[Promoting effect of the chymotrypsin inhibitor FK-448 on the intestinal absorption of insulin in rats].
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Biomedical subjects
Publications and source records attributed to S Fujii.
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A heritable open-eyelid mutant which arose spontaneously in the NC strain of mouse in 1982 has been maintained as the NC-eob line through brother-sister matings. When the line exceeded the 12th generation, its reproductive capabilities were initially compared with those of the NC strain. Then eye abnormalities were investigated morphologically and genetically. Although most of the reproductive parameters in the NC-eob line were comparable to those in the NC strain, a significant decrease was observed in the mean number of pups delivered, and the viability of pups at 7 days of age was reduced to 55%. The eyelids of pups were widely open at birth. The exposed cornea dried within a few hours and a bloody exudate appeared around the margin of the eyelids. At 1 day of age, the eye opening was smaller in size and covered with a scab. Histological examination demonstrated apparent inflammatory changes in the cornea and conjunctiva. At 21 days of age, the eyes revealed opacity, a rough surface, and microphthalmia. Histological findings in the cornea, such as keratosis and vascularization, coincided with the eye opacity. The weight and size of the eyeballs were almost the same as those in normal NC pups. However, a significant decrease in the length of the palpebral rima was evident and this was considered to be the cause of the microphthalmia. The results of genetic analysis indicated that these eye abnormalities were caused by an autosomal recessive gene, eob. These results suggested that the eob gene might be a new mutation manifesting semi-lethality as a pleiotropic effect.
Smooth-muscle cells were cultured from rat aortic media, then oxyhemoglobin and other agents including serotonin, norepinephrine, and angiotensin II were added separately to the medium. Contractile and ultrastructural changes of the cells were examined with electron microscopy during the first 2 weeks of incubation. Oxyhemoglobin not only produced progressive contraction of the arterial smooth-muscle cells, but it also caused ultrastructural changes that resembled myonecrosis. In contrast, there was no evidence of progressive contraction or ultrastructural changes either in control cultures or in cultures with the other vasoactive agents. Although washout of oxyhemoglobin 3 hours after administration prevented continued contraction of the cells, washout 24 hours or longer after administration had no preventive effect. Judging from these results and from the fact that the culture medium was changed every 2 days, it is unlikely that accumulation of exogenous vasoactive agents caused these changes. The contraction and suggestive myonecrosis of the arterial smooth-muscle cells are probably caused by some intrinsic process initiated by oxyhemoglobin. The culture of cerebral arterial smooth-muscle cells requires further technical improvement; nevertheless, these results obtained with the smooth-muscle cells of rat aortic media indicate that arterial smooth-muscle cells in culture provide a promising new experimental model for chronic in vitro study of cerebral arterial spasm. It is suggested from these results that cerebral arteries are particularly prone to vasospasm because of structural differences as compared to noncerebral arteries.
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Evaluation of acellular pertussis vaccine and components of B. pertussis was performed by the use of an in vivo assay system consisting of the mouse aerosol challenge test and the antibody responses in mice. Acellular pertussis vaccine (ACP), pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae or whole cell vaccine (WPV) were challenged intrapulmonarily with B. pertussis. The number of colonies of B. pertussis in the lungs of the mice were counted. 1. Does response relationships were observed between the dose of the vaccines, APV or WPV, and B. pertussis colony counts in the lungs of mice injected with one of the vaccines or immunogens. Higher doses of the vaccines or immunogens resulted in reduced numbers of colonies of B. pertussis in the lungs of mice. 2. When the amounts of total protein nitrogen were in the same range, APV and a mixture of PT and FHA showed higher protective efficacy than PT or FHA alone. 3. Rises in antibody titers were observed in mice injected with APV, WPV, PT or FHA.
The effectiveness and safety of cefmenoxime (CMX) in the treatment of respiratory tract infections were evaluated, mainly in relation to the appearance of hemorrhagic tendency. Out of 80 patients treated in this study, 57 were treated with CMX alone, and an effective rate was determined to be 75.4%. As for a tendency toward hemorrhage, none of the patients clinically exhibited a hemorrhagic tendency, while the prolongation of prothrombin time (PT) and/or activated partial thromboplastin time (APTT) was seen in 3 patients (3.8%), who were all at ages over 63. The prolongation of APTT was clearly related to CMX in 1 patient. Although the causal relation between CMX and the prolongation of PT or APTT was unclear in the remaining 2 patients because they had severe primary diseases (lung cancer and respiratory failure due to chronic obstructive lung disease in addition to severe hepatic disorder and received combination treatment with anticancer agents or other antibiotics), CMX might have a role in causing these phenomena. Even though none of the patients showed a hemorrhagic tendency clinically arousing problems, we should be careful in using CMX in the treatment of the aged and patients in poor general conditions because PT and/or APTT was observed to prolong with the use of CMX in some patients.
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Recently, normal cervical glandular cells have been reported to synthesize and secrete CA125 as a common constituent of normal cervical mucus. However, the levels of CA125 in the cervical mucus samples during the menstrual cycle and with cervical inflammatory diseases have not been determined. Therefore, we measured CA125 in cervical mucus samples in various phases of the menstrual cycle and in patients with cervical polyp or vaginitis. In addition to CA125, CEA and CA19-9 were also examined in the same samples. CA125 levels in the mucus samples of women (45 cases) without any gynecologic disorders (control) were 102,200 +/- 8,600 (M +/- S.E.) U/ml. Significantly higher levels were noted in the samples obtained in the follicular phase than in the luteal phase. CA125 levels in the mucus with atrophic vaginitis (12 cases) were significantly lower than those of controls. CEA and CA19-9 levels in the control samples were 3,400 +/- 550 ng/ml and 3,470 +/- 500 U/ml, respectively, and both of these showed no significant difference between the follicular and luteal phases. However, both CEA and CA19-9 levels in the cervical mucus with cervical polyps (15 cases) or vaginitis were much higher than in the controls. Accordingly, the present study revealed that CA125 in the cervical mucus fluctuates during the menstrual cycle, probably under the influence of ovarian sex steroids. In addition, CEA and CA19-9 in the cervical mucus samples obtained from women without any gynecologic disorders showed low levels, but those with inflammatory diseases were high, and this suggested that inflammatory diseases in the cervix and/or vagina may affect the constituent of the tumor-associated carbohydrate antigens in the cervical mucus.
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We investigated the relationships between antitumor activity and the inhibition of Thymidylate Synthase (TS) activity after oral administration of 5-fluorouracil (FUra) and its derivatives, FT, UFT, HC-FU, PH-FU and 5'-DFUR, using mainly Sarcoma 180 as an experimental tumor model. The inhibition of TS activity in the tumor, after oral administration of these drugs to Sarcoma 180 bearing mice, reached the plateau phase shortly after drug administration. The inhibition of TS activity remained at the same level for over 24 hours and was dose dependent. UFT and FT showed a very high correlation between the inhibition of TS activity and their antitumor activity. However, such a correlation was not found for other FUra derivatives despite their high TS inhibiting values. The relationship between the tumor growth inhibition (TGI) and the TS inhibition (TSI) of these drugs, presented as a ratio of ED50 of TGI to ED50 of TSI in case of UFT and FT, was shown to be 0.81 and 1.18, respectively (i.e., nearly 1.00). However, the above ratio for FUra and HCFU was shown to be 2.49 and 3.88, respectively. These findings demonstrate that it is necessary to take into account other mechanisms besides TS inhibition of some fluorinated pyrimidines to explain their total antitumor activity.
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The nonenzymatic glycosylation (glycation) of Cu-Zn-superoxide dismutase led to gradual inactivation of the enzyme (Arai, K. Iizuka, S., Tada, Y., Oikawa, K., and Taniguchi, N. (1987) Biochim. Biophys. Acta 924, 292-296). The purified superoxide dismutase from human erythrocytes comprises both glycated and nonglycated forms. The nonglycated Cu-Zn-superoxide dismutase was isolated by boronate affinity chromatography. Incubation of the nonglycated superoxide dismutase with D-[6-3H]glucose in vitro resulted in the gradual accumulation of radioactivity in the enzyme protein, and Schiff base adducts were trapped by NaBH4. The sites of glycation of the superoxide dismutase were identified by amino acid analysis after reverse-phase high performance liquid chromatography of the trypsin-treated peptides. Lysine residues, i.e. Lys3, Lys9, Lys30, Lys36, Lys122, and Lys128, were found to be glycated. Three of the glycated sites lie in Lys-Gly, two in Lys-Ala, and one in Lys-Val. The inactivation of the superoxide dismutase on the glycation is due mainly to the glycation of Lys122 and Lys128, which are supposed to be located in an active site liganding loop. The remaining five sites, such as Lys-Glu, Lys-Asp, Lys-His, and Lys-Thr are relatively inactive as to the formation of either a Schiff base or an Amadori adduct.