Studies on hypolipidemic agents. III. Synthesis and esterase-inhibitory activity of omega-cycloalkyl-2-oxoalkyl arenesulfonates.
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Biomedical subjects
Publications and source records attributed to S Fujii.
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The hemolysate partially purified from human red cells was demonstrated to be capable of synthesizing fructose-2,6-bisphosphate (F-2,6-P2) from fructose-6-phosphate in the presence of adenosine triphosphate (ATP) indicating that human red cells contain fructose-6-phosphate,2-kinase. The effect of F-2,6-P2 on the rate-limiting enzymes of glycolysis, ie, hexokinase, phosphofructokinase (PFK), and pyruvate kinase, has also been examined. PFK was activated by this metabolite and the half-maximum activation was obtained at a concentration of 10(-7) mol/L. Neither hexokinase nor pyruvate kinase was affected by F-2,6-P2. These results suggest that human erythrocytes may contain this metabolite as one of the positive effectors for PFK.
DNA restriction endonuclease cleavage analysis and serum neutralization test were performed in strains of adenovirus types 19 (Ad-19) and 37 (Ad-37) isolated from patients with acute conjunctivitis in Sapporo (Japan), Kaohsiung (Taiwan) and Pusan (South Korea) during the period of 1977 to 1984. Ad-19 and Ad-37 could be roughly differentiated, but a fair degree of cross reactivity was noted by serological test. By DNA restriction endonuclease analysis, Ad-19 isolates, Ad-19 prototype strain and Ad-37 strains were clearly differentiated. It was suggested by DNA cleavage patterns that both Ad-19 and Ad-37 isolates in East Asia are the same as those currently found in Europe and the USA. A new subtype of Ad-37 was found by DNA cleavage analysis among the isolates obtained in Sapporo and Kaohsiung in 1980.
2, 6-Dihydroxy-3-cyano pyridine (CNDP) was found from the study of inhibitory effects of pyrimidine and pyridine derivatives on 5-FU degradation catalyzed by dihydrouracil dehydrogenase. CNDP, a new inhibitor on 5-FU degradation was 300 times more effective than uracil. Co-administration of an equi-molar CNDP with some fluorinated pyrimidine preparations potentiated their antitumor activity. Tegafur (FT-207) and EM-FU in combination with CNDP were found most effective. This potentiation was exhibited not only to 5-FU derivatives but also to FdUrd and its derivatives. BOF-A1 and BOF-A2, new compounds combined with CNDP were markedly active against mouse sarcoma 180 and rat Yoshida sarcoma.
The inhibitory effects of about 30 compounds, mainly pyrimidine and pyridine derivatives, on 5-fluorouracil degradation catalyzed by dihydrouracil dehydrogenase (DHU dehydrogenase) were investigated. The inhibitory activities of 5-substituted uracil derivatives decreased time-dependently during preincubation with liver extracts, indicating that these compounds are substrates of DHU dehydrogenase. During preincubation, 4,6-dihydroxypyrimidine derivatives were found to be converted to barbituric acid derivatives, which have stronger activities. The inhibitory activity of 2,4-dihydroxypyridine (3-deazauracil), which was stronger than that of uracil, did not change during preincubation, indicating that this compound is not a substrate but is an inhibitor of DHU dehydrogenase, and suggesting that 2,6-dihydroxypyridine (1-deazauracil) could be a potent inhibitor. In the light of these findings, we examined various derivatives of barbituric acid, 2,4-dihydroxypyridine and 2,6-dihydroxypyridine. Among these compounds, 3-cyano-2,6-dihydroxypyridine and 5-chloro-2,4-dihydroxypyridine were the strongest inhibitors with Ki values for DHU dehydrogenase of 2.3 X 10(-7) M and 3.6 X 10(-7) M, respectively.
A case of trigeminal neurinoma with marked extracranial extension is reported with a review of the literature. A 60-year-old female noticed numbness over the left side of the face during the proceeding 15 years. Two years prior to admission, she began to complain of itching and lancinating pain at the left lateral aspect of the nose. Neurologic examination on admission revealed diminished corneal reflex on the left side and hypesthesia in the distribution of the left trigeminal nerve. There was no weakness or atrophy of the ipsilateral masticatory muscles. The remaining cranial nerves and cerebellar functions were normal. Craniograms showed destruction of the left petrous apex, enlargement of the left superior orbital fissure and an extensive bone defect in the floor of the left middle cranial fossa. CT disclosed a huge heterogeneously enhancing mass lesion in the left middle cranial fossa, which extended posteriorly into the left cerebellopontine angle and inferiorly into the pterygoid and infratemporal fossae. Cerebral angiograms revealed medial displacement of the left internal cerebral artery in the ganglionic, cavernous and supraclinoid portions, and elevation of the left middle cerebral artery in the sphenoidal portion. Although the left meningohypophyseal trunk was dilated, no tumor stain was observed. A transantral biopsy specimen provided the diagnosis of neurinoma with Antoni type A tissue. The patient was followed up at the outpatient clinic as radical operations were not agreed upon. Eight cases of trigeminal neurinoma with extracranial extension are reviewed including the presented case. There were two males and six females, and the age varied from 16 to 65 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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Clinical efficiency and side effects of cefoperazone (CPZ) against 40 infectious diseases in the field of internal medicine were studied. In addition, relationship between clinical efficiency and the value of area under the time concentration curve (AUC) was evaluated. It was possible to evaluate clinical responses in 36 cases of 40 infections; Responses were excellent in 15, good in 16, fair in 3 and poor in 2. An overall efficacy rate was 86.1%. A high dose of CPZ (2 g X 2/day) produced a higher efficacy rate than a low dose of the drug (1 g X 2/day) [95.8% (23/24 cases) vs. 66.7% (8/12 cases)] but the difference was not statistically significant. It was possible to evaluate bacteriological efficacy in 32 cases. Bacteria were eradicated in 29 (90.6%) and decreased in 3. The value of AUC in the high dose group was significantly higher than that in the low dose group. Values of AUC in cases of excellent or good clinical responses tended to be higher than values in cases of fair or poor responses. Side effects were noted in 4 cases, but they were not serious and improvements were observed without withdrawal of the drug except 1 case.
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A very rare case of fibro-osteochondroma arising in uterine musculature was studied histologically. The tumor exhibited three types of cellular proliferation--fibroblastic, cartilaginous, and osseous--all within an abundant collagenous matrix. The three components were intermingled, and varied in the degree of differentiation of cartilaginous and osseous tissue. The more differentiated tissues were usually circumscribed by fibrocellular bands of spindle-shaped cells that seemed to have transformed into rounded cartilaginous cells. Presumably this tumor arose from undifferentiated mesenchymal cells in the myometrium, which proliferated to form fibroblasts, chondrocytes, and osteoblasts. The tumor may be designated fibrio-osteochondroma. It is histologically benign and exceedingly rare.
Fatty acid binding protein was purified from renal medulla, and its binding activity and fatty acid composition were determined in spontaneously hypertensive stroke-prone rats. Wistar-Kyoto rats were used as controls. Fatty acid binding activity was higher in 5-week-old prehypertensive spontaneously hypertensive stroke-prone rats (0.155 +/- 0.006 mol palmitic acid/mol protein) as compared with control values in Wistar-Kyoto rats (0.030 +/- 0.001). However, in 40-week-old rats, the activity was decreased only in spontaneously hypertensive stroke-prone rats with established hypertension (0.035 +/- 0.002), and it did not decrease in Wistar-Kyoto rats (0.028 +/- 0.003). Fatty acid compositions were similar among 5 and 40-week-old control rats and 5-week-old hypertensive rats (palmitic acid 24%, stearic acid 14%, oleic acid 30%, linoleic acid 29%, arachidonic acid 3%), although the total amount of bound long-chain fatty acids was decreased in 5-week-old hypertensive rats, explaining the high fatty acid binding activity in this preparation. Fatty acid binding protein from 40-week-old hypertensive rats had an elevated proportion of endogenous arachidonic acid, with other fatty acids being relatively reduced (palmitic acid 8%, stearic acid 2%, oleic acid 4%, linoleic acid 10%, arachidonic acid 76%), indicating increased arachidonic acid transport in the cytosol. These results show that genetically hypertensive rats had an alteration in fatty acid transport mediated by fatty acid binding protein; this alteration may be involved in the pathogenesis of hypertension.
The hyperosmolarity response was recorded with the electrooculogram in the dark before and after cataract extraction, to investigate a possible disorder in the retinal pigment epithelium after cataract extraction. The hyperosmolarity response was suppressed one week after surgery, especially after intracapsular extraction. The response recovered up to the preoperative level in most cases one or two months after surgery. These findings indicate reversible functional disorders of the pigment epithelium after cataract extraction, particularly intracapsular. This dysfunction can be revealed by the hyperosmolarity response. This response is clinically useful for diagnosis of pigment epitheliopathy after cataract extraction.