Biomedical subjects
Publications and source records attributed to Yong Tang.
[reaction: see text] Alkylidene or arylidene malonates reacted with arsonium allylides to give trans-disubstituted cyclopropane-1,1-dicarboxylates with high stereoselectivity in high yields. The mechanism of the cyclopropanation reactions has also been investigated.
Regional estimates of type I and type II vestibular hair cells (HC) and supporting cell (SC) numbers were obtained from the horizontal crista ampullaris by using design-based stereology in human. Cristae were microdissected from temporal bones obtained post-mortem (N=16, age range 26-98 years). Three groups were made according to age: group 1, n=5, ages between 26 and 67 years, average age 51 years; group 2, n=4, average age 84 years; and group 3, n=7, average age 94 years. For group 1, the average total HC number was 8,005+/-214, corresponding to 4,119+/-107 type I HC, 3,886+/-117 type II HC, and 10,274+/-224 SC. The type I:type II HC ratio was 1.06+/-0.01, and HC density was 0.80 cells/100 microm2. For group 2, the average total HC number was 7,074+/-489, corresponding to 3,733+/-212 type I HC, 3,341+/-314 type II HC, and 9,321+/-858 SC. The type I:II HC ratio was 1.12+/-0.06, and HC density was 0.75 cells/100 microm2. For group 3, the average HC number was 6,009+/-327, corresponding to 3,380+/-223 type I HC, 2,628+/-235 type II HC, and 10,185+/-182 SC. The type I:II HC ratio was 1.34+/-0.10, and HC density was 0.63 cells/100 microm2. A significant decline in type I, type II, and total HC number and density was found in groups 2 and 3, with individuals exceeding the average human life span.
The Michael addition-elimination of ylide to alpha,beta-unsaturated imines leads to a highly diastereoselective and enantioselective synthesis of vinylcyclopropanecarbaldehydes in good to high yields for the first time. A sequential cyclopropanation-aziridination protocol for the preparation of cyclopropylaziridines is also developed with good diastereoselectivity in good to high yields.
Gallium(III) triflate catalyzed the rearrangement of 2-substituted vinylepoxides into beta,gamma-unsaturated carbonyl compounds with high regio- and chemoselectivity (>97/3) in low catalyst loading (1-5 mol %). The alkyl-substituted trimethylsilylvinyl epoxides gave beta,gamma-unsaturated ketone, but aryl-substituted vinylepoxides gave the aldehydes instead.
A simple approach to a diverse set of chiral trisoxazolines is described. Deprotonation of bisoxazolines 2, followed by treatment of 2-chloromethyloxazolines 3, affords chiral trisoxazolines, including chiral homo- and hetero-trisoxazolines in good to high yields. These trisoxazolines are successfully applied in the asymmetric reaction of indole with benzylidene malonate, and ee's up to 93% were obtained.
BACKGROUND: Protein-protein, protein-DNA and protein-RNA interactions are of central importance in biological systems. Quadrapole Time-of-flight (Q-TOF) mass spectrometry is a sensitive, promising tool for studying these interactions. Combining this technique with chemical crosslinking, it is possible to identify the sites of interactions within these complexes. Due to the complexities of the mass spectrometric data of crosslinked proteins, new software is required to analyze the resulting products of these studies. RESULT: We designed a Cross-Linked Peptide Mapping (CLPM) algorithm which takes advantage of all of the information available in the experiment including the amino acid sequence from each protein, the identity of the crosslinker, the identity of the digesting enzyme, the level of missed cleavage, and possible chemical modifications. The algorithm does in silico digestion and crosslinking, calculates all possible mass values and matches the theoretical data to the actual experimental data provided by the mass spectrometry analysis to identify the crosslinked peptides. CONCLUSION: Identifying peptides by their masses can be an efficient starting point for direct sequence confirmation. The CLPM algorithm provides a powerful tool in identifying these potential interaction sites in combination with chemical crosslinking and mass spectrometry. Through this cost-effective approach, subsequent efforts can quickly focus attention on investigating these specific interaction sites.
The objective of this study was to obtain estimates of the number of nerve fibers in the human crista ampullaris and utricular macula from normal individuals using unbiased stereology and immunohistochemistry. Vestibular endorgans with the attached vestibular nerve stump were microdissected from the temporal bones. Specimens were divided into two groups. The first group (group 1, N = 8, age range, 68-98 years old, mean = 87 years) was fixed with paraformaldehyde and post-fixed with osmium tetroxide. The second group (group 2, N = 5, age range, 80-98 years old, mean = 86.6 years) was fixed with paraformaldehyde, immunoreacted with monoclonal antibodies against neurofilaments, and post-fixed with osmium tetroxide. The endorgans of both groups were embedded in resin and 2-mum thick sections were made. Estimates of the number of nerve fibers were obtained using an unbiased stereological method, the fractionator. The diameter distribution of nerve fibers was also obtained. The average number of fibers in the horizontal, posterior and superior cristae of individuals in group 1 (N = 14 cristae) was 1424+/-320 (CV = 0.22). The average percentage of small (less than 3 microm), medium (between 3 and 5 microm) and large (more than 5 microm) size fibers was 22.4%, 51.5% and 26.1%, respectively. In group 2 (N = 12), there was an average of 1792+/-99 (CV = 0.05) nerve fibers. The average percentage of small, medium and large size fibers was 22%, 51.2% and 26.8%. In the macula utricle from group 1, there was an average of 3026 nerve fibers (N = 2, ages 80 and 96 years old). There was an average 30.75% small, 56% medium and 13.2% large size fibers. In the utricular macula from group 2 (N = 3, ages 84, 92 and 96 years old), there was an average of 3715 nerve fibers. The average percentage of small, medium and large size fibers was 33.2%, 51.7% and 15.1%. The nerve fiber number in both groups is within the range of previous studies, however, the number of fibers in group 2 was significantly higher than that in group 1 (p = 0.01). This difference is likely due to increased sensitivity gained by the immunohistochemical staining of the axoplasm of nerve fibers in group 2. Results from the present study demonstrate the use of unbiased stereology and immunohistochemistry in human vestibular endorgans, as a reliable and efficient method to estimate the number of nerve fibers. These methods can be applied for studies of normal aging and pathological conditions of the vestibular periphery.
The development of suitable ligands that upon coordination to a metal facilitate enantioselective reactions or are able to selectively recognize a molecule are fundamental endeavours in organic chemistry. Chiral ligands that contain one or two oxazoline groups have been extensively studied and applied successfully to many metal catalyzed reactions. Accordingly, the development and application of chiral trisoxazolines has received increasing attention in the last decade. This tutorial review covers the synthetic methods for the preparation of chiral trisoxazolines, the application of chiral trisoxazolines in asymmetric catalysis and molecular recognition.
This paper describes an efficient kinetic resolution process of trisubstituted cyclic olefins via a chiral dioxirane generated in situ from a fructose-derived ketone and Oxone. The substrates presented include a variety of 1,3-disubstituted and 1,6-disubstituted cyclohexenes with the stereogenic centers at allylic positions. A sequential desymmetrization and kinetic resolution of 1,4-cyclohexadienes by the chiral dioxirane was also found to be feasible. The initially formed monoepoxides can be kinetically resolved by continuing the reaction, leading to the increase or decrease of the ee values of monoepoxides depending on the diene systems. In some cases, a prochiral directing group is not required and the first formed epoxide stereoselectively directs the second epoxidation. When the coupled desymmetrization and kinetic resolution is used synergistically, high enantiopurity can be obtained for an epoxide from an intrinsically less enantioselective substrate. The observed absolute and relative stereochemistry as well as the changing optical purity can be effectively rationalized by transition state analysis.
A high-throughput bioanalytical method based on automated sample transfer, automated solid phase extraction, and hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) analysis, has been developed for the determination of cetirizine, a selective H(1)-receptor antagonist. Deuterated cetirizine (cetirizine-d(8)) was synthesized as described and was used as the internal standard. Samples were transferred into 96-well plates using an automated sample handling system. Automated solid phase extraction was carried out using a 96-channel programmable liquid-handling workstation. Solid phase extraction 96-well plate on polymer sorbent (Strata X) was used to extract the analyte. The extracted samples were injected onto a Betasil silica column (50 x 3, 5 microm) using a mobile phase of acetonitrile-water-acetic acid-trifluroacetic acid (93:7:1:0.025, v/v/v/v) at a flow rate of 0.5 ml/min. The chromatographic run time is 2.0 min per injection, with retention time of cetirizine and cetirizine-d(8) both at 1.1 min. The system consisted of a Shimadzu HPLC system and a PE Sciex API 3000 or API 4000 tandem mass spectrometer with (+) ESI. The method has been validated over the concentration range of 1.00-1000 ng/ml cetirizine in human plasma, based on a 0.10-ml sample size. The inter-day precision and accuracy of the quality control (QC) samples demonstrated <3.0% relative standard deviation (R.S.D.) and <6.0% relative error (RE). Stability of cetirizine in stock solution, in plasma, and in reconstitution solution was established. The absolute extraction recovery was 85.8%, 84.5%, and 88.0% at 3, 40, and 800 ng/ml, respectively. The recovery for the internal standard was 84.1%. No adverse matrix effects were noticed for this assay. The automation of the sample preparation steps not only increased the analysis throughput, but also increased method ruggedness. The use of a stable isotope-labeled internal standard further improved the method ruggedness. Practical issues of analyzing incurred samples were discussed. This HILIC-MS/MS method for analysis of citirizine in human plasma was successfully used to support clinical studies.
OBJECTIVE: To find new potential biomarkers and establish the patterns for the detection of ovarian cancer. METHODS: Sixty one serum samples including 32 ovarian cancer patients and 29 healthy people were detected by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS). The protein fingerprint data were analyzed by bioinformatics tools. Ten folds cross-validation support vector machine (SVM) was used to establish the diagnostic pattern. RESULTS: Five potential biomarkers were found (2085 Da, 5881 Da, 7564 Da, 9422 Da, 6044 Da), combined with which the diagnostic pattern separated the ovarian cancer from the healthy samples with a sensitivity of 96.7%, a specificity of 96.7% and a positive predictive value of 96.7%. CONCLUSIONS: The combination of SELDI with bioinformatics tools could find new biomarkers and establish patterns with high sensitivity and specificity for the detection of ovarian cancer.
Analysis of domestic and overseas literature on the relationship between Alzheimer disease (AD) and neural stem cells (NSC) shows that inducing the proliferation and differentiation of hippocampal endogenous NSC in-situ by acupuncture is probably the mechanism of acupuncture therapy in treating AD, and that it may further improve the method for the research on AD.
OBJECTIVE: To probe the principle and the method to repair facial soft tissue defect with the prefabricated expander flap the neck with the vessels of temporalis superficialis. METHODS: The expander was implanted into the surface layer of the platysma in neck. The pedicle of the expander flap contained the arteria temporalis superficialis and its ramux parietalis. After 3 months, the prefabricated island expander flaps pedicled with the arteria temporalis superficialis and its ramux parietalis could be transferred to the face. From 1998 to 2003, 6 cases of facial soft tissue defects were repaired. The maximal flap size was 12 cm x 8 cm. The pedicle length was 7-8 cm. RESULTS: After a follow-up of 3-6 months, all expander flaps survived. The excellent function and cosmetic result were achieved. CONCLUSION: The prefabricated expander flaps of the neck pedicled with the arteria temporalis superficialis and its ramux parietalis can be transferred to the upper face to repair tissues defect. The supply of blood of the prefabricated expander flaps were safe and reliable. The survived areas of the flaps are directly proportional to the areas of temporalis superficialis fascia combining the expander flaps.
BACKGROUND: Pancreas transplantation is a valid therapy for patients with type 1 diabetes mellitus (IDDM). This study was undertaken to establish a stable pig model of whole pancreatoduodenal allotransplantation of physiologically coincidence for pancreas transplantation. METHODS: The IDDM pig model was made by resection of the pancreas from the recipient. The portal vein of the donor was end-to-side anastomosed to the anterior mesenteric vein (equal to the superior mesenteric vein) or the portal vein of the recipient. The far end of the celiac axis was anastomosed to each other. With end-to-side fashion, the duodenum of the donor was anastomosed to the jejunum of the recipient. RESULTS: In 16 transplantations, results were satisfactory. The anatomical results and immune function including the function of the pancreas were similar to those of human being. CONCLUSION: Of the pancreas of the pig, this study of pancreatic transplantation shows that the novel pig whole pancreatoduodenal allotransplantation model is ideal.
OBJECTIVE: To search for a new method to repair distal urethral stricture resulting from urethroplasty of hypospadias. METHODS: From February 2000 to March 2004, 16 patients with distal urethral stricture were treated by use of cutting stricture urethra and their distal urethra were reconstructed with phallic flap. RESULTS: All operations were successful without complication of flap necrosis. After 7 days of operation, the patients had free micturition and thick stream of urine. Eleven patients were followed 2 months to 4 years, the satisfactory result was obtained. CONCLUSION: It is a simple and good method to reconstruct the distal urethra by superimposing the phallic flap on the cut stricture urethra after urethroplasty of hypospadias.
OBJECTIVE: Lower eyelid ectropion is one of the most severe complications following lower eyelid blepharoplasty. Combination of multiple procedures was used to repair this deformity and the results were observed. METHODS: Severe lower eyelid ectropion following blepharoplasty was repaired with the combination method of multiple procedures, including transferring the island forehead flap, buried guiding suture of the lower eyelid skin to orbital periosteum and horizontal lid-shortening. 10 patients (15 eyelids) with lower eyelid ectropion after blepharoplasty were treated with the above method from Mar 2001 to Mar 2004. RESULTS: The lower eyelid ectropion was repaired effectively. All the patients were satisfied with the results. CONCLUSIONS: The combination method of multiple procedures was an effective method for severe lower eyelid ectropion.
While most studies have demonstrated damage to the cochlear and vestibular endorgan as the primary site of aminoglycoside toxicity, the effect on the primary afferent neurons of the vestibular ganglion remains to be determined. This study used the unbiased stereology-optical fractionator method to obtain estimates of the vestibular ganglion neuronal number. Archival temporal bone specimens from seven subjects with a history of gentamicin (n=3) and streptomycin (n=4) aminoglycoside ototoxicity were used. The post-ototoxicity survival time ranged from two months to 8 years, with an average of 2.2 years. Seven archival human temporal bone specimens from age-matched subjects with no history of audiovestibular symptoms or ototoxicity served as controls. Group means were compared using unpaired, two-tailed student's t test. The average vestibular ganglion neuronal number in the aminoglycoside ototoxicity group was 20, 733 neurons (CV=0.073), which was significantly lower (p<0.005) than the average number in the age-matched control group of 24, 902 neurons (CV=0.109). These findings may be consistent with either retrograde degeneration or a direct neurotoxic effect of the aminoglycosides on the vestibular ganglion neuron.
Earthworm fibrinolytic enzyme component A (EFE-a) possesses an S1 pocket, which is typical for an elastase-like enzyme, but it can still hydrolyze varieties of substrates, and it exhibits wide substrate specificity. Former structure studies suggested that the four-residue insertion after Val(217) might endow EFE-a with this specificity. Based on the native crystal structure at a resolution of 2.3A, we improved the native crystal structure to 1.8A and determined its complex structure with the inhibitor Meo-Suc-Ala-Ala-Pro-Val-CMK at a resolution of 1.9A. The final structures show that: (1) EFE-a possesses multisubstrate-binding sites interacting with the substrates; (2) significant conformation adjustment takes place at two loops binding to the N-terminal of the substrates, which may enhance the interaction between the enzyme and the substrates. These characteristics make the substrate-specificity of EFE-a less dependent on the property of its S1-pocket and may endow the enzyme with the ability to hydrolyze chymotrypsin-specific substrates and even trypsin-specific substrates.