Biomedical subjects
Publications and source records attributed to Y Bao.
By herbalogical study and investigation, "lideri" used by Mongolia doctors in different areas mainly contains 10 species from 4 genera of 4 families, but the quality materials only contains 3 species, Tinospora sinensis (Lour.) Merr., T. cordifolia Miers and T. capillipes Gagnep.
Quercetin glycosides are common dietary antioxidants. In general, however, potential biological effects of the circulating plasma metabolites (e.g., glucuronide conjugates) have not been measured. We have determined the rate of glucuronidation of quercetin at each position on the polyphenol ring by human liver cell-free extracts containing UDP-glucuronosyltransferases. The apparent affinity of UDP-glucuronosyltransferase followed the order 4'- > 3'- > 7- > 3, although the apparent maximum rate of formation was for the 7-position. The 5-position did not appear to be a site for conjugation. After isolation of individual glucuronides, the inhibition of xanthine oxidase and lipoxygenase were assessed. The K(i) for the inhibition of xanthine oxidase by quercetin glucuronides followed the order 4'- > 3'- > 7- > 3-, with quercetin-4'-glucuronide a particularly potent inhibitor (K(i) = 0. 25 microM). The glucuronides, with the exception of quercetin-3-glucuronide, were also inhibitors of lipoxygenase. Quercetin glucuronides are metabolites of quercetin in humans, and these compounds can retain some biological activity depending on conjugation position at expected plasma concentrations.
We studied three keratin (K) gene candidates, K13, K19, and K20 mRNAs, for detecting micrometastases in cervical lymph nodes (LNs) by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 166 histologically metastasis-negative nodes, 24 micrometastatic LNs (14. 4%) were detected based on K13 gene expression. Keratin 19 mRNA is an inadequate marker for the genetic diagnosis due to not only illegitimate gene expression from lymphatic tissue but also gene expression from the ectopic salivary gland. Keratin 20 mRNA showed low sensitivity. It is suggested that K13 mRNA may be a promising tumor marker among these keratin genes for detecting the micrometastases in cervical LNs of oral cancer.
BACKGROUND: This study was undertaken to determine whether glucose-insulin-potassium (GIK) would improve myocardial performance and limit morbidity after coronary artery bypass grafting in diabetic patients. METHODS: Forty consecutive coronary artery bypass grafting patients with medically treated diabetes mellitus were prospectively randomly assigned to either a GIK group (n = 20; 500 mL D5W + 80 U regular insulin + 40 mEq KCl 30 mL/hour) or a no-GIK group (n = 20; D5W at 30 mL/hour). The GIK was begun at anesthetic induction and continued for 12 hours postoperatively. RESULTS: Patients treated with GIK had higher postoperative cardiac indices (2.88 +/- 0.50 versus 2.20 +/- 0.39 L/minute per square meter; p < 0.0001), lower inotrope scores (0.40 +/- 0.68 versus 1.25 +/- 1.44; p = 0.05), less weight gain (5.80 +/- 3.76 versus 13.85 +/- 6.52 pounds; p < 0.0001), and had shorter times of ventilator support (8.35 +/- 2.60 versus 13.45 +/- 7.33 hours; p = 0.0128). They had a significantly lower prevalence of atrial fibrillation (15% versus 60%; p = 0.003), and shorter hospital stays (6.70 +/- 1.52 versus 10.15 +/- 6.62 days; p = 0.02). CONCLUSIONS: Substrate enhancement with GIK in diabetic patients improved myocardial performance and resulted in faster recovery after coronary artery bypass grafting.
The importance of finding good antisense sequences cannot be underestimated. Poor inhibition of the targeted protein can compromise the final outcome of an antisense experiment, making it difficult to arrive at a definitive understanding of the function of the protein of interest. In antisense therapeutics, identification of potent sequences becomes even more important. RNA mapping greatly increases the odds of finding active sequences. When antisense sequences are selected randomly or by gene walking, a substantial number of the oligonucleotides have little to no activity. In contrast, oligonucleotides selected by RNA mapping typically produce an antisense inhibition of greater than 50%. Oligonucleotides targeted to 60% of the accessible sites in the 5' portion of the multidrug resistance transcript inhibited P-glycoprotein function with high potency. In the angiotensin type 1 receptor system, oligonucleotides to the eight accessible sites examined inhibited AT1 receptor binding by at least 50%, with oligonucleotides to four of the sites producing at least 70% inhibition. The RNA mapping assay, which is based on standard molecular techniques, therefore provides an easy and reliable method for potent antisense sequence selection.
BACKGROUND: Brain tissue acidosis can result from ischemia when cerebral blood flow reduction reaches a critical value. The portable, battery-operated Khuri pH monitor has been used previously in a large number of patients undergoing cardiopulmonary bypass surgery to monitor the intramyocardial pH during aortic clamping. It was found to be easy to use, reliable, and a strong predictor of myocardial preservation. The goal of this study was to evaluate the applicability of this monitor in the measurement of brain pH. METHODS: Fifteen New Zealand white rabbits underwent general endotracheal anesthesia. A right frontal craniotomy was performed and a pH/temperature glass electrode was inserted in the frontal lobe. Both common carotid arteries were exposed in the neck and prepared for occlusion. Three rabbits were used as control; their brain pH was recorded over 60 minutes. Twelve rabbits underwent bilateral common carotid artery occlusion of varying duration and their brain pH measurements were recorded. RESULTS: There was no significant difference in pH levels at baseline in the two groups (p = 0.604). There were significant differences in pH over time between the control and occlusion group (p = 0.016). The pH dropped steadily and significantly in the occlusion group (p = 0.008), whereas little change in pH was noted over time in the control group (p = 0.366). CONCLUSION: The portable Khuri pH monitor has been used by cardiothoracic surgeons to monitor the myocardium during bypass procedures. Our experimental pilot study found it to be reliable in measuring the brain pH and to be relatively simple to use. It is approved by the Food and Drug Administration (FDA). We believe it may be of benefit to neurosurgeons.
The authors describe an ES cell technique that resolves the problems of time, expense, and inconsistency often encountered in the production of transgenic mice via DNA microinjection.
Replication of viral RNA genomes requires the specific interaction between the replicase and the RNA template. Members of the Bromovirus and Cucumovirus genera have a tRNA-like structure at the 3' end of their genomic RNAs that interacts with the replicase and is required for minus-strand synthesis. In Brome mosaic virus (BMV), a stem-loop structure named C (SLC) is present within the tRNA-like region and is required for replicase binding and initiation of RNA synthesis in vitro. We have prepared an enriched replicase fraction from tobacco plants infected with the Fny isolate of Cucumber mosaic virus (Fny-CMV) that will direct synthesis from exogenously added templates. Using this replicase, we demonstrate that the SLC-like structure in Fny-CMV plays a role similar to that of BMV SLC in interacting with the CMV replicase. While the majority of CMV isolates have SLC-like elements similar to that of Fny-CMV, a second group displays sequence or structural features that are distinct but nonetheless recognized by Fny-CMV replicase for RNA synthesis. Both motifs have a 5'CA3' dinucleotide that is invariant in the CMV isolates examined, and mutational analysis indicates that these are critical for interaction with the replicase. In the context of the entire tRNA-like element, both CMV SLC-like motifs are recognized by the BMV replicase. However, neither motif can direct synthesis by the BMV replicase in the absence of other tRNA-like elements, indicating that other features of the CMV tRNA can induce promoter recognition by a heterologous replicase.
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OBJECTIVE: To study the effects of B-ultrasonic scanning during pregnancy on reproductive outcome, including pregnant outcome and neonatal status. METHODS: Data of reproductive outcome and B-ultrasonic examination were extracted from the questionnaires and obstetric records of 12,224 primigravidas in eight hospitals of Beijing during May 1992 to April 1993. Their reproductive outcomes were analyzed according to frequency and gestational weeks they had B-ultrasonic examination taken, adjusted for potential confounding factors, such as age at pregnancy, smoking and drinking during pregnant period and history of spontaneous abortion, by logistic regression. RESULTS: There was no statistically significant difference in reproductive outcomes between groups, who had B-ultrasonic examination taken for two, three and four times or more and who had only once, respectively, who had more than four times and who had less than three times, and who had their first examination before and after the eighth week of gestation, or before and after the 12th week of gestation. CONCLUSION: No adverse reproductive outcome due to exposure to diagnostic dose of B-ultrasound radiation during pregnancy has been found.
OBJECTIVE: To evaluate the value and technique of Phacoemulsification in white cataract. METHODS: Ninty eyes of senile cataract were divided into two groups by the density of the nuclei. Different operative technique was done in two groups. RESULTS: The success rate of the continuous curvilinear capsulorhexis was 88.9%. Seventy five eyes have got the visual acuity over 0.5 on the first day after the operation. There was significant difference between two groups. The complications of operation were mild corneal edema and posterior capsule tear. CONCLUSIONS: It's difficult to complete the phacoemulsification of white cataract. The surgeons are required the skillful technique and experience. However, phacoemulsification is valuable in white cataract.
PURPOSE: Patients with fundus albipunctatus uniformly experience difficulty with vision at night. Their retinas are spotted with characteristic light yellow flecks of unknown composition that typically spare the macula. A defect in the transport or utilization of visual cycle retinoids is thought to underlie this recessive disorder with variable clinical expression. To elucidate the molecular defect we considered the genes for interphotoreceptor retinoid-binding protein (RBP3) and 11-cis retinol dehydrogenase (RDH5) as candidates for this disease. METHODS: We examined two unrelated families with fundus albipunctatus. The diagnosis was determined clinically and RBP3 and RDH5 were analyzed by molecular screening methods and direct genomic sequencing. RESULTS: Each family had two affected members with typical fundus albipunctatus. The affected members were siblings born to unaffected parents who were seventh cousins in the first family and unrelated in the second family. The probands from both families were clinically similar except for the fundus dots that were more extensive in the second family to the point of involving the parafoveal region. In the initial phase of genetic screening RBP3 defects were ruled-out as the cause of the disease in both families. In contrast, RDH5 mutations were found in the affected siblings in both families. The proband in one had a homozygotic Gly238Trp missense mutation (GGG -> TGG) involving exon 4 and in the other carried compound heterozygotic changes Arg280His (CGC -> CAC) and Ala294Pro (GCC -> CCC) in exon 5. The disease phenotype was only manifested in family members with two abnormal RDH5 alleles consistent with autosomal recessive inheritance in both pedigrees. CONCLUSIONS: These findings strongly implicate defects of RDH5 as the cause of fundus albipunctatus and point to a heterogeneity of RDH5 mutations in this form of congenital stationary night blindness with variable expressivity.
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BACKGROUND: Activation of complement during revascularization of ischemic myocardium accentuates myocardial dysfunction. Soluble human complement receptor type 1 (sCR1) is a potent inhibitor of complement, as are heparin-bonded (HB) cardiopulmonary bypass (CPB) circuits. This study sought to determine whether total complement inhibition with the combination of sCR1 and HB-CPB limits damage during the revascularization of ischemic myocardium. METHODS AND RESULTS: In 40 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, sCR1 (10 mg/kg) was infused 5 minutes after the onset of coronary occlusion (sCR1), 10 received HB-CPB only (HB-CPB), 10 received sCR1 and HB-CPB (sCR1+HB), and 10 received neither sCR1 or HB-CPB (unmodified). Addition of sCR1 to the HB group resulted in less myocardial tissue acidosis (DeltapH = -0.72+/-0.03 for unmodified; -0.46+/-0.05 for HB; -0.18+/-0.04 for sCR1; -0.13+/-0.01 for sCR1+HB), better recovery of wall motion scores (4 = normal to -1 = dyskinesia; 1.67+/-0.17 for unmodified; 2.80+/-0.08 for HB; 3.35+/-0.10 for sCR1; 3.59+/-0.08 for sCR1+HB), less lung water accumulation (5.46+/-0.28% for unmodified; 2.39+/-0.34% for HB; 1.22+/-0.07% for sCR1; 1.24+/-0.13% for sCR1+HB), and smaller infarct size (area necrosis/area risk = 44.6+/-0.7% for unmodified; 33.2+/-1.9% for HB; 19.0+/-2.4% for sCR1; 20+/-1.0% for sCR1+HB) (P<0.05 versus unmodified; P<0.05 versus unmodified and HB groups). CONCLUSIONS: Total complement inhibition with sCR1 and sCR1+HB circuits optimizes recovery during the revascularization of ischemic myocardium.
Human serum albumin (HSA) reduced the phospholipid hydroperoxide, 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl)-l-3-phosphatidylcholine (PLPC-OOH) to the corresponding hydroxy-derivative with a high apparent affinity (Km=9. 23+/-0.95 microM). Removal of bound lipid during purification increased this activity. At physiological concentration, HSA reduced the phospholipid hydroperoxide in the absence of a cofactor. However, in the presence of a cofactor (reductant), the rate of the reaction was increased. All of the major aminothiols in plasma could act as reductants, the best being the most abundant, cysteine (Km=600+/-80 microM). For every nanomole of PLPC-OOH reduced by HSA, 1.26 nmol of cystine was formed, indicating a reaction stoichiometry of 1 mol PLPC-OOH to 2 mol cysteine. We used chemical modification to determine which amino acid residues on HSA were responsible for the activity. Oxidation of thiol group(s) by N-ethylmaleimide led to a reduction in the rate of activity, whereas reduction of thiols by either dithiothreitol or the angiotensin-converting enzyme inhibitor, captopril, increased the activity. Both N-ethylmaleimide-modified HSA and dithiothreitol-treated HSA exhibited increased apparent affinities for PLPC-OOH. For a range of preparations of albumin with different modifications, the activity on PLPC-OOH was dependent on the amount of free thiol groups on the albumin (correlation coefficient=0.91). Patients with lowered albumin concentrations after septic shock showed lowered total plasma thiol concentrations and decreased phospholipid hydroperoxide cysteine peroxidase (PHCPx) activities. These results therefore show for the first time that HSA exhibits PHCPx activity, and that the majority of the activity depends on the presence of reduced thiol group(s) on the albumin.
Multiple, diverse sites in the coding region of the angiotensin type-1 receptor mRNA were targeted with 2'-deoxyribonucleotide antisense oligonucleotides (ONs). The uptake of 1 microM concentration of these ONs into Chinese hamster ovary cells was facilitated by the use of cationic liposomes. The antisense sequences reduced binding of 125I-angiotensin II by 57-73%, while mismatch ONs and reverse sequence ONs produced little reduction in receptor binding. These reductions in AT1 receptor binding were accompanied by comparable decreases in AT1 receptor mRNA levels. Furthermore, mRNA cleavage fragments corresponding in size to 3'-cleavage fragments were observed with two of the antisense ONs, consistent with the involvement of an RNase H-type enzyme. When 2'-methoxyribonucleotide analogs of these same sequences were tested, AT1 receptor mRNA levels were unchanged even though small reductions in AngII binding were observed. Antisense effects seen with these 2'-methoxyribonucleotide sequences may have arisen through a translational arrest mechanism. Direct comparisons between 2'-deoxyribonucleotide analogs and their 2'-methoxyribonucleotide counterparts show that antisense effects are significantly larger when they are mediated through an RNase H-type mechanism. 2'-methoxyribonucleotide sequences were most effective when they were directed against the translation initiation codon.
Telomerase is a ribonucleoprotein complex intimately involved in cell immortalization and carcinogenesis. This enzyme is activated and stabilizes telomere length in almost all types of cancer. Telomerase may be necessary for continuous cell proliferation. In this study, we analyzed telomerase activity in hamster experimental oral lesions (starting from epithelial hyperplasia through dysplasia, carcinoma in situ, and invasive carcinoma) evoked by 7,12-dimethylbenz[a]anthracene, and in normal mucosa. We also analyzed proliferative activity in these lesions by using immunohistochemical analysis and flow cytometry. Histologically normal epithelium expressed weak telomerase activity. The telomerase activity count increased rapidly in the early stage of carcinogenesis and gradually in the late stage. Cell-proliferative activity closely correlated with progression of disease. These findings indicate that telomerase activation is an early event and that increases in telomerase activity upregulate cell proliferation in chemically induced hamster oral carcinogenesis.
Glutathione (GSH) is known to play an important role in regulating oxidative damage to cells. The present study was initiated to examine the effect of exogenous GSH on oxidative injury in a retinal Müller cell line and to characterize GSH transport in these cells. Rat Müller cells (rMC-1) were incubated with varying concentrations of t-butylhydroperoxide (t-BHP) to induce oxidative stress, and cell viability was measured after addition of GSH. In other studies, kinetics of GSH uptake and Na+-dependency were examined by incubating cells with35S-GSH in Na+-containing and Na+-free buffers. GSH uptake was studied with GSH at concentrations varying from 0. 05-10 m m in NaCl buffer. In the presence of sodium, extracellular GSH provided protection against t-BHP-induced oxidant injury to rMC-1 cells; in contrast, the amino acid precursors of GSH did not have any effect on cell viability. GSH was taken up by rMC-1 cells in a concentration- and sodium-dependent manner. Kinetic studies revealed both a high affinity (Km approximately 0.31 m m) and low affinity Km( approximately 4.2 m m) component. Furthermore, GSH depletion had no significant effect on the rate of GSH uptake. The results show that physiological concentrations of GSH can protect Müller cells from oxidative injury. Both Na+-dependent and Na+-independent transport systems for GSH exist in Müller cells, and the Na+-dependent GSH transporter may be involved in the protective role of GSH.