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Biomedical subjects

S Cheng

Publications and source records attributed to S Cheng.

At least 181 records · Page 10Linked to original sources

[Accumulative trends of ephedrine and pesudoephedrine in Ephedra sinica].

In Yi Kezhao Alliance, the content of ephedrine and pseudoephedrine in Ephedra sinica is in a ratio of four to six. The total content of ephedine and pseudoephedrine form cultivated Ephedra sinica is higher than that of wild one, and in direct ratio with the years of plant. For the content enhance of total alkaloids, decreasing irrigation and applying middlingly fertilizer is more effective measure.

Alkaloids↗

Transgenic mice bearing a human mutant thyroid hormone beta 1 receptor manifest thyroid function anomalies, weight reduction, and hyperactivity.

BACKGROUND: Resistance to thyroid hormone (RTH) is a syndrome characterized by refractoriness of the pituitary and/or peripheral tissues to the action of thyroid hormone. Mutations in the thyroid hormone receptor beta (TR beta) gene result in TR beta 1 mutants that mediate the clinical phenotype by interfering with transcription of thyroid hormone-regulated genes via a dominant negative effect. In this study, we developed transgenic mice harboring PV, a potent dominant negative human mutant TR beta 1 devoid of thyroid hormone binding and transcriptional activation, as an animal model to understand the molecular basis of this human disease. MATERIALS AND METHODS: Standard molecular biology approaches were used to obtain a cDNA fragment containing mutant PV which was injected into the pronucleus of fertilized egg. Founders were identified by Southern analysis and the expression of PV in tissues was determined by RNA and immunohistochemistry. Thyroid function was determined by radioimmunoassays of the hormones and the behavior of mice was observed using standard methods. RESULTS: The expression of mutant PV was directed by the beta-actin promoter. Mutant PV mRNA was detected in all tissues of transgenic mice, but the levels varied with tissues and with different lines of founders. Thyroid function tests in transgenic mice with high expression of mutant PV showed a significantly (approximately 1.5-fold) higher mean serum total of L-thyroxine levels (p < 0.01) than those of nontransgenic mice. Moreover, thyroid-stimulating hormone levels were not significantly different from those of nontransgenic mice. In addition, these mice displayed decreased weights and a behavioral phenotype characterized by hyperactivity. CONCLUSIONS: These mice have phenotypic features consistent with the commonly observed clinical features of RTH and could be used as a model system to better understand the action of mutant TR beta 1 in a physiological context, which could lead to better treatment for this disease.

Animals↗

[Effect of ischemic preconditioning on adenine nucleotide levels of graft lung from canine donor].

Twelve canine left lung allotransplantation were performed. In the ischemic preconditioning group (Group IP, n = 6), left donor lung was preconditioned with 10 min ischemia followed by 15 min reperfusion using the occuluding left hilum before resection and cold perfusion. The control group (Group C, n = 6) underwent the same treatment but without ischemic preconditioning. Adenine nucleotides (ATP, ADP, AMP) of the donor lung tissue were measured using rHPLC after 2 hr of resection and cold perfusion with Euro-Collins solution (ECS). The results showed that contents of ATP and total adenine nucleotides (TAN) were much higher in Group IP than in Group C (322.9 +/- 61.2, 942.9 +/- 134.5 and 200.0 +/- 50.0, 668.4 +/- 59.6 mumol.g-1 respectively, P < 0.05). Histologic examination of the donor lung in Group IP showed less damage than in Group C after 2 hr of transplantation. The results suggest that IP combined with cold ECS perfusion can reduce the energy metabolism in canine donor lung.

Adenosine Diphosphate↗

[Effects of ischemic preconditioning on protection of canine donor lung].

The authors examined the effects of ischemic preconditioning on lung preservation using a canine single left lung transplantation. Twelve adult mongrel dogs underwent left lung allotransplantation. Donor lungs were perfused and flushed with cold Euro-Collins solution (ECS) and stored at 4 degrees C ECS for 2 hours. Six donors were preconditioned by occuluding left lung hilum for 10 minutes and releasing for 15 minutes before flushing (Group PC); other six donors without ischemic preconditioning served as the controls (Group C). Left inferior pulmonary vein blood gas analysis, mean pulmonary artery pressure measurement and donor lung histology examination were made to evaluate the function of transplanted lung after transplantation. Oxygen tension at 2 hrs after reperfusion were significantly better in Group PC than in Group C (431 +/- 130 mmHg vs 246 +/- 66 mmHg, P < 0.05); mean pulmonary artery pressure was much lower in Group PC than in Group C after reperfusion (20.6 +/- 1.3 mmHg vs 36.9 +/- 3.1 mmHg, P < 0.01). Histological findings showed less injury in Group PC. These indicate that ischemic preconditioning combined with cold ECS perfusion is superior to cold ECS perfusion alone in canine lung preservation of 3 hours ischemia with 2 hours reperfusion.

Animals↗

Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy.

To formally test the hypothesis that the granulocyte/macrophage colony-forming unit (GM-CFU) cells can contribute to early hematopoietic reconstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitative in situ polymerase chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1) vector, and by a quantitative GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the products of two different transduction protocols: "suspension transduction" and "stromal growth factor transduction." However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector posttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the cells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit by in situ or in solution PCR assay (a difference that is significant at the P = 0.0065 level by the Fisher exact test). These data suggest that only very small subsets of the GM-CFU fraction of myeloid cells, if any, contribute to the repopulation of the hematopoietic tissues that occurs following intensive systemic therapy and transplantation of autologous hematopoietic cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Purification and properties of HuD, a neuronal RNA-binding protein.

HuD is a human neuronal specific RNA-binding protein. In this study we have purified HuD and examined its RNA binding properties in detail. HuD binds to mRNAs that contain an AU-rich element with high affinity. In the case of the c-fos AU-rich element, HuD binds to a 27-nucleotide core element comprising AUUUA, AUUUUA, and AUUUUUA motifs. Mutation in any two of these motifs abrogates binding. HuD contains two tandem RNA recognition motifs (RRM), a basic domain, and a third RRM. Deletion analysis has shown that only the first and second RRMs are essential for RNA binding. Thus, these specific RNA binding properties support the idea that the HuD regulates gene expression at the posttranscriptional level.

Base Sequence↗

HLA-DQ8 transgenic mice lacking endogenous class II molecules respond to house dust allergens: identification of antigenic epitopes.

We have introduced HLA-DQ8 (HLADQB*0302 and HLA-DQA*0301) genes into A beta 0 knockout mice. Transgenic animals were immunized with a whole body extract of Dermatophagoides pteronyssinus (Der p), one of the causative agents of house dust mite allergy. Transgenic mice expressing HLA-DQ8 genes elicited HLA-DQ8-restricted responses driven by CD4+ T cells. Synthetic-overlapping peptides representing a major allergen of house dust mite (Der p 2) were synthesized and used as immunogens. HLA-DQ8+ mice responded to three peptides: 8 (residues 61-80), 11 (residues 91-110), and 13 (residues 111-129). The mice produced IL-2, IL-4, and IL-6 response to Der p challenge, suggesting a mixed Th1/Th2 response. These mice represent a new model for studies of the immune basis of allergy.

Allergens↗

Cloning and characterization of HuR, a ubiquitously expressed Elav-like protein.

The neuronal-specific Elav-like proteins (HuD, Hel-N, and HuC) contain three RNP-type concensus motifs and bind to AU-rich elements. We have identified and cloned a fourth member of this family (HuR) that is expressed in a wide variety of cell types. The purified recombinant protein binds avidly to the AU-rich element in c-fos and interleukin-3 mRNAs. In the case of the c-fos AU-rich element, HuR binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA, and AUUUUUA motifs. Mutational analysis has shown that all three AU motifs are required for maximal binding.

Amino Acid Sequence↗

Immune response of HLA-DQ8 transgenic mice to peptides from the third hypervariable region of HLA-DRB1 correlates with predisposition to rheumatoid arthritis.

The major histocompatibility complex class II genes play an important role in the genetic predisposition to many autoimmune diseases. In the case of rheumatoid arthritis (RA), the human leukocyte antigen (HLA)-DRB1 locus has been implicated in the disease predisposition. The "shared epitope" hypothesis predicts that similar motifs within the third hypervariable (HV3) regions of some HLA-DRB1 alleles are responsible for the class II-associated predisposition to RA. Using a line of transgenic mice expressing the DQB1*0302/DQA1*0301 (DQ8) genes in the absence of endogenous mouse class II molecules, we have analyzed the antigenicity of peptides covering the HV3 regions of RA-associated and nonassociated DRB1 molecules. Our results show that a correlation exists between proliferative response to peptides derived from the HV3 regions of DRB1 chains and nonassociation of the corresponding alleles with RA predisposition. While HV3 peptides derived from nonassociated DRB1 molecules are highly immunogenic in DQ8 transgenic mice, all the HV3 peptides derived from RA-associated DRB1 alleles fail to induce a DQ8-restricted T-cell response. These data suggest that the role of the "shared epitope" in RA predisposition may be through the shaping of the T-cell repertoire.

Amino Acid Sequence↗

HLA-DQ8 transgenic mice are highly susceptible to collagen-induced arthritis: a novel model for human polyarthritis.

Genetic studies have indicated that susceptibility to rheumatoid arthritis (RA) maps to the HLA-DR locus of the major histocompatibility complex. Strong linkage disequilibrium between certain HLA-DQ genes and HLA-DR genes associated with RA, however, suggests that HLA-DQ molecules may also play a role in RA susceptibility. To examine the role of HLA-DQ molecules in arthritis, we generated transgenic mice expressing the DQA1*0301 and DQB1*0302 genes from an RA predisposing haplotype (DQ8/DR4Dw4). The transgenes were introduced into mouse class II-deficient H-2Ab0 mice, and their susceptibility to experimental collagen-induced arthritis was evaluated. The HLA-DQ8+,H-2Ab0 mice displayed good expression of the DQ8 molecule, while no surface expression of endogenous murine class II molecules could be detected. The DQ8 molecule also induced the selection of CD4+ T cells expressing a normal repertoire of V beta T cell receptors. Immunization of HLA-DQ8+,H-2Ab0 mice with bovine type II collagen (CII) induced a strong antibody response that was cross-reactive to homologous mouse CII. Also, in vitro proliferative responses against bovine CII, which were blocked in the presence of an antibody specific for HLA-DQ and mouse CD4, were detected. Finally, a severe polyarthritis developed in a majority of HLA-DQ8+,H-2Ab0 mice, which was indistinguishable from the disease observed in arthritis susceptible B10.T(6R) (H-2Aq) controls. In contrast, HLA-DQ8-,H-2Ab0 fullsibs did not generate CII antibody and were completely resistant to arthritis. Therefore, these results strongly suggest that HLA-DQ8 molecules contribute to genetic susceptibility to arthritis and also establish a novel animal model for the study of human arthritis.

Animals↗

Characterization of large CTG repeat expansions in myotonic dystrophy alleles using PCR.

The CTG trinucleotide repeat expansions that are associated with myotonic dystrophy can be up to several thousand repeat units in length. We have developed a PCR protocol that has the potential to amplify mutant alleles with very large numbers of CTG repeats. The amplification uses the rTth DNA polymerase, XL system for long PCR targets together with primers which do not closely flank the repeat region and partial substitution of 7-deaza-dGTP for dGTP. Alleles containing up to approximately 800 CTG repeats were detected directly in agarose gels stained with ethidium bromide. Larger CTG repeat expansions required Southern blot transfer and detection with a repeat sequence probe; using this method, alleles containing up to approximately 2700 CTG repeats were detected. The PCR-based method described here was comparable to previous Southern blots of EcoRI-restriction digested genomic DNA in both the approximate size and heterogeneity of mutant alleles detected, but provided more precise sizes of the CTG repeat expansions than the restriction digest approach. This PCR protocol could potentially simplify current mutation detection protocols in the molecular diagnosis of myotonic dystrophy, and facilitate molecular studies of the disease.

Alleles↗

A solution-phase strategy for the synthesis of chemical libraries containing small organic molecules: a universal and dipeptide mimetic template.

A general approach to the solution phase, parallel synthesis of chemical libraries, which allows the preparation of multi-milligram quantities of each individual member, is exemplified with both a universal and dipeptide mimetic template. In each step of the sequence, the reactants, unreacted starting material, reagents and their byproducts are removed by simple liquid/ liquid or liquid/solid extractions providing the desired intermediates and final compounds in high purities (> or = 90-100%) independent of the reaction yields and without deliberate reaction optimization.

Dipeptides↗

Outcome studies for burn patients in Hong Kong: patients' satisfaction.

With the recent advances in burns treatment, many more survive the burn to experience pain, scarring, physical deformity, loss of function and psychological trauma. Pressure therapy prescribed by occupational therapists for more than 20 years in Hong Kong has proved its effectiveness in treating the visible scars. However, the inconvenience and impaired appearance that is brought about by these garments during the long phase of therapy bears some weight in worsening patients' social acceptance and happiness in life, also their families especially in children. The objects of the studies were to measure the subjective rating of the effectiveness of pressure therapy through patients' satisfaction towards treatment effectiveness and its effect on daily life. Seventy cases with burn injuries over 1 year previously were selected randomly among the centres for the survey. The scale used was ordinal from 1 to 6. Eleven items concerning treatment effectiveness, life at home, work and leisure aspects were questioned. Results were analysed into two streams-satisfaction towards pressure therapy and change of life satisfaction pre- and post-injury. Non-parametric tests were used for data analysis. Through the Wilcoxon Sign Rank Test and Cluster analysis, major determinants were identified. These factors also showed significant correlation with this demographic data. The conclusions helped to evaluate and improve the existing service in both the garment properties and our scope of therapy for these patients, especially in work rehabilitation and finally (sexual) counselling which should be addressed by a team with interdepartmental support.

Activities of Daily Living↗

Feasibility of analysing [13C]urea breath tests for Helicobacter pylori by gas chromatography-mass spectrometry in the selected ion monitoring mode.

BACKGROUND: The [13C]urea breath test for Helicobacter pylori is nonradioactive, as well as noninvasive, but few clinical laboratories have the expensive isotope ratio mass spectrometer used for analysis. METHODS: To demonstrate the feasibility of analysing [13C]urea breath tests with a gas chromatograph-mass spectrometer routinely used for drug testing, 13CO2 standards for breath tests and breath samples from patients in a multiple-blind study were analysed. The breath samples were also analysed by isotope ratio mass spectrometry, and the diagnoses were compared with biopsy results. RESULTS: The precision of the enrichment measurements by gas chromatography-mass spectrometry was 1.1 parts per thousand, and the calculated differences in enrichment between standard gases equaled the certified values. The sensitivity (94%), specificity (94%), and percentage agreement (94%) for diagnosis of Helicobacter pylori (n = 34) were as high or higher than for analysis of replicate breath samples by isotope ratio mass spectrometry and comparable to the values reported for diagnosis of the bacterium by other currently accepted tests. CONCLUSIONS: The study demonstrates that a gas chromatograph-mass spectrometer can be used to analyse [13C]urea breath tests, thus potentially lowering the cost of the test and increasing the number of laboratories that can perform the test.

Breath Tests↗

Serum and urine markers of type I collagen metabolism in elderly women with high and low bone mineral density.

The serum markers of bone formation (carboxy-terminal propeptide of type I collagen, PICP) and resorption (pyridinoline cross-links containing telopeptide of type I collagen, ICTP), as well as urinary resorption markers, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), were studied in 78-year-old women with high (n = 18) and low (n = 17) bone mineral density (BMD) measured from the calcaneus and tibia. The low-BMD group had higher values for PICP (P = 0 center dot 025), Pyr (P = 0 center dot 001) and Dpyr (P < 0 center dot 001) than the high-BMD group. No inverse relationship between these markers and BMD was, however, observed within the study groups. ICTP, Pyr and Dpyr correlated with each other in both groups and with PICP in the high-BMD group. Higher levels of both the formation and resorption markers of type I collagen suggest an increased rate of bone turnover and remodelling in osteopenic elderly women.

Aged↗

Severe upper gastrointestinal tumor bleeding: endoscopic findings, treatment, and outcome.

BACKGROUND AND STUDY AIMS: The aim of the present study was to review endoscopic findings, treatment, and clinical outcomes in patients with severe upper gastrointestinal bleeding due to tumors. PATIENTS AND METHODS: A retrospective analysis was made of prospectively gathered data on all patients with severe upper gastrointestinal bleeding who were admitted to two large referral centers during a 45-month period. RESULTS: Nine hundred thirty-five patients had severe upper gastrointestinal bleeding, of whom 42 (5%) were found to have tumors. Histologically, nearly all of the tumors were of a malignant type. Fifty-two percent of the patients had acute severe upper gastrointestinal bleeding as the initial presentation of their tumor. The most common tumor was gastric adenocarcinoma, and all of these cases were at advanced stages. Endoscopic hemostasis with thermal probes or epinephrine injection, or both, was carried out in seven patients (17%), with successful hemostasis in all of the tumors. Regardless of the treatment given, patients with upper gastrointestinal tumor bleeding, had a 30-day surgery rate of 43%, a 30-day rebleed rate of 33%, a 30-day mortality rate of 10%, and a 1-year mortality rate of 89%. CONCLUSIONS: Most tumors that cause severe upper gastrointestinal bleeding are of a malignant histologic type and are already at an advanced stage. Endoscopic hemostasis of bleeding upper gastrointestinal tumors is safe and initially effective, and may provide time for elective surgical palliation. Regardless of therapy, upper gastrointestinal tumors with severe bleeding have a poor one-year survival.

Endoscopy, Digestive System↗