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Biomedical subjects

Y Shiina

Publications and source records attributed to Y Shiina.

At least 73 records · Page 4Linked to original sources

[Incidence of ovarian metastasis in patients with cancer of the uterine cervix].

With the recent advances in general surgery, the treatment of cervical cancer has been markedly improved to increase the five-year survival rate after radical hysterectomy. Therefore, the operative main attention has recently been directed towards conservative surgery for the function of pelvic organs as well as towards the therapeutic improvement of cervical cancer. The most crucial point for the preservation of the ovary at the time of the operation is whether the cancer metastasizes to the ovaries or not. In order to answer this question, the factors influencing metastasis, such as; the clinical stages, the cancer cell types and the cancer extension to the uterine corpus, were studied. A total of 679 cases of cervical cancer stage 0 and stage Ia were treated surgically with a simple hysterectomy preserving the ovaries in orthotopic position during the period of 1970 to 1984. Three hundred eleven patients of invasive carcinoma in stage Ib to stage IIIb were operated on by a radical hysterectomy with lymphadenectomy from 1977 to 1985. Histopathological examination was performed on specimens of the ovaries to determine the metastasis. In order to study the incidence of the ovarian metastasis in advanced cancer patients, the data of the autopsied 674 cases who died of cervical cancer without surgical therapy were obtained from Annual of the Pathological Autopsy Cases in Japan (1965-1978). Follow-up observations on the 679 patients of stage 0 or stage Ia after the operation revealed no recurrence in these cases. This indicates that almost no ovarian metastasis occurs in the patients of early cervical carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

The mechanism of end-organ resistance to 1 alpha,25-dihydroxycholecalciferol in the common marmoset.

The common marmoset, a New World monkey, requires a large amount of cholecalciferol (110 i.u./day per 100g body wt.) to maintain its normal growth. In a previous report, we demonstrated that the circulating levels of 1 alpha, 25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] in the marmosets are much higher than those in rhesus monkeys and humans, but the marmosets are not hypercalcaemic [Shinki, Shiina, Takahashi, Tanioka, Koizumi & Suda (1983) Biochem. Biophys. Res. Commun. 14, 452-457]. To compare the effect of the daily intake of cholecalciferol, two rhesus monkeys were given a large amount of cholecalciferol (900 i.u./day per 100g body wt). Their serum levels of calcium, 25-hydroxycholecalciferol and 24R,25-dihydroxycholecalciferol were markedly elevated, but the serum 1 alpha,25(OH)2D3 levels remained within a range similar to those in the rhesus monkeys fed the normal diet (intake of cholecalciferol 5 i.u./day per 100g body wt). Intestinal cytosols prepared from both monkeys contained similar 3.5 S macromolecules to which 1 alpha,25(OH)2D3 was bound specifically. However, the cytosols from the marmosets contained only one-sixth as many 1 alpha,25(OH)2D3 receptors as those from the rhesus monkeys. Furthermore, the activity of the 1 alpha,25(OH)2D3-receptor complex in binding to DNA-cellulose was very low in the marmosets. These results suggest that the marmoset possesses an end-organ resistance to 1 alpha,25(OH)2D3 and is a useful animal model for studying the mechanism of vitamin D-dependent rickets, type II.

Animals↗

Syntheses and differentiating action of vitamin D endoperoxides. Singlet oxygen adducts of vitamin D derivatives in human myeloid leukemia cells (HL-60).

Singlet oxygen adducts of various vitamin D derivatives, 6,19-dihydro-6,19-epidioxyvitamin D (vitamin D endoperoxides, 2 and 2'), were chemically synthesized, and their biological activity in inducing differentiation of a human myeloid leukemia cell line (HL-60 cells) was examined. The potency of the endoperoxides derived from vitamin D derivatives possessing the 1 alpha-hydroxyl group such as 1 alpha, 25-dihydroxyvitamin D3 endoperoxides (2b and 2b') was markedly (10(-2)) diminished relative to the respective parent vitamin D compounds. In contrast, 25-hydroxyvitamin D3 endoperoxides [25-(OH)D3 endoperoxides, 2a and 2a'] and their analogues fluorinated at the 24- or 26- and 27-positions were 2.5-10 times more potent than 25-hydroxyvitamin D3 (1a) in spite of the absence of the conjugated triene structure typical of vitamin D compounds. The potency of these vitamin D endoperoxides (2 and 2'), especially those lacking the 1 alpha-hydroxyl group, in inducing differentiation of HL-60 cells was not correlated with their activity in binding to the cytosol receptor for 1 alpha, 25-dihydroxyvitamin D3 (1b). The binding efficiency to the receptor was relatively lower than the differentiating activity. To examine the action of vitamin D endoperoxides, carbon analogues of 25-(OH)D3 endoperoxides, two C-6 epimers of 25-hydroxy-6,19-dihydro-6,19-ethanovitamin D3 (6 and 6'), were synthesized. The carbon analogues (6 and 6') had no potential to induce differentiation of HL-60 cells. These results suggest that vitamin D endoperoxides (2 and 2') express their biological activity probably after being converted to some other compounds.

Binding, Competitive↗

Mechanism of the differentiating action of 25-hydroxyvitamin D3 endoperoxides in human myeloid leukemia cells (HL-60).

The action of 25-hydroxy-6,19-dihydro-6,19-epidioxyvitamin D3 [25-(OH)D3 endoperoxides, 2a and 3a] in inducing differentiation of human myeloid leukemia cells (HL-60) was studied by using their radioactive derivatives (2a' and 3a'). When HL-60 cells were incubated with the labeled endoperoxides (2a' and 3a') in serum-free RPMI 1640 medium, no radioactivity was incorporated into either the cytosol or the chromatin fraction of the cells. When the radioactive endoperoxide (2a') was incubated in the culture medium for 3 days, with or without HL-60 cells, about 45% of the compound was similarly converted to 19,25-dihydroxy-6,19-dihydro-6,19-epoxyvitamin D3 (4a) and about 10% to 25-hydroxy-6,19-epoxyvitamin D3 (6a). These two new vitamin D derivatives were synthesized chemically and tested for their biological activities. Both compounds (4a and 6a) were about 2 times as active as 25-(OH)D3 endoperoxides (2a and 3a) and about 7 times as active as 25-hydroxyvitamin D3 (1a) in inducing differentiation of HL-60 cells. The differentiating activity of these compounds was well correlated with their activity in binding to the cytosol receptor for 1 alpha, 25-dihydroxyvitamin D3 in HL-60 cells. The in vitro bone-resorbing activity of 25-hydroxy-6,19-epoxyvitamin D3 (6a) and 25-(OH)D3 endoperoxide (2a) was higher than that of 25-hydroxyvitamin D3 (1a), indicating that the differentiating activity also paralleled the bone-resorbing activity in these vitamin D derivatives. These results suggest that 25-(OH)D3 endoperoxides (2a and 3a) induce differentiation of HL-60 cells and bone resorption after being converted to these two compounds.

Animals↗

[Immunohistochemical study of carcinoembryonic antigen of the tissue and cell levels in adenocarcinoma of the uterus].

UNLABELLED: Immunohistochemical staining was performed for carcinoembryonic antigen (CEA) in tissues taken from 41 cases of cervical and 67 cases of endometrial adenocarcinomas. Utilizing this method, smear specimens from 21 cases with cervical and 25 cases with endometrial adenocarcinomas were investigated at the cell level. THE RESULTS: 1) The investigation at the tissue level indicated that CEA staining was positive in 80% of cases of cervical adenocarcinoma. On the other hand, the positive rate was as low as 55% of the endometrial adenocarcinoma cases. It further declined to 35% when limited to pure adenocarcinoma without squamous elements. In addition, a difference was recognized between the cervical and endometrial groups in their localization. It was apparent that while even the cytoplasm in most of the cervical adenocarcinoma appeared to be markedly stained, such a tendency was observed and was weak in only a part of the cell membrane in the endometrial adenocarcinoma cases. 2) The studies with smear specimens indicated that while 57% (13/21) of the cervical adenocarcinoma cases were CEA positive, only 12% (3/25) were positive in endometrial adenocarcinoma cases. Therefore, a difference was recognized between the two at the cell level in their CEA staining characteristics. 3) Our observation revealed that CEA was more prominent in the poorly differentiated type than in the well differentiated one, in both cervical and endometrial adenocarcinoma. This seems to indicate a relationship between the histological differentiation and production of CEA. On the basis of the above findings, it was inferred that although both cervical and endometrial adenocarcinoma occur in the common Müllerian duct organ, they might have different biological characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

1 alpha, 25-Dihydroxyvitamin D3 directly induces fusion of alveolar macrophages by a mechanism involving RNA and protein synthesis, but not DNA synthesis.

The results of our present study indicate that 1 alpha, 25-dihydroxyvitamin D3[1 alpha, 25(OH)2D3] directly induces fusion of mouse alveolar macrophages without any participation of T-lymphocytes by a mechanism involving RNA and protein synthesis but not DNA synthesis. We have reported that 1 alpha, 25(OH)2D3 induces fusion of alveolar macrophages by a direct mechanism and by a spleen cell-mediated indirect mechanism [(1983) Proc. Natl. Acad. Sci. USA 80, 5583-5587]. Alveolar macrophages pretreated with or without anti-Thy 1.2 antibody and complement fused similarly when they were incubated with 1 alpha, 25(OH)2D3. The vitamin suppressed DNA synthesis, but it significantly enhanced RNA and protein synthesis. The 1 alpha, 25(OH)2D3-induced fusion was blocked by adding actinomycin D or cycloheximide, but not by hydroxyurea.

Animals↗

Activation and fusion induced by 1 alpha,25-dihydroxyvitamin D3 and their relation in alveolar macrophages.

1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] induces fusion of murine alveolar macrophages. This effect was observed in growth medium containing 5% human serum but not in the medium with 5% fetal bovine serum. Unlike 1 alpha,25-(OH)2D3, bacterial lipopolysaccharides (LPS) did not induce fusion of alveolar macrophages. However, both 1 alpha,25-(OH)2D3 and LPS activated alveolar macrophages, as measured by glucose consumption, increase in Fc receptors, and induction of cytotoxicity. The number of Fc receptors on the surface of multinucleated giant cells induced by 1 alpha,25-(OH)2D3 was much smaller than that on the surface of mononuclear macrophages treated with the hormone. These results indicate that 1 alpha,25-(OH)2D3 induces both fusion and activation of alveolar macrophages, whereas LPS elicits activation only.

Animals↗

Agonadism with positive H-Y antigen.

A 30-year-old phenotypic female was investigated because of absence of the vagina. Her serum gonadotropins were elevated while testosterone was in the normal range for females. Stimulation with human chorionic gonadotropin (hCG) gave no response of testosterone. No uterus, Fallopian tubes, Wolffian derivatives, or the gonads were found at laparotomy. Chromosome analysis showed a 46,XY karyotype. The expression of the H-Y antigen was positive. The results suggest that testicular degeneration in agonadism is not caused by a defective H-Y antigen.

Adult↗

Malignant potential of homozygous and heterozygous complete moles.

There are two main mechanisms of origin for complete hydatidiform mole: (a) fertilization of an empty egg by a haploid sperm followed by duplication (monospermic mole); and (b) fertilization of such an egg by two haploid spermatozoa (dispermic mole). The former is inevitably homozygous (homozygous mole), whereas the latter may be heterozygous for a given genetic marker (heterozygous mole). A recent cytogenetic study showed that three cases of choriocarcinoma were undoubtedly heterozygous, which prompted us to compare the incidence of postmolar sequelae between patients with homozygous moles and those with heterozygous moles. Making use of chromosomal heteromorphisms and human lymphocyte antigen and phosphoglucuromutase 1 polymorphisms, we established the androgenetic origin of a complete mole in 49 of 56 cases. Homozygosity was confirmed in 21 moles, and heterozygosity was confirmed in five. Three of five patients with heterozygous moles developed postmolar trophoblastic disease, whereas none of the 21 patients with homozygous moles suffered postmolar trophoblastic disease except one who showed signs of degenerating residual trophoblasts. Consistent with this observation is the fact that all of the four destructive moles studied here were of dispermic origin. Thus, heterozygous moles seem to have a higher malignant potential than do homozygous moles.

Chromosome Aberrations↗

[The age incidence of spontaneous abortion].

A series of studies on the age incidence of spontaneous abortion was conducted. The results of the studies is summarized as follows: A total of 16,179 deliveries accompanied by 1,537 cases of spontaneous abortion in 5 hospitals was investigated. The ratio (spontaneous abortion/deliveries) was 0.095 (1,537/16,179) in all age groups, 0.197 (15/76) in the under 20 years age group, 0.089 (215/2,422) in 20-24 years age group, 0.083 (705/8,478) in 25-29 years age group, 0.090 (404/4,496) in 30-34 years age group, 0.232 (149/641) in 35-39 years age group, 0.650 (39/60) in 40-44 years age group and 1.169 (7/6) in the over 45 years age group. The ratio in the under 20 years age group was higher than the ratio in 20-34 years age group (P less than 0.05). The ratio in the over 35 years age group was higher than the ratio in 20-24 years age group (P less than 0.001). This results indicated that spontaneous abortions depended on the maternal age. Deliveries in 20-34 years old occupied 95.2% of all 16,179 deliveries and the incidence of spontaneous abortions in 20-34 age group was stable. It is suggested, that the spontaneous abortion is natural selection in the mother's body and nature protects the older mother's body from deliveries and child-rearing.

Abortion, Spontaneous↗

1 alpha,25-dihydroxyvitamin D3 induces differentiation of human promyelocytic leukemia cells (HL-60) into monocyte-macrophages, but not into granulocytes.

The differentiating action of 1 alpha,25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3] in hematopoietic cells was examined in 3 tumor cell lines. 1 alpha,25-(OH)2D3 induced common differentiation-associated properties in macrophages and granulocytes similarly in mouse myeloblastic leukemia cells (M1), human promyelocytic leukemia cells (HL-60) and human histiocytic monoblast-like lymphoma cells (U937). 1 alpha,25(OH)2D3 markedly induced alpha-naphthyl acetate esterase activity, a typical marker of monocyte-macrophages, in M1 and HL-60 cells. In HL-60 and U937 cells, the vitamin also induced binding of the monoclonal antibody MAS 072, specific for monocyte-macrophages, but not of MAS 067, specific for granulocytes. These results clearly indicate that 1 alpha, 25(OH)2D3 induces differentiation of all cell lines examined preferentially along the monocyte-macrophage pathway.

Calcitriol↗

Extremely high circulating levels of 1 alpha,25-dihydroxyvitamin D3 in the marmoset, a new world monkey.

Compared to most mammals, the marmoset, a new world monkey, requires particularly large amounts of vitamin D to maintain normal growth. We compared serum concentrations of vitamin D metabolites in marmosets with rhesus monkeys and humans. The circulating levels of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] in marmosets were 4 to 10 times higher than those in rhesus monkeys and humans. But none of the marmosets exhibited hypercalcemia. In two marmosets which had suffered bone fractures, the 1 alpha,25(OH)2D3 levels were particularly elevated. These results suggest that the marmoset has an end-organ resistance to 1 alpha,25(OH)2D3.

24,25-Dihydroxyvitamin D 3↗

Biological activity of 24,24-difluoro-1 alpha, 25-dihydroxyvitamin D3 and 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone in inducing differentiation of human myeloid leukemia cells.

Vitamin D compounds added to the culture medium induce differentiation of human myeloid leukemia cells (HL-60 cells) by binding to a specific cytosol receptor protein. This system provides a biologically relevant and technically simple assay to examine the relationship between molecular structure and biological activity of vitamin D compounds. Using this culture system, the biological activity of 24,24-F2-1 alpha,25(OH)2D3 and 1 alpha,25(OH)2D3-26,23-lactone was assayed. 24,24-F2-1 alpha,25(OH)2D3 was four to seven times more potent than 1 alpha,25(OH)2D3 in inducing phagocytosis and C3 rosette formation of HL-60 cells, though both compounds bound equally well to the cytosol receptor, suggesting that the defuorination at the 24-carbon position may stimulate membrane permeability of the compound. 1 alpha,25(OH)2D3-26,23-lactone, on the other hand, was only 1/200th as active as 1 alpha,25(OH)2D3. The binding affinity of the lactone for the cytosol receptor was identical with that of 1 alpha (OH)D3, suggesting that the lactone formation between the 26 and 23 positions masks the function of the 25-hydroxyl group. The binding affinity of vitamin D3 derivatives to the specific cytosol receptor of HL-60 cells was well correlated with that of intestinal cytosol protein specifically bound to 1 alpha,25(OH)2D3.

Calcitriol↗

1 alpha,25-dihydroxyvitamin D3 promotes fusion of mouse alveolar macrophages both by a direct mechanism and by a spleen cell-mediated indirect mechanism.

Extensive fusion was induced in mouse alveolar macrophages by treatment with conditioned media obtained from spleen cell cultures treated with 15 micrograms of phytohemagglutinin or concanavalin A per ml or with 12 nM 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3]. The fusion rate was 80-90% on day 3. In addition, 1 alpha,25(OH)2D3 added directly to alveolar macrophages induced fusion of about 35% of the cells on day 3, whereas direct addition of phytohemagglutinin and concanavalin A did not enhance fusion at all. When conditioned media from spleen cell or T cell cultures treated with 12 nM 1 alpha,25(OH)2D3 were applied to a Sephadex G-100 column, a fusion factor (Mr 37,000-70,000) could be separated from 1 alpha,25(OH)2D3. 1 alpha,25(OH)2D3 induced fusion at 0.012-120 nM in a dose-dependent manner both by direct action and by spleen cell-mediated indirect action, but the fusion rate was always much greater in the latter than in the former at each concentration of the vitamin. Of the vitamin D3 derivatives tested, 1 alpha,25(OH)2D3 was the most potent, followed successively by 1 alpha,24R,25-trihydroxyvitamin D3, 1 alpha-hydroxyvitamin D3, 25-hydroxyvitamin D3, and 24R,25-dihydroxyvitamin D3. These results clearly indicate that 1 alpha,25(OH)2D3 induces fusion of mouse alveolar macrophages by both a direct and an indirect mechanism, the latter mediated by spleen cells, probably by T cells.

Animals↗