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Biomedical subjects

Yue Zhang

Publications and source records attributed to Yue Zhang.

118 records · Page 7Linked to original sources

A mouse model of human L1 retrotransposition.

The L1 retrotransposon has had an immense impact on the size and structure of the human genome through a variety of mechanisms, including insertional mutagenesis. To study retrotransposition in a living organism, we created a mouse model of human L1 retrotransposition. Here we show that L1 elements can retrotranspose in male germ cells, and that expression of a human L1 element under the control of its endogenous promoter is restricted to testis and ovary. In the mouse line with the highest level of L1 expression, we found two de novo L1 insertions in 135 offspring. Both insertions were structurally indistinguishable from natural endogenous insertions. This suggests that an individual L1 element can have substantial mutagenic potential. In addition to providing a valuable in vivo model of retrotransposition in mammals, these mice are an important step in the development of a new random mutagenesis system.

3' Untranslated Regions↗

Evidence consistent with human L1 retrotransposition in maternal meiosis I.

We have used a unique polymorphic 3' transduction to show that a human L1, or LINE-1 (long interspersed nucleotide element-1), retrotransposition event most likely occurred in the maternal primary oocyte during meiosis I. We characterized a truncated L1 retrotransposon with a 3' transduction that was inserted, in a Dutch male patient, into the X-linked gene CYBB, thereby causing chronic granulomatous disease. We used the unique flanking sequence to localize the precursor L1 locus, LRE3, to chromosome 2q24.1. In a cell culture assay, the retrotransposition frequency of LRE3 is greater than that for any other element that has been tested to date. The patient's mother had two LRE3 alleles that differed slightly in the 3'-flanking genomic DNA. The patient had a single LRE3 allele that was identical to one of the maternal alleles; however, the patient's insertion matched the maternal LRE3 allele that he did not inherit. Other data indicate that there is only a small chance that the father (unavailable for analysis) carries the precursor LRE3 allele. In addition, paternal origin of the insertion would have required that an LRE3 mRNA transcribed before meiosis II be carried separately from its precursor LRE3 allele in the fertilizing sperm. Since the mother carries a potential precursor allele and the insertion was on the patient's maternal X chromosome, it is highly likely that the insertion originated during maternal meiosis I.

Adult↗

Catalytic oxidative carbonylation of primary and secondary diamines to cyclic ureas. Optimization and substituent studies.

W(CO)(6)-catalyzed oxidative carbonylation of 1,3-propanediamine to the corresponding urea has been examined under a variety of conditions. Following optimization, the Thorpe-Ingold effect on ring closure was studied using 2,2-dialkyl-1,3-propanediamines. For the 2,2-dimethyl- and 2,2-dibutyl-1,3-propanediamines, the yields were increased significantly as compared to that of the unsubstituted case. The eight-membered cyclic urea 5-butyl-5-ethyl-1,3-diazepan-2-one (5f) was formed in 38% yield, while only trace amounts of the cyclic urea were produced from the parent 1,5-pentanediamine. In a study of secondary diamines, yields from the carbonylation of N,N'-dialkyl-2,2-dimethyl-1,3-propanediamines were lower than those obtained from the primary diamines. The main byproducts from secondary diamines were tetrahydropyrimidine derivatives formed from a competitive reaction of the substrate with the oxidant and base.

Journal Article↗

[Extraocular muscle surgery for thyroid associated ophthalmopathy].

OBJECTIVE: To identify the indication, method and therapeutic results of extraocular muscle surgery for thyroid associated ophthalmopathy (TAO). METHODS: The results of extraocular muscle surgery in 11 patients with TAO were analyzed. The main purpose of the surgery was to release the restriction induced by fibrotic extra-ocular muscles. Recession was used in most of the patients. RESULTS: Different degrees of realignments were gained, and restricted ocular movements were improved in 11 patients postoperatively. Nine (9/11) patients restored binocular vision in functional positions of gaze. Better alignment was gained in 2-month-follow-up. CONCLUSIONS: Diplopia and restricted ocular movements are the main indications of extra-ocular muscle surgery in TAO. Timing of surgery is crucial, and it is better to be carried out when the disease has been stationary for 4 - 6 months. Under local anesthesia, the doctor can adjust the position of muscle to insure an excellent result. The extra-ocular muscular surgery for TAO is a good functional rehabilitative measure.

Adult↗

[Expression of core-binding factor a1 by human skin fibroblasts induced in vitro].

OBJECTIVE: To investigate the probabilities of core-biding factor a1 (Cbfa1) expression by human skin fibroblasts induced in vitro. METHODS: The fibroblasts were isolated, purified from human skin, and were grown in incubation in the media of TNF-alpha, BMP-2, and combined TNF-alpha and BMP-2 at certain concentrations, respectively. The changes in biological features of these fibroblasts correlated with osteogenesis were detected by immunohistochemistry and RT-PCR assay. RESULTS: TNF-alpha could switch phenotype of collagen in fibroblasts from Type I and III to Type I and induce fibroblasts to express Ras and BMP type I receptor (BMPR-IA). TNF-alpha in combination with BMP-2 could induce fibroblasts to express Cbfa1 and osteocalcin mRNA. CONCLUSION: Human skin fibroblast could be induced into pro-osteoblast expressing Cbfa1, an osteoblast-specific transcription factor and a regulation of osteoblast differentiation, and combined use of TNF-alpha and BMP-2 was one of the regulating factors.

Bone Morphogenetic Protein 2↗

[Cloning of Ig Fab genes of patients with chronic B lymphocytic leukemia and sequences analysis of their variable regions].

OBJECTIVE: Sequences analysis of Ig variable regions from the peripheral blood mononuclear cells (PBMC) of patients with chronic B lymphocytic leukemia. METHODS: Total RNA was isolated from PBMC of patients with chronic B lymphocytic leukemia, oligo-dT-primed cDNA was synthesized from RNA. The cDNA was amplified by Taq DNA polymerase with a set of specific 5' primers corresponding to Ig FR1 and 3' primers corresponding to CH1 (C micro /C) or CL (Ckappa/Clambda), the PCR products of variable regions of Ig heavy (IgH) and light (IgL) chains were sequenced by ABI PRISM Dye terminator cycle sequencing ready reaction kit and ABI PRISM 310 Genetic Analyzer. The gene homology of variable regions of IgH and IgL chains was compared by using DNA tools 5.1 system and "the international immunogenetics database". RESULTS: Four light chains and 3 heavy chains were amplified from 4 and 3 patients respectively. Homology analysis of the sequences of 4 light chains and 3 heavy chains were performed by DNA tools system. The sequences of light chains are high homologous. And the sequences of heavy chains are quite different. The homologous analysis of the sequences of variable region by using "the international immunogenetics database" showed that the sequences were higher homologous to idiotype gene of some B lymphocytic leukemia. Four VL genes belong to human Ig Vkappa subgroup I, 2 of 3 VH genes belong to VH3 family and 1 belongs to VH5 family. CONCLUSION: Ig genes have idiotype and same disease may have same idiotype.

Base Sequence↗

[Study on the mechanism of the interaction between montmorillonite and bacterium].

AIM: To investigate the mechanism of the interaction between montmorillonite and bacteria by studying the reactions of different charges of montmorillonites with bacteria. METHODS: Bacteriostatic test: one loop of E. coli and Staphylococcus aureus at the concentration of 1 x 10(6).mL-1 was incubated to the plate culture medium containing different concentrations of montmorillonite, and incubated 24 h to observe the growth of bacteria. Bacterial adsorptive test: different amounts of montmorillonite were added into the artificially simulated intestinal solution (containing bacteria 1 x 10(7).mL-1). After the culture, the bacterial colonies were counted. RESULTS: The results showed that montmorillonite per se showed no bacteriostatic or bactericidal effect, but after exchange with metal ion and functional groups which inhibits bacteria, then it showed these activities. Adsorption was the main way between montmorillonite and bacteria. The special way of fixing bacteria into the "carriage" of montmorillonite gel which carry this structure was its pharmacological basis of curing diarrhea. The adsorption effect was related to layer charge density of the montmorillonites. CONCLUSION: Montmorillonite showed adsorption ability of bacteria with minus related to its layer charge, but has no bacteriostatic and bactericidal effect.

Adsorption↗

[Improvement of the general anesthesia method for microlaryngoscopic surgery with self-retaining laryngoscope: a study on 31 cases].

OBJECTIVE: To investigate the improvement of general anesthesia method for microlaryngoscopic surgery with self-retaining laryngoscope. METHOD: 31 cases with laryngeal lesion who had undergone the microlaryngoscopic operation with self-retaining by anesthesia were reviewed retrospectively from October 1, 1997 to December 31, 2000. RESULT: All patients undergone the microlaryngoscopic surgery and their specimens were examined by pathology, 30 cases were benign lesion, 1 case was squamous cell cancer of the vocal cord. Their voice recovers very satisfactorily except for 2 patients. There were no recurrence after 6-38 months follow-up. CONCLUSION: This study suggests that the general aneathesia with plastic jet ventilating tube controlling respiratory for microlaryngoscopic surgery is easier, more effective and safer than the other methods.

Adolescent↗

[Otorhinolaryngological neurofibromatosis].

OBJECTIVE: To investigate the growth characteristic, clinical manifestation, diagnosis and treatment of neurofibromatosis (NF) in otorhinolaryngology. METHODS: Eleven cases of NF from 1989 to 2000 were analyzed retrospectively, among which, there were 5 and 2 cases occurring in nasal cavity and parapharynx (NF I), respectively, and 4 bilateral acoustic neuromas (NF II). RESULTS: NF I and NF II had long courses of 2-30 years, with common clinical features and unique characteristics. All patients with NF were operated on under general anesthesia. The NFs in the nasal cavity and sinus were resected through the paranasal approach and parapharyngeal NF through the lateral cervical approach. Unilateral acoustic neuromas were removed via the sigmoid sinus posterior suboccipital approach, one case bilateral acoustic neuromas was operated on in 2 stages. No death happened in this series. CONCLUSION: Surgical treatment is the best way for the treatment of NF. Radiotherapy can be considered in case of NF I with an extensive invasion, obscure border and recurrence.

Adult↗

Engineering an arginine catabolizing bioconjugate: Biochemical and pharmacological characterization of PEGylated derivatives of arginine deiminase from Mycoplasma arthritidis.

Arginine is an important metabolite in the normal function of several biological systems, and arginine deprivation has been investigated in animal models and human clinical trials for its effects on inhibition of tumor growth, angiogenesis, or nitric oxide synthesis. In order to design an optimal arginine-catabolizing enzyme bioconjugate, a novel recombinant arginine deiminase (ADI) from Mycoplasma arthritidis was prepared, and multi-PEGylated derivatives were examined for enzymatic and biochemical properties in vitro, as well as pharmacokinetic and pharmacodynamic behavior in rats and mice. ADI bioconjugates constructed with 12 kDa or 20 kDa monomethoxy-poly(ethylene glycol) polymers with linear succinimidyl carbonate linkers were investigated via intravenous, intramuscular, or subcutaneous administration in rodents. The selected PEG-ADI compounds have 22 +/- 2 PEG strands per protein dimer, providing an additional molecular mass of about 0.2-0.5 x 10(6) Da and prolonging the plasma mean residence time of the enzyme over 30-fold in mice. Prolonged plasma arginine deprivation was demonstrated with each injection route for these bioconjugates. Pharmacokinetic analysis employed parallel measurement of enzyme activity in bioassays and enzyme assays and demonstrated a correlation with the pharmacodynamic analysis of plasma arginine concentrations. Either ADI bioconjugate depressed plasma arginine to undetectable levels for 10 days when administered intravenously at 5 IU per mouse, while the subcutaneous and intramuscular routes exhibited only slightly reduced potency. Both bioconjugates exhibited potent growth inhibition of several cultured tumor lines that are deficient in the anabolic enzyme, argininosuccinate synthetase. Investigations of structure-activity optimization for PEGylated ADI compounds revealed a benefit to constraining the PEG size and number of attachments to both conserve catabolic activity and streamline manufacturing of the experimental therapeutics. Specifically, ADI with either 12 kDa or 20 kDa PEG attachments on 33% of the primary amines retained about 60% or 48% of enzyme activity, respectively; the Km and pH profiles were nearly unchanged; IC50 values were diminished by less than 30%; while stability studies demonstrated full retention of activity at 4 degrees C for 5 months. A comparison of the enzymatic properties of a second ADI from Pseudomonas putida illustrated the superior characteristics of the M. arthritidis ADI enzyme.

Amino Acid Sequence↗