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Biomedical subjects

Z Guo

Publications and source records attributed to Z Guo.

At least 433 records · Page 24Linked to original sources
PubMed1993

In vitro granuloma formation by spleen cells treated with psoralen plus long-wave ultraviolet radiation.

In vitro granulomas are induced by culturing murine spleen cells with artificial microparticles, dextran beads. In the presence of 0.5 microgram/mL 8-methoxypsoralen, UVA radiation (0.2-2.0 J/cm2) suppressed granuloma formation in a UVA dose-dependent manner. The doses of PUVA did not affect the cell viability as assessed by trypan blue exclusion. The time course of granuloma formation in 0.5 J/cm2 PUVA-treated cells was similar to that of normal spleen cells, with a maximum granuloma index at day 3 of culture, although a 49-63% suppression of granuloma formation was observed. PUVA-treated, nonadherent cells produced the same granuloma index when cultured with normal adherent cells. In contrast, a smaller granuloma index was observed in PUVA-treated adherent cells even when they were cultured with normal nonadherent cells. These data suggest that PUVA alters macrophages, resulting in the suppression of granuloma formation in vitro.

Animals↗
PubMed1993

Signals that produce 3' termini in CYC1 mRNA of the yeast Saccharomyces cerevisiae.

The cyc1-512 mutant was previously shown to contain a 38-bp deletion, 8 nucleotides upstream from the major wild-type poly(A) site, in the CYC1 gene, which encodes iso-1-cytochrome c of the yeast Saccharomyces cerevisiae. This 38-bp deletion caused a 90% reduction in the CYC1 transcripts, which were heterogeneous in size, aberrantly long, and presumably labile (K. S. Zaret and F. Sherman, Cell 28:563-573, 1982). Site-directed mutagenesis in and adjacent to the 38-bp region was used to identify signals involved in the formation and positioning of CYC1 mRNA 3' ends. In addition, combinations of various putative 3' end-forming signals were introduced by in vitro mutagenesis into the 3' region of the cyc1-512 mutant. The combined results from both studies suggest that 3' end formation in yeast cells involves signals having the following three distinct but integrated elements acting in concert: (i) the upstream element, including sequences TATATA, TAG ... TATGTA, and TTTTTATA, which function by enhancing the efficiency of downstream elements; (ii) downstream elements, such as TTAAGAAC and AAGAA, which position the poly(A) site; and (iii) the actual site of polyadenylation, which often occurs after cytidine residues that are 3' to the so-called downstream element. While the upstream element is required for efficient 3' end formation, alterations of the downstream element and poly(A) sites generally do not affect the efficiency of 3' end formation but appear to alter the positions of poly(A) sites. In addition, we have better defined the upstream elements by examining various derivatives of TATATA and TAG ... TATGTA, and we have examined the spatial requirements of the three elements by systematically introducing or deleting upstream and downstream elements and cytidine poly(A) sites.

Alleles↗
PubMed1993

[Electroacupuncture promotes the regeneration of different fibers in rat's tibial nerve].

METHODS: 45 rats (150-200g) were divided into 9 groups. The experimental steps as follows: (1) injured left tibial nerve (group 1-8) and sham operation (group 9); (2) three days after operation, group 1, 3, 5 and 7 were stimulated with electro-acupuncture (EA) in Huantiao (+) and Sanyinjiao (-); (3) according to different survival time (group 1, 2/10 days, group 3, 4/15 days, group 5, 6/20 days, group 7, 8, 9/25 days), 48h before sacrifice, the left femoral nerve was cut, HRP was injected into the hypodermis of paw pad and gastrocnemius; (4) observe HRP labelled cells in the lumber sympathetic ganglia, ganglion spinale (L4-6) and cornu ventrale of spinal cord (L3-S3). RESULTS: EA 7 days, 2-5 labeled cells were only found in ganglion spinales of group 1; EA for 12 days, the more HRP labeled cells were observed in the lumber sympathetic ganglions (mean = 2.6), ganglion spinales (mean = 4.8) and cornu ventrale (mean = 6) of group 3 as compared with group 4 (P < 0.05); 25 days after operation, the quantity of labeled cells in group 8 was close to group 9. CONCLUSION: (1) EA promote the regeneration of three or more kinds of fibers in tibial nerve; (2) The regeneration velocity of sensory fibers was faster than sympathetic and somatic efferent fibers.

Animals↗
PubMed1993

[Inhibitory effect of intraventricular administration of morphine on the hyperviscosity and elevation of blood pressure induced by stress in the rat].

Experiments were performed on 99 Wistar rats. It was found that hyperviscosity and elevation of blood pressure (BP) could be induced by hanging and restraining conscious rats with their four limbs tied on a frame. These effects were unaffected by bilateral vagotomy. By intravenous injection of propranolol or phentolamine, elevation of BP could be reduced, while stress-induced hyperviscosity could only be reduced by propranolol (i.v.). Stress-induced hyperviscosity and elevation of BP could be inhibited by electroacupuncture applied to the right hind leg or microinjection of morphine into 4th ventricle of the brain. On the other hand, if opiate receptor antagonist naloxone was given into the 4th-ventricle, the stress-induced hyperviscosity and elevation of BP could no longer be inhibited by electroacupuncture. It is suggested that the hyperviscosity and elevation of BP induced by hanging and restraining are mediated by excitatory cardiovascular sympathetic outflow with the result of activation of adrenoreceptors. Activation of the opiate receptors in the hindbrain may be responsible for decrease in stress-induced hyperviscosity and elevation of BP and for the inhibitory effect of electroacupuncture of the right hind leg on stress-induced hyperviscosity and elevation of BP.

Animals↗
PubMed1993

Age- and gender-related variations in the activities of drug-metabolizing and antioxidant enzymes in the white-footed mouse (Peromyscus leucopus).

The effects of aging on the activities of drug-metabolizing enzymes and antioxidant enzymes were studied in male and female White-Footed mice (Peromyscus leucopus) at ages of 6, 8, 12, 18, 24, 30, 36, and 48 months. Male mice had significantly higher liver microsomal cytochrome P450 (P450) content and NADPH:cytochrome P450 oxidoreductase (P450 reductase) activities than females at all age groups. Many of the P450-dependent enzyme activities were also generally higher in males. Female mice showed age-dependent decreases in P450 content and the activities of P450 reductase, pentoxyresorufin O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMAd) in the liver from 6 to 24 months; while, the males showed an age-dependent decrease only for the liver PROD activity from 6 to 24 months. The old males (30-month old) appeared to have significantly higher activities for 6 beta-, 2 beta-, 16 alpha- and 16 beta-testosterone and androstenedione formation than the middle-aged (6- to 18-month old) and very old (48-month old) males. Females showed age-dependent decreases for the formation of 6 beta-, 2 beta-, 16 alpha- and 16 beta-testosterone in liver microsomes from 6 to 24 months. Lung microsomes from 6- and 8-month old males had much higher activities of ethoxyresorufin O-deethylase (EROD) and PROD than older males. The total NNK alpha-hydroxylation activities changed in the same pattern as lung microsomal EROD and PROD activities in both male and female mice. The activities of several phase II drug-metabolizing enzymes: glutathione S-transferase (GST), DT-diaphorase, sulfotransferase and UDP-glucuronosyl-transferase (UDPGT) did not show any significant age-dependent changes, with the possible exception that the GST activity in males decreased from 18 to 36 months. Males had about 3-fold higher UDPGT activities than females among all age groups. Glutathione peroxidase activities were drastically lower in old and very old males, and 6 to 24 months old males had significantly higher activities than the corresponding females. In females, superoxide dismutase activities decreased linearly to extremely low levels as mice aged. Catalase activities showed a tendency for increase with age in males. In conclusion, some P450-dependent activities and antioxidant enzymes, but not phase II drug-metabolizing enzymes, showed age-dependent changes; and most of these changes occur from 6 to 24 months. The demographic attributes of the White-Footed mouse are well-suited for physiological and biochemical studies of aging and can complement the more standard laboratory mouse model with its typical two year life span.

Age Factors↗
PubMed1992

Quantitative structure-activity relationships of benzamide derivatives for anti-leukotriene activities.

To determine the structural requirements of the benzamide derivatives reported by Nakai et al. (J. Med. Chem. 1988, 31, 84-91) for antileukotriene activity, we studied their conformational characteristics in comparison with those of leukotriene. By superimpositions of the conformations of antagonists on that of leukotriene, we found that the conformations of the conjugated benzamide moiety, tetrazole ring, and benzopyran or benzodioxan ring of the antagonists correspond to the triene moiety, peptide carboxylic acid residue, and cysteine residue of leukotriene, respectively, but that no moiety of the antagonists corresponds to the terminal aliphatic carboxylic acid moiety of leukotriene. Furthermore, the stable conformations of alkyl and alkoxy groups of the antagonists were quite different from that of the omega-chain of leukotriene. However, conformational analyses taking all the possible rotations of these flexible chains into consideration showed that antagonists in which these flexible chains can most feasibly adopt the same lengths as those of the omega-chain exhibit potent antagonist activity. From these results, we deduced the structural features of benzamide derivatives necessary for potent antileukotriene activity.

Animals↗
PubMed1992

Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in human lung and liver microsomes and cytochromes P-450 expressed in hepatoma cells.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-specific carcinogen in animals, has been linked to tobacco-related cancers in humans. The cytochrome(s) P-450 (P-450) responsible for the metabolic activation of NNK in humans has not been identified. The present work investigated the ability of human lung and liver microsomes and 12 forms of human P-450, expressed in Hep G2 (hepatoma) cells, to metabolize NNK. Of the 12 P-450 forms, P-450 1A2 had the highest activity in catalyzing the conversion of NNK to the keto alcohol, 4-hydroxy-1-(3-pyridyl)-1-butanone. P-450s 2A6, 2B7, 2E1, 2F1, and 3A5 also had measurable activities in the formation of keto alcohol. The apparent Km and Vmax for the formation of keto alcohol in the P-450 1A2-expressed Hep G2 cell lysate were 309 microM and 55 pmol/min/mg protein, respectively. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol, a reductive product, was the major metabolite formed, whereas the formation of keto alcohol and its aldehyde and acid derivatives (all alpha-hydroxylation products) constituted approximately 1% of the initial amount of NNK in P450-expressed Hep G2 cell lysate. A similar metabolite pattern was observed with human lung or liver microsomes. In human lung microsomes, the apparent Kms for the formation of 4-hydroxy-4-(3-pyridyl)butyric acid, 4-oxo-1-(3-pyridyl)-1-butanone, NNK-N-oxide, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were 526, 653, 531, and 573 microM, respectively; the formation of keto alcohol was not observed. For human lung microsomes, there was no sex-related difference in NNK metabolism. Carbon monoxide (90% atmosphere) significantly inhibited the metabolism of NNK in human lung and liver microsomes. 7,8-Benzoflavone, an inhibitor of P-450s 1A1 and 1A2, had no effect on NNK metabolism in human lung microsomes but decreased the formation of keto alcohol by 47% in human liver microsomes. Similarly, antibodies against human P-450s 1A2 and 2E1 decreased keto alcohol formation by 42% and 53%, respectively, in human liver microsomes but did not affect NNK metabolism in lung microsomes. Inhibitory antibodies against P-450s 2A1, 2C8, 2D1, or 3A4 had little or no effect on the metabolism of NNK in human liver or lung microsomes.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies↗
PubMed1992

The catalytic consequences of experimental evolution. Studies on the subunit structure of the second (ebg) beta-galactosidase of Escherichia coli, and on catalysis by ebgab, an experimental evolvant containing two amino acid substitutions.

1. The ratio of ebgA-gene product of ebgC-gene product in the functional aggregate of ebg beta-galactosidases was determined to be 1:1 by isolation of the enzyme from bacteria grown on uniformly radiolabelled amino acids and separation of the subunits by gel-permeation chromatography under denaturing conditions. 2. This datum, taken together with a recalculation of the previous ultracentrifuge data [Hall (1976) J. Mol. Biol. 107, 71-84], analytical gel-permeation chromatography and electron microscopy, strongly suggests an alpha 4 beta 4 quaternary structure for the enzyme. 3. The second chemical step in the enzyme turnover sequence, hydrolysis of the galactosyl-enzyme intermediate, is markedly slower for ebgab, having both Asp-97----Asn and Trp-977----Cys changes in the large subunit, than for ebga (having only the first change) and ebgb (having only the second), and is so slow as to be rate-determining even for an S-glycoside, beta-D-galactopyranosyl thiopicrate, as is shown by nucleophilic competition with methanol. 4. The selectivity of galactosyl-ebgab between water and methanol on a molar basis is 57, similar to the value for galactosyl-ebgb. 5. The equilibrium constant for the hydrolysis of lactose at 37 degrees C is 152 +/- 19 M, that for hydrolysis of allolactose is approx. 44 M and that for hydrolysis of lactulose is approx. 40 M. 6. A comparison of the free-energy profiles for the hydrolyses of lactose catalysed by the double mutant with those for the wild-type and the single mutants reveals that free-energy changes from the two mutations are not in general independently additive, but that the changes generally are in the direction predicted by the theory of Burbaum, Raines, Albery & Knowles [(1989) Biochemistry 28, 9283-9305] for an enzyme catalysing a thermodynamically irreversible reaction. 7. Michaelis-Menten parameters for the hydrolysis of six beta-D-galactopyranosylpyridinium ions and ten aryl beta-galactosides by ebgab were measured. 8. The derived beta 1g values are the same as those for ebgb (which has only the Trp-977----Cys change) and significantly different from those for ebgo (the wild-type enzyme) and ebga. 9. The alpha- and beta-deuterium secondary isotope effects on the hydrolysis of the galactosyl-enzyme of 1.08 and 1.00 are difficult to reconcile with the pyranose ring in this intermediate being in the 4C1 conformation.

Biological Evolution↗
PubMed1992

The effect of averaging cardiac Doppler spectrograms on the reduction of their amplitude variability.

The effect of averaging cardiac Doppler spectrograms on the reduction of their amplitude variability was investigated in 30 patients. Beat-to-beat variations in the amplitude of Doppler spectrograms were also analysed. The quantification of amplitude variability was based on the computation of the area under the absolute value of the derivative function of each spectrum composing mean spectrograms. Fast Fourier transform using a Hanning window was used to compute Doppler spectra. Results obtained over systolic and diastolic periods showed that the reduction of amplitude variability followed an exponentially decreasing curve characterised by the equation f (r) = 100 e-beta(r-1), where r is the number of cardiac cycles, beta the exponentially decreasing rate, and 100 the normalised variability for r = 1. In systole, the decreasing rate beta was 0.165, whereas in diastole it was 0.225. Reductions of the variability in systole for a number of cardiac cycles of 5, 10, 15, and 20 were 48, 77, 90 and 96 per cent, respectively. In diastole, reductions of the variability for the same numbers of cardiac cycles were 59, 87, 96 and 99 per cent, respectively. Based on these results, it can be concluded that no significant improvement in the reduction of amplitude variability may be obtained by averaging more than 20 cardiac cycles.

Echocardiography, Doppler↗
PubMed1992

Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by inducible and constitutive cytochrome P450 enzymes in rats.

The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces tumor formation in the liver, lung, nasal cavity, and pancreas of rats. Metabolic activation is required for the tumorigenicity of this compound. The involvement of cytochrome P450 enzymes in NNK bioactivation was investigated in rats by studies with chemical inducers and antibodies against P450s. Liver microsomal enzymes catalyzed the formation of 4-oxo-1-(3-pyridyl)-1-butanone (keto aldehyde), 4-hydroxy-1-(3-pyridyl)-1-butanone (keto alcohol), 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) from NNK. When the activity was expressed on a per nanomole P450 basis, treatments of rats with 3-methylcholanthrene (MC), phenobarbital (PB), pregnenolone 16-alpha-carbonitrile (PCN), Aroclor 1254 (AR), safrole (SA), and isosafrole (ISA) increased the keto aldehyde formation in liver microsomes 2.0-, 2.4-, 3.8-, 2.5-, 2.1-, and 1.8-fold, respectively; PB, AR, SA, and ISA increased the keto alcohol formation 1.7-, 1.3-, 2.0-, and 1.3-fold, respectively. The extents of induction were more pronounced when expressed on a per milligram protein basis, due to the higher microsomal P450 contents in the induced microsomes. The formation of NNK-N-oxide was markedly increased by PB and PCN and slightly increased by AR, SA, and ISA. However, the formation of NNAL, the major metabolite due to carbonyl reduction, was not increased by the treatments but was decreased by AR, ISA, and acetone (AC). The kinetic parameters of NNK metabolism by control, MC-, PB-, and PCN-induced liver microsomes were obtained. A panel of monoclonal (anti-1A1, -2B1, -2C11, and -2E1) and polyclonal (anti-1A2, -2A1, and -3A) antibodies were used to assess the involvement of constitutive hepatic P450 enzymes in NNK metabolism. Keto aldehyde formation was inhibited by anti-1A2 and anti-3A (about 15%) but not by others; the formation of keto alcohol was inhibited by anti-1A2, anti-2A1, and anti-3A (by 13-26%). In incubations with lung microsomes, the formation of keto aldehyde, keto alcohol, NNK-N-oxide, and NNAL were observed. With nasal mucosa microsomes, however, only keto aldehyde and keto alcohol formation were appreciable. SA and AC significantly decreased NNK metabolism in lung and nasal mucosa microsomes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

The effects of non-interval PUVA treatment on Langerhans cells and contact hypersensitivity.

Although application of topical psoralen followed immediately by ultraviolet-A irradiation (non-interval PUVA) was reported to be effective in the treatment of psoriasis, its precise mechanisms of action have not yet been explored. Since regular topical PUVA therapy, consisting of the topical application of psoralen followed by UVA exposure 1-2 h later, can change the number and morphology of Langerhans cells (LCs) and inhibit contact hypersensitivity (CHS), we investigated whether these same effects may be induced by non-interval PUVA. Our results showed that no differences exist between these two types of PUVA treatment. Non-interval PUVA treatments of 3 J/cm2 produced no erythematous reactions and resulted in changes in the number and morphology of LCs. The non-interval regimen also inhibited CHS to dinitrofluorobenzene applied to the treated skin by inducing the suppressor lymphocytes. These results suggest that there might be a link between the observed changes of the LCs and the effectiveness of non-interval PUVA therapy in the treatment of psoriasis, through a mechanism other than the inhibition of DNA synthesis of psoriatic keratinocytes.

Animals↗
PubMed1992

Effects of phenethyl isothiocyanate, a carcinogenesis inhibitor, on xenobiotic-metabolizing enzymes and nitrosamine metabolism in rats.

Phenethyl isothiocyanate (PEITC), a constituent of cruciferous vegetables, has been shown to inhibit chemical carcinogenesis, possibly due to its ability to block the activation or to enhance the detoxification of chemical carcinogens. The present study was conducted to elucidate the biochemical mechanisms involved by characterizing the effects of PEITC on phase I and phase II xenobiotic-metabolizing enzymes. A single dose of PEITC to F344 rats (1 mmol/kg) decreased the liver N-nitrosodimethylamine demethylase (NDMAd) activity (mainly due to P450 2E1) by 80% at 2 h and the activity of NDMAd remained decreased by 40% at 48 h after treatment. The liver pentoxyresorufin O-dealkylase (PROD) activity and P450 2B1 protein level were elevated 10- and 7-fold at 24 h after treatment respectively. The liver microsomal ethoxyresorufin O-dealkylase (EROD) (mainly due to P450 1A) and erythromycin N-demethylase (mainly due to P450 3A) activities were decreased at 2-12 h after treatment and recovered afterwards. The lung microsomal PROD and EROD activities were not significantly affected; whereas, the nasal microsomal PROD and EROD activities were decreased by 40-50%. After a treatment with PEITC, the rates of oxidative metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were decreased in liver microsomes by 40-60% at 2 h and recovered gradually; the rates in lung microsomes were markedly decreased by 60-70% at 2 h and remained at the decreased level at 24 h; and the rates in nasal mucosa microsomes were decreased gradually with the lowest activities observed at 18 h (50%) followed by a gradual recovery. Furthermore, the treatment with PEITC resulted in a maximal 5-fold increase of NAD(P)H:quinone oxidoreductase and 1.5-fold increase of glutathione S-transferase activities in the liver, but the activities of these two enzymes were not significantly affected in the lung and nasal mucosa. The sulfotransferase activity in the liver was decreased by 32-48% at 24-48 h after treatment; the nasal activity was increased by 1.8- to 2.5-fold, but the lung activity was not significantly changed. The hepatic UDP glucuronosyltransferase activity was slightly decreased at 2 h but slightly increased at 48 h after treatment, but no changes were observed for the lung and nasal activities. The study demonstrates that PEITC selectively affects xenobiotic-metabolizing enzymes in the liver, lung and nasal mucosa and it is especially effective in inhibiting the P450-dependent oxidation of NNK in the lung and of NDMA in the liver.

Animals↗
PubMed1992

Kinetics and enzyme involvement in the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in microsomes of rat lung and nasal mucosa.

The rat lung and nasal cavity are two target organs for carcinogenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In order to characterize further the enzymes involved in the bioactivation of NNK, detailed kinetic and inhibitory studies were conducted with rat lung and nasal mucosa microsomes, and the results were compared with previous studies. The enzymes in rat lung microsomes catalyzed the alpha-hydroxylation, pyridine N-oxidation and carbonyl reduction of NNK. The apparent Km for the formation of the NNK-derived keto aldehyde, NNK-N-oxide, the NNK-derived keto alcohol and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were 28.8, 10.4, 7.0 and 178.1 microM respectively. In rat nasal microsomes, alpha-hydroxylation was the predominant pathway and the rate was approximately 200 times higher than that in lung microsomes. The apparent Kms for keto aldehyde and keto alcohol formation in rat nasal microsomes were 9.6 and 10.1 microM respectively. The cytochrome P450 inhibitors metyrapone and carbon monoxide markedly inhibited the metabolism of NNK in both rat lung and nasal microsomes. In rat lung microsomes, alpha-naphthoflavone and monospecific antibodies against P450s 1A2, 2A1 and 2B1 inhibited the formation of keto aldehyde by 39, 46, 64 and 23% respectively. In rat nasal microsomes, alpha-naphthoflavone and antibodies against P450s 1A2, 2A1 and 3A inhibited the metabolism of NNK by 80, 35, 20 and 14% respectively. The results indicate that cytochromes P450 play a major role in the metabolic activation of NNK in rat lung and nasal microsomes, and that there are tissue-related differences in NNK metabolism.

Animals↗
PubMed1992

[A case-control study on the relationship between smoking and genetic background and lung cancer].

A case-control study on the relationship between smoking and genetic background and lung cancer was carried out. The cases (probund) were death cases of lung cancer diagnosed between 1984 and 1986 in Quanshan County, and the controls were healthy people at the same period. Cases and controls were 1:1 in match with sex, age and residence. 196 pairs were so matched. The results were adjusted for smoking habit and family history of lung cancer using conditionally logistic regression model. There were significant differences shown in quantity of smoking (packet/year) (beta = 0.070 9) and age to start (years) (beta = -0.055 6) between cases and controls. There were also significant differences in history of lung cancer of first and second relatives (living together or not) between cases and controls. The positive interaction between smoking habit and genetic background of lung cancer was also found.

Case-Control Studies↗