Search PubMed⌕ Search

Biomedical subjects

K Zhao

Publications and source records attributed to K Zhao.

At least 109 records · Page 6Linked to original sources
PubMed1994

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a potent mutagen in the mouse small intestine.

Mutations in long lived stem cells are critical events in carcinogenesis. The Dlb-1 assay detects intestinal stem cell mutation at the Dlb-1 locus in Dlb-1a/b heterozygous mice by visualizing mutated clones of epithelial cells in situ which do not bind the lectin Dolichos biflorus agglutinin. We have used this assay to show that the food-derived heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a potent intestinal mutagen when administered either i.p. or p.o. This contrasts with the inactivity of the structurally related mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the assay which we have described previously. Immunocytochemical localization of the P-450 enzyme CYP1A2, which is responsible for the primary activation of these mutagens, shows that in untreated mice it is present in liver hepatocytes and in occasional villus epithelial cells but is absent from the target intestinal stem cell population. In addition, liver microsomes, unlike intestinal microsomes, were able to convert PhIP to the proximate mutagen N-hydroxy-PhIP. CYP1A2 immunoreactivity in beta-napthoflavone-induced animals was elevated in liver hepatocytes and increased to a lesser extent in duodenal villus epithelial cells. Treatment with beta-napthoflavone produced an unexpected 46% decrease in the number of Dlb-1 mutations in response to PhIP. Following treatment with PhIP, there was no difference in the number of Dlb-1 locus mutations between the proximal and distal ends of the small intestine in uninduced animals, indicating that the bile duct is unlikely to be responsible for transport of mutation inducing metabolites of PhIP to the small intestine. Our results demonstrate that metabolic activation of an indirect acting genotoxic agent can occur at a site other than the target tissue, and absence of the enzymes required for activation of a mutagen does not necessarily protect that tissue from its genotoxic effects.

Animals↗
PubMed1994

Metabolism of the food derived mutagen and carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) by human liver microsomes.

Animal studies have shown that 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) undergoes both activation to a genotoxic metabolite and detoxication, catalysed by CYP enzymes. In this study, using direct chemical analysis, we have examined PhIP metabolism by the microsomal fraction of human liver for comparison to that occurring in animals. PhIP was incubated with human liver microsomes in the presence of an NADPH regenerating system and the reaction mixture then analyzed by HPLC. Only one metabolite, identified as N-hydroxy PhIP, was produced. The N-hydroxylation of PhIP by human liver microsomal fraction obeyed Michaelis-Menten kinetics, with a Km of 55 microM and a Vmax of 666 pmol/min/mg protein. Furafylline, a potent and specific inhibitor of CYP1A2 in man, inhibited this reaction by > 95%, with an IC50 of 0.6 microM. PhIP inhibited high affinity phenacetin O-deethylase activity of human liver microsomes, an activity catalysed specifically by CYP1A2, with an IC50 of about 80 microM. These data indicate that, in human liver microsomes, N-hydroxylation is the only route of oxidative metabolism of PhIP, yielding a genotoxic species, and that this reaction is catalysed almost exclusively by CYP1A2. Furthermore, the exclusive oxidative activation of PhIP by human liver is in direct contrast to PhIP metabolism in rodents and non-human primates where oxidative detoxication products predominate.

Carcinogens↗
PubMed1994

[The prognostic implication of determination of activation of leucocyte in severe burns].

Using NBT test, the relationship between the percentage change of activated neutrophils with the survival time of animals after severe burns was observed. The results showed that the NBT positive rate of neutrophils increased markedly after burn, and the NBT positive rate at 5 h postburn was negatively related to the survival time of burned animals. Continuous monitoring of neutrophil indicated that if the NBT positive rate after burn remained in the normal range, or increased initially to high level and then decreased to lower than normal, the survival time was longer. However, if the NBT positive rate increased continuously after burn, the survival time was shorter. Therefore, continuous assay of neutrophil activation with NBT is an important index for the prognosis of severe burns. Lowering of NBT positive rate was observed in rats treated with polygonum cuspidatum, and these rats lived much longer than those without the treatment.

Animals↗
PubMed1994

Functional superficial parotidectomy.

PURPOSE: To clinically test a new type of parotid surgery termed functional superficial parotidectomy (FSP) to preserve the function of the residual gland. PATIENTS AND METHODS: Sixteen human parotid specimens were dissected, and 19 patients underwent FSP. RESULTS: It was shown that 91.4% of the main parotid ducts were found deep to the surface of the facial nerve. Physical examination, sialography, and scintigraphy showed that function of the residual gland was well preserved by FSP. CONCLUSION: A comparison of the main complications between FSP and conservative superficial parotidectomy showed a significant decrease (P < .01) of Frey's syndrome with FSP.

Adenolymphoma↗
PubMed1993

Antibody-catalyzed degradation of cocaine.

Immunization with a phosphonate monoester transition-state analog of cocaine provided monoclonal antibodies capable of catalyzing the hydrolysis of the cocaine benzoyl ester group. An assay for the degradation of radiolabeled cocaine identified active enzymes. Benzoyl esterolysis yields ecgonine methyl ester and benzoic acid, fragments devoid of cocaine's stimulant activity. Passive immunization with such an artificial enzyme could provide a treatment for dependence by blunting reinforcement.

Animals↗
PubMed1993

SAR-dependent mobilization of histone H1 by HMG-I/Y in vitro: HMG-I/Y is enriched in H1-depleted chromatin.

An experimental assay was developed to search for proteins capable of antagonizing histone H1-mediated general repression of transcription. T7 RNA polymerase templates containing an upstream scaffold-associated region (SAR) were highly selectively repressed by H1 relative to non-SAR control templates. This is due to the nucleation of H1 assembly into flanking DNA brought about by the numerous A-tracts (AT-rich sequences containing short homopolymeric runs of dA.dT base pairs) of the SAR. Partial, selective titration of these A-tracts by the high mobility group (HMG) protein HMG-I/Y led to the complete derepression of transcription from the SAR template by inducing the redistribution of H1 on to non-SAR templates. SARs are associated with many highly transcribed regulated genes where they may serve to facilitate the HMG-I/Y-mediated displacement of histone H1 in chromatin. Indeed, HMG-I/Y was found to be strongly enriched in the H1-depleted subfraction which can be isolated from chromatin.

Animals↗
PubMed1993

Expression of connexin-43 in human myometrium and leiomyoma.

OBJECTIVES: The expression of connexin-43 was examined in human leiomyomas and in autologous myometrium. STUDY DESIGN: Indirect immunofluorescence was used to detect connexin-43 gap junctions in myometrial and leiomyoma tissues and in primary cultures. Immunoblot and Northern analyses were used to examine the levels of connexin-43 protein and cx43 messenger ribonucleic acid in primary cultures. RESULTS: Connexin-43 gap junctions were detected in leiomyoma tissue from nonpregnant premenopausal women but not in autologous myometrial tissue. Connexin-43 gap junctions form spontaneously in primary cultures of myometrium and leiomyoma in the presence of 17 beta-estradiol. Fluorescent dye injection confirmed that the gap junctions were coupled in the primary cells. Connexin-43 protein and messenger ribonucleic acid levels generally were higher in leiomyoma cells compared with those of autologous myometrial cells. Steady-state levels of cx43 messenger ribonucleic acid decreased with addition of medroxyprogesterone acetate to the cultures. CONCLUSIONS: Differences in the levels of cx43 expression in leiomyoma and myometrial cells may reflect differences in responses to steroid hormones.

Adult↗
PubMed1993

Molecular dosimetry of the food-borne carcinogen MeIQx using adducts of serum albumin.

Incubation of mouse serum albumin with the food borne carcinogen [2-14C]-Amino-3,8,-dimethylimidazo[4,5-f]quinoxaline (14C-MeIQx) in the presence of mouse hepatic microsomes and an NADPH-regenerating system in vitro resulted in the formation of adducts of MeIQx with albumin, which increased proportionately with time for at least 120 min (approximately 1 pmol equivalents/mg of protein/min). We have previously shown in male Swiss Webster mice in vivo that 14C-MeIQx bound covalently to serum proteins and that the formation of adducts was dose dependent. 14C-MeIQx (100 mg/kg, i.p.) was administered to male (MF1) mice which were killed 24 h later. Serum albumin was purified by affinity chromatography and covalent binding of 14C-MeIQx was assessed. Total covalent binding of MeIQx to albumin was 14.0 +/- 5.2 pmol per mg albumin, which was 5-fold greater than to haemoglobin. Following mild acid hydrolysis, 1.25 pmol MeIQx per mg albumin was liberated as free amine, as determined by gas chromatography negative ion mass spectrometry (GC-MS). This represents 9% of total MeIQx adducted to albumin in vivo (cf 1.3% adducted to haemoglobin). These results suggested that adducts of MeIQx with serum albumin should provide a significantly more sensitive dosimeter than those with haemoglobin. We therefore investigated this approach with serum protein samples from three volunteers. Human serum albumin and non-serum albumin protein fractions were separated by affinity chromatography, before being subjected to GC-MS analysis for hydrolysable adducts of MeIQx. The levels of MeIQx in control samples, and from the release of the putative sulphinamide adducts in hydrolysed samples were below the limits of detection of the GC-MS assay (29 +/- 2.6 amol MeIQx/mg albumin). Despite an increase of 2 orders of magnitude in sensitivity, compared with haemoglobin, it is unlikely that the sulphinamide adduct of MeIQx with human serum albumin can be used as a dosimeter for human aminoimidazoazaarene exposure.

Adult↗
PubMed1993

Field evaluation of bednets impregnated with deltamethrin for malaria control.

Trials were undertaken in a hypoendemic area of malaria in an area bordering Vietnam, in Napo County of Guangxi Zhuang Autonomous Region, China. The aim was to compare the relative cost effectiveness of DDT residual spraying and of bednets impregnated with deltamethrin in the malaria control program. The trials were divided into three subgroups: (1) two farming areas and one coal mining area with a total population > 20,000, where the trial consisted of mass bednets impregnated with deltamethrin 15 mg/m2 net surface once a year, (2) one farming area with a population of approximately 3,600 where DDT residual spraying at 2g/m2 was carried out twice a year in May and August; (3) one farming area and one coal mining village with a population of > 4,000 were used as a control. The malaria vector population consisted mainly of Anopheles minimus and An. anthropophagus with a small contribution from An. sinensis. After bednets were impregnated with deltamethrin the mosquitos resting on the surface of the bednets decreased significantly, although there was less effect on the total vector population. The results showed that malaria incidence decreased significantly both in areas where impregnated bednets were used and in areas where residual spraying was undertaken. The positive IFAT rates of residents who slept under impregnated bednets decreased significantly in farming areas, especially in that area where bednet impregnation as a vector control measure had been undertaken for two years, but there was no change in the IFAT rate in DDT sprayed or control areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Bedding and Linens↗
PubMed1989

The function of micF RNA. micF RNA is a major factor in the thermal regulation of OmpF protein in Escherichia coli.

The role of chromosomally derived micF RNA as a repressor of outer membrane protein OmpF of Escherichia coli was examined for various growth conditions. Levels of micF RNA as determined by Northern analyses are found to increase in response to cell growth at high temperature, in high osmolarity or in the presence of ethanol. After a switch to higher growth temperature, the levels of ompF mRNA and of newly synthesized OmpF decrease with time in E. coli strain, MC4100 but these decreases are not observed in isogenic micF deletion strain, SM3001. In addition, while levels of ompF mRNA are substantially reduced in both strains in response to high osmolarity or ethanol at 24 degrees C, the reduced levels in the parental strain are still 4-5-fold lower compared with the micF deletion strain. These findings indicate that chromosomally derived micF RNA plays a major role in the thermal regulation of OmpF and represses OmpF synthesis in response to several environmental signals by decreasing the levels of ompF mRNA. Analyses of the effect of a multicopy micF plasmid on the levels of OmpF and ompF mRNA after an increase in temperature indicated that multicopies of micF RNA markedly inhibited OmpF synthesis but did not accentuate ompF mRNA decrease. These data suggest that multicopy micF inhibits OmpF synthesis primarily through translational inactivation of ompF mRNA and that a limiting factor in addition to micF RNA is necessary to destabilize ompF mRNA.

Bacterial Outer Membrane Proteins↗