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Biomedical subjects

K Zhao

Publications and source records attributed to K Zhao.

At least 91 records · Page 5Linked to original sources
PubMed1997

The scs' boundary element: characterization of boundary element-associated factors.

Boundary elements are thought to define the peripheries of chromatin domains and to restrict enhancer-promoter interactions to their target genes within their domains. We previously characterized a cDNA encoding the BEAF-32A protein (32A), which binds with high affinity to the scs' boundary element from the Drosophila melanogaster 87A7 hsp70 locus. Here, we report a second protein, BEAF-32B, that differs from 32A only in its amino terminus. Unlike 32A, it has the same DNA binding specificity as the complete BEAF activity affinity purified from Drosophila. We characterize three domains in these proteins. Heterocomplex formation is mediated by their identical carboxy-terminal domains, and DNA binding is mediated by their unique amino-terminal domains. The identical middle domains of 32A and 32B are dispensable for the functions described here, although they may be important for boundary element function. 32A and 32B apparently form trimers, and the ratio of 32A to 32B varies at different loci on polytene chromosomes as judged by immunofluorescence. The scs' element contains a high- and low-affinity binding site for BEAF. We observed that interaction with the low-affinity site is facilitated by binding to the high-affinity site some 200 bp distant.

Amino Acid Sequence↗
PubMed1996

Binding of matrix attachment regions to nuclear lamin is mediated by the rod domain and depends on the lamin polymerization state.

The nuclear matrix maintains specific interactions with genomic DNA at sites known as matrix attachment regions (M/SARs). M/SARs bind in vitro to lamin polymers. We show that the polymerized alpha-helical rod domain of lamin Dm0 provides by itself the specific binding to the ftz M/SAR. In contrast, unpolymerized rod domain does not bind specifically to this M/SAR. Non-specific binding to DNA is also observed with Dm0 containing a point mutation that impairs its ability to polymerize or with the isolated tail domain. These data suggest that the specific binding of lamins to M/SARs requires the rod domain and depends on the lamin polymerization state.

Amino Acid Sequence↗
PubMed1996

New pentapeptides from Aster tataricus.

Three pentapeptides have been isolated from the roots of Aster tataricus and their structures elucidated on the basis of spectroscopic analysis as well as chemical and enzymatic methods.

Amino Acid Sequence↗
PubMed1996

Heterocyclic amines: evaluation of their role in diet associated human cancer.

1. Heterocyclic amines are formed in parts per billion levels when meat is cooked. 2. The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food. 3. We have shown that MeIQx and PhIP, both in vitro and in vivo, are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines. 4. MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt, we have shown that PhIP induces a characteristic mutational 'fingerprint'. 5. MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational 'fingerprint' has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats.

Animals↗
PubMed1996

Developmental changes in hepatic activation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in rabbit.

MeIQx, a potent bacterial mutagen formed when meat is cooked, requires metabolic activation to exert its genotoxicity, a reaction catalysed primarily by CYP1A2 in adult mammals. Little is known about mammalian developmental changes in the mutagneic activation of compounds such as MeIQx. In rabbits we have shown previously that expression of CYP1A2 increases with age and is inducible by 3-methylcholanthrene (MC) from as early as 4 days pre-parturition. We have therefore investigated the effect of age on rabbit liver activation of MeIQx (assessed in an Ames test using Salmonella typhimurium TA98) before and after treatment of the animals with MC. MeIQx activation could not be detected using hepatic microsomal fractions from rabbits of <17 days of age. Thereafter activation increased with age to peak in weanling animals. Following MC treatment MeIQx activation was increased, being detectable in samples from rabbits as young as 9-11 days. The inducibility of MeIQx activation increased with age, reaching a plateau between 17 and 35 days. These rates of activation were broadly parallel to the changes in CYP1A2 specific content. These results indicate that the ability of rabbit liver to activate MeIQx is dependent on CYP1A2 activity, the expression of which is developmentally regulated. Although it has been established that human activation of MeIQx is also CYP1A2 dependent, whether a similar situation exists in infant humans has yet to be determined, although there is evidence that CYP1A2-dependent activity reaches a peak in late childhood.

Age Factors↗
PubMed1996

Treatment of old mice with IL-2 corrects dysregulated IL-2 and IL-4 production.

Splenic T cells from old BALB/c mice, activated in vitro with antibody to CD3epsilon, secrete more IL-4 but less IL-2 than splenic T cells from young mice. The age-associated increase in IL-4 secretion is associated with a significantly increased concentration of intracellular IL-4 and its mRNA, although there is no increase in the number of activated T cells with intracellular IL-4. In contrast, the age-associated decrease in IL-2 secretion is associated with a significant decrease in the number of activated T cells with intracellular IL-2. In vivo there is a similar age-associated change in the number of activated T cells with detectable cytokine. The number of activated T cells with intracellular IL-4 is comparable in old and young mice, while the number of activated T cells with intracellular IL-2 is significantly decreased in old compared with young mice. Of great interest is the fact that old mice continuously exposed to IL-2 in vivo following the transplantation of J558 cells expressing the transfected IL-2 gene product have an increased number of splenic T cells with intracellular IL-2 that equals the level of such cells observed in young mice. Most important, the effect of continuous IL-2 administration in vivo was stable as spleen cells from old, IL-2-treated mice when stimulated in vitro with anti-CD3epsilon had a young-like pattern of both intracellular IL-2 and IL-4 expression as well as IL-2 and IL-4 secretion following in vitro activation. Thus, it appears that exposure of old mice to exogenous IL-2 can redress the age-associated imbalance in cytokine expression in vivo and cytokine secretion in vitro.

Age Factors↗
PubMed1996

Progestin represses human connexin43 gene expression similarly in primary cultures of myometrial and uterine leiomyoma cells.

The mechanism by which progestin represses the expression of the human connexin43 (cx43) gene was analyzed in primary cultures of human myometrial cells, and for comparison, in primary cultures of uterine leiomyoma cells. Within 24 h, the levels of connexin43 (Cx43) protein in primary cells treated with progestin were reduced to about 50% of that in untreated cells, and these levels were maintained for up to 120 h. A plateau in the reduction of Cx43 protein levels was reached at progestin concentrations of 50-100 nM. No significant difference was found in a comparison of progestin-mediated reduction of Cx43 protein in autologous myometrial and leiomyoma primary cultures. Levels of cx43 mRNA levels also decreased to about 50% in myometrial and leiomyoma cells within hours after treatment with progestin, and these new levels were maintained for up to 48 h. Nuclear run-on transcription analysis showed that 100 nM progestin partially repressed transcription of the cx43 gene in both myometrial and leiomyoma primary cultures. The amount of decrease in cx43 transcription in cells treated with progestin was paralleled by a corresponding decrease in cytoplasmic cx43 mRNA levels. Progesterone receptor (PR)-mediated transcription was also determined to be similar in the two types of primary cells as evidenced by transient expression assays. Thus progestin down-regulates the expression of the human cx43 gene primarily by repressing transcription of the gene in myometrial cells, and it acts similarly in leiomyoma cells.

Cells, Cultured↗
PubMed1996

[Nosocomial transmission of Helicobacter pylori through fiberoptic gastroscopy].

The relationship of nosocomial transmission of Helicobacter pylori (Hp) by fiberoptic gastroscopy was investigated. Hp was cultured from the materials obtained from the suction/biopsy channel (4/12 times) and biopsy forceps (3/10 times). The positive rate of Hp was increased with times undertaking endoscopy in the past in elder patients with chronic gastritis. The rate from Hp negative transforming into positive also increased with the times of receiving endoscopic follow-up in the past in patients with Hp negative chronic gastritis. The average age of Hp positive patients were older in those patients under follow-up studies than that in randomly age-matched normal or chronic gastritis controls. The results suggested that the contamination of gastroscopic equipment played a potential role as vehicle causing nosocomial infection of Hp. The risks of Hp transmission correlated with times of undertaking endoscopy, especially in the elderly.

Adult↗
PubMed1996

Pentapeptides from the roots of Aster tataricus.

Asterinin D and E, pentapeptides, have been isolated from the roots of Aster tataricus L.f. (Compositae, syn. Asteraceae, subtribe Asteroideae) and their structures have been elucidated on the basis of spectroscopic analysis, as well as chemical and enzymatic methods.

Amino Acid Sequence↗
PubMed1996

[Autotransfusion of shed mediastinal blood after open heart operation].

This prospective study was designed to determine whether the autotransfusion of shed mediastinal blood (ATS) after open heart surgery is safe and effective. Forty-two patients undergoing cardiac operation were randomized to receive either nonwashed shed mediastinal blood (group 1; n = 22) or banked blood (group 2: n = 20). No difference in mean age (group 1: 49 +/- 11 years; group 2: 45 +/- 12 years), coronary artery bypass grafting (group 1: n = 5, 23%; group 2: n = 6, 30%), valve replacement (group 1: n = 17, 77%, group 2: n = 14, 70%), and mean preoperative hemoglobin level (group 1: 13.7 +/- 2.3, group 2: 14.4 +/- 1.6) was noted between non-ATS and ATS groups (p = not significant). The mean hemoglobin levels after operation were similar in the two groups (group 1: 11.89 +/- 1.52; group 2: 12.03 +/- 1.34). No difference in the mean blood loss 4, 6 and 24 hours after operation (group 1: 33 +/- 190, 420 +/- 340 and 550 +/- 300; group 2: 340 +/- 230, 420 +/- 280 and 670 +/- 380) was observed between the two groups. The mean volume autotransfused in group I was 380 +/- 230 ml (200 approximately 1300 ml). In group I, the patients required bank blood 1080 +/- 720, compared with 1780 +/- 1045 in group II. The bank blood requirement in group I reducted by 40%. These data demonstrate that ATS after open heart surgery is safe and effective.

Adult↗
PubMed1995

Visualization of chromosomal domains with boundary element-associated factor BEAF-32.

We have purified two proteins from Drosophila that bind to the scs' boundary element of the hsp70 domain at locus 87A7. Their palindromic binding sites (CGATA-TATCG) symmetrically abut the previously mapped hypersensitive site of scs'. We have cloned a cDNA for one of these proteins, BEAF-32 (boundary element-associated factor of 32 kDa). It encodes a novel protein that is bound to scs' but not scs in vivo. Immunostaining localizes BEAF to hundreds of interbands and many puff boundaries on polytene chromosomes, suggesting that a chromosomal domain consists of a band (or puff) and part of the flanking interbands. Enhancer blocking assays implicate the palindromic binding site in boundary function. The lack of enhancer blocking in transiently transfected cells suggests an involvement of chromatin, nuclear structure, or both in boundary function.

Amino Acid Sequence↗
PubMed1995

[Chemical constituents of Euphorbia nematocypha Hand.-Mazz].

Four compounds were isolated from the roots of Euphorbia nematocypha. Three of them were identified as A'-neogammacer-22(29)-en-3 beta-ol (18 beta.21 alpha) (II), jolkinolide E (III) and beta-sitoesterol (IV). Among them, II was obtained from the genus Euphorbia and III from this plant for the first time.

Diterpenes↗
PubMed1995

Enzymatic studies of the activation of heterocyclic food mutagens in man.

2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are amongst the most abundant of the heterocyclic aromatic amines formed during the cooking of beef. Both compounds are genotoxic and carcinogenic in rodents. These effects are manifested only after activation of the amines by P450. Human liver is very active at converting these amines to mutagenic products. Studies in vitro have established that, for both amines, mutagenicity with human liver microsomes is entirely via the N-hydroxylamine, essentially the only oxidation product of either amine. Both N-hydroxylation and mutagenicity of the amines can be almost completely inhibited by furafylline, a potent and highly selective inhibitor of CYP1A2 in man. These data, together with the work of others, show that the N-hydroxylation and hence the mutagenicity of both MeIQx and PhIP in man is catalyzed almost exclusively by CYP1A2. Liver from cynomolgus monkeys, unlike that from humans and marmosets, is very poor at activating MeIQx or PhIP to mutagenic products. Studies with anti-peptide antibodies of defined specificity revealed that this is due to the absence of CYP1A2, suggesting that this species should not be used to assess the possible risk posed to man by these amines. The marmoset would be a better species for this purpose.

Animals↗