Biomedical subjects

M Maeda

Publications and source records attributed to M Maeda.

At least 379 records · Page 21Linked to original sources

PubMed1998

Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by citrus auraptene in rats.

The modifying effects of citrus auraptene given during the initiation and post-initiation phases of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. At 6 weeks of age, animals were divided into experimental and control groups, and fed the diets containing 100 ppm or 500 ppm auraptene. At 7 weeks of age, all animals except those treated with auraptene alone and control groups were given 4-NQO (20 ppm) in the drinking water for 8 weeks to induce tongue carcinoma. Starting 7 days before the 4-NQO exposure, groups of animals were fed the diets containing auraptene (100 and 500 ppm) for 10 weeks and then switched to the basal diet. Starting 1 week after the cessation of 4-NQO exposure, the groups given 4-NQO and a basal diet were switched to the diets mixed with auraptene (100 and 500 ppm), and maintained on these diets for 22 weeks. The other groups consisted of rats fed auraptene alone (500 ppm) or untreated rats. All rats were necropsied at the termination of the study (week 32). The incidences of tongue lesions (neoplasms and preneoplasms), polyamine levels in the tongue tissue and cell proliferation activity estimated by 5-bromodeoxyuridine (BrdU)-labelling index were compared among the groups. In addition, the activities of gluthathione S-transferase (GST) and quinone reductase (QR) in liver and tongue of rats gavaged various doses of auraptene (0, 200, 400 and 800 mg/kg body wt) for 5 days were assayed. Feeding of auraptene at both doses during the initiation phase caused a significant reduction in the frequency of tongue carcinoma (100 ppm auraptene, 91% reduction, P < 0.001; 500 ppm auraptene, 63% reduction, P < 0.05). When fed auraptene after 4-NQO exposure, the frequency of tongue carcinoma was also decreased (100 ppm auraptene, 100% reduction, P < 0.001; 500 ppm auraptene, 74% reduction, P < 0.01). The incidences of tongue severe dysplasia in these groups were significantly smaller than those in carcinogen controls (P < 0.05). There were no pathological alterations in rats treated with 500 ppm auraptene alone or those in an untreated control group. Dietary administration of auraptene significantly decreased BrdU-labelling index and polyamine concentrations in the oral mucosa (P < 0.05). In addition, auraptene administration significantly increased the activities of GST and QR in the liver and tongue. Although dose-dependent effect was not found, citrus auraptene is effective in inhibiting the development of oral neoplasms induced by 4-NQO. Thus, suppression by the initiation-feeding of auraptene might relate to elevation in the phase II enzymes GST and QR of the liver and tongue, and inhibition occurring during the post-initiation might be related to suppression of increased cell proliferation caused by 4-NQO in the oral mucosa.

4-Nitroquinoline-1-oxide↗

PubMed1998

Peripheral blood mononuclear cells stimulate progesterone production by luteal cells derived from pregnant and non-pregnant women: possible involvement of interleukin-4 and interleukin-10 in corpus luteum function and differentiation.

Human luteal cells have been reported to express human leukocyte antigen-DR and lymphocyte functional antigen-3 on the cell surface, suggesting physiological interaction between luteal cells and T-lymphocytes through the menstrual cycle into early pregnancy. To elucidate the role of peripheral lymphocytes on corpus luteum differentiation, the effect of peripheral blood mononuclear cells (PBMC) on steroidogenesis by luteal cells was investigated. The production of Th-2 cytokines such as interleukin (IL)-4 and IL-10 by the co-cultured cells was also examined, and the effects of these cytokines on progesterone production by luteal cells were investigated. Corpora lutea were obtained from eight non-pregnant women in the luteal phase and five women in early pregnancy for luteal cell culture. PBMC were isolated from unrelated women in the follicular phase, secretory phase, and early pregnancy. After coculture with allogenic PBMC for 48 h, progesterone production was significantly enhanced by PBMC from the secretory phase and early pregnancy in the non-pregnant luteal cell culture. In the pregnant luteal cell culture, a significant increase in progesterone production was also observed by the co-culture with PBMC from women in early pregnancy, showing that PBMC have a luteotrophic effect. The stimulatory effects of PBMC were also observed in co-culture conditions which prevented direct cell-to-cell interaction with luteal cells, showing the minor influence of mixed lymphocyte reaction. By co-culture with PBMC, the production of IL-10, but not IL-4, was significantly augmented in luteal cell culture derived from non-pregnant women, whereas the production of both IL-4 and IL-10 was significantly enhanced in the luteal cell culture derived from pregnant women. Moreover, IL-4 and IL-10 promoted progesterone production by cultured luteal cells, especially in the luteal cell culture derived from corpora lutea of early pregnancy. These findings indicate that PBMC stimulate progesterone production by luteal cells and suggest the involvement of PBMC in corpus luteum function and differentiation probably via the Th-2-type lymphocytes.

Adult↗

PubMed1998

Administration of thymocytes derived from non-pregnant mice induces an endometrial receptive stage and leukaemia inhibitory factor expression in the uterus.

We have previously reported that intravenous administration of splenocytes prepared from mice in the early stages of pregnancy promoted embryo implantation in pseudopregnant mice. Since a T-lymphocyte-rich, but not a monocyte-rich preparation from splenocytes enhanced embryo implantation, similar effects of thymocytes from non-pregnant mice on implantation were examined in this study. Thymocytes were prepared from immature 21 day old ICR female mice and the supernatant of a thymocyte suspension (Th-sup) was used as the control. Thymocytes or Th-sup were injected into the caudal vein of recipient mice on pseudopregnancy day 2, and blastocysts were transferred into the endometrial lumen. The implantation rates per recipient were significantly higher in the thymocyte-treated group. ICR mice were then oophorectomized on pseudopregnancy day 3. After 3-day progesterone supplementation, blastocysts were transferred with intravenous injection of thymocytes or Th-sup. Under progesterone supplementation, successful implantations were observed in the thymocyte-treated group, but not in the Th-sup-treated group. Reverse transcriptase-polymerase chain reaction analysis revealed that mRNA expression of leukaemia inhibitory factor in the uterus was induced by thymocyte administration, but not by Th-sup. Thymocytes were divided into two populations, CD4(+/-)CD8(-) group and CD4(-)CD8(+/-) group, by separation columns. On pseudopregnancy day 2, the separated thymocytes in each group or their supernatant were injected into the endometrial stroma of the recipient mice, and blastocysts were transferred into the endometrial lumen. The administration of CD4(+/-) CD8(-) lymphocytes significantly promoted implantation rates, but no effect was observed in the CD4(-) CD8(+/-) group. These findings showed that thymocytes, especially CD4-positive lymphocytes, facilitate embryo implantation, probably by regulating endometrial differentiation.

Animals↗

PubMed1998

A monoclonal antibody, HCL-2, raised against human luteal cells reacts with apolipoprotein-B and detects the uptake of low density lipoprotein by luteinizing granulosa cells.

A monoclonal antibody, HCL-2, was raised by immunizing mice against human luteal cells. HCL-2 reacted with luteal cells and villous trophoblasts. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis profile of immunopurified antigens from corpus luteum, chorionic villi, and placenta showed the same main protein band, the molecular mass of which is >200 kDa. The sequence of a portion of the N-terminal region of the antigenic protein purified from placenta was identical to that of apolipoprotein-B. The antigen purified from human serum and low density lipoprotein (LDL) using HCL-2 showed the same protein band as that from corpus luteum. Furthermore, the amino acid sequence (20 amino acids) of the protein purified from serum was also identical to that of apolipoprotein-B. Thus, we concluded that HCL-2 antigen is apolipoprotein-B. Human luteinizing granulosa cells isolated from the patients undergoing in-vitro fertilization treatment were cultured in the medium containing lipoprotein-deficient serum with or without supplementation of LDL. Using HCL-2, apolipoprotein-B was immunocytochemically detected on granulosa cells only in the presence of LDL. These findings showed that the uptake of LDL by granulosa cells was detected by immunocytochemical staining of apolipoprotein-B, indicating that HCL-2 is useful for analysing dynamic utilization of LDL by ovarian cells.

Adult↗

PubMed1998

Stage-specific uptake of apolipoprotein-B in ovarian follicles and corpora lutea of the menstrual cycle and early pregnancy.

A monoclonal antibody (mAb), HCL-2, was raised which reacts with apolipoprotein-B, and it was shown by immunohistology that HCL-2 can be used to analyse the uptake of apolipoprotein-B by steroid-producing cells in vivo. In this study we have investigated the dynamic utilization of low density lipoprotein (LDL) in human ovary by immunohistological localization of apolipoprotein-B and LDL receptors using HCL-2 and anti-LDL receptor mAb. In antral follicles, including those of <1 mm in diameter, both apolipoprotein-B and LDL receptors were localized to theca interna cells, but not granulosa cells. In pre-ovulatory follicles, the LDL receptor was expressed on all granulosa cells. Apolipoprotein-B was also detected in granulosa cells located at the basal layer, suggesting that they utilize LDL through the basal lamina before ovulation. In mid-luteal phase, large luteal cells seemed to stain more intensely for apolipoprotein-B than did small luteal cells, suggesting that large lutal cells are the main sites of LDL utilization. In regressing corpora lutea, the expression of LDL receptor was weak, and apolipoprotein-B was rarely detected. In corpora lutea of early pregnancy, LDL receptor and apolipoprotein-B were localized to both luteal cells. These findings show the precise dynamic changes in LDL uptake by human ovarian cells during their differentiation in vivo.

Adolescent↗

PubMed1998

Membrane-bound carboxypeptidase-M is expressed on human ovarian follicles and corpora lutea of menstrual cycle and early pregnancy.

We have previously reported that membrane-bound aminopeptidases were expressed on human follicles and corpora lutea (CL) and we showed that these aminopeptidases are involved in follicular growth, probably by regulating extracellular peptide concentrations. In this study, the expression of membrane-bound carboxypeptidase-M (CP-M), which cleaves carboxyl-terminal amino acids from peptides extracellularly, on human follicles and CL was examined. In growing and pre-ovulatory follicles, CP-M was immunohistochemically detected with weak or moderate intensity on theca interna cells. Although CP-M was not detected on granulosa cells in growing and pre-ovulatory follicles, it was strongly detected on the cell surface of luteinizing granulosa cells isolated from patients undergoing in-vitro fertilization treatment, indicating that CP-M was rapidly expressed on granulosa cells during ovulation. In menstrual and pregnant CL, CP-M was clearly detected on luteal cells. In menstrual CL, the expression of CP-M mRNA was observed by reverse transcription-polymerase chain reaction (RT-PCR). Western blotting analysis revealed that the molecular mass of the CP-M extracted from mid-luteal CL was 62 kDa. These results indicate that CP-M is a cell surface differentiation-related molecule of human granulosa, theca, and luteal cells. The rapid expression on granulosa cells during ovulation strongly suggests the involvement of CP-M in the ovulation and CL formation processes.

Blotting, Western↗

PubMed1998

Human large luteal cells in the menstrual cycle and early pregnancy express leukotriene A4 hydrolase.

Leukotriene (LT) A4 hydrolase (EC3.3.2.6) converts LTA4 to LTB4 which shows a chemotactic activity to leukocytes. To investigate the involvement of LTB4 in human corpus luteum (CL) function, the localization of LTA4 hydrolase in human ovarian tissues was examined by immunohistochemistry with a rabbit polyclonal antibody against LTA4 hydrolase. The enzyme was weakly expressed on granulosa cells of the follicles. After ovulation, the intensity of LTA4 hydrolase on large luteal cells increased and was highest in the midluteal phase. High expression was also observed in the CL of early pregnancy. In theca interna and small luteal cells, LTA4 hydrolase was weakly detected in all developmental stages. Immunoblot analysis demonstrated that the molecular mass of LTA4 hydrolase expressed in CL was 62 kDa, and confirmed that LTA4 hydrolase expression increased during CL formation and remained high in early pregnancy. The sequence encoding mRNA of LTA4 hydrolase, which was isolated from CL and amplified by polymerase chain reaction, was shown to be identical to the previously reported one. Immunocytochemistry showed that LTA4 hydrolase expression in cultured granulosa cells increased over 4 days in vitro and was enhanced by human chorionic gonadotrophin treatment. These expression profiles of LTA4 hydrolase suggest the involvement of LTB4 in luteal cell function during CL formation and early pregnancy.

Adolescent↗

PubMed1998

D-erythrulose reductase can also reduce diacetyl: further purification and characterization of D-erythrulose reductase from chicken liver.

We have discovered new characteristics of D-erythrulose reductase, namely, that it can catalyze reduction of not only D-erythrulose but also such diketones as diacetyl. These substrates have a common structure with two neighboring carbonyls possibly in s-cis plane structure, showing that the enzyme may rigorously distinguish between substrates and other compounds. D-Erythrulose reductase was predominantly located in the kidney and the liver of the chicken. The obtained results suggest that D-erythrulose reductase plays an important role in metabolizing alpha-dicarbonyls in animal organs, because these diketones widely occur in natural foods.

Animals↗

PubMed1998

Multiple DNA elements for sterol regulatory element-binding protein and NF-Y are responsible for sterol-regulated transcription of the genes for human 3-hydroxy-3-methylglutaryl coenzyme A synthase and squalene synthase.

The expression of the human SREBP-2 gene is transcriptionally regulated in a cooperative manner by sterol regulatory element-binding proteins (SREBPs) and the general transcription factor NF-Y [Sato, R., Inoue, J., Kawabe, Y., Kodama, T., Takano, T., and Maeda, M. (1996) J. Biol. Chem. 271, 26461-26464]. To understand the sterol-dependent transcriptional regulation by these factors in detail, we have examined the regulation of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase and squalene synthase genes, whose promoters have multiple potential sterol regulatory elements (SRE, SREBP binding site) and NF-Y binding sites. The promoter of the human HMG CoA synthase gene was cloned, sequenced, and functionally characterized by means of reporter gene assays. The results indicate that an inverted CCAAT box, two SRE motifs and two Sp1 sites localized in a 90-bp region coordinately regulate the transcription. In the case of the human squalene synthase promoter, two SRE motifs and an inverted CCAAT box between the motifs localized in a 51-bp region are responsible for the sterol-regulated transcription of the gene. Gel mobility shift assay reveals that these two inverted CCAAT boxes are recognized by NF-Y. The involvement of multiple responsive elements in the transcription of HMG CoA synthase and squalene synthase seems to induce a higher level of sterol-dependent regulation (3.5 to 5. 8-fold) compared with that of the SREBP-2 promoter, which contains a single pair of SRE motif and CCAAT box (1.8 to 2.6-fold). Reporter gene assays using constructs containing various nucleotide spacing lengths between the SRE motif and the CCAAT box demonstrate that the 16 to 20-bp spacing range is required for maximal transcriptional regulation. These results agree with the findings that the distances between the two motifs in the known sterol responsive elements in several genes, including the human HMG CoA synthase and squalene synthase genes, are in this range.

Base Sequence↗

PubMed1998

Genetic variation in the promoter region of the beta-fibrinogen gene is associated with ischemic stroke in a Japanese population.

Evidence suggests that an allelic variation in the beta fibrinogen gene may confer an increased risk of coronary artery disease and stroke. The role of the beta fibrinogen gene polymorphism and fibrinogen levels in ischemic stroke has not been determined in Japanese, who are more prone to stroke than to coronary artery disease compared with Caucasians. We investigated the associations between ischemic stroke, plasma fibrinogen level, and a HaeIII restriction fragment length polymorphism (G/A(-455)) located at -455 bp from the start of transcription of the beta fibrinogen gene in 85 hypertensive patients with ischemic stroke (stroke group), 85 hypertensive patients without ischemic stroke (nonstroke group) and in 84 normotensive subjects matched for age, sex, and smoking status recruited at an annual health examination (normotensive group). The frequency of non-cutting allele (designated A(-455) allele) in the control group was 0.07 [95% CI: 0.03-0.11]; this value was significantly lower than that previously reported in Caucasians (0.19-0.26). The A(-455) allele frequency of the nonstroke group and stroke group were 0.08 [95% CI: 0.04-0.12] and 0.15 [95% CI: 0.10-0.21]. A(-455) allele frequency of the stroke group was significantly higher than that of the control group chi2 = 5.63, P= 0.018) and the nonstroke group chi2 = 4.00, P= 0.043). The mean +/- SD fibrinogen level was significantly higher in the stroke group than that in the normotensive group (277 +9/- 64 mg/dl versus 257 +/- 52 mg/dl, P < 0.03), but that of the nonstroke group was not significantly different compared with both normotensive and stroke groups. In conclusion, the positive association between the fibrinogen genotype G/A(-455) and ischemic stroke in hypertensive patients was independent of other risk factors. These results suggest that fibrinogen A(-455) allele may be an independent risk factor for ischemic stroke in the Japanese population.

Age Factors↗

PubMed1998

Ultrastructural observation of platelets from patients with progressive systemic sclerosis (PSS).

We observed the ultrastructure of platelets from patients with PSS (7 cases; 48.2 +/- 12.3 y-old; M:F = 1:6_ and healthy controls (HC) (5 cases; 44.8 +/- 8.0 y-old; M:F = 1:4) by using transmission (TEM) and freeze-fracture electron microscopy (FEM). The open canalicular system (OCS) connected with the plasma membrane (PM) formed pinhole-like invaginations (50 nm in diameter) in the cleaved face (P-face) of the plasma membrane seen from the outside of the platelets and sharply elevated structures in the cleaved face (E-face) of PM seen from the inside of the platelets by FEM. The density of OCS on the surface of the platelets from PSS patients was 3 +/- 1/micron 2, which was higher than that from HC (1 +/- 0.5/micron 2) (p < 0.02). Dome-shaped structures, which clearly differ from OCS and were 80-150 nm in diameter without intramembranous particles, were seen in the P-face, and the complementary depressed structures were seen in the E-face. These structures were thought to be vesicles fused onto the PM of the platelets. The total volume of platelets (7.62 +/- 0.11 micron 3), total volume of granules (0.79 +/- 0.01 micron 3) and vacuoles including OCS (0.78 +/- 0.05 micron 3), and the total surface area of platelets (17.25 +/- 1.30 micron 2) from four PSS patients calculated by the morphometrical method were similar to those from four HC (7.32 +/- 0.25 micron 3, 0.76 +/- 0.03 micron 3, 0.80 +/- 0.05 micron 3, 18.75 +/- 0.35 micron 2, respectively); there were no statistical significances between the data from PSS patients and HC. The total volumes of vacuoles in platelets from both PSS patients and HC significantly decreased after a 2 min-vibration stress of the hands (p < 0.02) and the total volume of granules in platelets from PSS patients decreased significantly after the same stress (p < 0.002), although that from HC showed no similar significant change. However, there were no statistically significant differences in total volume or total surface of platelets from PSS patients and HC after the stress. These data may suggest that depletion of granules occurred due to activation of platelets from PSS patients following a secretion of their proteins, because their plasma protein levels were elevated after the stress (Jpn J Dermatol, 98; 1205, 1988). Higher density of OCS on the surface of the platelets from PSS patients may play an important role in secretion of their proteins, although the detailed mechanism of secretion of specific proteins derived from platelet granules is still unknown. These ultrastructural abnormalities of platelets may correlate with some involvement of a platelet disorder and with a possible role for the activation of platelets from PSS patients.

Adult↗

PubMed1998

The increase of memory T cell subsets in children with idiopathic nephrotic syndrome.

Two-color and three-color flow cytometry was carried out to determine whether the memory T cells (CD45RO+ T cells) play a major role in lymphocyte dysfunction of 26 children with idiopathic nephrotic syndrome (INS). The INS patients were divided into three groups: (1) 10 patients who were not receiving glucocorticoid hormone (GCH) and were suffering from acute nephrotic state were referred to as N1; (2) 8 patients who were in remission maintained by GCH therapy alone were referred to as N2; (3) 8 patients who were free of GCH therapy for at least 4 months were referred to as N3. Group N1 demonstrated a significant increase in the percentage of CD45RO+CD4+ T cells and CD45RO+CD8+ T cells (p < 0.05) compared with 11 controls, and these subsets were noted to have a tendency to decrease to control levels in groups N2 and N3. Furthermore, interleukin-2 receptor-alpha expressed subsets in CD45RO+CD4+ T cells (CD45RO+CD4+CD25+ T cells) were also increased only in group N1 (p < 0.02). A similar tendency of absolute counts was observed in these subsets. These results suggest that activated memory T cells reflect lymphocyte dysfunction at initial onset or relapse in INS children.

Antibodies, Monoclonal↗

PubMed1998

Physiological roles of integrin alpha 6 beta 1 in ovarian functions.

We previously reported that human ovarian cells express integrin beta 1 families. The physiological role(s) of integrins was investigated using in vitro human granulosa cell culture and in vivo mouse ovulation model. In human luteinizing granulosa cell culture obtained from the patients undergoing in vitro fertilization treatment, laminin, which is a ligand for integrin alpha 6 beta 1, suppressed the production of progesterone by granulosa cells. On the other hand, the anti-alpha 6 monoclonal antibody (mAb) GoH3, which partially inhibits the interaction between integrin alpha 6 beta 1 and laminin, enhanced production of progesterone by 2-fold of the control under the culture with laminin, indicating that integrin alpha 6 beta 1 regulates the luteinization of human granulosa cell during the periovulatory phase. In an immature superovulated 13-day-old ICR (CD-1) mice model, intraperitoneal administration of GoH3 induced successful ovulation, whereas no ovulation was observed in the GoH3-nontreated groups, showing that integrin alpha 6 beta 1 is related to gonadotropin-induced follicular growth. These findings suggest that the interaction between integrin alpha 6 beta 1 and laminin plays an important role in the corpus luteum formation and follicular growth.

Animals↗

PubMed1998

Continuous administration of basic fibroblast growth factor (FGF-2) accelerates bone induction on rat calvaria--an application of a new drug delivery system.

Some studies have shown that locally applied basic fibroblast growth factor (FGF-2) enhances bone regeneration at a fracture site, while others have not been in agreement. We developed a new continuous FGF-2 delivery system designed to accelerate cytokine-induced new bone formation. A subperiosteal pocket was surgically formed in 36 eight-week-old male Wistar rats. The rats were administered 0, 1, 10, or 100 ng of FGF-2 contained in a collagen minipellet, mixed with allogeneic demineralized bone matrix in a dome-shaped Millipore filter and then placed into the pocket. New bone formation in the dome was evaluated at 2, 4, and 8 wks after placement. Soft x-ray radiographs disclosed an apparently larger radiopaque region in the 1-ng group at 4 wks compared with those in the other groups. Morphometrical analysis revealed that the new bone area in the 1-g group was significantly larger than that in the 0-g group (p<0.01). In the 100-ng FGF-2 group, new bone formation seemed suppressed. We concluded that continuous slow administration of a small amount of FGF-2 accelerates bone-derived osteogenic cytokine-induced new bone formation.

Animals↗

PubMed1998

Endothelin-converting enzyme-1 is expressed on human ovarian follicles and corpora lutea of menstrual cycle and early pregnancy.

We have previously reported that membrane-bound amino- and carboxypeptidases were expressed on the human follicles and corpora lutea (CL), and we proposed that these peptidases are involved in ovarian functions, probably by regulating the extracellular peptide concentrations. In this study, we examined the expression of endothelin-converting enzyme-1 (ECE-1) on human follicles and CL, which is a membrane-bound endopeptidase and is known to convert big endothelin-1 to endothelin-1. In the preovulatory follicles, immunohistochemical study showed that ECE-1 was expressed, with moderate intensity, on the theca interna cells and weakly on the granulosa cells. In the menstrual and pregnant CL, ECE-1 was highly expressed on both large and small luteal cells, indicating that ECE-1 expression increases during luteinization. Western blotting analysis revealed that the molecular mass of the ECE-1 extracted from the menstrual CL was 130 kDa and that ECE-1 was more strongly expressed on the CL in early and midluteal phases than the CL in late luteal phases. In the isolated luteinizing granulosa cells obtained from patients undergoing in vitro fertilization, ECE-1 was immunohistochemically detected on their cell surface. The activity of ECE-1 was also detected on cultured luteinizing granulosa cells by measuring endothelin-1 production from its precursor. The activity of ECE-1 was significantly enhanced by the treatment of human CG (10 U/mL) and interleukin (IL)-1 (10 ng/mL) during 4-day culture, whereas no significant alteration was observed by IL-4 (10 ng/mL) and IL-10 (10 ng/mL) treatment. These results indicate that ECE-1 is a cell surface differentiation-related molecule of human granulosa and of theca interna cells and suggest that the expression of ECE-1 is regulated by LH/human CG and cytokines.

Adult↗

PubMed1998

Structures of P-type transporting ATPases and chromosomal locations of their genes.

P-type ATPases (E1E2-ATPases) are primary active transporters which form phospho-intermediates during their catalytic cycle. They are classified into P1 to P4 based on the primary structure and potential transmembrane segments. Although the classic P-type ATPases are cation transporters, two new members have recently been found; one is a flippase catalyzing the flip-flop movement of aminophospholipids, but the substrate and function of the other one remain unknown. It would be interesting to determine whether the cations and aminophospholipids are transported by similar or different mechanisms. P-type ATPases are believed to have been derived from a common ancestor, and their genes are found to be distributed in various chromosomal loci. However, gene duplication events can be traced from the tandem arrangement of genes and their linkage map. Na+/K+- and H+/K+-ATPases have not only closely related a subunits but also similar beta subunits. Renal Na+/K+-ATPase has an additional subunit gamma. Similar small polypeptides (phospholemman, Mat-8 and CHIF), which induce Cl- and K+ currents, have been found. The idea of their functional and structural coupling with P-type ATPases, especially with H+/K+-ATPase, is intriguing. Each P-type ATPase must have specific domains or sequences for its intracellular trafficking (sorting, retention and recycling). Identification of such regions and studies on the molecules playing role in their recognition may facilitate the unveiling of various cellular processes regulated by P-type ATPases.

Adenosine Triphosphatases↗

PubMed1998

Basic studies on N''-ursodeoxycholyldiethylenetriamine-N,N,N'-triacetic acid for the dissolution of calcified gallstones.

A novel calcium-chelating agent, N"-ursodeoxycholyldiethylenetriamine-N,N,N'-triacetic acid (UDCA-DTTA), was synthesized to study its ability to dissolve calcified gallstones. The chelating activity of the compound was demonstrated by dissolving calcium carbonate in vitro at a high dissolution rate. In the presence of the agent, sliced human gallstone with a composition of more than 50% calcium bilirubinate was thoroughly dissolved, indicating that calcium bilirubinate was dissolved from the gallstone. The ability to dissolve calcium was comparable to that of EDTA. However, the laminar structure of the sliced gallstone did not disappear in the presence of EDTA, whereas the structure disappeared in the presence of UDCA-DTTA. All these results indicate that UDCA-DTTA is an interesting compound as a parent substance for developing a prodrug for an oral or intravenous agent to dissolve calcium-containing gallstones.

Administration, Oral↗

PubMed1998

In vitro antitumor activities of new synthetic bistetrahydrofuran derivatives as analogs of Annonaceous acetogenins.

We investigated the in vitro antitumor activities toward mouse and human cell lines of optically active synthetic bistetrahydrofuran (bis-THF) derivatives as analogs of Annonaceous acetogenins, which contain bis-THF, long unbranched alkyl chains, hydroxyl groups, and an alpha, beta-unsaturated gamma-lactone. These bis-THF derivatives were synthesized in a stereocontrolled manner, and have several modified structures at the alkyl side chains. We found that: 1) the unsaturated gamma-lactone contributes to high potency in combination with the other less-functionalized alkyl chain, 2) the same absolute configuration of the bis-THF skeleton as that of the natural products produces more potent activity than the counterpart, 3) the alkyl chains and hydroxyl groups are crucial for exhibiting antitumor activity, 4) hydroxyl groups adjacent to the bis-THF skeleton may be replaced by amino or acylamino groups.

4-Butyrolactone↗