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Biomedical subjects

Y Mori

Publications and source records attributed to Y Mori.

At least 19 recordsLinked to original sources

Manipulation of thromboxane synthesis by novel 26,27-dialkyl analogues of 1 alpha,25-dihydroxyvitamin D3 in human promyelocytic leukemia (HL-60) cells.

Using new steroidal side-chain-lengthened 26,27-dialkyl analogues of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3], we manipulated the synthesis of thromboxane and thromboxane-producing enzymes, cyclo-oxygenase and thromboxane synthase, in human promyelocytic leukemia (HL-60) cells in serum-free culture. The order of potency of the analogues for stimulating thromboxane B2 synthetic activity from arachidonic acid (reflecting combined cyclo-oxygenase activity and thromboxane synthase activity) and from prostaglandin H2 (thromboxane synthase activity only) as well as for cyclo-oxygenase induction was 1 alpha,25-(OH)2D3 > or = 1 alpha,25-(OH)2-26,27-CH3)2D3 > 1 alpha,25-(OH)2-26,27-(C2H5)2D3 >> 1 alpha,25-(OH)2-26,27-(C3H7)2D3. These results suggest that there are functional and structural limits to the chain length of C-26 and C-27 dialkyl groups flanking the C-25-OH group in the 1 alpha,25-(OH)2D3 molecule for expressing thromboxane synthetic activity in HL-60 cells. Removal of the C-1 alpha-OH group from 1 alpha,25-(OH)2D3 led to markedly decreased thromboxane synthetic activity in HL-60 cells. These structure-activity relationships indicate that both the C-25-OH and C-1 alpha-OH groups in the 1 alpha,25-(OH)2D3 molecule are essential for expressing thromboxane synthesis in HL-60 cells. Also, the rank order for stimulating thromboxane synthesis correlated well with the binding affinity of these dialkyl analogues for the 1 alpha,25-(OH)2D3 receptor of HL-60 cells, suggesting a 1 alpha,25-(OH)2D3 receptor-mediated induction mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol

Establishment and characterization of human uterine leiomyosarcoma heterotransplanted into nude mice.

Human uterine leiomyosarcoma is a rare gynecological malignancy with a generally poor prognosis. We have established a human uterine leiomyosarcoma tumor line in nude mice, designated UTS-1, and describe the characteristics of this tumor. The UTS-1 tumor doubled in 12.1 days and retained the histological characteristics of leiomyosarcoma, even after 14 serial generations. Ultrastructurally, the tumor is characterized by nuclear pleomorphism typical of smooth muscle, intracytoplasmic filaments with dense bodies, a relative paucity of micropinocytotic vesicles, and an incomplete external lamina. Immunohistochemically, the UTS-1 cells reacted with antibodies against vimentin, desmin, smooth-muscle actin and myosin, but not with antibodies against keratin, CEA and S-100 protein. Serum levels of AFP, CA125, CEA and SCC ranged within normal limits in tumor-bearing mice. The serum level of immunosuppressive acidic protein correlated well with an activity of the tumor. Estrogen and progesterone receptors were not detected in the tumor. Chromosomal analysis showed a human karyotype with some marker chromosomes and a modal number of 85 chromosomes. The UTS-1 tumor should prove a useful model to explore the biological characteristics and treatment of human uterine leiomyosarcoma.

Animals

Molecular cloning and characterization of a novel calcium channel from rabbit brain.

The complete amino acid sequence of a novel calcium channel (designated BII) from rabbit brain has been deduced by cloning and sequencing the cDNA. The BII calcium channel is structurally more closely related to the BI calcium channel than to the cardiac and skeletal muscle L-type calcium channels. Blot hybridization analysis of RNA from different tissues and from different regions of the brain shows that the BII calcium channel is distributed predominantly in the brain, being abundant in the cerebral cortex, hippocampus and corpus striatum.

Amino Acid Sequence

Effect of magnesium hydroxide on methylazoxymethanol acetate-induced epithelial proliferation in the large bowels of rats.

The effect of magnesium hydroxide on the epithelial proliferation of the large bowel was examined using rats given methylazoxymethanol (MAM) acetate. Dietary administration of magnesium hydroxide at 250, 500, 1000 or 2000 ppm. for 1, 3 or 5 weeks did not influence the cell cycle of the cryptal cells of the large bowel. However, the exposure to magnesium hydroxide under these conditions lowered the bromodeoxyuridine labeling index of the cells of the large bowel of the rats which had been initiated by MAM acetate (25 mg/kg, 3 times). The decrease in labeling index was more apparent in the proximal segment than in the distal segment. Such an inhibitory effect on the DNA synthesis of the epithelial cells by magnesium hydroxide may be related to the suppressive action of the trace element on the carcinogen-induced large bowel carcinogenesis.

Animals

[Electrophysiological studies on the hypothalamic GnRH pulse generator].

Gonadal function in mammals depends on gonadotropins secreted from the pituitary gland in a pulsatile manner. This pulsatility is governed by the periodic activation of the hypothalamic GnRH pulse generator. By means of multiple unit activity (MUA) recording techniques, characteristics increases in the neuronal activity, each of which is associated with the initiation of pulsatile LH secretion, have been recorded in the medial basal hypothalamus of the monkey, rat and goat. An unambiguous unitary relationship between the increased electrical activity (volley) and the LH pulse under a variety of physiological and experimental conditions indicates that the MUA volleys represent the electrical activity of the GnRH pulse generator. Hypothalamic MUA recordings provide direct access to the central component of the neuroendocrine control system which governs reproductive function.

Animals

Effects of interleukin-6 on the metabolism of connective tissue components in rheumatoid synovial fibroblasts.

OBJECTIVE: High levels of interleukin-6 (IL-6) have been found in the synovial fluid of patients with rheumatoid arthritis (RA). We undertook the present study to investigate the role of IL-6 in this disease. METHODS: We examined the effects of IL-6, in comparison with IL-1, on the biosynthesis of extracellular matrix macromolecules and of matrix-degrading proteinases in rheumatoid synovial fibroblasts. RESULTS: In rheumatoid synovial fibroblasts, IL-6 by itself enhanced the production of plasminogen activator, its inhibitor, and tissue inhibitor of metalloproteinases, whereas it did not modulate the biosynthesis of precursor of matrix metalloproteinase 1 (proMMP-1) (tissue collagenase), proMMP-3 (stromelysin), or connective tissue components. However, IL-1-induced production of proMMP-1 and proMMP-3 was preferentially augmented by IL-6. CONCLUSION: These results suggest that in RA, IL-6 may participate along with IL-1 in fine tuning of the catabolism of connective tissue components, by modulating the balance between connective tissue-degrading enzymes and their inhibitors.

Arthritis, Rheumatoid

Induction of external abnormalities in offspring of male mice irradiated with 252Cf neutron.

To assess the genetic effects of fission neutron, the induction of external malformations was studied in F1 fetuses after F0 male mice were irradiated. Male mice of the ICR:MCH strain were irradiated with 252Cf neutron at doses of 0.238, 0.475, 0.95 and 1.9 Gy. They were mated with non-irradiated female mice at 71-120 days after the irradiation. Pregnant females were autopsied on day 18 of gestation and their fetuses were examined for deaths and external abnormalities. No increases of pre- and post-implantation losses were noted at any dose. External abnormalities were observed at rates of 1.40% in the 0.238 Gy, 2.23% in the 0.475 Gy, 3.36% in the 0.95 Gy and 3.26% in the 1.9 Gy groups; the rate in the control group was 1.65%. The dose-response curve was linear up to 0.95 Gy, and then flattened out; the induction rate of external abnormalities was 2.7 x 10(-4)/gamete/cGy based on the linear regression. These results indicated that fission neutron effectively induces external abnormalities in F1 fetuses after spermatogonial irradiation.

Abnormalities, Radiation-Induced

User and manufacturer's requirements for IMAC standardization in Japan.

Many radiologists and radiological technologists understand that Picture Archiving and Communication Systems (PACS) are useful not only for image management but also for improving the quality of patient care. However, such systems have not yet been widely installed in hospitals. In order to determine why radiologists have not installed a PACS in their hospitals, we carried out a written survey of 400 Japanese hospitals asking them to describe the current image management activities, the problems inherent in PACS and the problems related to standardization. 216 hospitals responded, and the following suggestions were compiled concerning possible improvements to PACS. (1) PACS benefit needs to be improved with respect to patient care. (2) The cost of PACS should be reduced. (3) The system should be easier to operate and should save time. (4) Standardization is needed to allow simplified, cost-effective networking. We also carried out a written survey of 25 PACS and related equipment manufacturers asking them to describe the opinions inherent in current PACs and the problems related to standardization. Ten manufacturers responded, and the various suggestions were compiled concerning possible improvements to the PAC system.

Japan

Complement component C3a or C3a desArg as a new marker for estimation of local vital reactions in incised skin wounds.

The anaphylatoxin C3a or its desArg form (C3a/desArg) generated during complement activation could be detected in the vicinity of incised skin wounds of guinea pigs using immunoblotting methods. The C3a/desArg peptides were detectable immediately after injury in local sites up to 3 mm from the wound edge. In subsequent determinations of up to at least 3-day-old antemortem wounds, the maximum concentration of these peptides was largely localized up to 6 mm from the wound edge at 2 h after injury. In postmortem wounds, however, these peptides were undetectable. When they were released in antemortem wounded tissues they could be detected up to 1 day at 22 degrees C after death. These results suggest that the detection of C3a/desArg in wounds using immunoblotting methods can be useful for distinguishing ante- from postmortem wounds.

Animals

Effects of vitamin D-binding proteins on HL-60 cell differentiation induced by 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D.

Monocytic differentiation-inducing activity of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 [26,27-F6-1 alpha,25-(OH)2D3] was re-evaluated in human promyelocytic leukemia (HL-60) cells in serum-supplemented or serum-free culture. The order of in vitro potency for reducing nitroblue tetrazolium (NBT) was 26,27-F6-1 alpha,25-(OH)2D3 greater than 1 alpha, 25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] = 26,26,26,27,27,27-F6-1 alpha,23(S), 25-trihydroxyvitamin D3 [26,27-F6-1 alpha,23(S), 25-(OH)3D3] under serum-supplemented culture conditions, whereas the order was 1 alpha, 25-(OH)2D3 = 26,27-F6-1 alpha,25-(OH)2D3 greater than 26,27-F6-1 alpha,23(S), 25-(OH)3D3 under serum-free culture conditions. This rank order for differentiation-inducing activity under serum-free culture conditions correlated well with the binding affinity of these analogs for vitamin D3 receptor of HL-60 cells. The order of relative % binding affinity for the vitamin D-binding protein in fetal calf serum was 1 alpha,25-(OH)2D3 (100%) much greater than 26,27-F6-1 alpha,25-(OH)2D3 (5.1%) greater than 26,27-F6-1 alpha,23(S), 25-(OH)3D3 (less than 1%). These results suggest that serum vitamin D-binding proteins apparently modulate monocytic differentiation of HL-60 cells by 26,27-F6-1 alpha,25-(OH)2D3 under serum-supplemented culture conditions.

Binding, Competitive

Chemotactic factor in the pregnant rabbit uterine cervix.

OBJECTIVE: Neutrophil accumulation is one of the characteristic changes observed in uterine cervical stroma at term pregnancy, but chemotactic activity in the tissue is obscure. Our study examined the existence and production of chemotactic factor in the rabbit uterine cervix. STUDY DESIGN: Uterine cervical explants of rabbits at term pregnancy and nonpregnant rabbits were cultured with and without interleukin-1 alpha. Rat neutrophilic chemotaxis in culture media was evaluated with a Boyden chamber. RESULTS: Tissue extract from the pregnant rabbit uterine cervix at term pregnancy contained more chemoattractive activity than the nonpregnant cervix. Production of chemoattractant from cultured rabbit cervical explants at term pregnancy was also higher than that from nonpregnant explants. The addition of interleukin-1 alpha to the culture system promoted its production. This chemoattractant was characterized as a true chemotactic factor and heat-stable and trypsin-sensitive protein with an apparent relative molecular mass of 16,200. So far, these properties are very similar to those of the interleukin-8 family. Rabbit uterine cervical fibroblast is characterized as a chemotactic factor-producing cell in the rabbit uterine cervix. CONCLUSION: These results indicate that interleukin-8-like chemotactic factor participates in the cervical ripening at term pregnancy and that the production of this factor is controlled effectively by interleukin-1.

Animals

Human chorionic gonadotropin induces c-myc mRNA expression via TSH receptor in FRTL-5 rat thyroid cells.

To elucidate the gene regulation of the thyroid-cell growth-promoting activity by human chorionic gonadotropin (hCG), we investigated the effect of hCG on c-myc proto-oncogene expression in cultured rat FRTL-5 cells by the Northern blot method. hCG induced c-myc mRNA expression, which peaked at 60-120 min. A dose-dependent increase in c-myc mRNA levels was also ascertained. In the presence of crude immunoglobulin G (IgG) from 2 patients with primary hypothyroidism who had blocking type TSH-receptor antibody, c-myc mRNA expressions induced by hCG were decreased to 82% and 62%, compared with that in the presence of normal IgG. The present results suggest that the expression of c-myc mRNA is a part of the molecular mechanism through which hCG regulates the proliferation of thyroid cells, and that hCG-induced c-myc mRNA expression is presumed to be mediated in part by TSH receptors.

Adenoma

Cell kinetic analysis of the mucosal epithelium and assay of ornithine decarboxylase activity during the process of 1-hydroxyanthraquinone-induced large bowel carcinogenesis in rats.

Cell kinetics and activity of ornithine decarboxylase (ODC) were studied during the process of 1-hydroxyanthraquinone (1-HA)-induced intestinal carcinogenesis in rats. Starting at 6 weeks of age, a total of 37 male ACI/N rats were divided into two groups and treated as follows: group I (18 rats) received diet containing 1% 1-HA for 12 months; group II (19 rats) was given the basal diet alone. Sub-groups of 5-7 rats were sequentially killed at 4, 8 and 12 months for evaluation of the length, cell numbers and 5-bromo-2'-deoxyuridine (BrDU) labeling indices of large bowel crypts together with ODC activity. All kinetic and ODC data indicated increased DNA synthesis and proliferation at all time points. Morphological observation of the intestines also revealed melanosis, crypt abscesses and erosion, becoming more pronounced with length of exposure to the anthraquinone. The data thus suggest that cell proliferation in the crypts of the cecum or colon is important for 1-HA-induced intestinal carcinogenesis.

Animals

Tumor necrosis factor-alpha stimulates the biosynthesis of matrix metalloproteinases and plasminogen activator in cultured human chorionic cells.

To investigate the role of tumor necrosis factor-alpha (TNF alpha) in advanced collagenolysis and degradation of connective tissue components in preterm parturition, the effects of human recombinant TNF alpha (hrTNF alpha) on the production of matrix metalloproteinase 1 (MMP-1)/tissue collagenase, MMP-3/stromelysin, tissue inhibitor of metalloproteinases (TIMP), urokinase type-plasminogen activator (uPa) and prostaglandin (PG) E2 in human chorionic cells were examined in vitro. Human chorionic cells, but not amniotic cells, were found to respond to macrophage-conditioned medium (contains mainly interleukin 1) to produce MMP-1 and MMP-3. This indicated that the chorionic cell is one of the MMP-producing cells of fetal membranes. When confluent chorionic cells were treated with hrTNF alpha, the production of MMP-1 and MMP-3 as well as of uPa and PGE2 was greatly increased in a dose-dependent manner. In contrast, the production of TIMP was suppressed by hrTNF alpha. These results suggested that TNF alpha may participate in destruction of collagen and other connective tissue matrix components of fetal membranes and in promotion of uterine contractility in preterm parturition with intraamniotic infection.

Amnion

Plasma calcitonin gene-related peptide levels in patients with various hypertensive diseases.

OBJECTIVE: To clarify the pathophysiological role of calcitonin gene-related peptide (CGRP) in hypertensive diseases. METHOD: Using a sensitive radioimmunoassay established in our laboratory, plasma CGRP levels were evaluated in control subjects and in patients with essential hypertension, phaeochromocytoma or primary aldosteronism. RESULTS: The CGRP levels in the three hypertensive groups were significantly higher than in normal controls, but no statistically significant difference was observed among CGRP levels in the three hypertensive groups. In the three cases of secondary hypertensives (one patient with phaeochromocytoma and two with primary aldosteronism), a significant decrease in plasma CGRP levels and a marked reduction in blood pressure were observed after adrenalectomy. CONCLUSION: These results suggest that increased plasma CGRP levels in hypertensive patients could be a compensatory reaction to elevated blood pressure.

Adrenal Gland Neoplasms