Biomedical subjects

Y Mu

Publications and source records attributed to Y Mu.

At least 19 recordsLinked to original sources

PubMed2002

Treatment of melasma with Pycnogenol.

Melasma (or chloasma) is a common disorder of cutaneous hyperpigmentation predominantly affecting sun-exposed areas in women. The pathogenesis of melasma is not fully understood and treatments are frequently disappointing and often associated with side effects. Pycnogenol is a standardized extract of the bark of the French maritime pine (Pinus pinaster), a well-known, potent antioxidant. Studies in vitro show that Pycnogenol is several times more powerful than vitamin E and vitamin C. In addition, it recycles vitamin C, regenerates vitamin E and increases the endogenous antioxidant enzyme system. Pycnogenol protects against ultraviolet (UV) radiation. Therefore its efficacy in the treatment of melasma was investigated. Thirty women with melasma completed a 30-day clinical trial in which they took one 25 mg tablet of Pycnogenol with meals three times daily, i.e. 75 mg Pycnogenol per day. These patients were evaluated clinically by parameters such as the melasma area index, pigmentary intensity index and by routine blood and urine tests. After a 30-day treatment, the average melasma area of the patients decreased by 25.86 +/- 20.39 mm(2) (p < 0.001) and the average pigmentary intensity decreased by 0.47 +/- 0.51 unit (p < 0.001). The general effective rate was 80%. No side effect was observed. The results of the blood and urine test parameters at baseline and at day 30 were within the normal range. Moreover, several other associated symptoms such as fatigue, constipation, pains in the body and anxiety were also improved. To conclude, Pycnogenol was shown to be therapeutically effective and safe in patients suffering from melasma.

Adult↗

PubMed2001

Generation of three selenium-containing catalytic antibodies with high catalytic efficiency using a novel hapten design method.

A novel strategy for design of haptens that were used to produce catalytic antibodies was developed and three monoclonal antibodies, 3G5, 2F3, and 5C9, were generated using this strategy. These monoclonal antibodies were converted into selenium-containing abzymes by chemically modifying the hydroxyl group of serines followed by sodium hydrogen selenide displacement. These selenium-containing abzymes exhibited remarkable glutathione peroxidase activity, which surpasses the activity of some native glutathione peroxidases. The activities of the selenium-containing abzymes Se-3G5, Se-2F3, and Se-5C9 which catalyzed reduction of hydroperoxides by glutathione were 2.23, 4.20, and 3.79 times that of rabbit liver glutathione peroxidase, respectively. Detailed steady-state kinetics study on Se-2F3 was carried out and the value of k(cat)/K(m) (H(2)O(2)) was found to be 2.11 x 10(7) M(-1) min(-1) which was supposed to be one of the highest among the known catalytic antibodies. The data of association constants and glutathione peroxidase activities of these catalytic antibodies and the steady-state kinetics of Se-2F3 showed that the method might be a remarkably efficient one for generating catalytic antibodies with glutathione peroxidase activity.

Amino Acid Sequence↗

PubMed2001

A novel dicyclodextrinyl ditelluride compound with antioxidant activity.

Reactive oxygen species (ROS) primarily arise from products of normal metabolic activities and are thought to be the etiology of many diseases. A novel dicyclodextrinyl ditelluride (2-TeCD) compound was designed to be a functional mimic of the glutathione peroxidase that normally removes ROS. 2-TeCD exhibited highly catalytic efficiency and good water solubility. Antioxidant activity was studied by using ferrous sulfate/ascorbate-induced mitochondria damage model system. 2-TeCD protected the mitochondria against oxidative damage in a dose-dependent manner and exhibited also great antioxidant ability in comparison with 2-phenyl-1,2-benziososelenazol-3(2H)-one. The mimic may result in better clinical therapies for the treatment of ROS-mediated diseases.

Animals↗

PubMed2001

Cloning and expression of a single-chain catalytic antibody that acts as a glutathione peroxidase mimic with high catalytic efficiency.

Glutathione peroxidase (GPX) has a powerful role in scavenging reactive oxygen species. In previous papers we have developed a new strategy for generating abzymes: the monoclonal antibody with a substrate-binding site is first prepared, then a catalytic group is incorporated into the monoclonal antibody's binding site by using chemical mutation [Luo, Zhu, Ding, Gao, Sun, Liu, Yang and Shen (1994) Biochem. Biophys. Res. Commun. 198, 1240-1247; Ding, Liu, Zhu, Luo, Zhao and Ni (1998) Biochem. J. 332, 251-255]. Since then we have established a series of catalytic antibodies capable of catalysing the decomposition of hydroperoxides by GSH. The monoclonal antibody 2F3 was raised against GSH-S-2,4-dinitrophenyl t-butyl ester and exhibited high catalytic efficiency, exceeding that of rabbit liver GPX, after chemical mutation. To produce pharmaceutical proteins and to study the reason why it exhibits high catalytic efficiency, we sequenced, cloned and expressed the variable regions of 2F3 antibody as a single-chain Fv fragment (2F3-scFv) in different bacterial strains. The amounts of 2F3-scFv proteins expressed from JM109 (DE3), BL21 (DE3), and BL21 (coden plus) were 5-10%, 15-20% and 25-30% of total bacterial proteins respectively. The 2F3-scFv was expressed as inclusion bodies, purified in the presence of 8 M urea by Co(2+)-immobilized metal-affinity chromatography (IMAC) and renatured to the active form in vitro by gel filtration. The binding constants of the active 2F3-scFv for GSH and GSSG were 2.46 x 10(5) M(-1) and 1.03 x 10(5) M(-1) respectively, which were less by one order of magnitude than that of the intact 2F3 antibody. The active 2F3-scFv was converted into selenium-containing 2F3-scFv (Se-2F3-scFv) by chemical modification of the reactive serine; the GPX activity of the Se-2F3-scFv was 3394 units/micromol, which approaches the activity of rabbit liver GPX.

Amino Acid Sequence↗

PubMed2001

Subpicosecond conformational dynamics of small peptides probed by two-dimensional vibrational spectroscopy.

The observation of subpicosecond fluctuations in the conformation of a small peptide in water is demonstrated. We use an experimental method that is specifically sensitive to conformational dynamics taking place on an ultrafast time scale. Complementary molecular-dynamics simulations confirm that the conformational fluctuations exhibit a subpicosecond component, the time scale and amplitude of which agree well with those derived from the experiment.

Computer Simulation↗

PubMed2001

Kinetics study of a selenium-containing ScFv catalytic antibody that mimics glutathione peroxidase.

The steady-state kinetics study and some enzymatic characterization of a selenium-containing scFv catalytic antibody (Se-scFv2F3) were carried out. A novel reaction formula of this abzyme-catalyzed reaction was proposed and a rate equation was obtained according to the formula. The constants in the equation were compared with Dalziel's parameters and the exact meanings of these constants were analyzed. The obtained kinetics parameters from the kinetics study of Se-scFv2F3 were analyzed and compared with those of native glutathione peroxidase.

Antibodies, Catalytic↗

PubMed2001

Kinetics study of a selenium-containing ScFv catalytic antibody that mimics glutathione peroxidase.

The steady state kinetic study and some enzymic characterization of a selenium-containing scFv catalytic antibody (Se-scFv2F3) was carried out. A novel reaction formula of this abzyme-catalyzed reaction was proposed and a rate equation was gotten according to the formula. The constants in the equation were compared with Dalziel's parameters and the exact meanings of these constants were analyzed. The gotten kinetics parameters from the kinetics study of Se-scFv2F3 were analyzed and compared with that of native glutathione peroxidase.

Antibodies, Catalytic↗

PubMed2001

A novel glutathione peroxidase mimic with antioxidant activity.

Many diseases are associated with the overproduction of hydroperoxides that inflict cell damage. A novel cyclodextrin derivative, 6A,6B-diseleninic acid-6A',6B'-selenium bridged beta-cyclodextrin (6-diSeCD), was synthesized to be a functional mimic of glutathione peroxidase (GPX) that normally removes these hydroperoxides. The mimic had high catalytic GPX activity of 13.5 U/micromol, which is 13.6-fold higher than ebselen (PZ51), and was chemically and biologically stable in vitro. Antioxidant activity was studied by ferrous sulfate/ascorbate-induced mitochondria damage model system. These data show that the mimic has great antioxidant activity. Such mimics may result in better clinical therapies for diseases mediated by hydroperoxides.

Animals↗

PubMed2001

ESR studies on reaction of saccharide with the free radicals generated from the xanthine oxidase/hypoxanthine system containing iron.

The free radicals generated from the iron containing system of xanthine oxidase and hypoxanthine (Fe-XO/HX) were directly detected by using spin trapping. It was found that not only superoxide anion (O(2)*-) and hydroxyl radical (OH*), but also alkyl or alkoxyl radicals (R*) were formed when saccharides such as glucose, fructose and sucrose were added into the Fe-XO/HX system. The generated amount of R* was dependent on the kind and concentration of saccharides added into the Fe-XO/HX system and no R* were detected in the absence of saccharides, indicating that there is an interaction between the saccharide molecules and the free radicals generated from the Fe-XO/HX system and saccharide molecules are essential for generating R* in the Fe-XO/HX system. It is expected that the toxicity of R* would be greater than of hydrophilic O(2)*- and OH* because they are liposoluble and their lives are longer and the active sites of biomolecules are closely related with lipophilic phase, thus they can damage cells more seriously than O(2)*- and OH*. The R* generated from the saccharide containing Fe-XO/HX can be effectively scavenged by selenium containing abzyme (Se-abzyme), indicating Se-abzyme is a promising antioxidant.

Animals↗

PubMed2001

A Chinese homozygote of familial hypercholesterolemia: identification of a novel C263R mutation in the LDL receptor gene.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in the low-density lipoprotein receptor (LDLR) gene; it is characterized by a high concentration of LDL, which frequently gives rise to tendon xanthomas and premature coronary artery disease (CAD). Individuals with heterozygous FH in China often exhibit a milder phenotype than those in other countries. The diagnosis of heterozygous FH relies on the clinical phenotype and this does not always permit unequivocal diagnosis of the disease. In the course of investigation of FH in a Chinese population sample, we found a family whose proband showed a markedly raised concentration of LDL cholesterol in plasma, and the presence of skin and tendon xanthomata. We used single-strand conformation polymorphism (SSCP) analysis to screen all the 18 exons and the exon-intron boundaries of the LDLR gene. One novel homozygous mutation, replacing T by C at nucleotide 850 in exon 6 was identified. This change substituted cysteine for arginine at codon 263 (C263R) of the LDLR. By means of mutant allele-specific amplification, we unequivocally diagnosed six heterozygotes with this novel mutation in the proband's family. forms of heterozygous FH are characterized by high serum LDL cholesterol levels, which are usually associated with premature coronary heart disease (CHD) and tendon xanthomas in early middle age, while homozygous FH individuals frequently suffer fatal CHD by their third decade (Goldstein et al. 1995). To date, more than 200 different mutations of the LDLR gene have been characterized worldwide (Hobbs et al. 1990; Hobbs et al. 1992; Varret et al. 1997). Chinese individuals with heterozygous FH are often recognized by virtue of their being parents of offspring with mutations in both alleles of the LDLR gene (Mak et al. 1998). Unlike their heterozygous parents, the Chinese homozygous FH patients are as severely affected, as are those elsewhere (Sun et al. 1994). In this article, we present an investigation of a Chinese family whose proband, with severe hypercholesterolemia, carried a novel mutation of the LDLR gene in a homozygous form, while the other six patients in the family, who carried this mutation in a heterozygous form, have a milder phenotype of FH. The main objective of our analysis was to delineate the full spectrum of mutations that underline FH in the Chinese population; our work represents a first step towards the implementation of nationwide DNA testing for this disease.

Base Sequence↗

PubMed2001

The use of psychoactive substances among adolescent students in an area in the south-west of China.

AIM: To survey drug/psychoactive substance use among adolescent students in a south-west province of China. DESIGN: A cluster sample was drawn from this province of nine districts or cities. Each district/city provided two schools from grade 11 senior high school, A total of 18 schools were selected randomly. FINDINGS: A total of 2649 students completed this self-report questionnaire, mean age 17.1 +/- 0.9 years. The response rate was 92.7-95.6% for each of the specific substances or drugs. The 'life-time prevalences of regular substance use' (at least 15 times during in any one month) were, in rank order of prevalence: tobacco 6.3%, non-steroid anti-inflammatory drugs (NSAID) 2.9%, alcohol 2.9%, solvent 0.3%, sedative/hypnotic 0.2% and cannabis 0.04%. The life-time prevalences of at least some use were: alcohol 66.1%, NSAID 59.3%, tobacco 27.4%, sedative/hypnotic 5.2%, heroin 3.1%, solvents 2.8%, amphetamine-type stimulants (ATS) 0.7% and cannabis 0.3%. The 'prevalences of current regular use' (at least 15 times in the past month) were: tobacco 4.2%, alcohol 1.6%, NSAID 0.8%, sedative/hypnotic 0.1%, solvents 0.1% and cannabis 0.1%. The 'prevalences of current use at any level' were: alcohol 15.2%, NSAID 9.6%, tobacco 7.1%, sedative/hypnotic 0.5%, solvents 0.4%, cannabis 0.1%, heroin 0.1%, and ATS 0.04%. The median age at onset substance use was between 10.7 and 13.4 9.6%. CONCLUSIONS: Drug misuse has appeared among teenage students in this area. The most widely used substances were alcohol and cigarettes. The rates of solvent, tobacco and alcohol use among males were substantially higher than in females.

Adolescent↗

PubMed2001

Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor.

We established a steroidogenic human ovarian granulosa-like tumor cell line, designated KGN, from a patient with invasive ovarian granulosa cell carcinoma. KGN had a relatively long population doubling time of about 46.4 h and had an abnormal karyotype of 45,XX, 7q-, -22. A steroid analysis of the cultured medium by RIA performed 5 yr after the initiation of culture showed that KGN was able to secrete pregnenolone and progesterone, and both dramatically increased after stimulation with (Bu)(2)cAMP. However, little or no secretion of 17alpha-hydroxylated steroids, dehydroepiandrosterone, androstenedione, or estradiol was observed. The aromatase activity of KGN was relatively high and was further stimulated by (Bu)(2)cAMP or FSH. These findings showed a pattern similar to that of steroidogenesis in human granulosa cells, thus allowing analysis of naturally occurring steroidogenesis in human granulosa cells. Fas-mediated apoptosis of KGN was also observed, which mimicked the physiological regulation of apoptosis in normal human granulosa cells. Based on these findings, this cell line is considered to be a very useful model for understanding the regulation of steroidogenesis, cell growth, and apoptosis in human granulosa cells.

Apoptosis↗

PubMed2001

Therapeutic potential of bone morphogenetic proteins.

Recently, there has been substantial progress in the area of bone morphogenetic protein (BMP) research. This review serves as an up-to-date summary of the history of BMPs, the mechanisms of BMP signalling and the role of BMPs in adipose, kidney, liver, bone and nervous system. The potential of BMPs as therapeutic agents will also be discussed.

Animals↗

PubMed2001

[A gene analysis of the low density lipoprotein receptor in Chinese with homozygous familial hyperchol-esterolemia].

OBJECTIVE: To investigate low density lipoprotein receptor(LDLR) gene mutations in Chinese with familial hyperchol-esterolemia(FH). METHODS: Genomic DNA was extracted from five unrelated children with clinical diagnosis of homozygous FH, together with their family members. Promoter and all of the 18 exons of LDLR gene were amplified by polymerase chain reaction (PCR) and were analyzed by single strand conformation polymorphism (SSCP). The PCR products of abnormal patterns shown by SSCP were sequenced directly. RESULTS: Two point mutations (A606T, C263R) were found in two families respectively. The two mutations were only found in China, and C263R is a novel mutation. CONCLUSION: The two mutations of LDLR gene are the cause of FH and there may be LDLR gene mutations only carried by FH patients in China.

Asian People↗

PubMed2001

[Study of the pulmonary heart disease computer-aided diagnosis system based on combining neural network].

We have constructed an expert sub-system for diagnosing pulmonary heart disease with back-propagation (BP) model of typical artificial neural network and BP-Hamming. The system can obtain and represent clinical data, and it has solved the problems such as obtaining automatic knowledge, representation and self-learning. The results of testing demonstrate that the method of neural network can be regarded as an expert sub-system to make intelligent diagnosis of pulmonary heart disease.

Algorithms↗

PubMed2001

National survey on prevalence of cancer pain.

OBJECTIVE: To collect nationwide basic data about cancer related pain. METHODS: Sixty cancer patients in each province were randomly selected to participate in this survey. The subjects represented all stages of cancer, tumor sites, and different demographic characteristics. Two self-designed structured questionnaires including reasons, types of pain and pain management were used by patients and physicians respectively. Subjects were asked to report whether he/she had experienced any type of cancer related pain and filled out the equivalent questionnaire. The severity of pain was assessed by using "visual analogue scale". Original data input and analysis were using EPI-INFO software package. RESULTS: The result showed that 61.6% (958/1555) of patients had different types of cancer related pain. Majority of pain (85.1%) were caused by advanced cancer. The major reasons (64.4%) for poor management or impedimental factors of pain care are due to patient including over-concern on opioid analgesic addiction, reluctance to report pain or refused to use opioid analgesic until at times when pain is intolerable; 26.8% belonged to physician's reasons including fear to cause addiction on opioid and lack of knowledge about cancer pain management; 16.2% are due to lack of different kinds of opioid analgesic for use and 16.1% belonged to drug regulation. CONCLUSIONS: The results showed that majority of patients (61.6%) had different types of cancer related pain. In most of patients, cancer pain was relieved when they were treated. The major reason for under-treatment or impeded factors for effective relief of cancer pain was fear of opioid addiction by both medical professionals and patients.

Adolescent↗

PubMed2000

Antitumor activity of tumor necrosis factor-alpha conjugated with polyvinylpyrrolidone on solid tumors in mice.

We attempted the development of a novel polymer conjugation to further improve the therapeutic potency of antitumor cytokines compared with PEGylation for clinical application. Compared with native tumor necrosis factor (TNF)-alpha in vitro, specific bioactivities of polyvinyl-pyrrolidone (PVP)-modified TNF-alphas (PVP-TNF-alphas) were decreased by increasing the degree of PVP attachment. PVP-TNF-alpha fraction 3, Mr 101,000, had the most effective antitumor activity of the various PVP-TNF-alphas in vivo. PVP-TNF-alpha fraction 3 had >200-fold higher antitumor effect than native TNF-alpha, and the antitumor activity of PVP-TNF-alpha fraction 3 was >2-fold higher than that of MPEG-TNF-alpha (Mr 108,000), which had the highest antitumor activity among the polyethylene glycol (PEG)-conjugated TNF-alphas. Additionally, a high dose of native TNF-alpha induced toxic side effects such as body weight reduction, piloerection. and tissue inflammation, whereas no side effects were observed after i.v. administration of PVP-TNF-alpha fraction 3. The plasma half-life of PVP-TNF-alpha fraction 3 (360 min) was about 80- and 3-fold longer than those of native TNF-alpha (4.6 mm) and MPEG-TNF-alpha (122 min), respectively. The mechanism of increased antitumor effect in vivo caused the prolongation of plasma half-life and increase in stability. These results suggested that PVP is a useful polymeric modifier for bioconjugation of TNF-alpha to increase its antitumor potency, and multifunctionally bioconjugated TNF-alpha may be a potentiated antitumor agent for clinical use.

Animals↗

PubMed2000

A bis-cyclodextrin diselenide with glutathione peroxidase-like activity.

A diselenide, 2,2'-diseleno-bis-beta-cyclodextrin (2-SeCD), was synthesized to imitate the antioxidant enzyme glutathione peroxidase (GPX). The GPX mimic accepts a variety of hydroperoxides as substrates. The GPX activities, reduction of H(2)O(2), tert-butyl hydroperoxide and cumenyl hydroperoxide by glutathione, are 7.4, 4.5 and 10.2 U/micromol, respectively. In contrast to ebselen (PZ51), the diselenide displays high GPX-like activity. The reduction of hydroperoxide by glutathione in the presence of a radical trap shows that the mimic catalyzes the reaction via a non-radical mechanism. A ping-pong mechanism was observed in the steady-state kinetic studies of the 2-SeCD-catalyzed reaction.

Animals↗