Biomedical subjects

Sheng Yang

Publications and source records attributed to Sheng Yang.

At least 37 records · Page 2Linked to original sources

PubMed2005

[Treatment effect of DICE regimen on patients with relapsed or refractory intermediate and high grade non-Hodgkin's lymphoma].

BACKGROUND & OBJECTIVE: So far, there is still no standard salvage regimen for relapsed or refractory non-Hodgkin's lymphoma (NHL). The response rates (RR) of NHL patients received common salvage regimens, such as DICE, ESHAP, MINE, and EPOCH, are only 30%-70%. This study was to evaluate the efficacy and safety of DICE regimen, as a salvage regimen, in treating patients with relapsed or refractory intermediate and high grade NHL. METHODS: Thirty-five patients with relapsed or refractory intermediate and high grade NHL, who had been pretreated with chemotherapy dominated by CHOP or CHOP-like regimen with a median of 6 cycles (ranged 2-12 cycles), were salvaged by DICE regimen from Jun. 1999 to Jan. 2004. Of the 35 patients, 14 were T-cell original, and 21 were B-cell original. RESULTS: The 35 patients received DICE regimen with a median of 4 cycles (ranged 2-7 cycles). All patients were assessable in the efficacy and adverse events. The total RR was 74.3% with complete response (CR) rate of 31.4%, median response time (MST) of 4 months (ranged 1-30 months), median time to failure (TTF) of 7 months (ranged 2-34 months),median survival time (MST) of 14 months (ranged 3-51 months), and 2-year survival rate of 33.3%. The RRs of T-cell and B-cell NHL were 85.7% and 66.7%. The CR rate was higher in T-cells NHL than in B-cell NHL (50.0% vs. 19.0%, P=0.073). Elevated serum lactate dehydrogenase (LDH) and bulky disease were high risk factors of the efficacy of DICE regimen (P < 0.05). The response to DICE reginmen was an independent prognostic factor of patients with relapsed or refractory NHL (P = 0.001). The major toxicity was myelosuppression. Incidences of neutropenia and thrombocytopenia of grade III-IV were 71.4% and 8.6%. CONCLUSIONS: DICE regimen is a safe and effective salvage regimen for the patients with relapsed or refractory intermediate and high grade advanced NHL. Elevated serum LDH and bulky disease are the adverse prognostic factors. The response to DICE regimen may directly influence survival time of patients with relapsed or refractory NHL.

Adolescent↗

PubMed2005

[Involvement of N-type calcium channels in pain and antinociception].

N-type voltage-dependent calcium channels are critical for pain transduction and modulation. These channels are highly present at the presynaptic terminals of nociceptive neurons in dorsal horn of the spinal cord where they regulate the release of the key pro-nociceptive neurotransmitters such as glutamate and substance P. Consistent with this, the selective blockers of the N-type channels are powerful analgesics, and, mice lacking the N-type Ca(v)2. 2 subunit have higher pain thresholds compared to wild-type. The N-type channels are also present at synapses in the autonomic system and the central nervous system, the inhibition of these synapses is the main reason of the side effects in analgesic therapy with current N-type channel blockers. Recently, a unique splice isoform of the N-type channels was found exclusively expressed at the nociceptive neurons in dorsal root ganglia, which may represent a novel target for pain management.

Animals↗

PubMed2005

[Inhibitory effect of active fraction of tiaoxin recipe on beta-amyloid protein induced long-term potentiation in CA1 area of rats' hippocampal slices].

OBJECTIVE: To study the effect of the active fraction of Tiaoxin recipe (TXR-A), in inhibiting long-term potentiation (LTP) induced by beta amyloid protein (beta-AP) in CA1 area of rats' hippocampal slices. METHODS: The population spike (PS) in CA1 area of hippocampal slices incubated in different medium was recorded before and after LTP was evoked by a 100 Hz, 100 trains high frequency stimulation (HFS), using extracellular microelectrode recording techniques. RESULTS: The amplitude of PS significantly decreased after HFS in hippocampal slices incubated in medium containing 0.2 micromol/L beta-AP for more than 1.5 hour, as compared with that incubated in normal cerebrospinal fluid, the difference was significant, suggesting that beta-AP could inhibit LTP in hippocampal slices. The average amplitude of PS in slices incubated in beta-AP containing medium could be significantly enhanced by adding high-concentration TXR-A or TXR into the medium, and TXR-A showed a better effect of enhancing than that of TXR, indicating that TXR-A could increase the amplitude of LTP. CONCLUSION: TXR-A may be the chief ingredient extracted from TXR for improving beta-AP induced LTP in CA1 area of rats' hippocampus, to antagonise the inhibition of beta-AP on LTP is possibly one of the mechanisms for its intelligence benefiting action.

Alzheimer Disease↗

PubMed2004

Development of miniaturized competitive immunoassays on a protein chip as a screening tool for drugs.

BACKGROUND: Doping in sports has become a serious problem. Gas chromatography-mass spectrometry (GC-MS) serves as an effective reference method, but it is limited by low throughput and is therefore not suitable for large-scale screening. Use of protein chips for high-throughput screening of all athletes for prohibited substances could become an important complementary tool to GC-MS. METHODS: We developed a protein chip based on an aldehyde-activated glass slide containing 10 physically isolated arrays. The chip was used to screen urine from 1347 athletes for prohibited substances and to screen a negative control group consisting of 200 females and 120 males. Urine samples from 66 individuals known to be abusers, provided by the China Doping Control Center (CDCC), and 129 standard prohibited substances were tested as positive controls. RESULTS: All 1347 urine samples screened by means of the protein chips were also subjected to reference analysis by GC-MS at the CDCC. There was no qualitative difference between the results obtained with the two methods. The correlation coefficient (r(2)) for the quantitative results obtained with the protein chip and GC-MS was 0.991. CONCLUSIONS: The protein chip could be used to screen for a series of 16 prohibited drugs in urine samples. This system has the potential to become an effective screening method to test substances prohibited by the International Olympic Committee.

Doping in Sports↗

PubMed2004

The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus infected Vero-E6 cells.

Spike protein is one of the major structural proteins of severe acute respiratory syndrome-coronavirus. It is essential for the interaction of the virons with host cell receptors and subsequent fusion of the viral envelop with host cell membrane to allow infection. Some spike proteins of coronavirus, such as MHV, HCoV-OC43, AIBV and BcoV, are proteolytically cleaved into two subunits, S1 and S2. In contrast, TGV, FIPV and HCoV-229E are not. Many studies have shown that the cleavage of spike protein seriously affects its function. In order to investigate the maturation and proteolytic processing of the S protein of SARS CoV, we generated S1 and S2 subunit specific antibodies (Abs) as well as N, E and 3CL protein-specific Abs. Our results showed that the antibodies could efficiently and specifically bind to their corresponding proteins from E.coli expressed or lysate of SARS-CoV infected Vero-E6 cells by Western blot analysis. Furthermore, the anti-S1 and S2 Abs were proved to be capable of binding to SARS CoV under electron microscope observation. When S2 Ab was used to perform immune precipitation with lysate of SARS-CoV infected cells, a cleaved S2 fragment was detected with S2-specific mAb by Western blot analysis. The data demonstrated that the cleavage of S protein was observed in the lysate, indicating that proteolytic processing of S protein is present in host cells.

Animals↗

PubMed2004

Glutathione metabolism and its implications for health.

Glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) is the most abundant low-molecular-weight thiol, and GSH/glutathione disulfide is the major redox couple in animal cells. The synthesis of GSH from glutamate, cysteine, and glycine is catalyzed sequentially by two cytosolic enzymes, gamma-glutamylcysteine synthetase and GSH synthetase. Compelling evidence shows that GSH synthesis is regulated primarily by gamma-glutamylcysteine synthetase activity, cysteine availability, and GSH feedback inhibition. Animal and human studies demonstrate that adequate protein nutrition is crucial for the maintenance of GSH homeostasis. In addition, enteral or parenteral cystine, methionine, N-acetyl-cysteine, and L-2-oxothiazolidine-4-carboxylate are effective precursors of cysteine for tissue GSH synthesis. Glutathione plays important roles in antioxidant defense, nutrient metabolism, and regulation of cellular events (including gene expression, DNA and protein synthesis, cell proliferation and apoptosis, signal transduction, cytokine production and immune response, and protein glutathionylation). Glutathione deficiency contributes to oxidative stress, which plays a key role in aging and the pathogenesis of many diseases (including kwashiorkor, seizure, Alzheimer's disease, Parkinson's disease, liver disease, cystic fibrosis, sickle cell anemia, HIV, AIDS, cancer, heart attack, stroke, and diabetes). New knowledge of the nutritional regulation of GSH metabolism is critical for the development of effective strategies to improve health and to treat these diseases.

Cysteine↗

PubMed2004

Cloning, overexpression, and characterization of a novel thermostable penicillin G acylase from Achromobacter xylosoxidans: probing the molecular basis for its high thermostability.

The gene encoding a novel penicillin G acylase (PGA), designated pgaW, was cloned from Achromobacter xylosoxidans and overexpressed in Escherichia coli. The pgaW gene contains an open reading frame of 2586 nucleotides. The deduced protein sequence encoded by pgaW has about 50% amino acid identity to several well-characterized PGAs, including those of Providencia rettgeri, Kluyvera cryocrescens, and Escherichia coli. Biochemical studies showed that the optimal temperature for this novel PGA (PGA650) activity is greater than 60 degrees C and its half-life of inactivation at 55 degrees C is four times longer than that of another previously reported thermostable PGA from Alcaligenes faecalis (R. M. D. Verhaert, A. M. Riemens, J. V. R. Laan, J. V. Duin, and W. J. Quax, Appl. Environ. Microbiol. 63:3412-3418, 1997). To our knowledge, this is the most thermostable PGA ever characterized. To explore the molecular basis of the higher thermostability of PGA650, homology structural modeling and amino acid composition analyses were performed. The results suggested that the increased number of buried ion pair networks, lower N and Q contents, excessive arginine residues, and remarkably high content of proline residues in the structure of PGA650 could contribute to its high thermostability. The unique characteristic of higher thermostability of this novel PGA provides some advantages for its potential application in industry.

Achromobacter denitrificans↗

PubMed2004

Feature selection based on mutual information and redundancy-synergy coefficient.

Mutual information is an important information measure for feature subset. In this paper, a hashing mechanism is proposed to calculate the mutual information on the feature subset. Redundancy-synergy coefficient, a novel redundancy and synergy measure of features to express the class feature, is defined by mutual information. The information maximization rule was applied to derive the heuristic feature subset selection method based on mutual information and redundancy-synergy coefficient. Our experiment results showed the good performance of the new feature selection method.

Algorithms↗

PubMed2004

Preferential codons enhancing the expression level of human beta-defensin-2 in recombinant Escherichia coli.

Human beta-defensin-2 (hBD2) is a small antimicrobial peptide with potential as a therapeutic agent. The effect of codon usage on the expression of hBD2 in Escherichia coli was studied. Two coding sequences encoding the same hBD2 precursor were both expressed as fusion protein with thioredoxin in E. coli BL21 (DE3). One is the wild-type human cDNA and the other is a gene synthesized by a PCR-based method in which rare codons were altered to those frequently used in E. coli. The expression level of recombinant hBD2 was over 50% of the total cellular protein when the synthetic gene with preferential codons was employed which was a 9-fold enhancement over the wild-type cDNA. The result shows the codon bias of the host was a major barrier in high-level expression of recombinant hBD2 and suggests a similar approach may be used in the expression of other defensins in E. coli.

Amino Acid Sequence↗

PubMed2004

[Clinical and pathological analysis of 15 cases with primary breast lymphoma].

BACKGROUND & OBJECTIVE: Primary breast lymphoma (PBL), a rare disease, is likely to be misdiagnosed, and its treatment still remains controversial. This study was to investigate the clinical and pathological features of PBL, summarize the treatment experience, and obtain a better profile of the disease. METHODS: The clinical and pathological records of 15 PBL patients admitted in the Cancer Hospital, Chinese Academy of Medical Science from January 1986 to December 2003 were analyzed. RESULTS: The median age of the 15 patients was 39 years. Of all cases, 93.3%(14/15) were B-cell origin, 6.7% (1/15) were T-cell origin, 40% (6/15) were diffuse large B-cell lymphoma, and 26.6% (4/15) were mucosa associated lymphoid tissue lymphoma. No local relapse occurred in the 8 patients who were given local mastectomy combined with chemoradiotherapy, with a median follow-up of 34.5 months (ranging from 4 to 214 months). Two of the 6 patients with low grade PBL, who did not receive chemotherapy, relapsed after a short remission; 2 of the remaining 4 patients who received chemotherapy gained a constant remission, while after salvage chemoradiotherapy the other 2 gained a second remission up to now. The overall 3-, and 5-year survival rates were 88.9%, and 66.7%. CONCLUSION: The majority of PBL was B-cell origin, diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma were the most frequent entities. Radical mastectomy was not necessary for good local control of combination of local mastectomy and chemoradiotherapy. PBL must be regarded as a kind of systemic disease in spite of its pathologic type. Chemotherapy should be included in the multi-modality treatment of PBL.

Adult↗

PubMed2004

[Free radical homeostasis].

Although free radicals have reactive chemical properties, the characteristics of free radical homeostasis have been maintained during the evolution of oxygen-requiring organisms. These characteristics are implicated in performing diverse physiological functions and none of deleterious effects resulting from neat balance of production and scavenging of free radicals, as well as the repair of radical-induced damage of bio-macromolecules under physiological conditions. Nutrients and their metabolites along with "essential" antioxidants play crucial roles in maintaining free radical homeostasis. Glutathione homeostasis interrelates synergistically with free radical homeostasis. Free radical homeostasis should be maintained well in healthy humans at different ages and under various living conditions in order that oxidative stress and its induced oxidative damage will be prevented or ameliorated before aging.

Animals↗

PubMed2004

[Amplification and sequencing of the gene coding for mucin-like protein from Schistosoma japonicum].

OBJECTIVE: To amplify and sequence the partial gene coding for mucin-like protein from Chinese isolates of Schistosoma japonicum (SjMLP). METHODS: The antigenic determinants of SmMLP were predicted by PCGENE software and specific oligonucleotide primers were designed and synthesized. Total RNA was isolated from adult worms of S. japonicum using Trizol reagent and the coding region gene of SjMLP was amplified by RT-PCR technique. RESULTS: The coding region of SjMLP gene was specifically amplified by RT-PCR and the size of amplified fragment was 756 base pairs. The DNA sequence analysis result indicated that the coding sequence of the MLP was highly homologous between S. mansoni and S. japonicum. CONCLUSION: The amplified fragment is consistent to the predicted one, providing a basis for cloning and further study on DNA immunization.

Amino Acid Sequence↗

PubMed2003

Presynaptic alpha-7 nicotinic acetylcholine receptors modulate excitatory synaptic transmission in hippocampal neurons.

The effects of presynaptic nicotinic acetylcholine receptors (nAChRs) on excitatory synaptic transmission in CA1 pyramidal neurons of the rat hippocampus were examined by blind whole-cell patch clamp recording from hippocampal slice preparations. Local application of the nAChRs agonist dimethylphenyl-piperazinium iodide (DMPP) did not induce a postsynaptic current response in CA1 pyramidal cells. However, DMPP enhanced the frequency and amplitude of spontaneous excitatory postsynaptic current (sEPSC) in these cells in a dose-dependent manner. This enhancement was blocked by the selective nicotinic alpha-7 receptor antagonist alpha-bungarotoxin, but not by the antagonist mecamylamine, hexamethonium or dihydro-beta-erythroidine. The frequency of miniature excitatory postsynaptic current (mEPSC) in CA1 pyramidal neurons was also increased by application of DMPP, indicating a presynaptic site of action of the agonist. Taken together, these results suggest that activation of presynaptic nAChRs in CA1 pyramidal neurons, which contain alpha-7 subunits, potentiates presynaptic glutamate release and consequently modulate excitatory synaptic transmission in the hippocampus.

Animals↗

PubMed2003

Thymosin alpha-1 modulates excitatory synaptic transmission in cultured hippocampal neurons in rats.

Thymosin alpha-1 (Talpha1) not only possesses immunoregulatory properties in periphery but also is expressed in the central nervous system (CNS) and affects the function of the CNS. To further elucidate the role of Talpha1 in the CNS, the whole-cell recording technique was used to observe the effect of Talpha1 on the spontaneous excitatory synaptic transmission in cultured rat hippocampal neurons. The results showed that acute treatment with Talpha1 significantly enhanced the frequency of AMPA-mediated spontaneous excitatory postsynaptic current (sEPSC) at the concentrations of 1 and 10 microg/ml and also enhanced the frequency of AMPA-mediated miniature excitatory postsynaptic current (mEPSC) at 10 microg/ml. However, the amplitude of both sEPSC and mEPSC were not changed by Talpha1. Those results suggested that Talpha1 involves in the regulation of excitatory synaptic transmission in hippocampal neurons, which contribute to its neurophysiological function in the CNS.

Animals↗

PubMed2003

[Enhancement of the production of SAM by overexpression of SAM synthetase in Pichia pastoris].

S-Adenosyl-L-methionine(SAM) is an important metabolic intermediate in the metabolic flux of sulphur. SAM is involved in three key metabolic pathways: transmethylation, transsulfuration and polyamine synthesis. As a potential therapeutic agent, SAM is being used as over the counter drug and nutrient supplement. An expression vector, harboring SAM synthetase 2 gene from S. cerevisiae and regulated by the glyceraldehyde-3-phosphate dehydrogenase gene promoter P(GAP), was transformed into GS115 strain of P. pastoris. Through zeocin resistance and expression screening, a recombinant strain was obtained that had high SAM yield and the fermentation conditions were optimized. The results showed that carbon source, nitrogen source, pH and dissolved oxygen had significant effects on the accumulation of SAM. The SAM production of the recombinant cells reached 2.49 g/L after fermentation for three days under the optimized conditions. The present studies show that fermentation of recombinant P. pastoris strain, expressing heterologous SAM synthetase gene, may be a promising approach for the production of SAM.

Bleomycin↗

PubMed2003

Purification and characterization of Alcaligenes faecalis penicillin G acylase expressed in Bacillus subtilis.

The Alcaligenes faecalis PGA gene encoding heterodimeric penicillin G acylase (PGA) was cloned and successfully expressed in Escherichia coli and Bacillus subtilis respectively. In contrast to E.coli hosts where the enzymes were retained in the periplasm, B. subtilis cell secreted the recombinant enzyme into the medium. Contrary to limited expression yield of E. coli (pETAPGA), PGA extracellularly expressed by B. subtilis (pBAPGA) and B. subtilis (pMAPGA) reached the highest yield of 653 u/L. This yield increased 109-fold higher than the native expression of A. faecalis CICC AS1.767. The enzyme was fractionated with (NH(4))(2)SO(4) and purified by DEAE-Sepharose CL-6B with a yield of 81%. The purified enzyme had a specific activity of 1.469 u/mg. Furthermore, some enzyme characteristics, such as the pH and temperature optimum, the stability against organic solvent and the ratio of cepholexin synthesis to hydrolysis were determined. By overexpressing A. faecalis PGA in B. subtilis and purifying secreted enzyme from culture medium one could readily obtain a large amount of an alternative source of PGA.

Alcaligenes↗

PubMed2003

[Second-line Hycamtin in the treatment of lung cancer].

OBJECTIVE: To discuss the therapeutic effect and toxicity of second line Hycamtin for lung cancer patients. METHODS: Ten of these 21 patients had been treated with operation. All these 21 patients received second line Hycamtin treatment; given at the dose of 1.2 mg/m(2) per day, four consecutive days as one cycle and 21 days as one course. A total of 1 - 4 courses were given according to the patient's tolerance. Four of these 21 patients also received combination of cisplatin. RESULTS: Among the 13 un-operated patients, two patients showed CR, six showed PR, three SD and two PD, giving an effective rate of 62%. Among the 8 operated patients, seven showed SD but one developed distant metastasis. The 1-year survival rate was 88%. TOXICITY: leukopenia I-II degree 14 (66.7%), leukopenia III-IV degree 5 (23.8%), thrombocytopenia III-IV degree 1 (4.8%) and one patient died of high fever and neutocytopenia. Nausea 8 (38.1%), vomiting 3 (14.3%) and diarrhea 2 (9.5%) alopecia 4 (19.1%). Were the other side-effects. CONCLUSION: Hycamtin is indicated for second line therapy for lung cancer giving tolerable toxicity.

Adult↗

PubMed2003

Improving the specific synthetic activity of a penicillin g acylase using DNA family shuffling.

Penicillin G Acylas (PGA) of Providencia rettgeri (ATCC 25599) was evolved using a modified DNA family shuffling method. The identity of pga genes from Escherichia coli, Kluyvera citrophila and Providencia rettgeri ranges from 62.5% to 96.9%. The pga genes from above three species were recombined and shuffled to create interspecies pga gene fusion libraries. By substituting assembled chimaeras for corresponding region of pETPPGA, different recombinants were constructed and expressed in E. coli JM109(DE3). Mutants with obvious beta-lactam synthetic activity were selected from the plates and the ratios of synthesis to hydrolysis (S/H) were determined subsequently. It was shown that the primary structures of selected positives exhibited significant diversity among each library. The best mutant possessed 40% higher synthetic activity than the wild type enzyme of PrPGA. It was further proved in this study that the domain of alpha subunit contributed much more to improve the specific activity of synthesis. Results showed a recombinant PGA with higher synthetic activity was acquired by the method of DNA shuffling.

DNA Shuffling↗