Biomedical subjects
Publications and source records attributed to M Numata.
A new method for the activation of thioglycosides was developed by use of benzeneselenenyl triflate (PhSeOTf), which, upon reaction with either a primary or secondary sugar HO-group, afforded O-glycosides under extremely mild reaction conditions. The reaction was applicable to various l-thiohexosides 2-6 as well as to a 2-thioglycoside 20 derived from N-acetylneuraminic acid (NeuAc).
The factors that frequently cause the development of acute gastric mucosal lesions (AGML) were studied in 37 mongrel dogs. Bacterial shock was induced by bolus injection of E. coli live bacterial flora (10(10) cells/kg body weight) under parietal cell-stimulated condition by intravenous administration of 0.008 mg/kg per hour of pentagastrin. In addition, 0.01 mg/kg per hour of neostigmine sulfate was administered intravenously during the experiment. Frequent development of AGML was observed in the neostigmine-administered canines without significant changes in the gastric corporal and antral tissue blood flow. In the neostigmine-administered group, AGML was observed in the antrum, although in the other group AGML was mostly observed in the corpus. These results suggest that a neostigmine-induced systemic vagostimulated condition by intravenous administration of neostigmine plays an important role in the development of AGML in dogs subjected to bacterial shock.
Cytochrome P-460 of Nitrosomonas europaea [Erickson, R.H. and Hooper, A.B. (1972) Biochim. Biophys. Acta 275, 231-244] was further purified to an electrophoretically homogeneous state. The cytochrome molecule was composed of three molecules of subunits with Mr of 17,300-18,500, and contained three atoms of iron, which seemed to be heme iron, and six cysteine residues, but did not contain nonheme iron or inorganic sulfide. The cytochrome showed absorption peaks at 460 and 688 nm with a broad shoulder at 635 nm in the reduced form. The ESR spectrum of ferricytochrome P-460 showed signals at g = 5.91, 5.63, and 1.99, indicating that the protein was a high spin hemoprotein. The heme of the cytochrome was not cleaved by the methods which were available for cleavage of heme c. The pyridine ferrohemochrome of the hemoprotein did not show the distinct alpha and beta peaks which are shown by the ferrohemochromes of many other cytochromes so far known. The N-terminal amino acid sequence of cytochrome P-460 differed from that of hydroxylamine oxidoreductase. Therefore, cytochrome P-460 did not seem to be the solubilized P-460 moiety of hydroxylamine oxidoreductase, in agreement with the finding by D.J. Miller et al. [J. Gen. Microbiol. 130, 3049-3054 (1984)]. However, cytochrome P-460 had several enzymatic activities which hydroxylamine oxidoreductase showed. Although most of the activities of the cytochrome were lower than the corresponding activities of the oxidoreductase, the hydroxylamine-cytochrome c-552 reductase activity of the cytochrome was about 5-times as high as that of the oxidoreductase.
The solution conformations of GM4 ganglioside [NeuAc(alpha 2----3)Gal (beta 1----1)Cer] in (2H3C)2SO and its component disaccharide in 2H2O were investigated with the aid of 1H-nuclear magnetic resonance spectroscopy (nuclear Overhauser effect, analysis of coupling constants) and by energy-minimum calculations. The existence of three low-energy conformers obtained by theoretical calculations was supported by experimental findings in the case of GM4, whereas the disaccharide appears to exist as a mixture of two conformers.
A case of oncocyte-type renal cell carcinoma was reported. The tumor had developed from the upper posterior portion of the left kidney and was well circumscribed. However, the tumor showed expansion into the intraparenchymal space, invasive growth, and venous invasion. Marked cell atypia was not observed.
From Nitrosomonas europaea which had been cultivated in a medium deficient in copper, cytochrome c oxidase (aa3-type) which did not have CuA was purified. The oxidase did not show the 830-nm peak and its ESR spectrum differed greatly from that of the normal enzyme, which has two copper atoms, CuA and CuB, per molecule. However, the oxidase which did not have CuA showed almost the same cytochrome c oxidizing activity as the normal oxidase.
Papillotubular adenoma of the ampullary region in a rare tumor which has the potential for malignant transformation. Although reported more frequently nowadays, ampullary tumors are difficult to diagnose before operation unless they cause obstructive jaundice. Occasionally they are detected by ultrasonography, computed tomography or ERCP in patients who complain of nonspecific upper abdominal discomfort. We report a case of a periampullary papillotubular adenoma causing generalized pruritus and weight loss but no jaundice. The tumor was extirpated by pancreaticoduodenectomy, and the patient has remained healthy for over five years.
Methyl (5-acetoxyacetamido-4,7,8,9-tetra-O-acetyl-3,5- dideoxy-D-glycero-beta-D-galacto-2-nonulopyranosyl chloride)onate, prepared from N-glycolyl-neuraminic acid, was used for the glycosylation of benzyl O-(2,6-di-O-benzyl-beta-D- galactopyranosyl)-(1----4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside to give benzyl O-[methyl (5-acetoxyacetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero- alpha- and beta-D-galacto-2-nonulopyranosyl)onate]-(2----3)-O-(2,6-di-O -benzyl-beta- D-galacto-pyranosyl)-(1----4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside, and a regioisomer. Compounds 9 and 13 were converted into the corresponding glycotriaosyl glycosyl donors which, upon coupling with (2S,3R,4E)-3-O-tert-butyldiphenylsilyl-2-N- tetracosanoylsphingenine, afforded completely protected hematoside and a stereoisomer 26, respectively. Deprotection of 22 and 26 completed the first total synthesis of both hematoside and a stereoisomer, beta-NeuGc-(2----3)-beta-Gal-(1----4)-beta-Glc-(1----1)-Cer.
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Described are total syntheses of O-[sodium (5-acetamido-3,5-dideoxy-D -glycero-alpha-D-galacto-2-nonulopyranosyl)onate]-(2----3)-O -beta-D -galactopyranosyl-(1----1)-(2R,3S,4E)-2-N-tetracosanoylsphingen ine,O-[sodium (5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosyl+ ++)onate] -(2----3)-O-alpha-D-galactopyranosyl-(1----1)-(2R,3S,4E)-2-N -tetracosanoylsphingenine, O-[sodium (5-acetamido-3,5-dideoxy-D-glycero-beta -D-galacto-2-nonulopyranosyl)onate]-(2----3)-O-beta-D-gal act opyranosyl -(1----1)-(2R,3S,4E)-2-N-tetracosanoylsphingenine, and O-[sodium (5-acetamido-3,5-dideoxy-D-glycero-beta-D-galacto-2-nonulopyranosyl++ +)onate] -(2----3)-O-alpha-D-galactopyranosyl-(1----1)-(2R,3S,4E)-2-N -tetracosanoylsphingenine by using O-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D -galacto-2-nonulopyranosyl)onate]-(2----3)-2,3,4,6-tetra-O-a cetyl-D -galactopyrano-syl trichloroacetimidate and O-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-beta -D-galacto-2-nonulopyranosyl)onate]-(2----3)-2,4,6-tri-O-ace tyl-D-galactopyranosyl trichloroacetimidate as key glycosyl donors, and (2S,3R,4E)-3 -O-benzoyl-2-N-tetracosanoylsphingenine as a key glycosyl acceptor.
Orally active 1-(alkyl substituted cyclohexyloxycarbonyloxy)alkyl ester prodrugs (9b-h) of 7 beta-[2-(2-aminothiazol-4-yl)acetamido]-3- [[[1-(2-dimethylaminoethyl)-1H-tetrazol-5-yl]thio]-methyl]ceph+ ++-3- em-4-carboxylic acid (cefotiam, CTM) have been studied as well as the thia (9i) and aza (9j) analogs. These represent derivatives of the 1-(cyclohexylacetoxy)ethyl ester (2) of CTM. The syntheses and oral bioavailability (BA) in mice are described. Among them, the 1-(cyclohexyloxycarbonyloxy)butyl ester (9h) gave the highest BA, 93.5%; the esters having a cyclohexyloxy group in the ester moiety gave BAs of more than 75%, although the BA of the 1-(ethoxycarbonyloxy)ethyl ester (9a) was only 23.9%. The thia analog showed a moderate BA, 46%, but the aza analog, 9j, did not show a BA of CTM. These results indicate that the 1-(substituted cyclohexyloxycarbonyloxy)alkyl group was the suitable promoiety to improve the oral BA of CTM. Chiral 1-(alkoxycarbonyloxy)alkyl groups used as the ester moiety, gave an almost 1: 1 mixture of diastereoisomeric esters. These were tested as such. However, an experiment in which the separated isomers of the 1-(cyclohexyloxycarbonyloxy)ethyl ester (9d) were administered orally confirmed that both diastereoisomers gave identical BAs.
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To determine the relationship between histocompatibility and circulation in the transplanted graft, which are the major factors influencing graft survival, the survival of the skin grafts and kidney transplants were compared between strong (ACI to Lewis) and weak (Fisher to Lewis) histocompatible strains, because rats given skin graft receive poor blood supply from a recipient, and the rats given kidney transplants receive immediate blood supply after transplant. In the group with a weak histocompatibility barrier circulation of the engrafted organ was better and the survival period longer. In the group with a strong histocompatibility barrier graft survival was little influenced by the circulatory disorder, and the degree of histocompatibility overwhelmed the circulatory condition.
A giant tumor developed on the right chest wall of a 52-year-old housewife over a 20-year period. It was accompanied by a spider-like invasion of skin, and a lymph node was palpated in the right axilla. Wide excision of the lesion was carried out. The cross-section of the tumor showed two different appearances. The tumor was histologically diagnosed as a syringadenocarcinoma papilliferum. The post-operative course was uncomplicated and without evidence of recurrence.
Ia-like antigen-positive (Ia+) and -negative (Ia-) cell populations were separated from human cord blood cells and bone marrow mononuclear cells by a rosette technique with a combined use of staphylococcal protein-A-coated bovine red blood cells and the monoclonal OKIa 1 antibody, or by using a cell-sorting technique. Colony-forming units-granulocytes-monocytes-macrophages (GFU-GM) were assayed in a semisolid agar culture, and colony-forming cells-granulocytes (CFC-G) were differentiated from colony-forming cells-monocytes-macrophages (CFC-M) by double staining for esterase activity. The majority of CFC-G in cord blood was grown in the Ia+ fraction; Ia+ CFC-G/Ia- CFC-G = 1.62 +/- 0.34 (mean +/- SD), which was similar to the ratio in bone marrow (Ia+/Ia- = 1.80 +/- 0.37). In contrast, the majority of CFC-M in cord blood was grown in the Ia- fraction; Ia+/Ia- for CFC-M = 0.50 +/- 0.09. The predominance of CFC-G in the Ia+ fraction in contrast to predominance of CFC-M in the Ia- fraction was confirmed by using a cell-sorting technique. T-lymphocyte depletion and the culture supernatants of Ia+ and Ia- cells did not affect differentiation of CFC-G and CFC-M. These data suggest that there are potent differences in the expression of Ia-like antigens between CFC-G and CFC-M, indicating that the Ia+ progenitor cell population generates predominantly CFC-G, whereas the Ia- population generates mainly CFC-M during the maturation process in granulopoiesis.
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A simplified technique to make an end-to-side or a side-to-side portacaval shunt in rats is described. The method requires no expensive special microsurgical instruments, and when the technique is completely mastered, one can make a portacaval shunt within 10 minutes. This is very useful when making many experimental models in rats. Moreover, this technique is fundamental for doctors who are intending to train in microsurgery.