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Biomedical subjects

A Yamaguchi

Publications and source records attributed to A Yamaguchi.

At least 775 records · Page 43Linked to original sources
PubMed1983

Pyridazinones. 2. Synthesis and antisecretory and antiulcer activities of thiourea and 2-cyanoguanidine derivatives.

In an effort to develop new types of antiulcer agents, we synthesized a series of novel 2-[omega-(thioureido)alkyl]- and 2-[omega-(cyanoguanidino)alkyl]-3(2H)-pyridazinone derivatives. All target compounds were evaluated for gastric antisecretory activity in the pylorus-lygated rat by the method of Shay, and selected compounds were evaluated in the stress-induced ulcer test in rats. Structure-activity relationships were established. Two series of the compounds had significant activity in antisecretory and/or antiulcer tests. The molecular features essential for the activities are a thiourea group or a 2-cyanoguanidine group, a phenyl group in the C-6 position of the 3(2H)-pyridazinone ring, a four-carbon chain length between the 3(2H)-pyridazinone ring and the functional group, and a methyl group at the N-3 position of the functional group. Among them, the three thiourea derivatives (24, 26, and 38) and the six 2-cyanoguanidine derivatives (61, 62, 65, 75, 85, and 86) had the most potent antisecretory and/or antiulcer activities. These compounds are not histamine H2-receptor antagonists.

Acetylcholine↗
PubMed1983

Pyridazinones. 3. Synthesis, antisecretory, and antiulcer activities of 2-cyanoguanidine derivatives.

3(2H)-Pyridazinone derivatives having a 2-cyanoguanidine moiety, as well as a sulfur or an oxygen atom in the alkylene side chain, were synthesized and evaluated for gastric antisecretory and antiulcer activities. The key intermediates, free amines having a thioether linkage, were synthesized by the reaction of 2-(omega-chloroalkyl) derivatives with cysteamine, while other intermediates having an ether linkage were synthesized from 2-(omega-chloroalkyl)oxymethyl derivatives. These free amines were converted via the 3-cyano-2-methyl-1-isothiourea derivatives into the desired 2-cyano-3-substituted-1-guanidine derivatives. All compounds synthesized were evaluated for gastric antisecretory activity in the pylorus-ligated rat by the method of Shay, and selected compounds were evaluated in the stress-induced ulcer test in rat. Structure-activity relationships are discussed. The molecular features for the best activities are a phenyl group in the C-6 position of the 3(2H)-pyridazinone ring, a four-atom chain length between the 3(2H)-pyridazinone ring and the 2-cyanoguanidine moiety, and a thioether rather than an ether linkage. Among them, compound 14, 2-[[[2-(2-cyano-3-methyl-1-guanidino)ethyl]thio]methyl]-6-phenyl-3 (2H)-pyridazinone, had the most potent antisecretory and antiulcer activities. These compounds are neither histamine H2 receptor inhibitors nor anticholinergic agents.

Animals↗
PubMed1983

Quantitative and qualitative analysis of stem cells of patients with aplastic anaemia.

3 different methods, (1) assays of CFU-Cs and CFU-Es, (2) responsiveness of CFU-Cs and CFU-Es to low doses of CSF and ESF, respectively and (3) effects of ALG on CFU-C colony formation in vitro, were used to evaluate the quantitative and qualitative defects of stem cells in 28 patients with aplastic anaemia. Some patients with aplastic anaemia who had attained complete remission several years previously, exhibited severely depressed in vitro CFU-C colony formation. This suggests that the defect persists for a long time after clinical complete remission. Residual marrow CFU-Cs and CFU-Es did not have defective responses to the humoral stimulating factors, CSF and ESF. No patient showed a rise of colony number after treatment with ALG in vitro.

Anemia, Aplastic↗
PubMed1983

Kinetic studies on inactivation of Citrobacter freundii cephalosporinase by sulbactam.

The inactivation kinetics for inhibition by sulbactam (CP45,899) of Citrobacter freundii GN346 cephalosporinase were studied in detail and compared with those of type Ib penicillinase or TEM-2 beta-lactamase mediated by R plasmid RGN823. The rate constant for progressive inactivation of the cephalosporinase was significantly larger than that measured with the penicillinase. The number of sulbactam molecules required to cause complete inactivation of one cephalosporinase molecule (turnover number) was 80. The turnover number for the penicillinase was 5,200. The powerful inhibition by sulbactam of this cephalosporinase is similar to clavulanic acid inhibition of the penicillinase (turnover number, 115; reported by others). The affinity of sulbactam for the cephalosporinase, expressed as Ki, was 500 microM; this value was much higher than that for the penicillinase, which was estimated to be 0.5 microM. These results indicated that sulbactam is an effective progressive inactivator but a poor competitive inhibitor for the cephalosporinase. Our study also revealed that the cephalosporinase and sulbactam formed a long-lived inhibitor-enzyme complex which we termed the pseudo-irreversible complex. The half-life of the complex was 550 min at pH 7.0 and 30 degrees C.

Binding, Competitive↗
PubMed1983

Concurrent malignant lymphoma of the jejunum and multiple synchronous colon cancers.

This paper describes a unique case of combined malignant lymphoma of the jejunum and multiple synchronous carcinomas of colon and rectum. The jejunal tumor developed obstructive growth without regional lymph node involvement. Histologically, it was a malignant lymphoma corresponding to medium-sized cell type of follicular lymphoma, suggesting B cell origin in the bowel wall. In the colon and rectum, except for the transverse segment, there were three encircling, annular infiltrative tumors, and six polyps with malignant change. They developed independently, separated by an intact mucosa suggesting multiple synchronous cancers. Histologically they showed adenocarcinoma with or without mucus production, adenosquamous cell carcinoma, and villotubular adenocarcinoma. A case report is presented with a brief review of the incidence and pathogenesis of both jejunal and colonic tumors.

Adenocarcinoma↗
PubMed1982

Pyridazinones. 1. Synthesis and antisecretory and antiulcer activities of thio amide derivatives.

In an effort to develop new types of antiulcer agents, a series of novel 3(2H)-pyridazinone derivatives and related analogues was synthesized. Substituted 3(2H)-pyridazinones and their 4,5-dihydro analogues were alkylated by omega-haloalkyl cyanides at the N-2 position under phase-transfer catalytic reaction, and the nitrile group was converted to the thio amide group by treatment with hydrogen sulfide alone or with the appropriate primary or secondary amines. Various substituents were introduced on the nitrogen of thio amide, on the carbon in the side chains, and on the 3(2H)-pyridazinone ring. The synthesized compounds were evaluated for gastric antisecretory activity in the pylorus-ligated rat, and selected compounds were applied to experimental ulcer models, such as Shay's, aspirin-induced, and stress-induced ulcers in the rat. Structure-activity relationships are discussed. 3(2H)-Pyridazinones with a C-6 phenyl group and an N-2 alkyl side chain with a terminal thio amide group (48, 49, 51, and 52) were the most potent among the compounds tested.

Animals↗
PubMed1982

Amyloid deposits in the aged tongue: a postmortem study of 107 individuals over 60 years of age.

The incidence and distribution of amyloid deposits in aged tongues obtained from 107 necropsies over 60 years of age were examined. Thirty-nine tongues were affected with amyloid deposits and the overall incidence was 36.4%. The incidence increased with each advancing decade, and the group over 90 years old showed the highest incidence of 59.6%. Although the amount of amyloid deposits differed in each case, severely affected cases were most frequently found in the advanced decades. Amyloid deposits were almost always confined to blood vessels, especially arterioles and arteries. They occasionally occupied the entire wall and occluded the lumen. Blood vessels affected with amyloid were usually located in the muscle layers of the tongue. Vessels in the subepithelial layer and lingual glands were, however, sometimes affected. Amyloid deposits were resistant to Congo red staining with the potassium permangante method, and stained positively with DMAB. The present study suggested that the tongue is an important organ as to the appearance of amyloid deposits in elderly persons.

Age Factors↗
PubMed1982

Phospholipid bilayer permeability of beta-lactam antibiotics.

Liposomes containing penicillinase or cephalosporinase were prepared from the phospholipids of Escherichia coli. After free beta-lactamase was inactivated by clavulanic acid or penicillanic acid sulfone followed by separation of inactivated enzyme and inhibitor from liposomes by gel filtration, the permeability of these liposomes to ampicillin, cefazolin and cephaloridine was estimated by measuring the hydrolysis of these antibiotics by the entrapped enzymes. The permeability parameter C (minute-1 microM lipid-1) of ampicillin, cefazolin and cephaloridine was calculated to be 2.35 X 10(-4), 0.33 X 10(-4) and 0.52 X 10(-4), respectively. The lipid bilayer permeability of these antibiotics was also measured by using the liposomes containing these antibiotics. About half of the initially entrapped ampicillin was released from the liposomes within 80 minutes, while no significant release of cefazolin and cephaloridine could be detected during the same period. These results clearly indicates that the lipid bilayer membrane is more permeable to ampicillin than cefazolin and cephaloridine, and they are consistent with the observations of Sawai et al., who showed that ampicillin was a more effective antibacterial drug than cefazolin and cephaloridine against the porin-deficient mutants.

Ampicillin↗