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Biomedical subjects

Z Guo

Publications and source records attributed to Z Guo.

At least 415 records · Page 23Linked to original sources

High density cultivation of a recombinant CD-1 cell line producing prourokinase using a Biosilon microcarrier culture system.

CD-1, a genetically-engineered CHO cell line, was cultivated with a Biosilon microcarrier culture system. We successfully cultivated CD-1 cells to a very high density (over 1 x 10(7) cells/ml). Prourokinase was stably secreted at about 180 IU/10(6) cells/24 h. Experiments showed that CD-1 cells growing on Biosilon microcarriers were able to spontaneously release from the microcarriers, then reattach and proliferate on fresh microcarriers. This makes it very easy to scale up production. The microcarriers could be reused several times without affecting adhesion, proliferation and prourokinase secretion. With CM-PECC membrane radial flow chromatography and MPG chromatography, the prourokinase in conditioned medium could be purified to a specific activity of 1 x 10(5) IU/mg of protein. The purification factor was about 600 fold, and approximately 90% of the biological activity was recovered.

Animals↗

[Clinical significance of intraoperative frozen biopsy of cervical lymph node for laryngeal cancer].

The results of intraoperative and postoperative pathologic examination in 102 cases of laryngeal cancer were reported. The overall consistent rate of intraoperative and postoperative biopsy was 114/116(98%). The consistent rate of positive result was 40/40(100%), while the consistent rate of negative result was 74/76(97%). The pathological and clinical results showed that the intraoperative frozen biopsy could confirm the metastasis of cervical lymph node. When frozen biopsy was positive, the neck dissection should be performed. When frozen biopsy was negative, the neck dissection should not be performed in most cases, or the functional neck dissection may be performed in some cases.

Adult↗

[Repair of the traumata caused by partial laryngectomy].

At present, the wound caused by partial laryngectomy are repaired by using many kinds of tissues in order to avoid infection, granuloma and laryngeal stenosis. It is unclear whether the traumata has to be repaired by transplant tissues or non-repaired traumata will lead to laryngeal dysfunction. This article analyzed 162 patients who received partial laryngectomy from April 1980 to March 1992. These patients had been divided into two groups: repaired group (78 cases) and non-repaired group (84 cases). Repair material used included sternohyoideus fascia (57 cases), thyro-hyoideus fascia (9 cases), throat musculus flap (6 cases), stemocleido-mastoideus fascia (3 cases) and throat flap (3 cases). The result indicated that there were no significant differences in respiration swallow recovery time and so on. So we concluded that non-repaired group has similar curative effect to repaired group and repairing the traumata (especially minor traumata) with the fascia around the traumata is an effective method.

Adult↗

[Carcinoma arising from postburn scars (report of 5 cases)].

Carcinoma arising from postburn scars is rare. We have encountered 5 patients suffering from this late complication of scars, accounting for 0.32% of 1563 admissions for late surgery after burn injuries. They were all males, with a mean age of 56 years. The mean latent period was 43.2 years, and it was apparently longer when the acute burn injury occurred earlier in life. The site of predilection was the lower extremity, and multiple biopsies of various sites of the lesion remained to be the measure of confirmation. Pathologically, they were all squamoon cell carcinoma, grade I in 4 cases and grade II in 1. Immunohistochemical staining with anti-proliferation cell nuclear antigen (PCNA) showed that PCNA positive nuclei of squamous cell carcinoma were more numerous, as compared with that in the neighboring pseudo -epitheliomatous hyperplasia (PEH) and in normal skin, denoting markedly augmented assimilation of DNA in malignant degeneration. On the contrary, the number of Langerhan's cells were smallest in cancer area, as compared with PEH and normal skin. The diagnosis, treatment and prevention of such malignant degeneration in postburn scars have been discussed.

Adult↗

[A study on relation between effect of HB vaccination and time of the second injection].

Three kinds of hepatitis B vaccination schedule in neonates were compared. The schedule included 0, 40 day, 6 month; 0, 50 day, 6 month; 0, 60 day, 6 month; and was controlled by the 0, 30 day, 6 month schedule. The results showed that there was no statistically significant difference among three kinds of schedule, no matter who were neonates of HBs Ag-positive mother or neonates of HBsAg-negative mother. These indicated that in areas with poor condition, such as mountain, island, the second injection of hepatitis B vaccine in neonates may be completed within 30-60 days.

Hepatitis B↗

[Long-term efficacy of hepatitis B vaccine in newborn and revaccination study].

Two-hundred and sixty-nine newborns were followed up for 4 and 5 years after completion of vaccination (10 micrograms x 3). The anti-HBs positive rates remained 82.54% and 72.03%, respectively. The low-level titer (> or = 10-99 mIU/ml) made up 44.61%, and the medium-level titer (> or = 100-99mIU/ml) 32.34%. The highest titer was 857 mIU/ml. A 10 micrograms dose of hepatitis B vaccine was given to these children. The anti-HBs level went up greatly in the first month after revaccination, but started to drop in the third month, decreased rapidly in the sixth month, and in the twelveth month the level trended to restore the level before revaccination. This paper indicated that the home-made hepatitis B vaccine was effective. Revaccination was not necessary within 5-7 years after initial vaccination. Revaccination to children whose anti-HBs level was < 10mIU/ml was beneficial but the anti-HBs persistence was short.

Child, Preschool↗

Bufuralol hydroxylation by cytochrome P450 2D6 and 1A2 enzymes in human liver microsomes.

Bufuralol 1'-hydroxylation is a prototypical reaction catalyzed by cytochrome P450 (P450) 2D6, an enzyme known to show debrisoquine/sparteine-type genetic polymorphism in humans. In the present study we further examined the roles of several human P450 enzymes, as well as P450 2D6, in the hydroxylation of (+/-)-bufuralol, using liver microsomes from several human samples and human P450 enzymes expressed in human lymphoblastoid cell lines or Escherichia coli. Kinetic analysis of bufuralol 1'-hydroxylation by liver microsomes showed that there were different Km and Vmax values in seven human samples examined; low Km values (approximately 0.05 mM) were observed in four samples (including sample HL-18), high Km values (approximately 0.25 mM) in two samples (including sample HL-67), and an intermediate Km value (approximately 0.1 mM) in one sample. Quinidine and anti-rat P450 2D1 antibody almost completely inhibited bufuralol 1'-hydroxylation in human sample HL-18 at a substrate concentration of 0.4 mM, whereas these effects were not so drastic when liver microsomes from human sample HL-67 were used. In contrast, a very low concentration (< 10 microM) of alpha-naphthoflavone or anti-human P450 1A2 antibody significantly inhibited bufuralol 1'-hydroxylation catalyzed by human sample HL-67, but not HL-18, with 0.4 mM bufuralol. When the relative contents of P450 2D6 and P450 1A2 in 20 human samples were determined, bufuralol 1'-hydroxylation in samples containing large amounts of P450 2D6 tended to be more sensitive to quinidine, whereas the P450 1A2-rich samples were highly susceptible to alpha-naphthoflavone. However, at low substrate concentrations bufuralol 1'-hydroxylation was shown to be catalyzed principally by P450 2D6, based on the inhibitory effects of anti-rat P450 2D1 antibody and quinidine, in both human samples HL-18 and HL-67. At least five other, minor, bufuralol products were formed by human liver microsomes, in addition to 1'-hydroxybufuralol. Two of them were identified as 4- and 6-hydroxybufuralol by 1H NMR spectroscopy and mass spectrometry. The formation of the 4- and 6-hydroxylated products was suggested to be catalyzed by P450 1A2, based on the results of correlation with P450 1A2 contents in 60 human samples and inhibition by anti-P450 1A2 and alpha-naphthoflavone. Purified recombinant P450 1A2 (expressed in E. coli) produced 1'-, 4-, and 6-hydroxybufuralol in a reconstituted system, although P450 2D6 (expressed in human lymphoblast cell lines) was found to catalyze only bufuralol 1'-hydroxylation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗

[Effects of ligustrazine and nitroglycerine on acute hypoxic pulmonary hypertension in anesthetized dogs].

The effects of ligustrazine and nitroglycerine on acute hypoxic pulmonary hypertension were observed in 10 anesthetized dogs. The results showed that ligustrazine (40 mg/kg) significantly reduced the hypoxic mean pulmonary artery pressure (PAPm) and pulmonary vascular resistance (PVR) the 10th and 15th minute after its injection into the right atrium, respectively. Its action was blocked by the continuous intravenous injection of methylene blue (1 mg/kg/min). It was suggested that the action of ligustrazine could be mediated by endothelium-derived relaxing factor. It was also discovered that nitroglycerine (40 micrograms/kg) could quickly decrease PAPm and PVR, indicating that nitroglycerine can be used to treat acute pulmonary hypertension and the aggravation of chronic cor pulmonale.

Acute Disease↗

High density cultivation of genetically-engineered CHO cell lines with microcarrier culture systems.

Genetically-engineered CHO cell lines, r beta-13 and CLF-8B2, were cultivated with the MC-1 microcarrier culture system. The cell density could be enhanced by increasing the concentration of microcarrier. At a microcarrier concentration of 10 mg/ml, the cell density could reach 4 to 5 x 10(6) cells/ml. It was shown that these cell lines would spontaneously release from the microcarrier to attach to and proliferate on fresh microcarriers. We were thus able to scale up cultivation using a simple method, i.e. by adding fresh microcarriers and medium directly into the culture system to about 2, 4 or 8 times the original volume. Using a perfusion culture system, we have successfully cultivated CLF-8B2 cells in a 2 L bioreactor for several weeks at medium perfusion rates of 0.5 to 3 working volumes. Prourokinase was stably secreted.

Animals↗

[Reoperation for advanced recurrent laryngeal cancer after surgery].

Thirty-four cases of advanced recurrent laryngeal cancers after operation were treated surgically with satisfactory results. Postoperative 1-, 3- and 5-year survival rates were 63%, 40% and 40% respectively. The surgical procedures and experiences were described. We believe that surgical extirpation should be considered the best method in the management of advanced recurrent laryngeal cancer in spite of operative difficulties and dangers.

Adult↗

Mechanisms of inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone bioactivation in mouse by dietary phenethyl isothiocyanate.

The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK), induces lung tumors in mice, rats, and hamsters. Phenethyl isothiocyanate (PEITC), which occurs as gluconasturtiin in cruciferous vegetables, is a potent inhibitor of NNK-induced carcinogenesis. The present study investigated the enzymatic basis for the bioactivation of NNK and the mechanisms of the inhibition of this process by dietary PEITC in mice. The apparent Km for the formation of keto aldehyde, keto alcohol, and NNK-N-oxide in lung microsomes was 4.9, 2.6, and 1.8 microM and, in liver microsomes, 5.5, 5.1, and 8.8 microM, respectively. Immunoinhibition studies suggested that cytochrome P450s (P450s) 2A1 and 2B1 or related forms are the major enzymes involved in the oxidative metabolism of NNK in mouse lung microsomes. When female A/J mice were fed diets containing 0, 1, or 3 mumol of PEITC/g of diet for 4 wk, the dietary PEITC had no significant effects on the food consumption and body weight of the mice. NNK oxidation in the lung microsomes of mice consuming the 1 or 3 mumol of PEITC/g of diet was decreased by 13 to 27% or 30 to 50%, respectively. In liver microsomes, whose NNK oxidative metabolism rates were about twice those of lung microsomes on a per mg of protein basis, the activities were decreased by 14 to 31% by the 3 mumol of PEITC/g of diet. The apparent Km remained unchanged, and the apparent Vmax decreased in the lung and liver microsomes of PEITC-fed mice, suggesting a noncompetitive nature of the inhibition. When added to the incubation mixture, PEITC decreased NNK metabolism in a concentration-dependent manner and exhibited a competitive inhibition with apparent Ki values of 51 to 93 nM. Dietary PEITC decreased the hepatic P450 content by 25%, but increased (2-fold) the O-dealkylase activities of 7-pentoxyresorufin (indicative of P450 2B1) and 7-ethoxyresorufin (indicative of P450 1A) in the liver microsomes of mice consuming the 3 mumol of PEITC/g of diet. The P450 2B level was increased in liver microsomes but slightly decreased in the lung microsomes. The p450 2E1 level was increased by dietary PEITC by 1.2- and 1.6-fold in the liver and lung microsomes, respectively. The activities of glutathione S-transferase and NAD(P)H-quinone oxidoreductase in liver and lung microsomes were not affected appreciably by the dietary PEITC treatment. The results suggest that chronic consumption of PEITC decreases the rate of metabolic activation of NNK by chemical inactivation and competitive inhibition of the enzyme(s) responsible for NNK oxidation.

Animals↗

M(r) 6,400 aurin tricarboxylic acid directly activates platelets.

ATA is a novel anticoagulant polymeric anionic aromatic compound that inhibits von Willebrand factor binding to platelet glycoprotein Ib and thereby prevents ristocetin- and shear stress-induced platelet aggregation. To investigate its mechanism of action, ATA fractions of homogeneous M(r) have been prepared by size exclusion chromatography. ATA fractions of M(r) > or = 2,500 are most effective at inhibiting vWF-mediated platelet aggregation, and ATA of M(r) = 2,500 also inhibits thrombin-induced platelet activation. Paradoxical results were observed in studies of ATA with M(r) = 6,400. This fraction of ATA stimulates aggregation of washed platelets or platelet-rich-plasma. The dose/response of aggregation shows a bell-shaped curve with maximal aggregation at approximately 2 micrograms/ml. Platelet aggregation is associated with phosphoinositide turnover and protein kinase C- and calcium-dependent protein phosphorylation. Platelet signalling responses to ATA are inhibited by platelet pretreatment with PGI2 or dibutyryl-cyclic AMP, but are unaffected by inhibiting platelet cyclooxygenase with aspirin. These results suggest that M(r) 6,400 ATA directly activates platelet phospholipase C to initiate platelet aggregation. This effect, unique to M(r) 6,400 ATA, could potentially mitigate ATA's beneficial anti-thrombotic effect on vWF-mediated platelet responses, and should be considered when analyzing results of experiments that utilize unfractionated ATA.

Aurintricarboxylic Acid↗

Protein kinase C is activated in platelets subjected to pathological shear stress.

High levels of fluid shear stress at the blood vessel wall directly stimulate von Willebrand factor (vWF)-mediated platelet adhesion and aggregation and thereby contribute to the pathogenesis of arterial thrombosis. We have found that a pathological level of arterial wall shear stress (90 dynes/cm2) induces platelet aggregation that is associated with the phosphorylation of pleckstrin, a M(r) 47,000 protein kinase C substrate (p47). Shear-induced p47 phosphorylation depends entirely on vWF binding to platelet glycoprotein (Gp) Ib and GpIIb-IIIa, and the specific inhibition of protein kinase C with the staurosporine analogue Ro 31-7549 inhibits the full aggregation response to shear. Shear stress-induced platelet p47 phosphorylation occurs independent of any measurable change in diacylglycerol mass or hydrolysis of phosphatidylinositol 4,5-bisphosphate. These results indicate that mechanical shear stress induces vWF to bind to platelet GpIb and GpIIb-IIIa, stimulating a diacylglycerol-independent pathway of protein kinase C activation that contributes to platelet aggregation in response to shear.

Blood Platelets↗

Comparison of spectral techniques for computer-assisted classification of spectra of heart sounds in patients with porcine bioprosthetic valves.

The diagnostic performance of two spectral techniques (the fast Fourier transform, FFT, and autoregressive modelling, ARM) combined with four windowing functions (rectangular, Hanning, Hamming, and sine-cosine) and two classifiers (Bayes and nearest neighbour) to detect valvular degeneration was evaluated in a group of 95 patients. Forty-seven patients had a porcine bioprosthetic valve inserted in the aortic position and 48 patients had a porcine bioprosthetic valve inserted in the mitral position. Among the aortic valves, 24 were normal and 23 were degenerated whereas among the mitral valves, 19 were normal and 29 were degenerated. The aortic and mitral valves were analysed separately. For each type of valve, 21 features were extracted from the spectra of the valve closure sounds to train and test the performance of four pattern recognition systems by using the leave-one-out method. The discriminant properties of all feature combinations between two and five among the 21 features selected were evaluated. Results show that the FFT combined to the nearest neighbour classifier provided the best performances: 87 per cent of correct classifications (CCs) for aortic valves when using the Hanning or the Hamming window and 94 per cent of CCs for mitral valves when using the rectangular window. The best performances obtained with the ARM were 81 per cent of CCs for the aortic valves (nearest neighbour classifier and the Hanning or the Hamming window) and 92 per cent of CCs for the mitral valves (nearest neighbour classifier and the Hamming window or the Bayes classifier and the Hanning or the Hamming window).

Aortic Valve↗

Cardiac Doppler blood-flow signal analysis. Part 1. Evaluation of the normality and stationarity of the temporal signal.

The normality (Gaussian property) and stationarity of the cardiac Doppler blood-flow signal were evaluated on short-time segments distributed over the cardiac cycle. The basic approaches used to perform statistical tests on the nonstationary and quasiperiodic cardiac Doppler signal are presented. The results obtained from the data of ten patients having a normal aortic valve and ten patients having a stenotic valve indicate that a complex Gaussian random process is an acceptable approximation for the clinical cardiac Doppler signal. For segments of 10 ms or less, 82 per cent of them were accepted to be stationary with a significance level of 0.05, whereas for durations greater than 40 ms, the percentage of stationary segments was less than 75 per cent. It was concluded that the 10 ms window generally used in practice is a good choice for Doppler spectrogram estimation, but a shorter time interval would be preferable.

Aortic Valve↗

Cardiac Doppler blood-flow signal analysis. Part 2. Time/frequency representation based on autoregressive modelling.

Doppler spectrograms obtained by using autoregressive (AR) modelling based on the Yule-Walker equations were investigated. A complex AR model using the in-phase and the quadrature components of the Doppler signal was used to provide blood-flow directions. The effect of model orders on the spectrogram estimation was studied using cardiac Doppler blood flow signals taken from 20 patients. The 'final prediction error' (FPE) and the 'Akaike's information criterion' (AIC) provided almost identical results in model-order selection. An index, the spectral envelope area (SEA), was used to evaluate the effect of window duration and sampling frequency on AR Doppler spectrogram estimation. The statistical analysis revealed that the SEA obtained from AR modelling was not sensitive to window duration and sampling frequency. This result verified the consistency of the AR Doppler spectrogram. The white-noise characteristics of the AR modelling error signal indicated that the Doppler blood-flow signal can be adequately modelled as a complex AR process. With appropriate model orders, AR modelling provided better Doppler spectrogram estimates than the periodogram.

Aortic Valve↗

A new hypothesis about the relationship between free radical reactions and hemorheological properties in vivo.

This paper is concerned with a hypothesis that disturbance of free radical reactions may lead to abnormality of hemorheological properties in vivo, and so the free radicals generated in vivo may damage certain tissue cells indirectly by reducing the supply of oxygen and nutrients to these cells through slowing the circulation of blood. This hypothesis is based on the following evidence: A. We have found that the whole blood viscosity at low shear rate correlates to the lipid peroxidation in the patients suffering from certain cardio- or cerebrovascular diseases, and in dogs during liver ischemia reperfusion or hemorrhagic pancreatitis. B. Reports have shown that several alterations of hemorheological properties may take place as a result of free radical reactions, such as lipid peroxidation. For instance, lipid peroxidation may lead to decrease of deformability of red cells, increase of aggregation of red cells, formation of liquid thrombin, etc. C. We have demonstrated that some alterations of hemorheological properties involve the role of free radicals in rats suffering from intestinal ischemia/reperfusion. As evidence for this conclusion, superoxide dismutase (SOD) used as a specific scavenger of superoxide anion radical (O2-) can significantly prevent the intestinal ischemia/reperfusion induced changes of lipid peroxidation, red cell aggregation, Cassion's viscosity and whole blood viscosity at low shear rate in rats.

Animals↗

Structure-activity relationships of arylalkyl isothiocyanates for the inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolism and the modulation of xenobiotic-metabolizing enzymes in rats and mice.

Many arylalkyl isothiocyanates are potent inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in rats and mice. In the mouse, 4-phenylbutyl isothiocyanate (PBITC) and 6-phenylhexyl isothiocyanate (PHITC) exhibited greater inhibition than benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC). The present study was conducted to investigate the structure-activity relationships of these four arylalkyl isothiocyanates for their inhibition of NNK oxidation and effects on xenobiotic-metabolizing enzymes in rats and mice. A single dose (0.25 or 1.00 mmol/kg) of each isothiocyanate was given to F344 rats 6 or 24 h before death. The rates of NNK oxidation were decreased in microsomes from the liver, lung and nasal mucosa of rats. Generally, PEITC was more potent than BITC but less potent than PBITC and PHITC. The rates in rat liver microsomes were decreased at 6 h but recovered or increased at 24 h; the rates in rat lung microsomes were markedly decreased at both 6 and 24 h; and the rates in rat nasal mucosa microsomes were also significantly decreased. The same treatment decreased the rat liver N-nitrosodimethylamine demethylase activity dramatically and ethoxyresorufin O-dealkylase and erythromycin N-demethylase activities moderately. However, the rat liver microsomal pentoxy-resorufin O-dealkylase activity was decreased at 6 h but increased at 24 h, with PEITC showing the most marked induction. The rat liver NAD(P)H:quinone oxidoreductase activity was increased 1.4- to 3.3-fold, with PEITC being most effective; and the glutathione S-transferase activity was increased slightly. Similarly, at a single dose of 0.25 mmol/kg (5 mumol/mouse) 24 h before death, PEITC, PBITC, PHITC but not BITC, decreased NNK oxidation in mouse lung microsomes by 40-85%, with PBITC and PHITC showing greater inhibition. Furthermore, all four isothiocyanates extensively inhibited NNK oxidation in rat lung and nasal mucosa microsomes as well as mouse lung microsomes in vitro, with PEITC (IC50 of 120-300 nM) being more potent than BITC (IC50 of 500-1400 nM) but less potent than PBITC and PHITC (IC50 of 15-180 nM). PHITC was a very potent competitive inhibitor of NNK oxidation in mouse lung microsomes with apparent K(i) values of 11-16 nM. These results indicate that PBITC and PHITC are more potent inhibitors of NNK bioactivation in rats and mice than PEITC. In addition, these arylalkyl isothiocyanates could be effective in protecting against the actions of a broad spectrum of carcinogenic or toxic compounds.

Animals↗