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Biomedical subjects

S Nakabayashi

Publications and source records attributed to S Nakabayashi.

At least 37 records · Page 2Linked to original sources

New aminothiazolylglycylcephalosporins with a 1,5-dihydroxy-4-pyridone-2-carbonyl group. II. Synthesis and antibacterial activity of MT0703 and its diastereomers.

A practical synthetic method for large scale production of MT0703, (6R,7R)-7-[(RS)-2-(2-aminothiazol-4-yl)-2-(1,5-dihydroxy-4-pyridon e-2- carboxamido)acetamido]-3-[[1-(2-hydroxyethyl)pyridinium-4- yl]thiomethyl]ceph-3-em-4-carboxylate, was established. Its two diastereomers on configuration of the aminothiazolylglycyl moiety were synthesized using chemico-enzymatic method. The S-isomer of MT0703 was found to be more active against Gram-positive and Gram-negative bacteria including beta-lactamase-producing strains than the R-isomer.

Animals↗

Platelet aggregability and in vivo platelet deposition in patients with ischemic cerebrovascular disease--evaluation by indium-111-platelet scintigraphy.

In ischemic cerebrovascular disease, it is not clear whether platelet function in vitro actually reflects the situation in vivo. Using indium-111 platelet scintigraphy as a method for detecting platelet activation in vivo, we tried to elucidate this problem. Twenty eight patients with chronic stage of ischemic cerebrovascular disease (CVD) and 17 control subjects were examined. Platelet scintigrams were positive in 9 of 28 patients in CVD, while all were negative in control. A comparison of the results obtained from qualitative platelet imaging and platelet aggregability was performed to evaluate whether threshold aggregation concentration (TAC) grade differed across the three groups (control, CVD patients without platelet deposition and CVD patients with platelet deposition). CVD patients with platelet deposition showed a higher TAC than those patients who did not show platelet deposition (P less than 0.05) or control subjects without platelet deposition (P less than 0.05). These results suggest that some patients in chronic stages of CVD may have active platelet deposition on carotid atheromatous lesions, and presence of platelet deposition in vivo could contribute to reduce platelet reactivity in peripheral blood.

Adult↗

Biosynthesis, in calf pancreas microsomes, of three lipid-linked oligosaccharide diphosphates from a synthetic dolichyl diphosphate tetrasaccharide.

Incubation of calf pancreas microsomes with synthetic alpha-D-Manp-(1----6)-beta-D-Manp-(1----4)-beta-D-GlcpNAc-(1 ----4)-alpha-D- GlcpNAc-PP-Dol and GDP-D-[14C]-mannose gave three major lipid-linked oligosaccharide diphosphates. After release of the phospholipid residue by mild acid hydrolysis, the corresponding [14C]oligosaccharides were analyzed by gel-filtration, liquid chromatography, degradation by endo-N-acetyl-beta-D-glucosaminidases D and H, by jack bean alpha-D-mannosidase and Aspergillus oryzae (1----2)-alpha-D-mannosidase, acetolysis, and binding to concanavalin A-Sepharose. From the results it could be inferred that the following reaction took place in calf pancreas microsomes: alpha-D-Manp-(1----6)-beta-D-Manp-(1----4)-beta-D-GlcpNAc-(1 ----4)-alpha-D- GlcpNAc-PP-Dol + GDP-D-Man gave GDP + alpha-D-Manp-(1----3)-[alpha-D-Manp-(1----6)]-beta-D-Manp -(1----4)- beta-D-GlcpNAc-(1----4)-alpha-D-GlcpNAc-PP-Dol. The next products to be formed were alpha-D-Manp-(1----2)-alpha-D-Manp-(1----3)-[alpha-D-Manp -(1----6)]-beta-D- Manp-(1----4)-beta-D-GlcpNAc-(1----4)-alpha-D-GlcpNAc-PP-Dol, followed by alpha-D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp+ ++-(1----3)- [alpha-D-Manp-(1----6)]-beta-D-Manp-(1----4)-beta-D-GlcpNAc- (1----4)-alpha- D-GlcpNAc-PP-Dol. The mannose incorporation was enhanced by Triton X-100 and inhibited by Mn2+, and it occurred in the presence of either Mg2+ or EDTA. It is likely that the mannose donor was GDP-mannose since, under the conditions used, the formation of dolichyl mannosyl phosphate was negligible and the dolichyl heptasaccharide diphosphate accumulated.

Acetylglucosaminidase↗

The preparation of a partially protected heptasaccharide-asparagine intermediate for glycopeptide synthesis.

The heptasaccharide O-alpha-D-mannopyranosyl-(1----6)-O-[alpha-D-mannopyranosyl-(1----3)]-O- alpha-D-mannopyranosyl-(1----6)-O-[alpha-D-mannopyranosyl-(1----3)]-O-be ta- D-mannopyranosyl-(1----4)-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)- (1----4)-2-acetamido-2-deoxy-D-glucopyranose, isolated from the urine of swainsonine-intoxicated sheep, was peracetylated and was converted into the glycosyl azide by three alternative procedures, the most successful of which was formation of peracetyl oxazoline by treatment with trimethylsilyl trifluoromethanesulfonate, followed by treatment with trimethylsilyl azide. Reduction of the glycosyl azide in the presence of Lindlar catalyst gave the glycosylamine derivative, which was coupled with 1-benzyl N-fluoren-9-ylmethoxycarbonyl-L-aspartate to yield a protected glycosylasparagine. The benzyl ester group was easily removed by hydrogenolysis to form an intermediate suitable for glycopeptide synthesis.

Asparagine↗

Synthesis of the tetrasaccharide lipid intermediate P1-dolichyl P2-[O-alpha-D-mannopyranosyl-(1----6)-O-beta-D-mannopyranosyl-(1----4) -O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----4)-2-acetamido-2- deoxy-alpha-D-glucopyranosyl] diphosphate.

O-alpha-D-Mannopyranosyl-(1----6)-O-beta-D-mannopyranosyl-(1----4)-O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----4)-2-acetamido-2-deoxy- D-glucopyranose was isolated from bovine or ovine mannosidosis urine. After peracetylation, treatment with trimethylsilyl trifluoromethanesulfonate gave a high yield of a peracetyl oxazoline, which was phosphorylated with dibenzyl phosphate to give a dibenzyl glycosyl phosphate that was converted into a peracetyl tetrasaccharide phosphate by catalytic hydrogenolysis. A coupling reaction with P1-dolichyl P2-diphenyl diphosphate, prepared in two stages from pig-liver dolichol, yielded a peracetyl diphosphoric diester, which on O-deacetylation gave P1-dolichyl P2-[O-alpha-D-mannopyranosyl-(1----6)-O-beta-D-mannopyranosyl-(1----4)-O -(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----4)-2-acetamido-2-deoxy- alpha-D- glucopyranosyl] diphosphate. This tetrasaccharide lipid intermediate was active as an acceptor of D-mannose residues from GDP-D-mannose in the presence of calf pancreas microsomes.

Acetylation↗

The effect of isosorbide dinitrate and isosorbide-5-mononitrate on prostacyclin (PGI2) and thromboxane A2 (TXA2) generation in rat and human arteries.

The mechanism by which nitrates produce relaxation of the vascular smooth muscle and anti-aggregatory effect on platelets has not been understood. Several reports have suggested that vasoactive prostaglandin generation may account for part of the pharmacological action of nitroglycerin. However, few studies have been reported that isosorbide dinitrate or its main metabolite, isosorbide-5-mononitrate, directly stimulates prostacyclin (PGI2) generation in blood vessels. We examined the effect of ISDN and 5-ISMN on PGI2 and thromboxane A2 (TXA2) generation in rat thoracic aorta and human thoracic aorta and coronary artery. The stimulation of PGI2 generation was dependent on the concentration of ISDN and the maximum PGI2 generation was effected by ISDN 5.0 ng/ml in both rat and human vessels. The ratio of peak to basal PGI2 generation was about 1.6 with rat thoracic aorta and about 1.6 with human thoracic aorta and about 1.3 with human coronary artery. On the other hand, TXA2 generation showed a smaller increase than that of PGI2 with ISDN used in the therapeutic dose range and 5-ISMN did not significantly affect PGI2 or TXA2 generation. Previous studies of the effect of cyclooxygenase inhibitor, for example indomethacin, on the vasodilating response to nitrates have given conflicting results. It is believed, however, that ISDN is partially, not wholly, associated with the hemodynamic and platelet antiaggregation effects due to vascular PGI2 generation, which may play a beneficial role in inhibiting coronary vasospasm during anginal attacks.

Aged↗

[A case of normal pressure hydrocephalus associated with cerebrovascular disorders].

There has been much argument in recent years about the diagnostic and pathogenetic differences between normal pressure hydrocephalus (NPH) and vascular dementia (Multi-infarct dementia) or Binswanger's disease. We experienced an interesting patient, a 54-year-old male, who had left hemiparesis due to two past attacks of cerebral infarction and possible hydrocephalus had been pointed out by CT findings in 1981. He was seen on May 22, 1982, with the chief complaints of dementia, gait disturbance and urinary incontinence. He had the clinical and pathogenetic features, common to NPH and MID or Binswanger's disease. The followings were observed. These symptoms (dementia, gait disturbance, urinary incontinence) and computed tomographic findings (bilateral ventricular dilatation, periventricular lucency), as is often the case in NPH, are at times similar to those of MID or Binswanger's disease and it is difficult to distinguish NPH from MID or Binswanger's disease. We consider that there are probably many patients who are on the borderline of these three diseases. For treatment, the V-P shunt was very effective in combination with the preceding bilateral STA-MCA shunt but it is not clear whether the preceding STA-MCA shunt was required before the V-P shunt. We believe that the clinical symptoms will not appear until the ventricle is dilated to a critical degree. There was a correlation between the degree of dementia and Huckman number, one of the assessment methods for ventricular dilatation.

Brain↗