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Biomedical subjects

S Katayama

Publications and source records attributed to S Katayama.

At least 433 records · Page 24Linked to original sources

[Pharmacokinetics of FT-207 rectum suppository in squamous cell carcinoma of the uterine cervix. (I) Pharmacokinetics in single administration at a dose of 1 gram].

In order to use FT-207 rectum suppository for a long-term maintenance chemotherapy of squamous cell carcinoma of the uterine cervix, we examined its pharmacokinetics by single administration at a dose of 1 g employing chemical assay. The results were as follows: 1. The blood level of FT-207 showed its peak of 30 mcg/ml at 2 hours after administration, of which half-time was 9 hours. Inter-individual differences were few in changes in the curve. 2. The blood level of 5-FU showed two peaks, 0.25 mcg/ml at 4 hours and 0.017 mcg/ml at 36 hours after administration. There were large inter-individual differences in its alteration. 3. At the time of operation, both FT-207 and 5-FU showed low concentrations in blood. 4. The level of 5-FU in cervical focus was 0.068 mcg/g which was the highest among those in all genital organs, and 2.7 times higher than the level of 5-FU in blood. 5. There was a significantly positive correlation at r = 0.174 (p less than 0.1) between the level of 5-FU in the focus of cervical cancer and the level of FT-207 in blood.

Carcinoma, Squamous Cell↗

[The evaluation of uterine endocervical lesions by cervicoscopy of lateral view type (clinical advantages for reduction of traditional surgical management of uterine cervical cancer)].

In this study an attempt was made to examine uterine endocervix by contact pan-endomicroscopy of the lateral view type (we call it cervicoscopy). Its clinical advantages are also investigated. 127 cases of uterine cervical neoplasms (including CIN) were examined to detect whether or not neoplastic foci existed in the cervical canal. It was found that vascular morphological configurations could be clearly observed. These findings are classified into several categories according to their morphological characteristics. It was found that there are many green asparagus-like vessels and/or root-like vessels in invasive foci but few in CIN foci. 56% of CIN foci, and 90% of advanced foci of endocervix were accurately diagnosed from the abnormal vascular findings. On the basis of what is described above, we examined the endocervical lesions from 40 conization candidates. 19 cases (48%) of the candidates were omitted because of negative advanced findings which were confirmed histopathologically afterwards. It suggested that a reduction in the number of conization candidates will be made possible with this new clinical examination.

Cervix Uteri↗

Acute effects of mercuric compounds on preimplantation mouse embryos in vitro.

The effects of mercuric compounds on the proliferation and protein synthesis of mouse blastocysts were examined in vitro by treating the embryos with methylmercury (MMC) or mercuric chloride (MC). Late blastocysts were exposed to various concentrations of mercuric compounds for 24 hr. and incubated for another 24 hr. in a mercury-free medium. The protein synthesis of the mercury-treated blastocysts was measured by counting the incorporation of L-[35S]methionine into the acid-insoluble protein fraction of a cell. 0.1 microM of MMC was equivalent to 20 microM of MC with regard to the inhibitory effect on proliferation, and equivalent to 2 to 5 microM of MC after 24 hours' culture, and 10 to 20 microM after 48 hours' culture with regard to the inhibitory effect on protein synthesis of the blastocysts. The results showed that MMC was approximately 200 times more toxic than MC with regard to cell number proliferation, and 20 to 50 times so with regard to protein synthesis capability.

Animals↗

[Deoxyribonucleic acid and protein synthesis in delayed mouse blastocysts in vitro].

Developmental ability, DNA and protein synthesis were examined in mouse blastocysts which were delayed by proteinase inhibitors (nitrophenol-p-guanidino benzoate (NPGB) & soybean trypsin inhibitor. Cell division is depressed in the culture which contains proteinase inhibitors: Delayed blastocysts showed no increase in number after 5 days of culture. Mitotic figures were absent 120 hours after culture. On the other hand, most of the blastocysts showed a substantial increase in number in the first few days following the onset of delay. The DNA synthesis of nuclei in delayed blastocysts was measured by autoradiography incorporating [3H]-TdR. Although the incorporation rate was 54 +/- 8 cells/embryo (83 +/- 7%) on the first day of culture, it was decreased to 1/3 (36 +/- 5, 24 +/- 1%) on the 10th day of culture. Protein synthesis was measured with the incorporation rate of [35S]-methionine. The incorporation rate of delayed blastocysts declined sharply on the 5th day of culture (1.6 +/- 0.4 pmol/embryo/hr.) in contrast to that of normal implanted blastocysts (2.5 +/- 0.3 pmol/embryo/hr.). Qualitative changes in synthesized protein were estimated by SDS-PAGE. About 110 of the autoradiographic bands on 1-D gel were observed in the 4th day blastocysts, and actin is the major protein synthesized, located between 50,000 and 55,000 daltons. No differences in these bands were seen between normal and delayed blastocysts. However, two-dimensional gel showed that the qualitative patterns of protein synthesis of delayed embryos are significantly different from those of normal implanted blastocysts. In delayed blastocysts, trophoblast-specific spots varied versatile. Above all, protein synthesis of trophoblast in delay is selectively suppressed by proteinase inhibitors, but not ICM. Therefore, delayed blastocysts are not always metabolically dormant.

Animals↗

Early stages of N-2-fluorenylacetamide-induced hepatocarcinogenesis in male and female rats and effect of gonadectomy on liver neoplastic conversion and neoplastic development.

The early stages of N-2-fluorenylacetamide [(2-FAA) CAS: 59-96-3]-induced liver carcinogenesis in inbred F344 male and female rats and the effect of gonadectomy on liver carcinogen biotransformation capability and hepatocarcinogenesis were studied. Feeding of 2-FAA induced more altered hepatocellular foci characterized by exclusion of cellular iron and gamma-glutamyl-transferase activity in male rats than in female rats. At 6-22 weeks after cessation of carcinogen exposure, only males developed liver neoplastic nodules. Liver cytochrome P450, aryl hydrocarbon hydroxylase, and uridine-5'-diphosphateglucuronosyltransferase activity toward p-nitrophenol, but not phenolphthalein, were greater in males than in females. Gonadectomy of males reduced the activities that were greater than in females, whereas none was significantly altered by gonadectomy of females. Gonadectomy of male rats prior to 2-FAA feeding suppressed the induction of both altered foci and neoplastic nodules, whereas in female rats gonadectomy prior to 2-FAA feeding enhanced the induction of foci. Gonadectomy of males after administration of 2-FAA slightly enhanced the persistence of foci at 6 and 12 weeks after removal of carcinogen, but it did not affect their persistence by 22 weeks post carcinogen or the incidence of neoplastic nodules. However, only the males that were gonadectomized after receiving 2-FAA developed hepatocellular carcinomas at 22 weeks. Gonadectomy of females after receiving 2-FAA did not affect the persistence of foci, and no liver neoplasms developed. Thus gonadectomy of male rats, which reduced liver carcinogen metabolism, when done before carcinogen feeding had the greatest effect on hepatocarcinogenesis.

2-Acetylaminofluorene↗

[A case of highly atypical hyperplasia--difficult to differentiate from carcinoma].

We present a 51-year-old nulliparous woman with highly atypical hyperplasia of the uterus induced by the prolonged use of exogenous estrogen. The patient was given nearly 1,415 mg of estradiol dipropionate intramuscularly for over 23 years after operation for bilateral ovarian cysts. She complained of vaginal bleeding and diagnostic endometrial curettage revealed highly atypical hyperplasia which was difficult to differentiate from well differentiated adenocarcinoma. On hysterectomy, atypical tissues were limited to the upper part of the posterior wall of the uterus with no muscle invasion.

Adenocarcinoma↗

Inhibition of phasic but not tonic pituitary secretion by 2-hydroxyoestrone in the rat: evidence of action as an oestrogen antagonist.

Rats with 4-day oestrous cycles, implanted with intracardiac catheters, were injected with 2-hydroxyoestrone at noon on pro-oestrus and their plasma LH levels monitored at frequent intervals thereafter. A dose of 100 micrograms 2-hydroxyoestrone completely abolished the preovulatory LH rise in four out of ten animals tested, showing no effect in the six others. When an injection of 10 micrograms oestradiol 1 h before the 2-hydroxyoestrone administration was given all the rats showed an absence of the preovulatory LH surge, while it remained intact in the controls treated with oestradiol only. The principal metabolite of 2-hydroxyoestrone, 2-methoxyoestrone, exhibited no influence on the pituitary gonadotrophin release. Repeated injections of 100 micrograms doses of 2-hydroxyoestrone to long-term ovariectomized rats produced no change in plasma LH and prolactin levels. In animals primed with oestradiol benzoate, 2-hydroxyoestrone given 1-2 h after the priming dose blocked the phasic release of the pituitary hormones on the afternoon of the 2 subsequent days. The LH and prolactin surges in the primed animals, however, were not affected when the catechol oestrogen was injected 2 h before their appearance. These results indicate that in the cyclic rat exogenous 2-hydroxyoestrone inhibits the preovulatory LH surge when its administration is coincident with the preovulatory oestradiol rise. In the ovariectomized rat 2-hydroxyoestrone inhibits the oestrogen-dependent priming step but does not affect either the oestrogen-independent expression of the induced surges or the tonic secretion of these pituitary hormones. These results indicate a dissociation of central and peripheral activities in this oestradiol metabolite and suggest that this catechol oestrogen functions as an oestrogen antagonist in neuroendocrine events. Since catechol oestrogens can be formed in the brain these pharmacological responses may reflect physiological mechanisms.

Animals↗

Milk of northern fur seal: composition, especially carbohydrate and protein.

The milk of northern fur seal was analyzed with special interest in carbohydrate and protein. High solids (61%) and fat (45.6%) were characteristics of its gross composition. Fatty acid distribution showed that more than 22% of the fatty acids had carbon chains longer than 20 and that approximately 70% contained one or more double bonds. Analysis of free sugars showed no lactose but 123 mg/100 ml of myo-inositol. In carbohydrates bound to casein, .99% of sialic acid and .2% of glucosamine were determined. The amino acid composition of casein showed higher tryptophan, lysine, serine, and glycine than bovine casein, and lower arginine, proline, and leucine. In whey, arginine, threonine, and valine were higher, whereas lysine, aspartic acid, isoleucine, and leucine were lower than in bovine whey. Amino acid patterns in casein and whey were similar to those of cat milk. The appearance of casein micelles was similar to bovine casein micelles. The mean diameter, however, was larger (approximately 330 nm). Electrophoretic pattern of casein showed five major bands in addition to minor components. One of the minor components was a glycoprotein, probably kappa-casein-like protein. The major whey protein had a mobility similar to that of bovine beta-lactoglobulin. No alpha-lactalbumin-like protein was observed.

Amino Acids↗

Effect of short-term administration of N-(4-hydroxyphenyl)-all-trans-retinamide on chemically induced mammary tumors.

Mammary cancer was induced in 50-day-old Sprague-Dawley rats with either 25 mg/kg body weight of N-methyl-N-nitrosourea (MNU) or 10 mg/rat of dimethylbenz(a)anthracene (DMBA). The retinoid N-(4-hydroxyphenyl)-all-trans-retinamide (RAHA) was begun in the diet (2.0 mmol/kg diet) of MNU-induced rats at 21, 48, or 52 days of age, and at 21 or 60 days of age for DMBA-induced rats. RAHA was terminated 12-17 weeks postinduction, and the animals were sacrificed at 28 weeks postinduction. Significant inhibition of tumor incidence or multiplicity was found in only one group (rats fed RAHA beginning at 48 days of age). This was not considered sufficient evidence to conclude that short-term administration of RAHA altered mammary tumor development.

9,10-Dimethyl-1,2-benzanthracene↗

Decreased Fc receptor avidity and degradative function of monocytes from patients with systemic lupus erythematosus.

We studied the binding and degradation of stable, soluble heat aggregates of 125I-IgG (A-IgG) by monocytes from 30 patients with systemic lupus erythematosus (SLE) and 30 normals. Relative avidities (KE) for Fc receptor (FcR) binding of A-IgG and maximal binding of A-IgG by monocytes were determined from Scatchard plots of binding data obtained at 4 degrees C. Rates of degradation (Vmax) of A-IgG at 37 degrees C were calculated from Lineweaver-Burke plots of the Michaelis-Menton equation. KE were decreased in SLE monocytes (15.5 X 10(-9) L/M) as compared with normals (20.1 X 10(-9) L/M, p less than 0.005) and Vmax were decreased for SLE (0.89 ng/hr) as compared with normals (1.11 ng/hr, p less than 0.005). The maximal FcR binding by SLE monocytes was not statistically different in SLE patients and normals, but monocytes from SLE patients with active disease showed a lower maximal binding capacity for A-IgG (4.9 ng/10(5) cells) than normals (5.4 ng/10(5) cells, p less than 0.05). KE and Vmax in SLE were also lower for patients with active disease than for normal subjects. KE in patients whose anti-ssDNA binding was greater than 20% were lower than for those with DNA binding of less than 20% (p less than 0.005). These data suggest that patients with active SLE have diminished numbers of available FcR on their circulating monocytes, possibly due to interiorization of FcR during endocytosis of endogenous circulating immune complexes.

Adolescent↗

[Treatment of cervical cancer in the aged].

The incidence of elderly patients in cervical cancer cases at The Department of Obstetrics & Gynecology, Okayama Medical School has been increases to 7.8% during the recent 5 years (1975-1979), comparing to that of the past period 1.9% (1934-1962). According to the statistics of The Ministry of Health and Welfare, the mortality of cervical cancer has been decreased in all the ages except the elderly patients, in which the mortality showed no marked fluctuation or somewhat elevation. According to the report of The Ministry of Health and Welfare, among the 2,014,843 cases of mass screening examination of cervical cancer, the incidence of elderly patient over 70 year old was 0.3% only, and the suspiciously malignant rate was 4.58% in this group. This means that in the elderly group, the incidence of mass screening examination was very low, and the morbidity was relatively high. Reviewing the elderly patients of the recent period, we found that about half of the patients were belong to the Stage III or IV, and even in the early cancer cases, the general diseases were complicated so much, that the main therapy was radiation rather than operation. Reviewing the prognosis and the irradiation dose in the radiation group, we found that the prognosis of the cases who received 4,000 rads external irradiation were better than that of the cases who received 5,000 approximately 6,000 rads. However, sometimes the complication of irradiation were too severe to continue, resulting in an incomplete treatment and bad prognosis. Considering about this, we select the cases to operate according to the physical state but not the age as indicated up to date, and the result was that, even in the aged group, the prognosis of the operable cases were comparable to that of the young aged. As a conclusion, the following can be said: 1) As the mean age has been prolonging, the incidence of the elderly cancer cases will increase progressively, and this will influence the treatment result of cervical cancer. 2) In the aged patients, the prognosis were influenced by the stage rather than the age, therefore, consideration of the treatment according to the stage is important.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗