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Biomedical subjects

Z Guo

Publications and source records attributed to Z Guo.

At least 361 records · Page 20Linked to original sources
PubMed1996

3'-end-forming signals of yeast mRNA.

The signals required for forming 3'-ends of mRNAs from the yeast Saccharomyces cerevisiae differ from the corresponding signals of higher eukaryotes. Yeast signals consist of three elements: (1) the efficiency element, which enhances the efficiency of downstream positioning elements; (2) the positioning element, which positions the poly(A) site; and (3) the actual poly(A) site. These three elements are not only necessary, but also sufficient for mRNA 3'-end formation in yeast.

Animals↗
PubMed1996

Antinociceptive actions of intrathecal xylazine: interactions with spinal cord opioid pathways.

We have studied rats with chronically implanted subarachnoid catheters. Xylazine, an alpha 2 adrenoceptor agonist, was injected intrathecally and nociceptive thresholds measured at two skin sites: the tail and the neck. Intrathecal xylazine (dose range 24.3-389 nmol) produced increases in electrical thresholds for nociception in the tail without any change in the neck; this observation suggested that the antinociceptive action of this drug was confined to the caudal part of the spinal cord responsible for tail innervation. The magnitude of this effect was dose-dependent. Tail flick latency also increased in these rats and the antinociceptive effects were antagonized in a dose-dependent manner by the selective alpha 2 adrenoceptor antagonist idazoxan (dose range 6.7-540 nmol). Intrathecal idazoxan also suppressed the increase in tail flick latency caused by the mu opioid agonist fentanyl (0.74 nmol) given intrathecally. This effect was also dose-dependent. The idazoxan dose-response curve for this suppression of fentanyl antinociception assessed with tail flick latency was the same as that for suppression of xylazine. In contrast, the antinociceptive effects of intrathecal xylazine were not affected by concurrent administration of opioid or GABAA antagonists. We conclude that intrathecal xylazine produced spinally mediated antinociceptive effects by combination with spinal cord alpha 2 adrenoceptors and that neither opioid nor GABA-containing propriospinal neurones were involved in the mediation of this effect. However, alpha 2 adrenoceptors in the spinal cord appear to be involved with antinociception produced by intrathecal fentanyl.

Adrenergic alpha-Agonists↗
PubMed1996

Antinociception by intrathecal midazolam involves endogenous neurotransmitters acting at spinal cord delta opioid receptors.

Intrathecal midazolam causes antinociception by combining with spinal cord benzodiazepine receptors. This effect is reversible with doses of naloxone, suggesting involvement of spinal kappa or delta but not mu opioid receptors. The antinociceptive effects of intrathecally administered drugs in the spinal cord were demonstrated by measurements of the electrical current threshold for avoidance behaviour in rats with chronically implanted lumbar intrathecal catheters. A comparison was made of suppression by two opioid selective antagonists (nor-binaltorphimine (kappa selective) and naltrindole (delta selective)) of spinal antinociception caused by equipotent doses of opioids selective for different receptor subtypes (U-50488H (kappa), DSLET and DSBULET (delta), fentanyl (mu)) and the benzodiazepine midazolam. Nor-binaltorphimine selectively suppressed the effects of U-50488H but not midazolam or fentanyl. However, the delta selective antagonist, naltrindole, caused dose-related suppression of antinociception produced by both delta opioid agonists and midazolam with the same ED50 (0.5 nmol). We conclude that intrathecal midazolam caused spinally mediated antinociception in rats by a mechanism involving delta opioid receptor activation.

Analgesics↗
PubMed1996

Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by human cytochrome P450 1A2 and its inhibition by phenethyl isothiocyanate.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent tobacco-specific nitrosamine in animals and has been suggested to play a role in human tobacco-related cancers. Our previous study demonstrated that cytochrome P450 (P450) 1A2 catalyzes the formation of 4-hydroxy-1-(3-pyridyl)-1-butanone (keto alcohol) (an alpha-hydroxylation product) from NNK in human liver microsomes. Phenethyl isothiocyanate (PEITC) inhibits NNK tumorigenesis by blocking the activation of NNK. The purpose of the present study was to elucidate the mechanism of inhibition of P450 1A2-catalyzed NNK activation by PEITC. Human P450 1A2 was expressed in Escherichia coli and purified to homogeneity. In a reconstituted system, P450 1A2 catalyzed the formation of keto alcohol and 4-oxo-1-(3-pyridyl)-1-butanone (keto aldehyde) from NNK, with the keto alcohol being the major metabolite. The apparent Km and Vmax values for keto alcohol formation was 380 microM and 1.7 nmol/min/nmol P450, respectively. For the tobacco-specific nitrosamine N-nitrosonornicotine (NNN), P450 1A2 catalyzed the formation of the derived 4-hydroxy-4-(3-pyridyl)butyric acid (hydroxy acid),4-oxo-4-(3-pyridyl)butyric acid (keto acid) and keto alcohol. In comparison to NNK, NNN had a lower rate of oxidation with P450 1A2. PEITC decreased the formation of the NNK-derived keto alcohol in a concentration-dependent manner, with an IC50 value of 0.14 microM. PEITC was a competitive inhibitor of P450 1A2, exhibiting a Ki value of 0.18 microM. Preincubation of PEITC with NADPH in the reconstituted system resulted in a further decrease (25%) in the catalytic activity of P450 1A2, suggesting that there is a slow metabolism-dependent inhibition of P450 1A2 by PEITC. The formation of keto aldehyde and keto alcohol was inhibited by PEITC in human liver microsomes with IC50 values of 9.5 and 4.6 microM respectively. Methoxyresorufin O-dealkylase activity, a marker for P450 1A2, was decreased by PEITC in a concentration-dependent manner, with an IC50 of 0.34 microM. The results suggest that PEITC itself is a potent inhibitor of P450 1A2 and that a metabolite(s) of PEITC can also inhibit P450 1A2. We conclude that PEITC may be an effective inhibitor of the carcinogenicity or toxicity of chemicals that are activated by P450 1A2.

Carcinogens↗
PubMed1996

Characterizations of neutral lipid fatty acids and cis-9,10-epoxy octadecanoic acid in Pneumocystis carinii carinii.

Pneumocystis carinii causes pneumonitis in immunodeficient individuals and is a prevalent opportunistic infection of patients with AIDS. This pathogen resides extracellularly in the hypophase lining the alveolar epithelium, which is highly enriched in lung surfactant lipids. Procedures yielding highly pure organism preparations that enable reliable biochemical analyses of organisms isolated from the lungs of infected laboratory animals have been developed. The results of the present study revealed that the fatty acid profiles of total lipids, the neutral lipid traction, and individual neutral lipid classes of lungs from normal and immunosuppressed rats as well as P. carinii were grossly similar, although some quantitative differences were detected. One qualitative exception found was the detection in P. carinii of the rare fatty acid cis-9,10-epoxy stearic acid, which was not detected in the lipids of rat lungs. The detection of this fatty acid in P. carinii may also have important taxonomic implications. Unlike phospholipids, many of the fatty acids of nonmembrane neutral lipids may be utilized by P. carinii for other cellular functions, such as stored reserves for energy production and precursors for organism-specific membrane lipids. The present study represents the first report of detailed fatty acid analyses of individual neutral lipid classes of this important opportunistic pathogen.

Animals↗
PubMed1996

Fatty acid composition of the major phospholipids of Pneumocystic carinii: comparison with those in the lungs of normal and methylprednisolone-immunosuppressed rats.

Large numbers of viable organisms can be isolated from the corticosteroid-immunosuppressed rat model of Pneumocystis carinii pneumonia. With the development of purification protocols that provide organism preparations of high purity, meaningful lipid biochemical analyses of this important opportunistic pathogen can now be conducted. The phospholipid class composition of the pathogen was reported earlier, together with observations of changes that occur in the rat lungs in response to methylprednisolone immunosuppression treatment. In this report, analyses of the effects of corticosteroids on the fatty acid compositions of the major lung phospholipids, individually isolated and purified by thin-layer chromatography, were elucidated and quantified by gas-liquid chromatography. In response to methylprednisolone, there was a relative increase in palmitate and there were decreases in several unsaturated fatty acids of the rat whole-lung total polar lipids leading to a doubling of the saturation index. Reciprocal changes in the relative concentrations of palmitate and stearate in phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, and cardiolipin were observed, suggesting that there is tight control of acylation of these phospholipids in the lung. Detailed phospholipid fatty acid analyses were also performed with mixed life cycle stages of P. carinii organisms. The most abundant phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol, had much higher concentrations of oleic acid and lower concentrations of palmitate in P. carinii than in lung tissue. Sphingomyelin in lung tissue and P. carinii differed from the glycerophospholipids by the presence of high levels of saturated C(22) and C(24) fatty acids. This study represents the most comprehensive fatty acid analysis of rat lung phospholipids and the changes that occur in response to corticosteroid treatment. It is the first report about the fatty acids of individual phospholipids of the opportunistic protist P. carinii carinii.

Animals↗
PubMed1996

Signals sufficient for 3'-end formation of yeast mRNA.

The following three elements were previously shown to be required for 3'-end formation of mRNA in the yeast Saccharomyces cerevisiae: (i) the efficiency element TATATA or related sequences, which function by enhancing the efficiency of downstream positioning elements; (ii) the positioning element AATAAA or related sequences, which position the poly(A) site; and (iii) the actual poly(A) site, which is usually Py(A)n. In this study, we synthesized a 39-pb poly(A) signal that contained the optimum sequences of these three elements. By inserting the synthetic 3'-end-forming signal into various positions of a CYC1-lacZ fusion gene, we showed that truncated transcripts of the expected sizes were generated. Furthermore, the poly(A) sites of the truncated transcripts were mapped to the expected poly(A) site within the synthetic signal. Our findings establish that the three elements are not only necessary but also sufficient for mRNA 3'-end formation in S. cerevisiae.

Base Sequence↗
PubMed1996

Apolipoprotein E polymorphism and stroke in a population sample aged 75 years or more.

BACKGROUND AND PURPOSE: We investigated apolipoprotein E polymorphism stroke risk in a population sample of 1810 persons aged 75 years or more in Stockholm (the Kungsholmen Project). Information on cognition at cohort inception (from 1987 to 1989) and on stroke occurrence (from 1969 to 1994) is available for the cohort. In the cohort, cognitive impairment is associated with the epsilon 4 allele, and longer survival in subjects aged > or = 85 years with good cognition is associated with the epsilon 2 allele and the absence of epsilon 4. METHODS: We compared stroke incidence in the 1077 of 1124 genotyped subjects who carried epsilon 2/3, epsilon 3/3, or epsilon 3/4 and estimated the proportion of cognitive impairment attributable to stroke. RESULTS: Risk of stroke did not vary with apolipoprotein E polymorphism (P = .82): 24% of 87 incident stroke patients during follow-up compared with 25% of 827 subjects with normal cognition and no stroke diagnosis at baseline carried the epsilon 3/4 genotype. An estimated 9% of cognitive impairment was attributable to stroke. Notably, a reduced epsilon 3/4 frequency of 20% was found in subjects who survived a prior stroke and were included in the cohort, and risk of hemorrhagic stroke tended to be associated with the presence of the epsilon 3/4 genotype and the absence of epsilon 2/3. CONCLUSIONS: This population-based study indicates that apolipoprotein E polymorphism is not a risk factor for ischemic stroke in subjects aged > or = 75 years (although it might possibly influence survival after stroke occurrence and be a risk factor for infrequent hemorrhagic stroke) and that approximately 10% of cognitive impairment in this age group is attributable to stroke.

Aged↗
PubMed1996

[Studies on multiple factor intervention in stroke of ten areas in northeast, north China and Shanghai].

In order to explore the ways to prevent from the disease, 4,793 subjects aged over 40 at high risk of stroke from a total population of 250,000 in communities with high incidence of it were studied with multiple factor intervention, by oral administration of "Nao An" capsules as a major measure in 10 areas of north and northeast China, as well as Shanghai, during 1990 to 1993. Three years after intervention, incidence of stroke decreased by 49.17% in the population, with reduction of systolic and diastolic blood pressure, levels of blood sugar, cholesterol and triglyceride. Lowering of stroke incidence correlated positively with that of blood pressure in the population. It suggests stroke can be prevented effectively by concentrated efforts in comprehensive intervention in individuals at high risk.

Cerebrovascular Disorders↗
PubMed1996

[Screening of high-risk population susceptible to stroke and their characteristics].

High-risk population susceptible to stroke were screened with self-designed scoring method for quantitatively evaluating the risk of stroke in 550,000 frame population in 22 areas with different incidence of stroke during 1990-1993 and its related factors were analyzed by a principal component analysis method. Results showed scoring value correlated positively with probabilities of stroke, which suggested its objectivity and feasibility. The first principal component correlated positively with age, blood pressure, blood sugar, blood cholesterol, body mass index, ect., which reflected the characteristics of high risk population susceptible to stroke, and 71.43% of those with stroke were in the first principal component class. The proportion of the population with the first principal component correlated positively with the incidence of stroke in the area, therefore, stroke prevention should be focused on such population.

Adult↗
PubMed1996

gamma-Aminobutyric acidA receptors and spinally mediated antinociception in rats.

Experiments were performed on rats with lumbar subarachnoid catheters, using four agonist drugs [gamma-aminobutyric acid (GABA), muscimol, midazolam and 5-hydroxytryptamine (5-HT)] and two GABA(A) antagonists (bicuculline and SR-95531) given intrathecally. All four agonists caused dose-related antinociception assessed by the electrical current threshold test. These effects were spinally mediated because the agonists caused increases in nociceptive thresholds in the skin of the tail and not the neck. In the same experiments, 5-HT and GABA caused simultaneous increases in tail-flick latency and electrical current thresholds in the tail. Both GABA(A) antagonists caused dose-related suppression of the antinociceptive effects of equieffective doses of all four agonists. Tail-flick latency increases caused by 5-HT were not suppressed by bicuculline in the same experiments in which bicuculline had suppressed the electrical current threshold effects of intrathecal 5-HT. The log dose-response curves for both antagonists for suppression of GABA effects were coincident, having a very shallow slope and covering the whole range of doses effective against the other agonists. The two GABA(A) antagonists were very different in relative potency for suppression of the spinally mediated antinociceptive effects of the other three agonists. The rank order of potency for bicuculline suppression of the effects of equieffective doses of the other agonists was muscimol > 5-HT > midazolam, whereas the rank order for SR-95531 was muscimol >> midazolam > 5-HT. We conclude that there exist in the spinal cord at least three different GABA(A) receptors responsible for spinally mediated antinociception caused by intrathecal injections of midazolam, muscimol and 5-HT. These are all targets for endogenous GABA.

Animals↗
PubMed1996

Effects of alveolar macrophage conditioned media from interstitial lung disease patients on the procollagen mRNA expression in human lung fibroblasts.

Progressive inflammation and fibrosis are the central processes in the pathogenesis of pulmonary fibrosis. It is believed that macrophages in areas of chronically inflamed lung play a key role in fibrotic response. Therefore, we investigated the effects of alveolar macrophage (Am phi) conditioned media from interstitial lung disease (ILD) patients on lung fibroblast proliferation and procollagen mRNA expression. After stimulating with Am phi conditioned media from ILD patients, the fibroblast proliferation increased 71.4% compared with the control, but for media from bronchial carcinoma (BC) patients, it just increased 14.3%. There is a significant difference between the two groups (P < 0.05). The procollagen alpha, (I) mRNA in fibroblasts stimulated with Am phi conditioned media from ILD patients was increased 21.3%, and alpha 1 (III) was 37.2% higher than control (P < 0.05). It increased 6.8% and 12.8% for media from BC patients respectively, but there was no difference when compared to the control. We considered that Am phi from ILD patients might be in an activated state and could release some growth factors to stimulate fibroblast proliferation and promote collagen DNA expression.

Carcinoma, Bronchogenic↗
PubMed1996

[A genetic epidemiological study on lung cancer].

Segregation ratio, heritability and relative risk of genetic susceptibility were estimated for 355 families of lung cancer in matched pair with genetic epidemiological methods. Results showed that segregation ratio for lung cancer was 0.09-0.12 (95% confidence interval, CI) and heritability of lung cancer was (40.58 +/- 4.01)% and (27.58 +/- 4.76)% for smokers and non-smokers, respectively. Relative risks of genetic susceptibility to lung cancer were 4.73 (95% CI 3.90-5.74) and 2.61 (95% CI 2.18-3.13) in their first and second degree relatives, respectively, after adjustment of smoking with a logistic regression model. It was also found that there was an interaction between smoking habit and genetic background of lung cancer. Thus, it is believed that genetic background is one of the multifactorial causes in lung cancer.

China↗
PubMed1996

Application of polymerase chain reaction for diagnosing amebic liver abscess.

Polymerase chain reaction (PCR) has been applied in diagnosing amebic liver infection by detecting pathogenic Entamoeba histolytica DNA in liver aspirates. Oligonucleotide primers found to be specific for the gene encoding the 30 kDa molecule of this pathogenic ameba were used in the test. Liver aspirates obtained from 23 patients with amebic liver abscess substantiated by typical clinical manifastation or with very high titres of anti-E histolytica antibodies by ELISA were found to be positive by PCR. Fourteen control samples (3 cases of bacterial liver abscess, 1 of liver cancer and 10 of other abscess) were all found to be negative to this reaction. The results suggested PCR to be a specific and sensitive tool for diagnosing amebic liver abscess infections.

Animals↗
PubMed1996

[Observation of the anastomoses of intrahepatic veins in normal men].

The purpose of this study is to identify the existence of hepatovenous intrahepatic anastomosis in normal men. A total of thirteen livers were investigated during the early autopsies of normal men who died in accidents. Perfusion venography of branches of hepatic veins using meglucamine diatrizoate was done in six cases; this method we used had not been reported in the literature. In one case, portal venography was performed. And in the other six cases, liver substance staining was done by injecting the ink through the middle hepatic vein, and such staining of the liver was observed by light microscope. The results show, (1) there are intrahepatic anastomoses between the hepatic veins within the liver; (2) there are anastomoses between the middle hepatic vein and the accessory hepatic veins; and (3) shunts exist between portal veins and hepatic veins. The above findings provide an anatomical basis for the performance of irregular hepatectomy and the rationale for one or two hepatic veins ligation should such veins were traumatized or invaded by liver cancer.

Adult↗
PubMed1996

[Effect of escharectomy during burn shock stage on bacterial and endotoxic translocation from the gut].

120 SPF rats (Wistar) were randomly divided into 3 groups (1) simple skin grafting group (Group A). (2) Escharectomy during burn shock group (Group B). (3) Routine escharectomy group (Group C) Full-thickness burn of 30% TBSA was produced in Group B and Group C. One hour after scald intravenous fluid replacement was instituted. First stage escharectomy has been performed 24 hours after burn and 5 days postburn. The results demonstrated that the contents of both plasma LPS and TNF in Group B were significantly lower as compared with these in Group C. Our data indicated escharectomy during burn shock would effectively eliminate the effects of the endotoxemia. Endotoxin play an important role in the bacterial and endotoxic translocation.

Animals↗
PubMed1995

Expression of cytochrome P450 2D6 in Escherichia coli, purification, and spectral and catalytic characterization.

Cytochrome P450 (P450) 2D6 is the classic human liver debrisoquine 4-hydroxylase, the first human P450 for which genetic polymorphism was clearly demonstrated. We prepared 11 different constructs of P450 2D6, with modification at the N-terminus, for expression in Escherichia coli with the vector pCW. These varied considerably in levels of expression of apo- and holoprotein, with the best yield being obtained in a system in which much of the N-terminal hydrophobic segment was removed. Production of holoprotein was highly dependent upon the addition of delta-aminolevulinic acid and FeCl3 to cultures, even though heme production should not be limiting in this system. The expressed protein was not tightly bound to the "heavier" membrane fraction but did not appear to behave as a soluble protein either. A purification strategy was developed involving fractional centrifugation, Triton X-114 phase separation, and flavodoxin affinity chromatography, which led to recovery of apparently electrophoretically homogeneous protein in good yield. Purified P450 2D6 had the expected N-terminal amino acid sequence and catalytic activities toward debrisoquine (4-hydroxylation) and bufuralol (1'-hydroxylation). The availability of a ready source of the recombinant protein should facilitate physical as well as functional studies and antibody production for other uses.

Amino Acid Sequence↗