high α(1,2-cis)-stereoselectivity in the reaction of galactosyl and galactosaminyl donors with a di-tert-butylsilylene (DTBS) group with several nucleophiles has been elucidated by means of experimental and computational approaches. DTBS overcomes any other cyclic protecting groups examined to date and the ß(1,2-trans)-directing effect due to the neighboring participation by CO groups at C2. Requirements for the α(1,2-cis)-stereoselectivity are as follows: (1) generation of an oxocarbenium ion; (2) a galacto-type glycosyl donor with a cyclic protecting group bridging O4 and O6 to form a six-membered ring; (3) through-space electron donation from O4 and O6 into the empty p-orbital of the anomeric carbon to stabilize the oxocarbenium intermediate; (4) steric hindrance due to bulky alkyl substituents on the cyclic protecting group to prevent nucleophilic attack from the ß-face; and (5) a 4,6-O-silylene structure. Furthermore, it was found that the strong stereodirecting effect of the DTBS group was unique and specific among the various cyclic protecting groups examined.

Long horns protect Hestina japonica butterfly larvae from their natural enemies.

Animals sometimes have prominent projections on or near their heads serving diverse functions such as male combat, mate attraction, digging, capturing prey, sensing or defence against predators. Some butterfly larvae possess a pair of long frontal projections; however, the function of those projections is not well known. Hestina japonica butterfly larvae have a pair of long hard projections on their heads (i.e., horns). Here we hypothesized that they use these horns to protect themselves from natural enemies (i.e., predators and parasitoids). Field surveys revealed that the primary natural enemies of H. japonica larvae were Polistes wasps. Cage experiments revealed that larvae with horns intact and larvae with horns removed and fitted with horns of other individuals succeeded in defending themselves against attacks of Polistes wasps significantly more often than larvae with horns removed. We discuss that the horns counter the paper wasps' hunting strategy of first biting the larvae's 'necks' and note that horns evolved repeatedly only within the Nymphalidae in a phylogeny of the Lepidoptera. This is the first demonstration that arthropods use head projections for physical defence against predators.

A first total synthesis of a hybrid-type ganglioside associated with amyotrophic lateral sclerosis-like disorder.

The hybrid ganglioside X1, which was identified in the bovine brain, was synthesized for the first time. Ganglioside X1 is believed to be involved in the development of amyotrophic lateral sclerosis-like disorders in patients with neurological disorders after treatment with bovine brain gangliosides. A convergent approach using two branched glycan units, the GM2-core trisaccharide and the lacto-ganglio tetrasaccharide, efficiently provided the highly branched heptasaccharide part of ganglioside X1, which was conjugated with the ceramide part to produce the protected ganglioside X1. Global deprotection delivered homogenous ganglioside X1, with which serum from the patient was reacted.

The first total synthesis of ganglioside GalNAc-GD1a, a target molecule for autoantibodies in Guillain-Barré syndrome.

The first synthesis of ganglioside GalNAc-GD1a, featuring efficient glycan assembly and a cyclic glucosyl ceramide as a versatile unit for ganglioside synthesis is described. Although ganglioside GalNAc-GD1a was first found as a brain ganglioside, IgG autoantibodies to GalNAc-GD1a were subsequently found to be closely related to a human peripheral-nerve disorder, Guillain-Barré syndrome, which is the commonest cause of acute flaccid paralysis worldwide. In this study, the characteristic hexasaccharide part carrying two sialic acid residues was synthesized efficiently by use of a readily accessible GM2-core unit as a common unit. The potentially difficult coupling of the oligosaccharide and ceramide moieties was carried out by using a cyclic glucosyl ceramide as a coupling partner for the hexasaccharide part, thereby successfully providing the framework of the target compound. Global deprotection delivered the homogenous ganglioside GalNAc-GD1a. An enzyme-linked immunosorbent assay showed that sera from patients with Guillain-Barré syndrome reacted both with natural and with synthetic GalNAc-GD1a.

[Prognostic factors and usefulness of chemotherapy with S-1 in patients received gastrectomy for stage IV gastric cancer].

Clinicopathological factors influencing the survival and the effect of chemotherapy with special reference to S-1 were retrospectively analyzed in 41 patients who underwent gastrectomy for stage IV gastric cancer. Significantly better outcomes were observed in patients with H0, P0 or M0 than those with H1, P1 or M1, respectively. Curability B surgery showed a significantly better result than curability C. A significantly better result was demonstrated in patients treated with S-1 alone than those treated with chemotherapy other than S-1 or in patients without chemotherapy. Multivariate analysis revealed that H0, M0 and chemotherapy with S-1 were significant and independent prognostic factors. Moreover, the patients treated with S-1 for more than 12 months showed a significantly better outcome than those treated with S-1 for less than 12 months. It is concluded that curative resection (curability B) and the longer period of postoperative chemotherapy with S-1 is the treatment of choice to improve the outcome of patients with stage IV gastric cancer.

Surgical treatment for gastric GIST with special reference to liver metastases.

BACKGROUND/AIMS: Gastrointestinal stromal tumor (GIST) is recently defined as a tumor expressing c-kit and sometimes showing liver metastasis. We investigated the outcomes of gastric GIST with special attention to the effect of repeated treatment for the patients with liver metastases. METHODOLOGY: Fourteen gastric GISTs were retrospectively reviewed and the significance of the NIH stratification system was examined. RESULTS: Liver metastasis was found in 4 of the 14 patients with gastric GISTs. Three of the 4 patients had metachronous liver metastases and underwent repeated hepatectomies after the initial operation for gastric GIST. The other patient had a synchronous liver metastasis and underwent total gastrectomy and partial resection of the liver as the initial treatment. Two of the 4 patients have received treatments 6 times, including hepatic resection, microwave coagulation therapy (MCT), radiofrequency ablation (RFA), or by imatinib. All 4 patients with hepatic metastases are alive after the first hepatectomy with a mean survival time of 64.8 months with or without imatinib treatment. None classified to very low risk and low risk groups by the NIH system showed liver metastasis, while 43% of the patients classified to the high risk showed liver metastasis. CONCLUSIONS: Repeated surgical and medical treatments for liver metastases from gastric GIST improve survival. Special attention should be paid to be the high risk group categorized by the NIH classification system.

Classification of the binding modes in bovine serum albumin using terminally substituted alkane analogues.

With the fluorescence probe of 8-anilino-1-naphthalenesulfonate (ANS), the binding modes of terminally substituted alkane analogues (C(n)X; X = COOH, OH, CHO, NH(3), CONH(2)) to bovine serum albumin (BSA) were investigated using a competitive binding technique. The Scatchard plot of the fluorometric titration of BSA with ANS showed that the maximum binding number of ANS, n(max), was 3.81, with the binding constant, K(bnd), of 1.42 x 10(6) mol(-1) dm(3). The binding modes of C(n)X to BSA were analyzed based on the fluorometric titration of the ANS and BSA mixture with C(n)X. C(n)COOH completely displaced the ANS bound to BSA, whereas C(n)OH and C(n)CHO displaced only about 40% of the ANS bound to BSA. In contrast, C(n)NH(2) and C(n)CONH(2) displaced very little bound ANS. By comparing these results, we classified the binding modes of C(n)X to BSA into three types. Two of them are detectable with the ANS fluorescence and the remaining one is not detectable with the fluorescence.

Determination of Detection Limits and Quantitation Limits for Compounds in a Database of GC/MS by FUMI Theory.

The aim of this paper is to propose a stochastic method for estimating the detection limits (DLs) and quantitation limits (QLs) of compounds registered in a database of a GC/MS system and prove its validity with experiments. The approach described in ISO 11843 Part 7 is adopted here as an estimation means of DL and QL, and the decafluorotriphenylphosphine (DFTPP) tuning and retention time locking are carried out for adjusting the system. Coupled with the data obtained from the system adjustment experiments, the information (noise and signal of chromatograms and calibration curves) stored in the database is used for the stochastic estimation, dispensing with the repetition measurements. Of sixty-six pesticides, the DL values obtained by the ISO method were compared with those from the statistical approach and the correlation between them was observed to be excellent with the correlation coefficient of 0.865. The accuracy of the method proposed was also examined and concluded to be satisfactory as well. The samples used are commercial products of pesticides mixtures and the uncertainty from sample preparation processes is not taken into account.

Laparoscopic anterior pelvic exenteration for locoregionally advanced rectal cancer directly invading the urinary bladder: A case report of low anterior resection with en bloc cystectomy for sphincter preservation.

Laparoscopic multi-visceral resection in patients with T4 colorectal cancer remains controversial. A 73-year-old man was admitted to the hospital for rectosigmoid cancer directly invading the urinary bladder trigone without distant metastasis. We successfully performed complete resection by laparoscopic anterior pelvic exenteration while preserving the anus. After laparoscopic mobilization of the rectum, urinary bladder, and prostate, the urethra and urethral catheter were dissected to reveal the lower rectum. By pulling the urethral catheter toward the head, the prostate was excised retrogradely from the lower rectum anterior wall. The lower rectum was resected and anastomosed by the double stapling technique with a safe distal margin from the tumor. Pathological findings of the resected specimen indicated no residual tumor in the surgical margin. There was no evidence of recurrence 34 months after surgery. En bloc, R0, laparoscopic anterior pelvic exenteration for T4 rectal cancer is feasible. However, further studies with long-term follow-up are required to resolve oncological outcomes.

Efficiently synthesizing lacto-ganglio-series gangliosides by using a glucosyl ceramide cassette approach: the total synthesis of ganglioside X2.

The first total synthesis of the hybrid ganglioside X2, which consisted of a highly branched octasaccharide and ceramide moieties, was accomplished by using a glucosyl ceramide cassette approach. With a disaccharyl donor, the heptasaccharide could not be constructed by glycosylation of the C4 hydroxy group of galactose at the reducing end of the pentasaccharide. In contrast, through an alternative approach with two branched glycan units, a GM2-core trisaccharide, and a lacto-ganglio tetrasaccharide, the heptasaccharyl donor could be prepared and subsequently joined with a glucosyl ceramide cassette to afford the protected ganglioside, X2. Finally, global deprotection completed the synthesis, thus affording the pure ganglioside X2.

Steady-state bioluminescence of bacterial luciferase using electrochemical regeneration of flavin substrate and its application to inhibitory analysis.

The model system for the biological reaction using a bacterial luciferase (BL) was developed and applied to the inhibitory analysis of the hydrophobic molecules for enzymatic reactions. The homemade flow electrochemical luminescence cell was embedded in the BL reaction system to regenerate the reduced form of the flavin mononucleotide, which is one of the substrates of the BL luminescence reaction, and to measure the luminescence intensity. The constant intensity of the continuous BL luminescence was observed using the continuous-flow BL reaction system. The proposed system was successfully applied to the inhibitory reaction of dodecaneamide on the BL luminescence reaction.

Factors influencing outcome after surgery for stage IV colorectal cancer.

PURPOSE: According to the classification system of the Japanese Society for Cancer of the Colon and Rectum, Stage IV colorectal cancer is characterized by distant metastasis, which is defined by four factors: liver metastasis (H factor), metastasis to organs other than the liver (M factor), peritoneal dissemination (P factor), and distant lymph node metastasis (N factor). We conducted this study to investigate the postsurgical prognosis of patients with Stage IV colorectal cancer (CRC), in reference to each of these four factors. METHODS: We analyzed the medical records of 73 patients who underwent surgery for Stage IV CRC at our hospital between 1991 and 2001. RESULTS: Univariate analysis revealed that P0 or P1 CRC (P < 0.001), absence of the M factor (P = 0.024), well or moderately differentiated adenocarcinoma (P < 0.001), resection of the primary tumor (P < 0.001), and curability B surgery (P < 0.0001) were associated with a better prognosis than other types of Stage IV CRC. Multivariate analysis revealed that tumor differentiation and surgical curability affected cancer-specific survival significantly. CONCLUSION: Surgery with curative intent should be considered for patients with Stage IV CRC defined by the P1 factor or H factor.

Sex difference in survival of patients treated by surgical resection for esophageal cancer.

BACKGROUND: Squamous cell carcinoma accounts for most of the esophageal cancers in Japan and is often related to excessive smoking and drinking. Although esophageal cancer occurs far more frequently in men than in women, it is not certain whether there are sex-specific differences in morbidity and mortality after surgical resection of the esophagus. We conducted a study to determine the influence of sex on the short- and long-term results of surgical resection in patients with esophageal cancer. METHODS: There were 295 patients with a newly diagnosed primary malignant neoplasm of the esophagus treated at our University hospital between January 1978 and December 2005. There were 185 patients (166 men, 19 women; age range 39-86 years) who underwent surgical resection for primary esophageal malignant neoplasms. Survival rates were calculated according to the Kaplan-Meier method and tested with the log-rank test. Cox proportional hazards model was used to assess independent predictors of survival. RESULTS: The cumulative amount of alcohol consumed and number of cigarettes smoked were significantly higher in men than in women. Postoperative complications occurred in 101 men (60.8%) and 9 women (47.4%), but significant sex differences in postoperative morbidity and mortality were not observed. Overall survival was significantly better for women than for men. CONCLUSION: Postoperative morbidity and mortality do not appear to differ between men and women with esophageal cancer treated by surgical resection. Long-term survival after surgical resection of the esophagus appears to be significantly better for women than for men.

Consecutive monitoring of lifelong production of conidia by individual conidiophores of Blumeria graminis f. sp. hordei on barley leaves by digital microscopic techniques with electrostatic micromanipulation.

Conidial formation and secession by living conidiophores of Blumeria graminis f. sp. hordei on barley leaves were consecutively monitored using a high-fidelity digital microscopic technique combined with electrostatic micromanipulation to trap the released conidia. Conidial chains formed on conidiophores through a series of septum-mediated division and growth of generative cells. Apical conidial cells on the conidiophores were abstricted after the conidial chains developed ten conidial cells. The conidia were electrically conductive, and a positive charge was induced in the cells by a negatively polarized insulator probe (ebonite). The electrostatic force between the conidia and the insulator was used to attract the abstricted conidia from the conidiophores on leaves. This conidium movement from the targeted conidiophore to the rod was directly viewed under the digital microscope, and the length of the interval between conidial septation and secession, the total number of the conidia produced by a single conidiophore, and the modes of conidiogenesis were clarified. During the stage of conidial secession, the generative cells pushed new conidial cells upwards by repeated division and growth. The successive release of two apical conidia was synchronized with the successive septation and growth of a generative cell. The release ceased after 4-5 conidia were released without division and growth of the generative cell. Thus, the life of an individual conidiophore (from the erection of the conidiophore to the release of the final conidium) was shown to be 107 h and to produce an average of 33 conidia. To our knowledge, this is the first report on the direct estimation of life-long conidial production by a powdery mildew on host leaves.