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Biomedical subjects

M Liu

Publications and source records attributed to M Liu.

At least 577 records · Page 32Linked to original sources

Microbial reduction of 1-(4-fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1- piperazinyl]butan-1-one.

Among various micro-organisms screened for the stereoselective reduction of 4-chloro-1-(4-fluorophenyl)butan-1-one (1), Hansenula polymorpha [American Type Culture Collection (A.T.C.C.) 26012 and 86014], Nocardia salmonicolor [Squibb Culture (S.C.) 6370], Arthobacter simplex (A.T.C.C. 6949), Mycobacterium vaccae (A.T.C.C. 29678), Candida boidinii (A.T.C.C. 13821) and Saccharomyces cerevisiae (A.T.C.C. 13792) reduced compound 1 to the corresponding (R)-(+)-alcohol (2). In contrast, Lactobacillus kefir (A.T.C.C. 35411), Pullularia pullulans (A.T.C.C. 16623), Trigonopsis variabilis (A.T.C.C. 10679) and Cunninghamella echinulata (A.T.C.C. 26269) reduced compound 1 to the (S)-(-)-alcohol (2). When 1-(4-fluorophenyl)-4-(1-piperazinyl)butan-1-one (3) was used as substrate for the reduction, only Nocardia globerula (A.T.C.C. 12505) and Saccharomyces cerevisiae (A.T.C.C. 13792) converted compound 3 into the corresponding (R)-(+)-alcohol (4). Organisms which reduced compound 1 were inactive for the reduction of compound 3. 1-(4-Fluorophenyl)-4-[4-(5-fluoro-2- pyrimidinyl)butan-1-one (5) was reduced to the corresponding (R)-(+)-alcohol (6) by Mortierella ramanniana (A.T.C.C. 38191) and to the (S)-(-)-alcohol (6) by Pullularia pullulans (A.T.C.C. 16623). (R)-(+)-compound 2 and compound 4 are key chiral intermediates in the total chemical synthesis of (R)-(+)-compound 6, an effective antipsychotic agent under development at Bristol-Myers Squibb. A single-stage (fermentation/biotransformation) process and two-stage (fermentation and subsequent biotransformation by cell suspensions) process were developed for the stereoselective reduction of compound 5 to (R)-(+)-compound 6 by Mortierella ramanniana (A.T.C.C. 38191). In both processes, the reaction yield of 98% and the optical purity of 99.4% were obtained for (R)-(+)-compound 6. The enzyme which catalysed the reduction of compound 5 to (R)-(+)-compound 6 was purified to homogeneity. The purified protein consisted of a single polypeptide of 29 kDa.

Bacteria↗

Individualizing drug dosage regimens: roles of population pharmacokinetic and dynamic models, Bayesian fitting, and adaptive control.

The role of population pharmacokinetic modeling is to store experience with drug behavior. The behavior of the model is then correlated with the clinical behavior of the patients studied, permitting selection of a specific serum level therapeutic goal that is based on each individual patient's need for the drug and on the risk of adverse reactions, both of which must be considered. A dosage regimen is then computed to achieve that goal with maximum precision. The patient should not run a greater risk of toxicity than is justified, and should obtain the maximum possible benefit within the acceptable risk. The regimen is given and the patient monitored.

Bayes Theorem↗

[Pathology of muscle contracture caused by injection and activity of phosphochesterase and insulin receptor].

The animal model of muscle contracture caused by injection was set up in the experiment. We used the model for excessive healing studies and researched the changes in its pathology, and activity of phosphochesterase and insulin receptor in this model. The experimental results revealed that the pathologic changes belonged to excessive proliferation of connective tissue (excessive healing). When occurred muscle degeneration, infiltration of inflammatory cells, proliferation of fibroblasts and descending of collagen fibers, the activity level phosphochesterase and insulin receptor became higher. The excessive healing occurrence may have something to do with the changes of phosphochesterase and insulin receptor.

5'-Nucleotidase↗

Gastrojejunal disconnection in the presence of purulent peritonitis as an alternative approach in gastroduodenal operations.

A two stage operation is presented, for example, a life-saving procedure that halts further leakage and drainage of abscess by a modification of the gastrojejunal disconnection and reconstruction. It may be considered as an alternative approach in gastroduodenal operations in the presence of purulent peritonitis, especially in delayed surgical treatment.

Duodenum↗

In vitro transcription of transfer RNAs with 3'-end modifications.

It is difficult to modify the 3'-end of RNA transcribed in vitro from recombinant plasmid or phagemid DNA because of the need to retain a restriction endonuclease recognition site at the downstream end of the template in order to linearize the DNA before transcription. To avoid limitations on the 3'-sequence of RNA transcripts, we have modified a template-containing phagemid by inserting a FokI site outside the RNA gene sequence, positioned to cleave the template DNA to yield the desired 3' terminus. We demonstrate that this phagemid is an efficient template for tRNA transcription and use it to prepare mutants of Escherichia coli tRNA(Val) with modifications at the 3'-CCA end. Phagemids containing a FokI site should be suitable for in vitro transcription of large quantities of RNA of any length and with an unlimited variety of 3'-terminal sequences.

Base Sequence↗

The use of fibrin adhesive for hemostasis after liver resection.

Bleeding, biliary fistula and subphrenic abscess represent the major postoperative complications after liver surgery. Many different adjuvant methods have been developed for control of hemorrhage from the raw surface of liver, but the superiority of any single method remains to be proved. The use of a two-component fibrin adhesive for the control of solid organ bleeding seems to be promising. This study was to evaluate the efficacy of this fibrin adhesive for control of postoperative bleeding in liver surgery. Forty patients were randomized into two groups, similar in all demographic and clinical conditions. Fibrin adhesive was applied to the raw surface of liver resections at the end of operations for 20 patients. Nothing was applied for the control group. Postoperative bleeding was estimated by multiplying the drain amount by the free hemoglobin concentration, every day. Estimated postoperative bleeding was 8.12 +/- 5.65 gm for patients with fibrin adhesive, 15.57 +/- 14.43 gm for control group. Fibrin adhesive has been used in the treatment of injury to the liver and spleen. In this study, it proved to be useful in the control of postoperative bleeding in liver resection, and hopefully decreasing morbidity.

Adult↗

[Molecular and clinical cytogenetic studies of a family with a 22p+ marker chromosome].

A male with gonadal dysgenesis and a 22p+ was observed. Molecular and Clinical Cytogenetic studies have been carried out on the members of the family. The results showed that there was a 22p+ marker chromosome transmitted from the maternal grandmother of the proband to 6 members of this family. Its short arm showed a homogeneously dull stained region in C-banded preparations and a narrow dark or light stained band in R-, G-banded preparations respectively. A large Ag-band or double NORs was also observed on p+. The chromosomal in situ hybridization with tritium labelled rRNA gene probe demonstrated that the distribution of the silver grains was along the entire p+ of the marker chromosome. The number of silver grains on the short arm of the p+ was 3.9 times as that of any other normal acrocentric chromosomes. Two cases of female with repeated spontaneous abortions and 2 cases of male with gonadal dysgenesis were found by family study. Our studies, combining with previous literatures suggested that these abnormalities were probably in association with p+ marker chromosome.

Adult↗

Altered positional specificity of human plasma lecithin-cholesterol acyltransferase in the presence of sn-2 arachidonoyl phosphatidyl cholines. Mechanism of formation of saturated cholesteryl esters.

The positional specificity of purified human lecithin-cholesterol acyltransferase (LCAT) was studied by analyzing the labeled cholesteryl ester (CE) species formed in the presence of proteoliposome substrates containing mixed chain phosphatidylcholine (PC) species, labeled cholesterol and apoprotein A-I. Whereas over 90% of the acyl groups used for CE synthesis were derived from the sn-2 position of most of the naturally occurring PC substrates, about 75% of the CE species formed in the presence of sn-1-myristoyl 2-arachidonoyl PC, sn-1-palmitoyl-2-arachidonoyl (PAPC) and sn-1-palmitoyl 2-docosahexaenoyl PC were derived from the sn-1-position. On the other hand, rat LCAT utilized mostly sn-2-acyl group from either PAPC or from sn-1-palmitoyl 2-linoleoyl PC. The positional specificity of the human enzyme was not affected by the alteration in the matrix fluidity, type of the apoprotein activator used, or by the free cholesterol/PC ratio in the substrate. These results show that the positional specificity of human plasma LCAT is altered in the presence of sn-2-arachidonoyl PC, or sn-2-docosahexaenoyl PC, probably due to steric restrictions at the active site, and this may account for the formation of disproportionately high concentrations of saturated CE, and low concentrations of long-chain polyunsaturated CE in human plasma, relative to the composition of sn-2-acyl groups in plasma PC.

Animals↗

Effect of apoprotein B conformation on the activation of lysolecithin acyltransferase and lecithin: cholesterol acyltransferase. Studies with subfractions of low density lipoproteins.

In order to determine the role of apoprotein (apo) B conformation in the activation of the lysolecithin acyl-transferase reaction, we studied the activation of purified enzyme by various subfractions of low density lipoprotein (LDL), isolated by density gradient centrifugation. The activation of LAT correlated positively with the density of LDL and negatively with cholesterol/protein and triglyceride (TG)/protein ratios. The enzyme activation was also positively correlated with the number of trinitrobenzenesulfonic acid-reactive lysine amino groups, which increased with increasing density of LDL. The immunoaffinity of the LDL subfractions for B1B6, a monoclonal antibody directed to the receptor-binding region of apoB, increased with increasing density, while the affinity toward C1.4, a monoclonal antibody directed to the amino-terminal region of apoB, was not altered. Enrichment of normal whole LDL with TG resulted in a 45% reduction in enzyme activation, a 27% decrease in the number of trinitrobenzenesulfonic acid-reactive lysine groups, and a marked reduction in the immunoaffinity for B1B6. All these parameters reversed to normal when the TG-enriched LDL was treated with milk lipoprotein lipase, which specifically reduced the TG content of LDL. The LDL subfractions also supported cholesterol esterification by the purified enzyme, in parallel with lysolecithin esterification, indicating that apoB can also serve as an activator of the lecithin-cholesterol acyltransferase reaction. These results strongly suggest that the localized conformational change of apoB which occurs during the TG depletion of the precursor particle is critical for its activation of acyltransferase reactions, in a manner analogous to its interaction with the cellular receptors.

1-Acylglycerophosphocholine O-Acyltransferase↗

A randomized comparative trial of the MLCu375, TCu220C, steel ring and uterine cavity-shaped IUDs.

The Stainless Steel Ring, Uterine Cavity-Shaped Device, TCu220C and MLCu375 IUDs were evaluated in a randomized trial of 1536 women in Guangdong Province, China. The first-year continuation and expulsion rates were significantly lower (p less than 0.05) for the latter 3 IUDs than for the Stainless Steel Ring. The first year pregnancy rates for the MLCu375 (0.76 per 100 women) and TCu220C (1.2 per 100 women) were significantly lower (p less than 0.05) than those of the other two devices (6.1 and 4.1 per 100 women). The results of the study show that the MLCu375 and TCu220C are the most suitable IUDs for women in Guangdong Province.

Adult↗

Biologic properties of eugenol and zinc oxide-eugenol. A clinically oriented review.

Eugenol-containing dental materials are frequently used in clinical dentistry. When zinc oxide-eugenol (ZOE) is applied to a dentinal cavity, small quantities of eugenol diffuse through the dentin to the pulp. Low concentrations of eugenol exert anti-inflammatory and local anesthetic effects on the dental pulp. Thus use of ZOE temporary filling may facilitate pulpal healing; on the other hand, high eugenol concentrations are cytotoxic. Direct application of eugenol to pulp tissue may result in extensive tissue damage. The ability of ZOE-based endodontic sealers to influence periapical tissue healing is considered in view of eugenol's anti-inflammatory and toxic properties.

Biocompatible Materials↗

Rotavirus VP3 expressed in insect cells possesses guanylyltransferase activity.

We have examined the possible function(s) of the protein VP3 encoded by the rotavirus SA11 genomic segment 3. Viral-associated VP3 in double-shelled and single-shelled particles was shown to bind GTP covalently and reversibly. These properties are similar to the unique characteristics of eukaryotic and viral guanylyltransferases, suggesting that VP3 is associated with a capping enzyme activity. Previous studies have shown that intact viral particles are required for transcription, making it difficult to unequivocally identify the functions of individual proteins within such particles. Characterization of VP3 produced in the baculovirus expression system showed that the expressed VP3 covalently bound GTP. These studies suggest that VP3 alone is the guanylyltransferase. GTP binding also was seen in core virus-like particles and single-shelled virus-like particles that lacked viral nucleic acid and were assembled in insect cells.

Animals↗

Heterologous expression of thermopsin, a heat-stable acid proteinase.

We have previously reported the isolation, characterization, and gene sequence of a new thermostable acid protease, thermopsin, from Sulfolobus acidocaldarius, a thermophilic archaebacterium. Thermopsin is similar to aspartic protease pepsin in specificity and pH dependence. However, it optimally catalyzes in the temperature range of 85 to 90 degrees C and it is not structurally related to pepsin. The current report describes the synthesis of recombinant thermopsin in E. coli and in insect cells. Several recombinant thermopsin fusion proteins were expressed as "inclusion bodies" in the cytosol of E. coli. Active thermopsin preparations were obtained by refolding from urea solutions. Recombinant thermopsin was also expressed in insect cells using a baculovirus expression system. The thermostability of recombinant thermopsin is similar to that of the native enzyme.

Amino Acid Sequence↗

Flosequinan, a new vasodilator: systemic and coronary hemodynamics and neuroendocrine effects in congestive heart failure.

OBJECTIVES: The aim of this study was to evaluate the immediate and long-term systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan in patients with congestive heart failure. BACKGROUND: Preliminary studies have shown that this new long-acting oral systemic vasodilator may have beneficial effects in patients with heart failure. METHODS: Thirteen patients with congestive heart failure were studied. Systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan were assessed acutely with repeat systemic hemodynamic studies after 6 weeks of treatment. RESULTS: The administration of flosequinan acutely and after long-term treatment, resulted in a significant increase in cardiac index, stroke work index and stroke volume index with a reduction in systemic and pulmonary vascular resistances. The improvement in ventricular function was associated with an improvement in left ventricular efficiency without a change in myocardial oxygen consumption or coronary sinus blood flow. Myocardial oxygen extraction and net myocardial lactate extraction also did not change significantly with flosequinan therapy. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma arterial and coronary sinus atrial natriuretic factor concentrations were elevated at baseline; the latter concentrations at the level of the great cardiac vein were significantly higher than those of arterial concentrations, indicating increased left ventricular release of atrial natriuretic factor in congestive heart failure. Both arterial and coronary sinus atrial natriuretic factor levels were significantly reduced with the administration of flosequinan at peak effect in association with an improvement in systemic hemodynamics. CONCLUSIONS: Flosequinan therapy in patients with congestive heart failure results in a sustained beneficial hemodynamic action and improved cardiac performance without an increase in metabolic demand or activation of the sympathetic nervous system.

Aged↗

Effects of CO2 laser energy on dentin permeability.

The effect of a CO2 laser on the structure and permeability of smear layer-covered human dentin was evaluated in vitro. Three different energy levels were used (11, 113, and 566 J/cm2). The lowest exposure to the laser energy increased dentin permeability, measured as a hydraulic conductance, due to partial measured as a hydraulic conductance, due to partial loss of the superficial smear layer and smear plugs. The intermediate energy level also increased dentin permeability by crater formation, making the dentin thinner. The lack of uniform glazing of the surface of the crater, leaving its surface porous and in communication with the underlying dentinal tubules also contributed to the increase in dentin permeability seen with the intermediate laser energy. The highest laser energy produced complete glazing of the crater surfaces and sealed the dentinal tubules beneath the crater. However, it also completely removed the smear layer in a halo zone about 100-microns wide around each crater which increased the permeability of the pericrater dentin at the same time it decreased the permeability of the dentin within the crater. The combined use of scanning electron microscopy and permeability measurements provides important complementary information that is essential in evaluating the effects of lasers on dentin.

Adolescent↗

Cigarette smoking among junior high school students in Beijing, China, 1988.

Prevalence, behavioural patterns and risk factors of cigarette smoking were studied in a sample of 8437 junior high school students in Beijing in 1988. Smoking at least occasionally was reported by 34.4% of boys and 3.9% of girls, though the intensity tended to be low. Smoking prevalence increased with age among boys. Inhaling smoke into the lungs was practised by 68.2% of the boys who smoked and 37.3% of the girls. 'Believing that one looks elegant when smoking', 'trying to be fashionable' and 'seeking stimulation' were the most important reasons for smoking. Of the boys 83.5% and of the girls 86.5% usually smoked with friends or schoolmates. Many more boys (19.2%) than girls (1.7%) smoked at home. Examinations of risk factors for teenage smoking showed that it was associated with a combination of familial, psychological and socio-school factors, with peer group pressure being the most important one.

Adolescent↗