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CAPD施行中に大腸憩室の穿孔による糞便性腹膜炎を併発した3症例を経験した. 症例1は, 32歳, 男性で, CAPD開始後16か月で腹膜炎症状で入院した. 抗生剤治療に反応せず, 入院3日目に筋性防御の出現とともに, 排液中に食物残渣を認めたため, 腸管穿孔の診断で緊急開腹術を施行した. S状結腸の憩室穿孔を認めたため, S状結腸切除を行い, 術後は血液透析に変更し, 軽快退院した. 症例2は, 73歳, 男性で, 14年間の血液透析後, CAPDに変更し, 17か月目に全身衰弱で入院した. 入院61日目に腹膜炎を併発し, CAPD排液からE. coli, K. pneumoniaeが検出されたため腸管穿孔を疑ったが, 全身状態の不良および本人, 家族の希望にて手術は行わず, 保存的に治療したが, 腹膜炎発症7日目に死亡した. 病理解剖において, S状結腸に憩室穿孔を認めた. 症例3は, 67歳, 男性で, CAPD開始から8年4か月後に腹膜炎で入院, 排液培養からE. coli, Bacteroides fragilis, Candida albicansが検出された. 入院7日目に開腹術を行い, 下行結腸の憩室穿孔を認め, 左半結腸切除および人工肛門を造設した. 術後腹腔内膿瘍を形成し, 手術2か月後に死亡した.CAPD施行中に, 憩室穿孔による糞便性腹膜炎を合併することは非常に稀なことであるが, 診断に困難を極めると同時に, 診断の遅れは, 生命予後に重大な影響を与えるため, CAPD患者に難治性腹膜炎をみた際には考慮すべき病態と考えられた.

Triglycerides with medium-chain fatty acids at the 1- and 3-positions and functional fatty acids at the 2-position are referred to as structured lipids. An attempt was made to produce a structured lipid containing docosahexaenoic and caprylic acids using 1,3-positional specific Rhizopus delemar lipase, which was immobilized on a ceramic carrier by coprecipitation with acetone. When a reaction mixture containing 5 g tuna oil and 10 g caprylic acid, 0.6 g immobilized lipase, and 0.3 g water was incubated at 30°C for 2 d with shaking, acidolysis proceeded effectively but hydrolysis occurred simultaneously. This hydrolysis could be repressed by omitting water from the subsequent reaction mixture. The immobilized lipase could be reused 14 times without any significant loss of activity, and approximately 65% of the fatty acids at the 1- and 3-positions in the tuna oil were exchanged for caprylic acid. All the triglyceride products contained one or two caprylic acid molecule(s). Docosahexaenoic acid bound at the 1(3)-position in tuna oil was not exchanged because of the low activity of the R. delemar lipase on it.

To investigate the role of the hyperpolarization-activated current (If) on the subsidiary pacemaker activity of the heart, we studied the effects of an I f inhibitor, zatebradine, and a L-type Ca channel inhibitor, verapamil, on the atrioventicular (AV) junctional rhythm and other cardiac responses to stimulation of the left ansa subclavia (LS) in the autonomically decentralized heart of open-chest anesthetized dog. AV junctional rhythm was induced by clamping the sinoatrial (SA) pacemaker region and confirmed by His-bundle electrograms. Zatebradine 0.1 and 0.3 μmol/kg intravenously (i.v.) similarly attenuated both the AV junctional rate and the increase in the junctional rate in response to LS. However, higher doses (1 and 3 μmol/kg i.v.) of zatebradine changed the junctional rhythm to the atrial rhythm in all cases and decreased the atrial rate further but not the increases in the atrial rate in response to LS. On the other hand, verapamil (0.06, 0.2, and 0.6 μmol/kg i.v.) attenuated the increase in the junctional rate induced by LS dose dependently but did not affect the junctional rate itself. After verapamil, zatebradine did not shift the pacemaker site during LS and it further attenuated the positive chronotropic response. These results demonstrate that zatebradine, an I f inhibitor, inhibits subsidiary pacemaker activities as well as SA nodal pacemaker activity in situ and suggest that an inhibition of I f alters the pacemaker sites due to the different participation of I f among the cardiac pacemaker cells.

Three lipases, isolated previously in our laboratory, and a known lipase fromCandida cylindracea were screened for the enrichment of arachidonic acid (AA). The enzyme fromC. cylindracea was the most effective for the production of oil with high concentration of AA. When a single-cell oil fromMortierella alpina, containing 25% AA, was hydrolyzed with this lipase for 16 h at 35°C, the resulting glycerides contained 50% AA at 52% hydrolysis. After this, no further hydrolysis occurred, even with additional lipase. However, when the glycerides were extracted from the hydrolyzate and were hydrolyzed again with new lipase, the resulting oil contained 60% AA, with a recovery of 75% of its initial AA content. Triglycerides were the main components of the resulting oil. The release of each fatty acid from the oil depended on the hydrolysis rate of its ester. The fatty acid, whose ester is the poorest substrate for the enzyme, is concentrated in the glycerides.

To better understand the biology of graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HSCT) and develop novel treatment strategies, accurate and clinically relevant experimental animal models are indispensable. The majority of our understanding of this potentially lethal complication is based on mouse models of bone marrow transplantation in major histocompatibility complex antigens (MHC) and/or minor histocompatibility antigen mismatched settings. These mouse models of GvHD provide us with an immeasurable wealth of information; however, many findings obtained from mouse models are not necessarily correlated with clinical GVHD in humans. In addition, these mouse models are not suitable for predicting the effectiveness of recent human-specific therapies such as monoclonal anti-human antibodies and adaptive cell immunotherapies. To overcome these limitations, xenogeneic GvHD models using severe immunodeficient mice are currently being used in worldwide and allow us to investigate in vivo human immune reactions. The major aim of our study is to clarify the precise mechanism of immune response in vivo and to determine the principle components responsible for xenogeneic GvHD. We first observed that immunodeficient NOG mice receiving either no or sublethal irradiation consistently showed gradual body weight loss and eventual severe GvHD following injection of human unmanipulated peripheral blood mononuclear cells (PBMCs). Histopathology performed at the late phase of GvHD showed extensive infiltration of human CD45+ mononuclear cells, most of which were T-cells, and tissue destruction in lungs, bone marrow, liver, and spleen, with a smaller number detected in gut and skin unlike in human GvHD. We identified the infiltration of human T-cells exclusively in lungs and spleen before the onset of GvHD. Flow cytometric analysis showed a marked reduce of naïve (CD45RA+CCR7+) and central memory (CD45RA-CCR7+) T-cells and an increase of effector memory (CD45RA-CCR7-) T-cells within CD4+ subset in lungs, suggesting that xenogeneic response by human cells in lungs occur preceding systemic inflammation. Of note, the distribution of human cells was similar between intraperitoneal and intravenous injection. These results indicated that the acute lung injury is not associated with cell trapping within mouse pulmonary microvasculature by intravenous delivery. We next subdivided human lymphocyte subsets by magnetic cell sorting before adoptive transfer to characterize human cells responsive for xenogeneic GvHD development. CD4+ T-cells mediated more rapid and severe GvHD than did an equal number of CD8+ T-cells, whereas neither natural killer cells nor γδT cells caused any symptoms of GvHD. All antigen presenting cells (APCs)-depleted PBMCs mediated GvHD as well, suggesting that human T-cells are activated independently of their own APCs in this model. CFSE cell division assay showed more rapid proliferation of CD4+ rather than CD8+ T-cells. It is a noteworthy that the proliferation of and the expression of early activation marker CD69 on CD8+ T-cells was accelerated in the presence of CD4+ T-cells, indicating that CD4+ T-cells are required for the rapid and more efficacious response of CD8+ T-cells. We also found a strong increase of human IL-2, IFN-γ, and TNF-α in serum of mice injected with whole T-cells. In contrast, we observed very low levels of these inflammatory cytokines in mice injected with isolated CD8+ T-cells alone. Taken together, these results suggest that the early activation of human naïve CD4 T-cells by recognition of foreign antigen on mouse APCs following cytokine production play a critical role in triggering systemic inflammation in xenogeneic GvHD model. This in vivo response was confirmed in vitro by demonstrating that human CD4 T-cells rapidly proliferated and expressed CD69 with significantly increase of IL-2 and IFN-γ in response to mouse dendritic cells. These findings are helpful for adequate evaluation of immune response and creation of optimal experimental conditions in xenogeneic GvHD model. Disclosures Kanda: Otsuka Pharmaceutical: Honoraria, Research Funding.

We examined the effect of an orally effective, nonpeptide AVP.V1-receptor antagonist, OPC21268, on urinary albumin excretion and renal hemodynamics in non-insulin dependent diabetes mellitus (NIDDM) patients (seven patients with microalbuminuria, four with overt nephropathy, and three with normoalbuminuria) and in three normal subjects. The oral administration of 100 mg of OPC21268, which is sufficient to suppress the vasoconstriction induced by exogenously infused AVP, caused a significant decrease in urinary albumin excretion only in NIDDM with microalbuminuria concomitantly with a slight decrease in filtration fraction and glomerular filtration rate (GFR). On the other hand, urinary beta 2 microglobulin excretion did not change at all during the study. Neither change in systemic blood pressure, in heart rate, nor in plasma vasoactive substance levels (ANP, renin activity, aldosterone, and AVP) was observed in all four groups. In conclusion, in NIDDM patients with microalbuminuria, an increase in the sensitivity of contraction of glomerular efferent arterioles via an activation of AVP.V1-receptor(s) is at least present, and AVP.V1-receptor antagonist causes a decrease in urinary albumin excretion due partly to decrease the intraglomerular capillary pressure. This compound may be useful for the treatment of NIDDM microalbuminuria.

The reaction of allyl α-diazoacetates with di-t-butylthioketene catalyzed by Rh2(OAc)4 gave 4-allyl-2-methylene-1,3-oxathiolan-5-ones through the 1,5-cyclization of a thiocarbonyl ylide intermediate followed by Claisen rearrangement with allene episulfide through the 1,3-cyclization of the intermediate. Other alkenyl and alkynyl diazoacetates also gave similar products through the thiocarbonyl ylide without affording its intramolecular 1,3-dipolar cycloadduct.

In the course of screening for microbial products with antitumor activity, new antitumor agents, clecarmycins, were isolated from culture broth of Streptomyces sp. DO-114. The antibiotics were produced in a fermentation medium supplemented with a highly porous polymer resin which adsorbs antibiotics and results in a increase of titer. Active materials were separated from the polymer resin by solvent extraction procedure and two components named clecarmycin A1 and C were isolated by silica gel column chromatography. These were active against bacteria, and showed antiproliferative activities against human HeLa S3 cells. Clecarmycins exhibited antitumor activity against leukemia P388 and sarcoma 180 in mice.

Glycosides with glycerol and trimethylolpropane (TMP) moieties at the reducing ends were esterified by mono- and diacylglycerol lipase from Penicillium camembertii . Several TMP glycosides were esterified to a greater extent than those of glycerol. The products from glucosyl TMP and oleic acid by Penicillium and Candida cylindracea lipases were isolated and their structures elucidated. The lipases formed two monoesters; a major monoester whose TMP moiety was esterified and a minor monoester bearing an oleic acid group at the glucose moiety. One of the two diesters has a diacylated TMP moiety, while the other has acyl groups at both TMP and glucose moieties. Candida lipase formed these diesters in an almost equal ratio. Penicillium lipase formed the latter one preferentially. Candida lipase synthesized tri- and tetraesters, which accounted for about 34% of all the products, while Penicillium lipase formed these highly esterified products at a level of only 4 % of the total products.

Glucoamylases from Aspergillus niger and Rhizopus niveus catalyzed condensation of 2-deoxy-D-glucose (dGlc) to yield deoxy-glucooligosaccharides with polymerization degrees of 2-5. The enzymes also gave a small amount of products from 3-deoxy-D-glucose, but no products from 6-deoxy-D-glucose. A. niger alpha-glucosidase also catalyzed condensation of dGlc, while Torula and Saccharomyces alpha-glucosidases had low activity. alpha-1,4-, 1,6-, and 1,3-linked deoxy-glucobioses were isolated and identified as the products of A. niger glucoamylase and A. niger alpha-glucosidase. In the reaction of the glucoamylase, 1,4- and 1,3-linked saccharides decreased with an increase of 1,6-linked one. A. niger alpha-glucosidase produced alpha-1,6-linked disaccharide predominantly during the whole course of the reaction.

The reaction of thioamides with DMAD gave the pyrrole derivatives in good yield and the thiophene derivatives as a byproduct. These were formed by 1,3-dipolar cycloaddition of themodynamicaly stable azomethine ylide or less stable thiocarbonyl ylide with DMAD, followed by elimination of thioaldehyde or imine derivatives.

A previous study of cases of myelodysplastic syndrome harboring der(5;19)(p10;q10) found that they displayed common characteristics including predominance in elderly men, dysplasia involving three hematopoietic lineages and CD7 expression in blasts. However, the whole-arm translocation der(5;19)(p10;q10) has not been fully analyzed because of its rarity. In this study we used flow cytometry to evaluate the immunophenotype of two patients' bone marrow mononuclear cells. Both patients had involved der(5;19)(p10;q10) in their karyotype analyzed by standard G-banding technique. Both patients had the CD7+ and CD41+ phenotype, and the CD41 positivity suggested that the myeloid neoplasms involving der(5;19)(p10;q10) were of megakaryoblastic origin. The der(5;19)(p10;q10) abnormality is associated with unique characteristics of the immunophenotype. We address the clinical, immunophenotypic and morphological aspects of hematological malignancy involving der(5;19)(p10;q10), along with a review of the literature.

We investigated whether the intracardiac parasympathetic ganglia for sinoatrial (SA) nodal pacemaker cells control the right atrial contractility selectively and totally in the autonomically decentralized heart of the open-chest anesthetized dog. Stimulation of the intracardiac parasympathetic nerves to the SA nodal area (SAP Stim) decreased the right atrial pressure (a wave pressure) and its first pressure derivative (dP/dt) as well as the atrial rate but did not change the atrioventricular (AV) conduction time. Stimulation of right and left cervical vagosympathetic complexes (CV Stim) decreased the a wave pressure, dP/dt, and atrial rate and prolonged the AV conduction time. When SAP and CV Stim decreased the atrial rate similarly, the decreases in a wave pressure and dP/dt in response to SAP Stim were less than those to CV Stim in unpaced and paced hearts. When treatment with hexamethonium bromide or tetrodotoxin into the SAP Stim locus abolished the decreases in atrial rate evoked by SAP and CV Stim, each treatment abolished the decrease in a wave pressure response to SAP Stim but only slightly attenuated the pressure response to CV Stim. These results demonstrate that right atrial pressure is modified by efferent parasympathetic neurons, which are located in a region that differs from that of efferent parasympathetic neurons controlling heart rate.

We compared the modes of cell-killing by DNA topoisomerase I and II inhibitors. The effects of camptothecin (CPT), KT-6528 and UCE6 upon colony formation by inhibiting DNA topoisomerase I, and of etoposide (VP-16), teniposide, amsacrine and UCT4-A as inhibitors of DNA topoisomerase II were analyzed based upon a kinetic method that distinguishes between cell cycle phase-specific and -nonspecific agents. Human colorectal cancer WiDr cells were exposed to several concentrations of each agent for various periods and 90%-inhibitory concentrations (IC90) at each time were determined by means of a clonogenic assay. When exposure times and corresponding IC90s were plotted on a log-log scale, all inhibitors of DNA topoisomerase II gave curves including a linear portion with a slope of -1, which is characteristic of cell cycle phase-nonspecific agents. In contrast, the curves for all inhibitors of DNA topoisomerase I had a much steeper slope than -1, which is typical of cell cycle phase-specific agents. In agreement with this finding, the cells were remarkably accumulated in the G2-M phase when exposed to VP-16, but in late S-phase when exposed to CPT as determined by a flow cytometric assay. These results indicated that the two classes of agents kill cells in a quite different manner although they are inhibitors of similar enzymes.

A purified trehalase from Lobosphaera sp. catalyzed the condensation not only of d-glucose but also of 2-deoxy-d-glucose, yielding α,α′-trehalose and 2,2′-dideoxy-α,α′-trehalose, respectively. Simultaneous incubation of d-glucose and 2-deoxy-d-glucose resulted in the formation of 2-deoxy-α, α′-trehalose in addition to the above disaccharides. The reaction under various conditions showed that the enzyme synthesized dideoxy-trehalose (yield, 16%) more than trehalose (5%). Monodeoxy-trehalose was produced most effectively in the reaction of d-glucose and 2-deoxy- d-glucose in a weight ratio of 2:5, and at this ratio, 6% of the total weight of two substrates was converted to the product.

Glycosides with glycerol (Gl) and trimethylolpropane (TMP) moieties were examined as substrates for the esterification by a lipase from Candida cylindracea . Monoglucoside (Glc-TMP) and diglucoside (Glc 2 -TMP) were effectively esterified with oleic acid and middle-chain fatty acids such as lauric and capric acids, at 40°C. Stearic, palmitic, and myristic acids also gave esters, when reaction temperature was elevated from 40°C to 60°C. Glc 3 -TMP was slightly esterified only with the middle-chain fatty acids. The reactivity of Gl-containing digalactosides were lower than Gl-containing monogalactosides and TMP-containing digalactoside. Lipases from porcine pancreas and Geotrichum candidum also exhibited considerable activities for the esterification of the glycosides.

External electric field effects on absorption, fluorescence, and fluorescence decay of p-HBDI that is a model compound of the chromophore of GFP have been examined in a poly(methyl methacrylate) film. The electroabsorption spectrum is similar in shape to the first derivative of the absorption spectrum, which results from the difference in molecular polarizability between the ground state and the Franck-Condon excited state. The electrophotoluminescence spectrum is dominated by the corresponding fluorescence spectrum, indicating the enhancement of the fluorescence intensity in the presence of external electric fields. The direct measurements of the electric field effect on the fluorescence decay profile suggest that the field-induced deceleration of the nonradiative process contributes to the increase in the fluorescence intensity in the presence of electric fields.

A microbial screen using a yeast strain with conditional deficiency in the GPA1 gene was carried out to search for inhibitors of protein farnesyltransferase (PFT). A strain of Streptomyces was found to produce active compounds named UCF1-A, UCF1-B, and UCF1-C. Structural determination of these compounds revealed that UCF1-C is identical to the known antibiotic, manumycin, whereas UCF1-A and UCF1-B are structurally related to manumycin. All three UCF1 compounds suppress the lethality of gpa1 disruption, with UCF1-C exhibiting the strongest activity. UCF1 inhibits yeast as well as rat brain PFT. Fifty percent inhibition of yeast PFT activity is observed with 5 microM UCF1-C. Kinetic analyses of the inhibition suggest that UCF1-C acts as a competitive inhibitor of PFT with respect to farnesyl pyrophosphate, exhibiting a Ki of 1.2 microM, whereas the same compound appears to act as a noncompetitive inhibitor of PFT with respect to the farnesyl acceptor, the Ras protein. UCF1-C shows significant activity to inhibit the growth of Ki-ras-transformed fibrosarcoma, raising the possibility of its use as an antitumor drug.

1. Galactanasses from Penicillium citrinum and Bacillus subtilis were purified and char-acterized. Two galactanases from P. citrinum had essentially the same properties and hydrolyzed β-1, 4-galactosidic linkages of soybean arabinogalactan (SAG) in an endo-manner. B. subtilis galactanase was an exo-enzyme which hydrolyzed SAG and oligosaccharides to produce galac-toboise from the non-reducing ends. 2. Transfer reaction catalyzed by the galactanases were studied. The P. citrinum enzyme degraded o-nitrophenyl-β-galactoside after a lag phase. A reaction mechanism which involved transglycosylation in addition to hydrolysis was proposed. The endo- and exo-galactanases showed broad acceptor specificities and transglycosylated various alcohols, phenols, sugar alcohols, and saccharides. Structural feature of the products from glycerol was different among the galactanases and Escherichia coli β-galactosidase : the galactanases transglycosylated preferentially the secondary OH-group of glycerol rather than primary OH-groups which were almost specifically transgalactosylated by the β-galactosidase. 3. Glycosides with glycerol and trimethylolpropane (TMP) moieties, which were prepared by the transfer reaction, acted as effective substrates for the lipase-catalyzed esterification.

The relative stereostructure of UCT4B was determined by means of chemical derivatization and spectral analysis, in relation to known antitumor antibiotics terpentecin, which was simultaneously produced with UCT4B by Streptomyces sp

O-β-D-Galactopyranosyl-(1→4)-β-D-glucopyranosyl α-D-glucopyranoside(glucosyl lactoside, GL-95) was hardly hydrolyzed by human saliva, artificial gastric juice and porcine pancreas, but was hydrolyzed about 30% by rat intestinal aceton powder in vitro. GL-95 was selectively utilized by Bifidobacterium, and hardly utilized by Clostridium, Eubacterium and Escherichia.

The glycosidation of (+)catechin, which has five hydroxyl groups with cyclodextrin glucanotransferase (CGTase, EC 2.4.1.19) and soluble starch has been studied. One of the transfer products was purified and its structure was determined to be (+)catechin 3ʹ-0-α-D-glucopyranoside. This glucoside noncompetitively inhibited the activity of tyrosinase from mushroom, IC50 being 5.8 mM, but didn’t inhibit that from mouse melanoma. In contrast, arbutin (hydroquinone-0-β-D-glucopyranoside) inhibited both tyrosinases.

A new tetrameric proanthocyanidin named davallin (1) and two new phenolic glycosides, 5-O-β-D-(6-O-vanilloylglucopyranosyl)gentisic acid (6) and 4-O-β-D-(6-O-vanilloylglucopyranosyl)vanillic acid (7), have been isolated from the rhizomes of Davallia mariesii MOORE together with six known compounds, procyanidin B-2 (2) and B-5 (3), epicatechin-(4β→8)-epicatechin-(4β→6)-epicatechin (4), epicatechin-(4β→6)-epicatechin-(4β→8)-epicatechin-(4β→6)-epicatechin (5), protocatechuic acid (8), and 1-naphthol-β-D-glucopyranoside (9). Structures of the three new compounds (1, 6, and 7) were determined by means of spectroscopic methods including two-dimensional NMR techniques.Among the compounds obtained, 1 and 2 inhibited protein kinase C with IC50 values of 3.5 and 8.6 μM, respectively.

症例は63歳男性. 1980年から高γグロブリン血症を伴う多発性単神経炎で加療中だったがしだいに増悪し, 1992年には独歩困難となった. 1997年2月28日, 排便後に呼吸困難を自覚した. 翌日の心臓超音波検査で右房から右室に連続する血栓と胸部CTで左右肺動脈に血栓を認め, 急性肺動脈血栓塞栓症と診断, 体外循環下に緊急血栓除去術を施行した. 血栓は, 右房右室内にはなく, 左右肺動脈内に存在した. 術後に行った下肢静脈造影で右総腸骨静脈に血栓を認めたため, IVC内に Greenfield filter を留置した. 術後経過は良好で, 現在まで再発を認めていない. 本例は長期臥床による深部静脈血栓が直接の原因と考えられるが, 高γグロブリン血症による hyperviscosity が血栓の形成に関与した可能性が示唆された.

The rhodium(II) acetate-catalyzed decomposition of α-diazocarbonyl compounds such as substituted α-diazoacetophenones, cyclic diazoketones, cyclic diazodiketones, and α-diazo-β-ketoesters in carbon disulfide gave 1,3-oxathiole-2-thione derivatives in good yields. Diazomalonates also gave alkyl 5-alkoxy-2-thioxo-1,3-oxathiole-4-carboxylates together with 3,5-bis[bis(alkoxycarbonyl)methylene]-1,2,4-trithiolanes. The formation of 1,3-oxathiole-2-thiones can be explained by the intermediacy of zwitterionic intermediate containing rhodium(II) acetate formed by the reaction of carbon disulfide with ketocarbenoids generated in the catalytic decomposition of the diazocarbonyl compounds.

The 1,3-dipolar cycloaddition of 1-methoxy-2-benzopyrylium-4-olate (2) generated by Cu(acac)2-catalyzed decomposition of methyl 2-diazoacetylbenzoate with various aryl isothiocyanates and methyl isothiocyanate gave 2 : 1-, 3 : 1-, 4 : 1-, and 5 : 1-adducts without affording 1 : 1-adduct. The first cycloaddition of 2 occurs on the C=N double bond of isothiocyanate. The cycloadditions of the following steps, such as second, third, fourth, and fifth cycloadditions, proceed on C=O group of the cycloadducts of each previous steps. The molecular structure of the 2 : 1-adduct of 2 with phenyl isothiocyanate was determined by means of X-ray crystallography. Colorless crystals of the adduct are monoclinic with the space group P21/a, and with the unit-cell dimensions of a = 12.619 (4), b = 16.432 (4), c = 11.238 (2) A, β = 97.39 (1)°, and Z = 4. The structure was calculated by direct methods (MULTAN 80) and refined by block-diagonal least-squares methods. All hydrogen atoms were revealed by a difference-Fourier syn...

The rhodium(II) acetate-catalyzed reaction of various α-diazocarbonyl compounds with alkyl, phenyl, and benzoyl isothiocyanates gave 2-imino-1,3-oxathioles in good yields. 2(3H)-Oxazolethione was o...

A novel antitumor antibiotic, UCE6 (1, 3, 8, 10, ll-pentahydroxy-2-methyl-10-(2-oxo-4-hydroxypentyl)naphthacene-5, 12-dione) with topoisomerase I-mediated DNA cleavage activity, was isolated from the culture broth of actinomycetes strain UOE6. Addition of silicone oil antifoam agent, KS69 (2%), to the fermentation enhanced the production of UCE6 by -3 fold. A total of 1.15 g of UCE6 was recovered as reddish orange crystals from a 100 liter fermentation supplemented with 2% KS69. UCE6 exhibited growth inhibitory activity against HeLa S3, HCT116 and Lu-65 cells comparable to that of camptothecin.

Johnson-Claisen and Eshenmoser-Claisen rearrangements of chiral γ-trifluoromethylated allylic alcohols, which were prepared viaeffective enzymatic resolution of the corresponding propargylic alcohols, are demonstrated. As a result, it is shown that both reactions could become important methods for the preparation of highly functionalized chiral trifluoromethylated materials.

Background. Chronic inflammation in haemodialysis (HD) patients indicates a poor prognosis. However, therapeutic approaches are limited. Hydrogen gas (H2) ameliorates oxidative and inflammatory injuries to organs in animal models. We developed an HD system using a dialysis solution with high levels of dissolved H2 and examined the clinical effects. Methods. Dialysis solution with H2 (average of 48 ppb) was produced by mixing dialysate concentrates and reverse osmosis water containing dissolved H2 generated by a water electrolysis technique. Subjects comprised 21 stable patients on standard HD who were switched to the test HD for 6 months at three sessions a week. Results. During the study period, no adverse clinical signs or symptoms were observed. A significant decrease in systolic blood pressure (SBP) before and after dialysis was observed during the study, and a significant number of patients achieved SBP

The rhodium(II) acetate-catalyzed reaction of various α-diazocarbonyl compounds with alkyl, phenyl, and benzoyl isothiocyanates gave 2-imino-1,3-oxathioles in good yields. 2(3H)-Oxazolethione was o...

The 1,3-dipolar cycloaddition of 1-methoxy-2-benzopyrylium-4-olate (2) generated by Cu(acac)2-catalyzed decomposition of methyl 2-diazoacetylbenzoate with various aryl isothiocyanates and methyl isothiocyanate gave 2 : 1-, 3 : 1-, 4 : 1-, and 5 : 1-adducts without affording 1 : 1-adduct. The first cycloaddition of 2 occurs on the C=N double bond of isothiocyanate. The cycloadditions of the following steps, such as second, third, fourth, and fifth cycloadditions, proceed on C=O group of the cycloadducts of each previous steps. The molecular structure of the 2 : 1-adduct of 2 with phenyl isothiocyanate was determined by means of X-ray crystallography. Colorless crystals of the adduct are monoclinic with the space group P21/a, and with the unit-cell dimensions of a = 12.619 (4), b = 16.432 (4), c = 11.238 (2) A, β = 97.39 (1)°, and Z = 4. The structure was calculated by direct methods (MULTAN 80) and refined by block-diagonal least-squares methods. All hydrogen atoms were revealed by a difference-Fourier syn...

The structure of davallialactone (1), obtained from the rhizomes of a fern, Davallia mariesii MOORE, was revised on the basis of chemical and spectroscopic evidence. Also, the absolute stereochemistry of 1 was determined to be 5'R, 6'S from a circular dichroism (CD) study of dihydrodavallialactone (2).

Three new compounds, (-)-epicatechin-5-O-β-D-glulcopyranodside (1), 5, 7-dihydroxychromone-7-O-β-D-glucuronide methyl ester (6), and a novel norcarotane sesquiterpene glucoside named marioside (7), have been isolated from the rhizomes of Davallia mariesii MOORE together with five known compounds, (-)-epicatechin-3-O-β-D-allopyranoside (2), coumaric acid-4-O-β-D-glucopyranoside (3), caffeic acid-4-O-β-D-glucopyranoside (4), vanillic acid-4-O-β-D-glucopyranoside (5), and L-tryptophan (8). The structures of the new compounds (1, 6, and 7) were determined by means of spectroscopic methods including two-dimensional nuclear magnetic resonance techniques.

Procyanidin B-5 (1), epicatechin-(4β→8)-epicatechin-(4β→6)-epicatechin (2), and epicatechin-(4β→6)-epicatechin-(4β→8)-epicatechin-(4β→6)-epicatechin (3), which showed an inhibitory effect toward protein kinase C, were isolated from the rhizomes of Davallia mariesii MOORE. Detailed analyses of their 1H- and 13C-nuclear magnetic resonance spectra were carried out by the use of two-dimensional nuclear magnetic resonance techniques.

N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) transfers sulfate to position 6 of GalNAc(4SO4) residues of chondroitin sulfate to yield chondroitin sulfate E (CS-E). We have previously demonstrated that phenyl-beta-D-GalNAc(4SO4) could serve as an acceptor for GalNAc4S-6ST, thereby inhibiting GalNAc4S-6ST competitively. In this paper we compared the inhibitory effects of various glycosides in which various hydrophobic aglycons were attached to D-GalNAc(4SO4) via ss anomeric configuration. p-Nitrophenyl-beta-D-GalNAc(4SO4) and p-chlorophenyl-beta-D-GalNAc(4SO4) were stronger inhibitors than phenyl-beta-D-GalNAc(4SO4). Among inhibitors examined here, 3-estradiol-beta-D-GalNAc(4SO4) was the strongest inhibitor; the Ki of 3-estradiol-beta-D-GalNAc(4SO4) for the competitive inhibition was 0.008 mM, which was much lower than the Ki of phenyl-beta-D-GalNAc(4SO4), 0.98 mM. In contrast, 7-estradiol-beta-D-GalNAc(4SO4) showed only weak inhibition to GalNAc4S-6ST. 3-Estradiol-beta-D-GalNAc(4SO4) did not inhibit chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase under the concentration where GalNAc4S-6ST was inhibited by 90%. When 3-estradiol-beta-D-GalNAc(4SO4) was added to the culture medium of chondrosarcoma cells expressing human GalNAc4S-6ST, a significant, albeit small, reduction in the cellular synthesis of CS-E was observed. These results suggest that estradiol group of 3-estradiol-beta-D-GalNAc(4SO4) may enhance the inhibitory activity of the glycoside through increasing the affinity to the enzyme and may allow the glycosides to diffuse at a low efficiency into the cells to inhibit cellular synthesis of CS-E.

Staurosporine was discovered at the Kitasato Institute in 1977 while screening for microbial alkaloids using chemical detection methods. It was during the same era that protein kinase C was discovered and oncogene v-src was shown to have protein kinase activity. Staurosporine was first isolated from a culture of Actinomyces that originated in a soil sample collected in Mizusawa City, Japan. Thereafter, indolocarbazole compounds have been isolated from a variety of organisms. The biosynthesis of staurosporine and related indolocarbazoles was finally elucidated during the past decade through genetic and biochemical studies. Subsequently, several novel indolocarbazoles have been produced using combinatorial biosynthesis. In 1986, 9 years since its discovery, staurosporine and related indolocarbazoles were shown to be nanomolar inhibitors of protein kinases. They can thus be viewed as forerunners of today's crop of novel anticancer drugs. The finding led many pharmaceutical companies to search for selective protein kinase inhibitors by screening natural products and through chemical synthesis. In the 1990s, imatinib, a Bcr-Abl tyrosine kinase inhibitor, was synthesized and, following human clinical trials for chronic myelogenous leukemia, it was approved for use in the USA in 2001. In 1992, mammalian topoisomerases were shown to be targets for indolocarbazoles. This opened up new possibilities in that indolocarbazole compounds could selectively interact with ATP-binding sites of not only protein kinases but also other proteins that had slight differences in ATP-binding sites. ABCG2, an ATP-binding cassette transporter, was recently identified as an important new target for indolocarbazoles.