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Biomedical subjects

Z Guo

Publications and source records attributed to Z Guo.

At least 343 records · Page 19Linked to original sources
PubMed1997

Oxygen free radical injury and its relation to bacterial and endotoxin translocation after delayed fluid resuscitation: clinical and experimental study.

OBJECTIVE: To examine whether there is generation of oxygen free radicals (OFR) and lipid peroxidation of cell membrane after volume replacement for burn shock, and to study the relationship between OFR injury and enterogenous endotoxemia. METHODS: Forty-seven burn patients were involved in this study. Among them, 18 had delayed fluid resuscitation (DR) and the others had early fluid resuscitation (ER) within 6 hours postburn. Sixty-six gnotobiotic rats were used in a collaborating experiment as burn models. They were divided into 4 groups: sham injury (n = 6), early resuscitation (n = 24), late resuscitation (n = 24) and vitamins E and C treatment group (n = 12). All the rats, except those in the sham injury group, were inflicted with 40% total body surface area (TBSA) third-degree burns. OFR was determined in the blood of patients with electron spin resonance (ESR). S/W ratio and tau c values of patients' erythrocytes were measured with ESR spectrometer. Blood superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities, malondialdehyde contents and plasma endotoxin levels were assayed. Rats were sacrificed at the 12th, 24th, 48th and 72nd hour after injury. Plasma endotoxin levels, mucosal SOD, GSHPx and malondialdehyde (MDA), as well as diamine oxidase activity of ileum were determined. Cultures of mesenteric lymph nodes (MLN), liver, spleen, heart, lung, kidney and blood were done. RESULTS: A significant increase in blood OFR contents and plasma MDA, and a significant decline in blood SOD and GSHPx were found after resuscitation in DR group as compared with those in ER group. Both strong to weak spectra component (S/W) ratio and tau c value were higher in DR group in contrast with those in ER group. Higher elevation in plasma endotoxin level in DR group was seen. In DR group, plasma MDA content was correlated with S/W ratio, tau c value and plasma endotoxin level. In rats, the level of mucosal MDA, plasma endotoxin and incidence of bacterial translocation (BT) were significantly higher. Mucosal SOD, GSHPx and diamine oxidase (DAO) activity were significantly lower in DR group as compared with those in ER group. In DR group, mucosal MDA content was negatively correlated with mucosal DAO activity, while the latter was negatively correlated with BT. After treatment with vitamins E and C, mucosal MDA content decreased, plasma endotoxin and BT significantly declined and mucosal DAO heightened. CONCLUSIONS: Tissue reperfusion might induce the production of OFR, resulting in lipid peroxidation injury, especially to intestinal mucosa, and resulting in disruption of mucosal barrier function followed by endotoxemia and BT.

Adolescent↗
PubMed1997

[Preclinical studies on thymidine kinase gene (TK) and gancyclovir system for treatment of malignant astrocytoma].

OBJECTIVE: To study preclinically TK gene mediated GCV system for treatment of human malignant astrocytoma. METHODS: The TK gene (TKc) was isolated from a Chinese strain of HSV-1 (17) and sequenced. A retroviral vector with TKc (pLTKcSN) and its package cell line (pLTKcSN/VPC) were constructed. The in vitro assay for its activity was performed by mixed cultures of TK producer cells and rat glioma C6 cells after treatment with GCV. The in vivo efficacy was examined by in situ inoculation of virus-producer cells after intracerebral implantation of C6 cells. Safety tests were analyzed by inoculation of pLTKcSN/VPC and injection of GCV, in mouse, rat, and Rhesus monkey, evaluated by histopathological examination and in situ hybridization with TK probe. RESULTS: TKc gene contained 5 nucleotide difference covering 2 amino acid variation. The retroviral vector pLTKcSN and its producer cell pLTKcSN/VPC (with a titer at 0.5-1.0 x 10(6) CFU/ml) can efficiently mediate cytotoxicity of GCV to C6 cells, both in vitro and in vivo. The above system had no serious adverse effect and remarkable or irreversible pathological changes in 48 mice, 24 rats and 6 Rhesus monkeys. CONCLUSION: The preclinical studies indicated that it would be effective and safe for clinical trial after approval.

Amino Acid Sequence↗
PubMed1997

Clinical, pathologic and genetic studies on mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.

OBJECTIVE: To study the clinical, pathological and genetic characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). METHODS: Eight cases of MELAS (6 of them were from 2 families) underwent clinical study, muscle biopsy, autopsy on one patient, brain biopsy on one patient and genetic research. RESULTS: In clinical report the average age of onset was 10-22 years old. Four cases from one family were 3 brothers and their nephew (sister's son). The death age of the three brothers was 16-20 years. Two cases from another family were a brother and a sister. The six patients of the two families showed the typical inherited characters of MELAS. The symptoms were myoclonic epilepsy, stroke-like episodes, paralysis of limbs, progressive mental retardation and neurological deaf. CT showed calcification in globus pallidus and MRI demonstrated clearly the abnormal prolongation of T2-weighed signals that distributed in frontal, parietal, occipital and temporal cortex as multiple focal, cystic and laminar necrotic areas. Pathological studies on brain showed multi-focal, cystic, and laminar or spongy necrotic abnormality primarily in gray matter of frontal, parental, temporal and occipital cortex. Decrease and loss of nerve fibers of the sub-cortical white matters of the lesion areas of cortex and calcification of globus pallidus were also observed. Red ragged fibers (RRF) and abnormal mitochondron were found by muscle biopsies. A point mutation (A-G transition) at nt 4243 in the mitochondrial tRNA Leu (UUR) was confirmed by using PCR and Southern Blot. CONCLUSION: Although great progress has been made in the clinical, pathological and genetic research of MELAS, the pathogenesis of the disease remains further research.

Adolescent↗
PubMed1997

[Repair of long segment bone defect of femur by free juxtaposed bilateral fibulae autograft].

There were several methods, such as free single and folded fibulae autograft, composed tissue autograft, however, it is still very difficult to repair long segment bone defect. In December 1995, we used free juxtaposed bilateral fibulae autograft to repair an 8 cm of femoral bone defect in a 4 years old child in success. The key procedure is to strip a portion of the neighboring periosteal sleeve of juxtaposed fibulae to make bare of the opposite sides of the bone shafts, suture the opposite periosteal sleeves, keep the nutrient arteries, and reconstruct the blood circulation of both fibular by anastomosis of the distal ends of one fibular artery and vein to the proximal ends of the other fibular artery and vein, and anastomosis of the proximal ends of the fibular artery and vein to lateral circumflex artery and vein. After 22 months follow up, the two shafts of juxtaposed fibulae fused into one new bone shaft. The diameter of the new bone shaft was nearly the same as the diameter of the femur. There was only one medullary cavity, and it connected to the medullary cavity of femur. This method also cold be used to repair other long segment bone defect.

Anastomosis, Surgical↗
PubMed1997

Effects of losartan and PD123319 on antigensin II-induced proto-oncogene expression and protein synthesis in cultured neonatal rat cardiac myocytes.

To study the effects of specific angiotension II (Ang II) receptor, type-1 (AT1) antagonist (Losartan) and type-2 (AT2) antagonist (PD123319), on Ang II-induced proto-oncogene expression and synthesis of RNA and protein in neonatal rat cardiac myocytes, we used respectively [3H]-uridine and [3H]-leucine incorporation to measure the rate of RNA and protein synthesis, and analyzed the c-myc mRNA level by Northern blot. We found that an acceleration in the rate of RNA and protein synthesis was observed when exposed to 2.5 x 10(-6) mol.L-1 [Sar1] Ang II for 24 h (P < 0.01). Losartan inhibited the action in a dose-dependent manner. The level of c-myc mRNA was up-regulated to 340% of control by 2.5 x 10(-6) mol.L-1 Ang II, and Losartan (10(-5) mol.L-1) suppressed the increase of c-myc mRNA stimulated by Ang II. PD123319 showed similar inhibition on Ang II-induced RNA and protein synthesis, but did not inhibit c-myc expression. Thus, Ang II-stimulated expression of c-myc is mainly mediated by AT1 receptors, and contributes to cardiac myocyte hypertrophy while AT2 receptors are involved in mediation of cellular growth without altering of c-myc expression.

Angiotensin Receptor Antagonists↗
PubMed1997

[Endocardial endothelium modulates lysophosphatidylcholine induced positive inotropism].

In isolated guinea pig papillary muscles, the endocardial endothelium (EE) was selectively damaged by exposing the muscles to a flow of dry air for 30s for removal of function EE. The results showed that LPC induced positive inotropic effect on papillary muscles was observed in a concentration-and time-dependent manner [PT after 15 mins' exposure to 5, 10 and 20 mumol.L-1 lysophosphatidylcholine (LPC) was increased by 104 +/- 7%, 110 +/- 6% and 124 +/- 10%, respectively]. The positive inotropic effect of 10 mmol.L-1 LPC on papillary muscles denuded of EE was significantly enhanced (PT: 163 +/- 23% vs 130 +/- 17% after exposing to LPC for 30 min). Scanning and transmission electronic microscopic studies exhibited signs of EE damage of papillary muscles incubated with LPC 10 mumol.L-1 for 30 minutes, such as disruption of gap junction between overlapping EE cells, retraction of the cell borders, fenestration on the EE, and denudation of the subjacent basal lamina. The present study suggests that the EE may affect the LPC-induced contractibility of papillary muscle via its barrier function signs, in addition, the present data provides further evidence that LPC may be a trigger for some kind of biological active factor release form EE.

Animals↗
PubMed1996

Molecular cloning of a high-affinity receptor for the growth factor-like lipid mediator lysophosphatidic acid from Xenopus oocytes.

Lysophosphatidic acid (1-acyl-2-lyso-snglycero-3-phosphate, LPA) is a multifunctional lipid mediator found in a variety of organisms that span the phylogenetic tree from humans to plants. Although its physiological function is not clearly understood, LPA is a potent regulator of mammalian cell proliferation; it is one of the major mitogens found in blood serum. In Xenopus laevis oocytes, LPA elicits oscillatory Cl- currents. This current, like other effects of LPA, is consistent with a plasma membrane receptor-mediated activation of G protein-linked signal transduction pathways. Herein we report the identification of a complementary DNA from Xenopus that encodes a functional high-affinity LPA receptor. The predicted structure of this protein of 372 amino acids contains features common to members of the seven transmembrane receptor superfamily with a predicted extracellular amino and intracellular carboxyl terminus. An antisense oligonucleotide derived from the first 5-11 predicted amino acids, selectively inhibited the expression of the endogenous high-affinity LPA receptors in Xenopus oocytes, whereas the same oligonucleotide did not affect the low-affinity LPA receptor. Expression of the full-length cRNA in oocytes led to an increase in maximal Cl- current due to increased expression of the high-affinity LPA receptor, but activation of the low-affinity receptor was, again, unaffected. Oocytes expressing cRNA prepared from this clone showed no response to other lipid mediators including prostaglandins, leukotrienes, sphingosine 1-phosphate, sphingosylphosphorylcholine, and platelet-activating factor, suggesting that the receptor is highly selective for LPA.

Amino Acid Sequence↗
PubMed1996

Seleno compounds and glutathione peroxidase catalyzed decomposition of S-nitrosothiols.

Seleno compounds such as selenocystamine and seleno-D, L-cystine were found to catalyze the decomposition of S-nitrosothiols (e.g. S-nitroso-glutathione and S-nitroso-N-acetyl-D, L-penicillamine) in the presence of different thiols (e.g. glutathione, N-acetyl-D-penicillamine and 2-mercaptoethanol), and liberate nitric oxide. It was also found that glutathione peroxidase itself can catalyze the decomposition of S-nitrosoglutathione without the presence of any thiol or H2O2.

Catalysis↗
PubMed1996

Kinetics and thermodynamics of folding of a de novo designed four-helix bundle protein.

A simple continuum model of a de novo designed model of a four-helix bundle is presented. The thermodynamics and kinetics of the model are studied using Langevin simulations. We use a three-letter minimal off-lattice representation of a de novo designed four-helix bundle protein. The native state of the model, which can be thought of as an alpha-carbon representation of the peptide chain, is a caricature of the sequence designed by Ho and Degrado and shows several characteristics found in the naturally occurring four-helix bundles. These include the structural aspects and the relative stability of the native conformation. The model four-helix bundle shows two characteristic temperatures T theta and Tf. The former is the temperature above which the structure resembles that of the random coil. Below the first-order folding transition temperature Tf the chain adopts the native conformation corresponding to the four-helix bundle. It is shown that in order to obtain a unique native structure a proper free energy balance between secondary and tertiary interactions is needed. The thermal denaturation starting from the unique native conformation indicates that at least a three-state analysis is required. The intermediates in the equilibrium thermal denaturation are all found to be native-like. The kinetics of refolding starting from an ensemble of denatured states shows that the acquisition of the native conformation takes place via a kinetic partitioning mechanism. A fraction of molecules, phi, reaches the native state by a topology inducing nucleation collapse mechanism, while the remainder (1-phi) follows a complex three-stage multipathway process. We suggest, in accord with our earlier studies, that phi is essentially determined by the intrinsic temperature scales T theta and Tf. Our studies indicate that better design of proteins can be achieved by making T theta as close to Tf as possible. Experimental implications for de novo design of proteins are briefly discussed.

Kinetics↗
PubMed1996

Identification of retained N-formylmethionine in bacterial recombinant mammalian cytochrome P450 proteins with the N-terminal sequence MALLLAVFL...: roles of residues 3-5 in retention and membrane topology.

An N-terminal block to Edman degradation was observed when any of five different mammalian cytochrome P450 (P450) proteins was expressed in Escherichia coli using the N-terminal sequence MALLLAVFL... This block was also seen in Salmonella typhimurium. With all proteins examined, the block could be removed by mild acid hydrolysis (0.6--6 N HCl, 23 degrees C) to expose Met as the N-terminus, suggesting N-formylMet retention. The N-terminal peptide of a modified P450 1A2 ("mutant 1", containing a thrombin-sensitive site inserted at residue 25) was released with thrombin and analyzed by electrospray mass spectrometry and found to yield the M(r) expected for the N-formyl derivative (+/- 0.8 amu). The region of positions 3--5 was altered by random mutagenesis, and three P450 1A2-expressing clones were analyzed for nucleotide and amino acid sequences. The changes from LLL were to RER (P450 1A2a), VDS (P450 1A2b), and WRH (P450 1A2c); these all show slightly dissimilar hydropathy plots compared to the MALLLAVFL... sequence. Mutant P450 1A2a had the N-terminal Met removed to yield N-terminal Ala; P450 1A2b contained an unmodified Met at the N-terminus; P450 1A2c had an approximately 80% block of the N-terminal Met. Experiments with bacterial membranes containing expressed P450 1A2 mutant 1 and P450 1A2 mutant 2 (thrombin-sensitive site inserted at residue 46) suggest that thrombin site 2, but not 1, is sequestered in the membrane. Spheroplasts of bacteria expressing P450 1A2 and the mutants at positions 3--5 were treated with proteinase K; amino acid analysis indicated that no cleavage occurred. These results are interpreted in a model in which most of the mammalian P450 expressed in the bacterium is located in the cytosol, the region near residue 46 is in the inner membrane, the region near residue 25 is in the cytosol, and the N-terminus is either imbedded in the membrane or free in the cytosolic space, depending upon the sequence. However, the possibility that the differences in N-terminal processing are the result of direct changes in interactions with the deformylase and Met aminopeptidase cannot be excluded.

Amino Acid Sequence↗
PubMed1996

Low blood pressure and dementia in elderly people: the Kungsholmen project.

OBJECTIVE: To examine the relation between blood pressure and dementia in elderly people. DESIGN: Cross sectional, population based study. SETTING: Kungsholmen district of Stockholm, Sweden. SUBJECTS: 1642 subjects aged 75-101 years. MAIN OUTCOME MEASURES: Prevalence and adjusted odds ratio of dementia by blood pressure. RESULTS: People with systolic pressure < or = 140 mm Hg were more often diagnosed as demented than those with systolic pressure >140 mm Hg: odds ratios (95% confidence interval) adjusted for age, sex, and education were 2.98 (2.17 to 4.08) for all dementias, 2.91 (1.93 to 4.38) for Alzheimer's disease, 2.00 (1.09 to 3.65) for vascular dementia, and 5.07 (2.65 to 9.70) for other dementias. Similar results were seen in subjects with diastolic pressure < or = 75 mm Hg compared with those with higher diastolic pressure. When severity and duration of dementia were taken into account, only moderate and severe dementia were found to be significantly related to relatively low blood pressure, and the association was stronger in subjects with longer disease duration. Use of hypotensive drugs and comorbidity with cardiovascular disease did not modify the results for all dementias, Alzheimer's disease, and other dementias but slightly reduced the association between vascular dementia and diastolic blood pressure. CONCLUSIONS: Both systolic and diastolic blood pressure were inversely related to prevalence of dementia in elderly people. We think that relatively low blood pressure is probably a complication of the dementia process, particularly Alzheimer's disease, although it is possible that low blood pressure may predispose a subpopulation to developing dementia.

Aged↗
PubMed1996

Recombinant human cytochrome P450 1A2 and an N-terminal-truncated form: construction, purification, aggregation properties, and interactions with flavodoxin, ferredoxin, and NADPH-cytochrome P450 reductase.

Previous work from this laboratory indicated that the N-terminus of recombinant human cytochrome P450 (P450) 1A2 expressed in Escherichia coli is blocked (P. Sandhu, Z. Guo, T. Baba, M. V. Martin, R. H. Tukey, and F. P. Guengerich, (1994) Arch. Biochem. Biophys. 30, 168 -177). A modification of this construct was done to insert an extra 12 residues containing a thrombin-sensitive site just beyond the most N-terminal hydrophobic segment, and the protein was expressed, purified, and cut with thrombin. Treatment of E. coli membranes in which the P450 1A2 with 12 extra residues was present with thrombin did not release the truncated form, suggesting that the added thrombin site may be imbedded in the membrane. The N-terminal of the recombinant proteins were blocked but mild acid hydrolysis generated the expected Met residues as analyzed by Edman degradation. Laser light scattering studies indicated that purified thrombin-cleaved P450 1A2 (devoid of the usual N-terminal 25 residues or the first 36 residues of the wild-type protein) was still aggregated in the absence of detergent and that some nondenaturing detergents could reduce the apparent size to that of a tetramer. The N-terminal truncated protein was as catalytically active as full-length P450 1A2 but required a higher concentration of NADPH-P450 reductase. P450 1A2 exhibited catalytic activity in E. coli cells, and activity of the purified enzyme could be supported by E. coli flavodoxin and NADPH-flavodoxin reductase. Spinach ferredoxin and NADPH-ferredoxin reductase could also substitute for NADPH-P450 reductase. These artificial electron donors did not require phospholipid for oxidation reactions; however, phospholipid was required for optimal activity when either P450 1A2 or the truncated form was used with NADPH-P450 reductase. Rates of oxidation of 7-ethoxyresorufin were considerably higher for both P450 1A2 and the truncated form when NADPH-P450 reductase was replaced with the "oxygen surrogate" iodosylbenzene, indicating that P450 reduction and oxygen activation are normally limiting in this P450 1A2 reaction.

Amino Acid Sequence↗
PubMed1996

Efficient and sustained transgene expression in mature rat oligodendrocytes in primary culture.

In order to evaluate the characteristics and efficiency of gene transfer in primary cultures of oligodendrocytes, four different techniques including particle bombardment (Accell gene gun), cationic liposome-mediated transfection (lipofection), calcium phosphate co-precipitation and retroviral infection were compared using the LacZ and luciferase reporter genes. Highly purified postnatal adult rat oligodendrocytes were obtained by sequential immunopanning, plated in culture, and transfected using various reporter and promoter genes. The most efficient expression of LacZ and luciferase genes was found with particle mediated gene delivery. The transgene expression level obtained with gene gun delivery was at least two- to 100-fold greater than three other tested gene transfer methods. Comparison of the relative strength of four viral and two cellular promoters in these primary oligodendrocytes cultures demonstrated that the CMV promoter was the strongest. Using a human growth hormone (hGH) reporter gene, a long-term transgene expression pattern in primary oligodendrocytes was demonstrated to be sustained in culture for the entire experimental period (4 weeks) after particle-mediated gene transfer. These results demonstrate that expression of a foreign gene can be effectively achieved in primary cultures of adult oligodendrocytes, especially by using the particle bombardment method. The results also suggest that the current ex vivo gene transfer system may be used to manipulate oligodendrocytes for future application in gene therapy studies.

Adenoviridae↗
PubMed1996

Protective effects of API0134 on myocardial ischemia and reperfusion injury.

Previous studies have demonstrated that a crude extract from Chinese medicinal herb Andrographis Paniculata Nees (APN) could prevent myocardial ischemia and reperfusion injury. A refined extract API0134 was studied further. LAD was ligated for 90 min in 20 dogs and then reperfused for 120 min. The animals were randomly divided into 2 groups, API0134 treated group (n = 10), 45 min after ischemia receiving a slow i.v. bolus of 1 mg/kg and then an infusion of 80 micrograms.kg-1/min for 60 min and control group (n = 10) which was given only 5% glucose in saline. Result showed that the hemodynamics in API0134 treated group showed better effects of preventing the increase of the LVEDP and maintaining relatively normal CO as compared with control group. Ischemic ECGs were significantly milder. Malignant arrhythmia did not appear in API0134 treated group. After reperfusion, the infarct size was smaller (5.06 +/- 2.67% vs 10.45 +/- 3.11%, P < 0.01), the damages found in myocardial ultrastructure were significantly milder. It is concluded that API0134 may protect the myocardium from ischemic reperfusion injury.

Animals↗
PubMed1996

Three-dimensional power Doppler imaging: a phantom study to quantify vessel stenosis.

This study investigated whether three-dimensional (3D) power Doppler imaging can be used to quantify arterial stenosis and its potential as an alternative to x-ray angiography. Three-dimensional power Doppler images of in vitro stenotic vessels were generated under different hemodynamic conditions with a 3D power Doppler imaging system. This system includes: a Macintosh Quadra 840AV computer used to perform 3D imaging acquisition, reconstruction and display; a computer-controlled motor-driven translation assembly used to move the transducer; and an ATL Ultramark 9 HDI ultrasound system. Three vascular- and tissue-mimicking phantoms containing three wall-less stenotic vessels with area reduction of 80%, 50% and 30% were imaged with different flow rates under both steady and pulsatile flow conditions and with different Doppler angles under steady flow condition. With the use of the blood mimic, experimental results demonstrated that power Doppler imaging is nearly independent on flow velocity and Doppler angle. It was also demonstrated that 3D power Doppler imaging can produce nonpulsatile angiographic-like 3D images of the flow field. The stenotic vessels were quantified with an overall accuracy of 8.3% of the vessel area and an overall precision of 7% of the vessel area under the conditions described in this paper. It is believed that 3D power Doppler imaging can be used to quantify arterial stenosis, and in some applications it could be an alternative to x-ray angiography.

Blood Flow Velocity↗