Assignment of a human putative RNA helicase gene, DDX3, to human X chromosome bands p11.3-->p11.23.
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Chromosome Mapping↗
Biomedical subjects
K Song
Publications and source records attributed to K Song.
Role of p53 and apoptosis in sensitization of cis-diamminedichloroplatinum antitumor activity by interleukin-1 in ovarian carcinoma cells.
We have previously reported that interleukin-1 (IL-1 ) sensitized cisplatin cytotoxicity against human ovarian NIH:OVCAR-3 tumor cells. We have further examined inter-actions of IL-1 with cisplatin in these ovarian cells. Treatment of cells with either IL-1 or CDDP or combinations resulted in a significant accumulation of cells in G1 phase and a concomitant decrease in the S phase of the cell cycle. IL-1 and CDDP treatment induced p53 protein in NIH:OVCAR-3 tumor cells. CDDP and IL-1 treatment decreased the steady-state expression of c-myc RNA and induced significant degradation of the genomic DNA into internucleosomal sized DNA fragments which was further increased in the presence of both agents in these cells. Taken together, these studies suggest that IL-1 may kill ovarian NIH:OVCAR-3 tumor cells by inducing a blockade at G1/S of the cell cycle, down-regulating c-myc gene and inducing p53-dependent apoptosis. The synergistic interactions of IL-1 with CDDP may involve the enhancement of p53-dependent apoptosis.
Apoptosis↗
[Clinical study on relieving labor pain used combined spinal and epidural anesthesia].
OBJECTIVE: To investigate the effect of combined spinal and epidural anesthesia (CSEA) on relieving and eliminating labor pain and the effect on newborns, labor process and delivery mode. METHODS: 80 cases without any obstetric complications and anesthetic contraindications were selected for the study group. CSEA was applied when cervix dilated for about 2-3 cm, 80 pregnant women with similar obstetric condition as control group without any anesthesia. We compared the labor pain, duration, delivery mode and fetal status of two groups. RESULTS: In study group CSEA showed good effect on relief of labor pain, shortening the active phase of labor course and acceleration of cervical dilation. There are no different in the incidence of fetal distress, neonatal asphyxia and postpartum hemorrhage between two groups. CONCLUSION: Apllication of CSEA is useful in relieving labor pain, accelerating labor course, lowering cesarean section rate without any side effect on fetus.
Analgesia, Obstetrical↗
Involvement of angiotensin II receptor subtypes during testicular development in rats.
Expression of testicular angiotensin II (AT2) receptors in Sprague-Dawley rats at various stages of development (1 and 5 days, 2, 3, 4 and 7 weeks postnatal) were studied by in vitro autoradiography and Northern blot analysis. The receptors were labelled with 125I-[Sar1, Ile8]AT2 and differentiated into two subtypes according to their susceptibility to AT1 (losartan, 5 microM) or AT2 (PD123319, 5 microM) antagonist. Total AT2 receptor binding in the testis was highest at 1 day of age (8.12 +/- 0.35 fmol/mg protein, mean +/- secEM, n = 8) and decreased gradually thereafter (5 days: 6.9 +/- 0.41, 2 weeks: 2.85 +/- 0.10, 3 weeks: 1.64 +/- 0.19, 4 weeks: 0.76 +/- 0.09, 6 weeks: 0.77 +/- 0.09 fmol/mg protein, n = 8-11). AT2 receptor binding was strikingly abundant in 1-day-old rat testis (6.98 +/- 0.34 fmol/mg protein), while considerably less AT1 receptor binding (1.46 +/- 0.19 fmol/mg protein) was observed. The relative amounts of each subtype did not change for the first 3 weeks but the 4-week-old rat testis contained almost exclusively AT1 receptors (0.63 +/- 0.05 fmol/mg protein). Northern blot analysis showed that mRNA expression of both AT1 and AT2 types decreased with age. Microscopic emulsion autoradiography was undertaken to clarify the localization of binding. At 10 days of age, both AT1 and AT2 receptors were present in the interstitial area, whereas seminiferous tubules contained mainly AT2 receptors. At 7 weeks of age, no significant binding was observed in the seminiferous tubule and the interstitial area contained AT1 receptors exclusively. These results demonstrate expression of AT2 receptors in the rapidly growing testis and suggest that change in the levels of AT2 receptor subtypes may be relevant to development and/or growth of the testis.
Angiotensin II↗
Genomic organization of the human DDX13 gene located between RD and RP1 in the class III MHC complex.
Recently we cloned a novel human cDNA homologous to yeast SKI2, reported a partial cDNA sequence, and mapped the gene to human chromosome 6p21 (Lee et al., 1995). It was a member of the DEAD/DExH family gene with seven conserved helicase domains; thus, it was named DDX13 consequently. We determined the complete genomic organization of the DDX13 gene. It consisted of 28 exons distributed over 11 kb of genomic DNA. An Alu element was present in introns 17 and 18, respectively. The major transcription start site was located 390 bp upstream from the translation initiation codon. The DDX13 gene was located in the class III region of the MHC between the genes coding for two other nuclear proteins, RD and RP1. The RD and DDX13 genes were oppositely oriented, and their first exons were overlapped. The distance between their first methionine codons was only 745 bp. It was of note that DDX13 and RD are in such proximity that their 5' regulatory regions overlap. The RP1 gene was located immediately downstream from the DDX13 gene in the same transcriptional orientation, and the distance between the stop codon of DDX13 and the translation initiation codon of RP1 was 2,272 bp.
Base Sequence↗
Sequence variation and phylogenetic analysis of the 5' terminus of hepatitis G virus.
We determined the nucleotide and deduced amino acid sequence of the 5' terminus of the hepatitis G virus (HGV) genome from isolates of varied geographical origins. Our analysis showed that the putative 5' non-coding region (NCR) contains several blocks of highly conserved sequences that may be useful for the development of a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for detection of HGV RNA. Overall, the degree of conservation within the 669-nucleotide (nt) 5'terminal sequence was found to range from 99.5% to 86% sequence identity. We also showed that the HGV NCR from some isolates contained conserved insertions or deletions that altered the translational reading frames at the 5'-end of the genome, resulting in different sizes of predicted polyproteins encoded by genomes of individual isolates. Specifically, the insertions/deletions affected the size of the peptide preceding the putative first envelope (E1) protein. Phylogenetic analysis of the nucleotide sequences suggested that the isolates examined can be classified into distinct groups that may be useful for studying the molecular evolution of HGV and possible relationships between isolate sequence characteristics and infection patterns.
Adenovirus E1 Proteins↗
Pharmacological profiles of a novel non-peptide angiotensin II type I receptor antagonist HR720 in vitro and in vivo.
The pharmacological properties of 2-butyl-4-(methylthio)-1-[[2'-[[[(propylamino)carbonyl] amino]sulfonyl](1,1'-biphenyl)-4-yl]methyl]-1H-imidazole-5-carboxylate (HR720), a novel non-peptide angiotensin (Ang) II type I (AT1) receptor antagonist, were characterized in both in vitro and in vivo systems. In vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand revealed that HR720 competitively inhibited the specific binding of the ligand to the adrenal cortex. The IC50 value for the adrenal cortex was 1.5 x 10(-8) M, and the IC50 for medulla was 1.4 x 10(-6) M. Similar results were obtained in the adrenal cortex with CV-11974, a known potent AT1-receptor antagonist. Since AT1 receptors are known to predominate in the adrenal cortex and AT2-receptors in the adrenal medulla, it is considered that HR720 is highly selective for AT1 receptors. HR720 inhibited the Ang II-induced contraction of isolated rabbit aortic strips and human gastroepiploic arteries in a noncompetitive manner, pD'2=9.40 and 9.62 for rabbit aorta and human artery, respectively. With CV-11974, pD'2 values of 9.84 in isolated rabbit aorta and 10.00 in human artery were obtained. HR720 did not affect the norepinephrine-, serotonin- or KCl-induced contraction even at a concentration of 1 x 10(-5) M. In anesthetized hamsters, HR720 induced a dose-dependent inhibition of the pressure response to Ang II. The potency of HR720 to antagonize the Ang II-induced pressure response was similar to that of CV-11974. These results demonstrate that HR720 is a potent and selective AT1-receptor antagonist.
Adrenal Glands↗
[Preliminary study on differentiation of syndromes during HDT -6 degrees bed rest with traditional chinese medicine].
Differentiation of syndromes during 21 d HDT -6 degrees bed rest was made in 15 healthy young men. The results indicated that the subjects showed mainly deficiency of kidney-Yin, deficiency of Yin and hyperactivity of Yang, insufficiency of spleen-Qi and blood stasis in various degrees during the bed rest. The syndromes were most serious on the 3rd day, and then deficiency of kidney and deficiency of Yin and hyperactivity of Yang became mild gradually but insufficiency of spleen-Qi and blood stasis remained the same. The pulse condition was normal through the bed rest period
Bed Rest↗
[Observation of EGG parameters during -6 degrees head-down bedrest for 21 days].
Electrogastography (EGG) was recorded in 15 healthy volunteers before and after meal during 21 days head down tilt -6 degrees bed rest. The results showed that nausea, distension and pain in the abdomen and loss of appetite appeared at the beginning of bed rest and body weight decreased significantly (P < 0. 01) after bed rest; Low frequency (Bradygastria) proportion of EGG (<2.4cpm) increased apparently after 8 days of bedrest, and there was significant difference (P <0.05) between preprandial and postprandial bradygastria. The dynamic parameters of bradygastria declined significantly and the rhythm of bradygastria increased with duration of bedrest. It indicates that simulated weightlessness may cause decrease of gastric rhythm and gastric motility.
Aerospace Medicine↗
[Ending diatomic molecular terms].
A method is discussed to find diatomic molecular terms of equivalent and non-equivalent configuration.
English Abstract↗
Sensitization of cis-platinum by a recombinant adenovirus vector expressing wild-type p53 gene in human ovarian carcinomas.
Mutations of the tumor suppressor wild-type p53 gene have been implicated in the development of resistance to anticancer drugs. We have examined the role of wild-type p53 in resistance to cis-diamminedichloroplatinum (II) (CDDP) in human ovarian cancer cells using a recombinant adenovirus containing human wild-type p53 cDNA (Adwtp53). In this study we used the human ovarian A2780 tumor cells (wtp53), which are sensitive to CDDP and A2780/CP tumor cells (nonfunctional/mutant p53) and are resistant to CDDP. Studies show that introduction of wtp53 protein via adenovirus gene transfer into A2780/CP cells significantly sensitized these cells to CDDP cytotoxicity, indicating wtp53 was involved in resistance to CDDP. We found that introduction of wtp53 protein also resulted in growth arrest of A2780/CP tumor cells whereas the parent A2780 cells were significantly less sensitive to Adwtp53. This synthesis of wtp53 protein induced by Adwtp53 in A2780/CP cells resulted in a significant increase in the expression of Bax protein without significantly effecting the expression of bcl2 protein, and induced a dose-dependent increase in the nucleosomal DNA fragmentation. The presence of CDDP further enhanced this apoptosis, causing a 30-fold sensitization of A2780/CP cells to CDDP. These results indicate that mutation of p53 protein in A2780/CP ovarian tumor cells resulted in the resistance to CDDP and that combination of wtp53 gene and CDDP may result in sensitization of mutant p53-containing tumors to chemogenetherapy.
Adenoviridae↗
Translocation of cytosolic phospholipase A2 to the nuclear envelope elicits topographically localized phospholipid hydrolysis.
Cytosolic phospholipase A2 (cPLA2) is a good candidate for mediating the agonist-stimulated release of arachidonic acid (AA) from membrane phospholipids. This enzyme undergoes a Ca(2+)-dependent translocation from the cytosol to a membrane site in a variety of cell types, and this site has recently been identified as the nuclear envelope in leucocytes. The functional correlate of this finding has not yet been established. The present study was therefore undertaken to determine whether translocation of cPLA2 to the nuclear envelope was associated with localized phospholipid hydrolysis at this site. Rat alveolar epithelial cells, previously shown to contain cPLA2, were prelabelled with [3H]AA and stimulated with the model agonist, ionophore A23187. Ionophore-induced AA release exhibited characteristics typical of a cPLA2-mediated response, in that it was Ca(2+)-dependent, sn-2 AA-selective, and inhibited by arachidonyl trifluoromethyl ketone. As determined by indirect immunofluorescence microscopic analysis as well as subcellular fractionation with immunoblotting, ionophore treatment resulted in a translocation of cPLA2 protein from the cytoplasm to the nuclear envelope. To determine whether the nuclear membrane was indeed the source of released AA, prelabelled cells were incubated in the presence or absence of A23187, after which the phospholipid radioactivity was quantified in nuclear and non-nuclear membrane fractions. [3H]AA was distributed in both nuclear and non-nuclear membrane phospholipids. Following A23187 stimulation, the loss of [3H]AA from nuclear membrane phospholipids accounted for 88.1 +/- 5.8% of the total loss from phospholipids and for 92.9 +/- 2.3% of the total [3H]AA released into the medium. These results demonstrate for the first time that agonist-stimulated translocation of cPLA2 to the nuclear envelope is associated with phospholipid hydrolysis which is preferentially localized to that site.
Animals↗
Elevated expression of Bcl-X and reduced Bak in primary colorectal adenocarcinomas.
Expression of several members of the BCL-2 family of genes was investigated by immunohistochemical methods in 30 primary colorectal adenocarcinomas and 24 adenomatous polyps. When compared to the intensity observed in adjacent normal mucosal epithelial cells, the intensity of Bcl-X immunostaining was elevated in 18 of 30 (60%) carcinomas (P = 0.0001) and 12 of 24 (50%) adenomatous polyps (P = 0.0001). Immunoblot analysis of five pairs of tumors and adjacent normal colonic tissue indicated marked elevations in the relative levels of the anti-apoptotic Bcl-XL, protein in all cases. In contrast to the increased Bcl-X expression, the intensity of Bcl-2 immunostaining was greater than that of normal colonic mucosa in only 3 of 30 (10%) carcinomas and, in fact, was lower than that of adjacent normal epithelia] cells in 25 (83%) cases (P = 0.0001). Furthermore, the percentage of Bcl-2 immunopositive cells was generally lower in carcinomas than in adenomas (mean +/- SE, 44 +/- 6% versus 73 +/- 5%, respectively; P = 0.001) and in moderately or poorly differentiated tumors than in well-differentiated tumors (39 +/- 6% versus 70 +/- 11%, respectively; P = 0.045). In addition, the proportion of tumors in which the Bcl-2 immunointensity was more than or equal to that of normal colonic mucosa was significantly lower in carcinomas than adenomas (5 of 30 versus 15 of 24, respectively; P < 0.001), suggesting that decreases in Bcl-2 expression represent a later event associated with the progression of colorectal cancers. When compared to that of normal adjacent colonic epithelium, the intensity of Mcl-1 immunostaining was reduced in 20 of 30 (67%) of carcinomas (P = 0.0001) compared to only 1 of 24 adenomas, suggesting that decreases in Mcl-1 expression represent a later event associated with progression from a benign to a malignant phenotype or with transition to a less-differentiated state, because most of the carcinomas evaluated here (25 of 30; 83%) were not well differentiated. The intensity of immunostaining for the pro-apoptotic protein Bak was reduced compared to that of normal mucosal epithelial cells in 27 of 30 (90%) carcinomas and 22 of 24 (92%) adenomas, suggesting that reductions in Bak expression occur early in colorectal tumor progression (P = 0.0001). In contrast, the intensity of immunostaining for the pro-apoptotic protein Bax was not significantly altered in carcinomas; compared to that of normal colonic mucosa, Bax immunointensity was reduced in only 7 of 30 (23%) carcinomas and 3 of 24 (13%) adenomas, and the percentage of Bax immunopositive cells was also not significantly different in any of the histological subgroups. Taken together, these results suggest that expression of Bcl-XL is increased in undifferentiated primary colorectal cancers, often with accompanying reciprocal decreases in the anti-apoptotic proteins Bcl-2 and Mcl-1 and the pro-apoptotic protein Bak, whereas Bax expression is relatively constant. Thus, a shift from expression of the anti-apoptotic proteins Bcl-2 and Mcl-1 to the Bcl-XL protein may occur during progression of colorectal tumors.
Adenocarcinoma↗
Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle.
Caveolin, a 21-24-kDa integral membrane protein, is a principal component of caveolar membranes in vivo. Caveolin interacts directly with heterotrimeric G-proteins and can functionally regulate their activity. Recently, a second caveolin gene has been identified and termed caveolin-2. Here, we report the molecular cloning and expression of a third member of the caveolin gene gamily, caveolin-3. Caveolin-3 is most closely related to caveolin-1 based on protein sequence homology; caveolin-1 and caveolin-3 are approximately 65% identical and approximately 85% similar. A single stretch of eight amino acids (FED-VIAEP) is identical in caveolin-1, -2, and -3. This conserved region may represent a "caveolin signature sequence" that is characteristic of members of the caveolin gene family. Caveolin-3 mRNA is expressed predominantly in muscle tissue-types (skeletal muscle, diaphragm, and heart) and is selectively induced during the differentiation of skeletal C2C12 myoblasts in culture. In many respects, caveolin-3 is similar to caveolin-1: (i) caveolin-3 migrates in velocity gradients as a high molecular mass complex; (ii) caveolin-3 colocalizes with caveolin-1 by immunofluorescence microscopy and cell fractionation studies; and (iii) a caveolin-3-derived polypeptide functionally suppresses the basal GTPase activity of purified heterotrimeric G-proteins. Identification of a muscle-specific member of the caveolin gene family may have implications for understanding the role of caveolin in different muscle cell types (smooth, cardiac, and skeletal) as previous morphological studies have demonstrated that caveolae are abundant in these cells. Our results also suggest that other as yet unknown caveolin family members are likely to exist and may be expressed in a regulated or tissue-specific fashion.
Amino Acid Sequence↗
Antinociceptive effects of angiotensin-converting enzyme inhibitors and an angiotensin II receptor antagonist in mice.
Potential involvement of brain endogenous angiotensin II in the nociception was investigated in mice by using ACE inhibitors and an angiotensin II antagonist. The mice were allocated to the groups which were orally treated with spirapril (5 mg/kg), trandolapril (5 mg/kg), enalapril (30 mg/kg), losartan (10 mg/kg), or vehicle for 1 day (single dose groups) and 7 days (repeated doses groups). Significantly longer jump latencies were obtained for the groups repeatedly treated with spirapril, trandolapril and losartan, while the group with enalapril gained no effect. In contrast, the single dosing of all agents failed to show antinociceptive effect. The brain ACE activity was determined ex vivo immediately after the hot-plate test, and showed to be suppressed for the groups repeatedly treated with spirapril or trandolapril. In the group repeatedly treated with losartan, ex vivo autoradiography depicted the marked decrease in angiotensin II-binding capacity to the sites containing exclusively AT1 receptors within the blood-brain barrier. The antinociceptive effects of repeated doses of spirapril and losartan were reversed by naloxone. These results suggest that brain endogenous angiotensin II is likely to be involved in central nociceptive mechanisms by its antagonistic interaction with endogenous opioid system.
Administration, Oral↗
High resolution localization of endothelin receptors in rat renal medulla.
The cellular localization of endothelin receptors in the inner medulla of the rat kidney was investigated by using high resolution light and electron microscopic autoradiography, with the microwave irradiation fixation methods. Kidney slices were incubated with 125I-endothelin-1 alone or with selective ligands for the endothelin ETB and/or ETA receptors for light microscopic autoradiography. At the microscopic level, 125I-endothelin-1 was found to bind specifically to the glomeruli, arterioles and peritubular spaces in the cortex and vasa recta and surrounding tissues in the inner medulla. These bindings were also observed when the tissue slices were incubated in the presence of IRL1620 (ETB receptor agonist) or 97-139 (ETA receptor antagonist). Electron microscopic autoradiography using 125I-endothelin-1 in the inner medulla revealed silver grains over endothelial cells of the vasa recta and interstitial and collecting duct cells. No grains were detected over inner lining cells of the thin limbs of Henle's loop. These interstitial cells contained abundant microorganelles and lipid droplets, and had extensive cytoplasmic processes that closely related to the basement membranes of the vasa recta and loop of Henle. These findings demonstrate that type 1 interstitial cells are also primary sites for endothelin receptors as well as endothelial cells of the vasa recta and collecting duct cells in the inner medulla.
Animals↗
A novel suppressor of ras1 in fission yeast, byr4, is a dosage-dependent inhibitor of cytokinesis.
A novel gene, designated byr4, was identified in Schizosaccharomyces pombe that affects the mitotic cell cycle and shows genetic interactions with the ras1 signaling pathways. Null alleles of byr4 cause cell cycle arrest in late mitosis and permit multiple rounds of septation. The multiple septa typically divide two nuclei, but the nuclei frequently do not stain equally with 4',6-diamidino-2-phenylindole (DAPI), suggesting that byr4 is required for proper karyokinesis. Overexpression of byr4 inhibits cytokinesis, but cell cycle progression continues leading to multinucleate cells. When byr4 is overexpressed, the early steps in the cytokinesis pathway, including formation of the medial F-actin ring, occur normally; however, the later steps in the pathway, including contraction of the F-actin ring, septation, and rearrangement of the medial F-actin following mitosis, rarely occur, byr4 shows two genetic interactions with ras1. The inhibition of cytokinesis by byr4 overexpression was exacerbated by null alleles of ras1 and scd1, suggesting a link between pathways needed for cell polarity and cytokinesis. Overexpression of byr4 also partially bypasses the need for ras1 for sporulation. The electrophoretic mobility of the byr4 protein varied in response to mutants that perturb cytokinesis and karyokinesis, suggesting interactions between byr4 and these gene products. A more rapidly migrating byr4 protein was found in cells with mutations in cdc16, which undergo repeated septation, and in cdc15, which fail to form a medial F-actin ring in mitosis. A slower migrating byr4 protein was found in cells with a mutation in the beta-tubulin gene, which arrests cells at the metaphase-anaphase transition.
Actins↗
Autoradiographic localization of active renin in the juxtaglomerular apparatus of the dog kidney: effects of sodium intake.
1. The effects of dietary sodium intake on active renin binding in the juxtaglomerular apparatus (JGA) of superficial and juxtamedullary cortex of the dog kidney were examined by quantitative in vitro autoradiography using a radiolabelled renin inhibitor [125I]-H77, which has high affinity for dog renin. 2. Changes in sodium intake resulted in marked alterations of active renin binding in the radiolabelled JGA. In comparison with the control kidney (190.8 +/- 7.7 Bq/mm3), a higher density of binding occurred in the labelled JGA of sodium-depleted kidney (277.7 +/- 6.2 Bq/mm3), while a lower density of binding was found in the labelled JGA of sodium-loaded kidney (99.3 +/- 7.4 Bq/mm3). 3. Active renin binding in the labelled JGA was significantly higher in superficial JGA than in their juxtamedullary counterparts, irrespective of sodium intake. 4. Pre-incubation with trypsin (0.5 mg/mL), a procedure known to activate prorenin, markedly increased active renin binding in the labelled JGA of control (+ approximately 35%; P < 0.01) and sodium-loaded kidneys (+ approximately 75%; P < 0.01), but had little effect on binding in the labelled JGA of the sodium-depleted kidney (+/- approximately 5-10%; NS). The proportions of active renin as a percentage of total renin were 60, 75 and 95% in the labelled JGA of sodium-loaded, control, and sodium-depleted kidneys, respectively. 5. Emulsion microscopic autoradiography revealed that the binding was exclusively localized in the JGA, including the afferent and efferent arterioles, macula densa and extraglomerular mesangium. Labelling extended to the interlobular arteries in sodium depleted kidney. 6. These results indicate that autoradiography combined with the in vitro binding of radiolabelled renin inhibitors may provide a useful tool to measure active and prorenin renin and thereby study the physiological regulation of renin in the kidney.
Animals↗