Comment on "Density matrix renormalization group study of the Haldane phase in random one-dimensional antiferromagnets".
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Journal Article↗
Biomedical subjects
K Yang
Publications and source records attributed to K Yang.
The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression.
Repair of mismatches in DNA in mammalian cells is mediated by a complex of proteins that are members of two highly conserved families of genes referred to as MutS and MutL homologues. Germline mutations in several members of these families, MSH2, MSH6, MLH1, and PMS2, but not MSH3, are responsible for hereditary non-polyposis colorectal cancer. To examine the role of MSH3, we generated a mouse with a null mutation in this gene. Cells from Msh3-/- mice are defective in repair of insertion/ deletion mismatches but can repair base-base mismatches. Msh3-/- mice develop tumors at a late age. When the Msh3-/- and Msh6-/- mutations are combined, the tumor predisposition phenotype is indistinguishable from Msh2-/- or Mlh1-/- mice. These results suggest that MSH3 cooperates with MSH6 in tumor suppression.
Animals↗
[Study on antagonistic effects of selenium and zinc on the renal impairments induced by fluoride in rats].
Wistar rats were provided with distilled water containing NaF(100 mg/L), and were administered through gavage with Na2SeO3[0.1 mg/(kgBW.d)] and/or ZnSO4[14.8 mg/(kg BW.d)]. The results of biochemical, pathological and ultrastructural examinations showed that fluoride could cause serious renal impairments. The major damage induced by fluoride was epithelia of proximal renal tubules. The lipid peroxidation might be one of the mechanisms of fluoride toxicity. Na2SeO3 and ZnSO4 could antagonize the renal impairments induced by fluoride through their antioxidation. The cooperative effect of Na2SeO3 and ZnSO4 was more powerful than either Na2SeO3 or ZnSO4 alone.
Animals↗
Prolonged transgene expression mediated by a helper-dependent adenoviral vector (hdAd) in the central nervous system.
Conventional adenoviral vectors such as E1-deleted first-generation adenovirus (fgAd) elicit striking host immune response, resulting in limited expression of the transgene. A recently described helper-dependent, or gutless, adenoviral vector (hdAd) can promote stable transgene expression in peripheral organs, including the liver. We therefore investigated the safety and durability of hdAd-mediated gene transfer to the central nervous system (CNS) of rats compared with gene delivery by fgAd. Equal amounts of either fgAd or hdAd carrying the beta geo transgene were stereotactically injected into the right hippocampus of adult rats. Transgene expression was assessed by histochemical staining, transgene stability by PCR analysis, and immune infiltration of T lymphocytes and macrophages by immunocytochemical methods. Strong transgene expression from either vector was detected in brain tissue examined on day 6 postinoculation. Thereafter, fgAd-mediated gene expression rapidly decreased, becoming undetectable by day 66, while expression from the hdAd vector persisted throughout the test period. PCR confirmed the presence of hdAd-associated DNA at 66 days postinoculation. The hdAd injection elicited apparently lower numbers of brain-infiltrating macrophages and T cells than did administration of fgAd. These results indicate improved transgene expression and reduced immunogenicity with use of hdAd to deliver genes to the CNS.
Adenoviridae↗
Guinea pig 11beta-hydroxysteroid dehydrogenase type 1: primary structure and catalytic properties.
The 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme is responsible for the interconversion of glucocorticoids and their inactive metabolites, and thus modulates the intracellular level of bioactive glucocorticoids. The present study was designed to clone and characterize 11beta-HSD1 in the guinea pig, a laboratory animal known for resistance to glucocorticoids. The cDNA encoding guinea pig 11beta-HSD1 was cloned by a modified 3'-RACE (rapid amplification of cDNA ends) protocol using the hepatic RNA as template. The cloned cDNA encodes a protein of 300 amino acids that shares 71 to 74% sequence identity with other known mammalian 11beta-HSD1 proteins. Sequence comparison analysis revealed that the deduced guinea pig 11beta-HSD1 was longer, by eight amino acids at the C terminus, than those of other mammals. Moreover, one of the two absolutely conserved consensus sites for N-glycosylation was absent. To examine the functional significance of these structural changes, we also characterized 11beta-HSD1 activity in the hepatic microsomes. Although the guinea pig hepatic enzyme was NADP(H)-dependent and reversible, it displayed equal affinity for cortisol and cortisone (apparent K(m) for both substrates was 3 microM). This is in marked contrast to 11beta-HSD1 in other mammals whose affinity for cortisone is approximately 10 times higher than that for cortisol (apparent K(m) of 0.3 vs. 3.0 microM). The apparent lower affinity of the guinea pig enzyme for cortisone would suggest that the intracellular bioformation of cortisol from circulating cortisone may be less efficient in this species. Northern blot analysis and RT-PCR revealed that the mRNA for 11beta-HSD1 was widely expressed in the adult guinea pig but at low amounts. In conclusion, the present study has identified distinct features in the deduced primary structure and catalytic function of 11beta-HSD1 in the guinea pig. Thus, the guinea pig provides a useful model in which the structural determinants of catalytic function of 11beta-HSD1 may be studied.
11-beta-Hydroxysteroid Dehydrogenases↗
Insulin attenuates the stimulatory effects of tumor necrosis factor alpha on 11beta-hydroxysteroid dehydrogenase 1 in human adipose stromal cells.
Obesity is frequently associated with insulin-resistance and abnormal glucose homeostasis. Recent evidence indicates that TNFalpha may play a role in mediating the insulin-resistance of obesity through its overexpression in adipose tissue. Previously, we have shown that human adipose stromal cells contain 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) mRNA and activity. The present study was designed to examine the effects of insulin on 11beta-HSD1 expression in human adipose stromal cells under basal and TNFalpha-stimulated conditions. The cells were obtained from breast adipose tissue by collagenase digestion, and grown to confluence under replicating conditions in 10% fetal bovine serum. The cells were transferred to serum-free medium for 24 h prior to treatment with either TNFalpha, insulin or both for a further 24 h. The level of 11beta-HSD1 reductase activity was determined by measuring the conversion of [(3)H]-cortisone to [(3)H]-cortisol at a substrate concentration of 10 nM. Treatment with TNFalpha at concentrations of 0.1-10 ng/ml resulted in a dose dependent increase in 11beta-HSD1 reductase activity from 1.5 to 10-fold. Insulin (0.1-100 nM) had no effect under basal conditions, but inhibited the stimulatory effects of TNFalpha (5 ng/ml) on 11beta-HSD1 reductase activity in a dose dependent fashion (8-66%) inhibition). Northern blot analysis revealed corresponding changes in the level of 11beta-HSD1 mRNA, suggesting that the effects of TNFalpha and insulin on 11beta-HSD1 activity are mediated at the level of gene transcription. The interaction between insulin and TNFalpha suggests that local and systemic factors may act in a concerted fashion to modulate glucocorticoid activity in adipose and other peripheral tissues.
11-beta-Hydroxysteroid Dehydrogenases↗
Analysis of the disulfide bonding pattern between domain sequences of recombinant prochymosin solubilized from inclusion bodies.
Prochymosin contains three disulfide bonds linking Cys45 to Cys50, Cys206 to Cys210, and Cys250 to Cys283. To analyze the disulfide bonding pattern between domain sequences in the recombinant prochymosin molecule solubilized from inclusion bodies by 8 M urea (designated as solubilized prochymosin), a simple peptide mapping method was established. This process consists of thiol alkylation, cleavage with cyanogen bromide, diagonal electrophoresis on polyacrylamide gel, and N-terminal sequencing. By using this procedure it was found that Cys45 and Cys50 located in the N-terminal domain are not mispaired with the cysteine residues, located in the C-terminal domain, in the solubilized wild-type prochymosin and its mutants. This result implies that Cys45 and Cys50, the partners of a native disulfide, are restricted in some ordered structures existing in inclusion bodies and remaining after solubilization. These native structural elements act as folding nuclei to initiate and facilitate correct refolding. The strategy of preserving the native-like structures including native disulfide in the solubilized inclusion bodies to enhance renaturation efficiency may be applicable to other recombinant proteins.
Chymosin↗
Chaperone-mediated refolding of recombinant prochymosin.
It has been verified that prochymosin is characterized by a two-stage refolding: dilution of unfolded protein into pH 11 buffer followed by neutralization at pH 8; the high-pH step is indispensable. Here we demonstrate that one-stage refolding around pH 8 can be achieved when GroE or 10-fold molar excess (rather than catalytic concentration) of protein disulfide isomerase (PDI) over prochymosin is present. The helping effect varies with the oxidation states of prochymosin. GroE and PDI increase the reactivation of the unfolded, partially reduced and the unfolded, oxidized prochymosin from 5% to 40% and from 50% to 100%, respectively. For the unfolded and fully reduced prochymosin, GroE does not have a positive effect, whereas PDI promotes renaturation from 2% to 28%. Based on our previous and present observations, we propose that at pH 8 there may be two kinds of incorrect interactions within and between prochymosin polypeptides leading to unproductive pathways: one prevents disulfide rearrangement, which can be avoided by high pH; the other interferes with acquisition of native conformation, which can be relieved by GroE and PDI.
Animals↗
T-DNA insertional mutagenesis for functional genomics in rice.
We have produced 22 090 primary transgenic rice plants that carry a T-DNA insertion, which has resulted in 18 358 fertile lines. Genomic DNA gel-blot and PCR analyses have shown that approximately 65% of the population contains more than one copy of the inserted T-DNA. Hygromycin resistance tests revealed that transgenic plants contain an average of 1.4 loci of T-DNA inserts. Therefore, it can be estimated that approximately 25 700 taggings have been generated. The binary vector used in the insertion contained the promoterless beta-glucuronidase (GUS) reporter gene with an intron and multiple splicing donors and acceptors immediately next to the right border. Therefore, this gene trap vector is able to detect a gene fusion between GUS and an endogenous gene, which is tagged by T-DNA. Histochemical GUS assays were carried out in the leaves and roots from 5353 lines, mature flowers from 7026 lines, and developing seeds from 1948 lines. The data revealed that 1.6-2.1% of tested organs were GUS-positive in the tested organs, and that their GUS expression patterns were organ- or tissue-specific or ubiquitous in all parts of the plant. The large population of T-DNA-tagged lines will be useful for identifying insertional mutants in various genes and for discovering new genes in rice.
Base Sequence↗
Preparation and characterization of mabs against different epitopes of CD226 (PTA1).
Recently the platelet and T-cell activation antigen 1 (PTA1) was assigned as CD226 at the 7th Conference and Workshop on Human Leukocyte Differentiation antigens (HLDA). PTA1 is mainly expressed on activated T cells, natural killer (NK) cells, platelets and stimulated endotheliocytes, and involved in the differentiation of cytotoxic T lymphocytes (CTL) and NK, as well as platelet activation and aggregation. We raised hybridomas secreting monoclonal antibodies (MAbs) to PTA1 by using the natural PTA1 as immunogen, which was purified from platelets via affinity chromatography. These MAbs, designated FMU1, FMU2, FMU3, FMU4, FMU5, FMU6 and FMU7, could recognize PTA1 cDNA transfected COS7 cells detected by flow cytometry (FCM), and also react with both natural PTA1 and PTA1/Ig fusion protein in indirect enzyme-linked immunoadsorbent assay (ELISA). The biosensor epitope mapping assay showed that the seven MAbs, together with previous PTA1-specific MAbs Leo A1 and New E1, could bind seven distinct epitopes of PTA1, respectively. The panel of MAbs might be new powerful tools to study the structure-function relationship of PTA1 molecule, and to search for the ligand of PTA1.
Animals↗
Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon.
In this study we investigated the chemopreventive effects of quercetin and rutin when added to standard AIN-76A diet and fed to normal and azoxymethane (AOM)-treated mice. Early changes in colonic mucosa were analyzed, including colonic cell proliferation, apoptotic cell death, cyclin D(1) expression and focal areas of dysplasia (FAD). The findings show that the number of colonic epithelial cells per crypt column increased (P: < 0.01) in each normal mouse group fed the flavonoids; AOM administration increased colonic crypt cell proliferation and resulted in a marked rise of bromodeoxyuridine-labeled cells in the lower proliferative zone of the crypt. Both supplementary dietary quercetin and rutin increased the apoptotic index and caused a redistribution of apoptotic cells along the crypt axis in normal mice fed a standard AIN-76A diet. The number of apoptotic cells/column and apoptotic indices markedly increased (P: < 0.01) in the AOM-treated group compared with untreated animals; apoptotic cells expanded throughout the colonic crypts after flavonoid supplementation and AOM administration. Positive cyclin D(1) expression was detected in mice on diets supplemented either with quercetin (P: < 0.01) or rutin (P: < 0.05). AOM administration resulted in the formation of FAD. Both the number of mice exhibiting FAD and the total numer of FAD observed were significantly reduced (P: < 0.01) in AOM-treated animals fed flavonoids compared with mice maintained on the standard AIN-76A diet. Surprisingly, however, quercetin alone was able to induce FAD in 22% of normal mice fed the standard AIN-76A diet.
Animals↗
An acyl-coenzyme A carboxylase encoding gene associated with jadomycin biosynthesis in Streptomyces venezuelae ISP5230.
Analysis of a region of chromosomal DNA lying between jadR1 and jadI in the gene cluster for jadomycin biosynthesis in Streptomyces venezuelae ISP5230 detected an ORF encoding 584 amino acids similar in sequence to the biotin carboxylase (BC) and biotin carboxyl carrier protein (BCCP) components of acyl-coenzyme A carboxylases. Multiple sequence alignments of the deduced Jad protein with acyl-coenzyme A carboxylases from various sources located the BC and BCCP components in the N- and C-terminal regions, respectively, of the deduced polypeptides. The organization and amino acid sequence of the deduced polypeptide most closely resembled those in other Gram-positive bacteria broadly classified as actinomycetes. Disrupting the gene, designated jadJ, severely reduced but did not eliminate jadomycin production. The disruption had no effect on growth or morphology of the organism, implying that the product of jadJ is not essential for fatty acid biosynthesis. It is concluded that jadJ supplies malonyl-coenzyme A for biosynthesis of the polyketide intermediate that is eventually processed to form the antibiotic jadomycin B.
Amino Acid Sequence↗
Characterization of the protocatechuic acid catabolic gene cluster from Streptomyces sp. strain 2065.
Protocatechuate 3,4-dioxygenase (EC 1.13.11.3) catalyzes the ring cleavage step in the catabolism of aromatic compounds through the protocatechuate branch of the beta-ketoadipate pathway. A protocatechuate 3,4-dioxygenase was purified from Streptomyces sp. strain 2065 grown in p-hydroxybenzoate, and the N-terminal sequences of the beta- and alpha-subunits were obtained. PCR amplification was used for the cloning of the corresponding genes, and DNA sequencing of the flanking regions showed that the pcaGH genes belonged to a 6. 5-kb protocatechuate catabolic gene cluster; at least seven genes in the order pcaIJFHGBL appear to be transcribed unidirectionally. Analysis of the cluster revealed the presence of a pcaL homologue which encodes a fused gamma-carboxymuconolactone decarboxylase/beta-ketoadipate enol-lactone hydrolase previously identified in the pca gene cluster from Rhodococcus opacus 1CP. The pcaIJ genes encoded proteins with a striking similarity to succinyl-coenzyme A (CoA):3-oxoacid CoA transferases of eukaryotes and contained an indel which is strikingly similar between high-G+C gram-positive bacteria and eukaryotes.
Amino Acid Sequence↗
Programmed cell death, proliferating cell nuclear antigen and p53 expression in mouse colon mucosa during diet-induced tumorigenesis.
Western-style diets (WDs) trigger and sustain the early phases of tumorigenesis in mouse colon, and when continued throughout the life span lead to the development of dysplastic crypts. In order to evaluate the roles both of cell proliferation and programmed cell death (PCD) in WD-induced tumorigenesis, immunohistochemical detection of proliferating nuclear antigen (PCNA), in situ end labeling (TUNEL) of DNA breaks, and p53 protein were carried out in mouse colonic mucosa during prolonged feeding of two WDs. PCNA Labeling Index of colonic crypts was significantly higher in WD-treated animals than in controls only at the beginning of the nutritional study, the gap rapidly bridged by increased cell proliferation spontaneously occurring in the colonic mucosa during aging. A transient early homeostatic activation of PCD at the base of the crypt also was observed in WD groups. No changes in PCD were seen in the upper third of the crypt or in surface epithelium throughout the study, indicating that PCD in that colonic crypt segment produces a constant flux of cell loss, uninfluenced by homeostatic fluctuations. A major finding was an irreversible, progressive, age-related decline of PCD at the crypt base in both control and treated animals that occurred during the second half of the rodents' life span. p53 protein was not immunohistochemically detected, suggesting that neither overexpression of wild-type nor mutated forms of the protein are involved in the above mentioned changes.
Animals↗
Spectroscopic properties of fluoroquinolone antibiotics and nanosecond solvation dynamics in aerosol-OT reverse micelles.
Among fluoroquinolone antibiotics, ofloxacin (OFL) and norfloxacin (NOR) have piperazinyl groups but flumequine (FLU) does not have this substitutent. The emission spectra of OFL and NOR are strong, broad structureless bands with large Stokes' shifts in water but the emission intensities are very weak in organic solvents. Thus we find that these compounds exist as different chemical species in various solvents. A continuous red shift in the emission bands for OFL and NOR is observed as the water concentration within the aerosol-OT (AOT; sodium 1,4-bis[2-ethylhexyl]sulfosuccinate) micelle increases or temperature of this solution rises. From the fluorescence anisotropy measurements of OFL and NOR, we assume the intramolecular charge transfer after excitation from the nitrogen of the piperazinyl group to the keto oxygen. Theoretical calculations further support this observation. Multifrequency phase and modulation experiments and time-resolved emission spectra clearly show the occurrence of intramolecular charge transfer and the subsequent nanosecond water reorganization around OFL or NOR in the AOT micelle. Upon increasing the water concentration within the AOT micelle, the relaxation rate increases because of the large amount of free water. The emission spectra of FLU do not exhibit any significant response to the physical properties of their environment.
Anti-Infective Agents↗
[The effect of intraperitoneal chemotherapy on retroperitoneal lymph node metastasis of ovarian cancer].
The objective of this study was to investigate the effect of intraperitoneal chemotherapy(repeated injections of cisplatin in small doses during a short time) on retroperitoneal lymph node metastasis of ovarian cancer. Thirty patients with ovarian cancer were selected and divided into two groups. The patients in the first group received intraperitoneal chemotherapy only once (48 hours before operation); the patients in the second group received intraperitoneal chemotherapy twice (96 hours and 48 hours before operation). After the intraperitoneal chemotherapy, according to the predicted time, the Pt concentrations of the tissues were measured by flameless atomic absorption spectrometry; the pathologic examinations of the lymph nodes were carried out. The results showed that the drug concentrations of the aortic, obturator and iliac lymph nodes of the first group were not significantly different, neither were the drug concentrations of the lymph nodes of the second group. The drug concentrations of the lymph nodes of the first and the second groups were 2.06 and 1.91 times that of the surrounding tissues respectively. Also, the drug concentrations of peritoneum of the first and the second groups were 4.14 and 2.50 times that of the lymph nodes. The drug concentrations of the iliac, obturator and aortic lymph nodes of the second group were 2.27, 2.75 and 2.54 times that of the first group (P < 0.005). Under light microscope, the metastatic cancer tissues in lymph nodes showed liquefaction necrosis in the second group. The results indicate that small doses of cisplatin given by repeated injections during a short time can lead to drug accumulation and consequently high efficacy with low toxicity, suggesting that this method may be used for the treatment of lymphatic metastasis of ovarian cancer.
Antineoplastic Agents↗
[Effects of selenium and zinc on the DNA damage caused by fluoride in pallium neural cells of rats].
To investigate the effects of fluoride on DNA damage as well as the effects of selenium and zinc against fluoride respectively or jointly in pallium neural cells of rats, single cell gel electrophoresis was used to detect the DNA damage of neural cells prepared in vitro. The results showed that the degree of DNA damage in the fluoride group and the selenium group were significantly greater than that in control group(P < 0.01). The damage in the fluoride group was even more serious. The damage in the fluoride + selenium group and fluoride + zinc group was slighter than that in the fluoride group but with no significant difference. The extent of DNA damage in the fluoride + selenium + zinc group was significantly slighter than that in the fluoride group(P < 0.05). It suggested that fluoride and selenium could induce DNA damage in pallium neural cells of rats respectively. Moreover, the joint antagonistic effect of selenium and zinc against fluoride was more obvious.
Animals↗
[Dynamic study of hepatocellular pathological change and uptake rate of 125I-insulin during experimental hepatocarcinogenesis].
This study was designed to observe the hepatocellular pathological change and uptake rate of 125I-insulin during experimental hepatocarcinogenesis in rats and clarify the possible mechanism of increasing uptake of 125I-insulin. 80 SD rats were divided into 2 groups, control and experimental groups. All of the rats were given common feed, and the rats of experimental group were given extra diethylnitrosamine (DENA) 70 mg/kg each week. At 6th, 11th, 15th and 20th week after start of the experiment, 10 control and 10 experimental rats were killed 1 hour post administration of 125I-insulin by tail vein. Blood, liver, lung, spleen, kidney, muscle and bone were collected; the radioactivity was measured and calculated %ID/g. The data of 2 groups were compared and examined with t-test. All of livers were pathologically examined. The results showed all livers of control group were normal. At 6th week, the surfaces of experimental rats' livers were coarse. Hepatocellular hyperplasia was observed, 125I-insulin-uptake rate was 1.86 time as much as that of control group. At 11th week, the liver's colour became lighter than that of control group. Hyperplasia and hepatocirrhosis were observed, 125I-insulin-uptake rate was 1.50 time as much as that of control group. At 15th week, hyperplastic nodules were observed in all experimental rats' livers. Hepatomacellulae were observed in 6 rat livers. 125I-insulin-uptake rate was 1.56 time as much as that of control group. At 20th week, the livers became enlarged out of shape. There were a lot of big or small greyish white nodules in all livers. Necrosis, liquefaction and hemorrhage were observed. Hepatomacellulae were observed in all of experimental rats livers. 125I-insulin-uptake rate was 1.46 time as much as that of control group. The differences of 125I-insulin-uptake rate between experimental and control groups were significant. These results demonstrated that the liver ability of uptaking 125I-insulin increased which mainly took place during the period of hepatocellular hyperplasia, and the hepatomacellulae kept this characteristic.
Animals↗