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Biomedical subjects

Yong Tang

Publications and source records attributed to Yong Tang.

At least 73 records · Page 4Linked to original sources

Controllable diastereoselective cyclopropanation. Enantioselective synthesis of vinylcyclopropanes via chiral telluronium ylides.

Novel chiral telluronium salts 1 are designed for asymmetric synthesis of 1,3-disubstituted 2-vinylcyclopropanes. The allylides, generated in situ from the corresponding telluronium salt in the presence of different base, reacted with alpha,beta-unsaturated esters, ketones, and amides to afford cis-2-silylvinyl-trans-3-substituted or trans-2-silylvinyl-trans-3-substituted cyclopropane derivatives with high diastereoselectivity and excellent enantioselectivity in good to high yields. Thus, either one of the two diastereomers could be enantioselectively synthesized at will just by the choice of LiTMP/HMPA or LDA/LiBr. The first examples of catalytic ylide reaction for enantioselective synthesis of 1,3-disubstituted 2-vinylcyclopropanes with high distereoselectivity is also achieved.

Alkenes↗

Estrogen increases the number of spinophilin-immunoreactive spines in the hippocampus of young and aged female rhesus monkeys.

It is well documented that estrogen increases dendritic spine density in CA1 pyramidal cells of young female rats. However, this effect is attenuated in aged rats. We report here a quantitative analysis of estrogen effects on hippocampal spine number as visualized with antispinophilin in young (6-8 years old) and aged (19-23 years old) female rhesus monkeys, a species with a pattern of female endocrine senescence comparable to that of humans. Monkeys were ovariectomized and administered either vehicle or estradiol cypionate 3 months postovariectomy, followed by an additional dose 3 weeks later, with perfusion 24 hours after the last estrogen treatment. Immunolocalization of spinophilin, a spine-associated protein, was used for quantitative stereologic analyses of total spinophilin-immunoreactive spine numbers in CA1 stratum radiatum and the inner and outer molecular layers of dentate gyrus. In both young and aged female monkeys, the estrogen-treated groups had an increase in spinophilin-immunoreactive spines (37% in young, P <.005; 35% in aged, P <.05) compared with the untreated groups that amounted to more than 1 billion additional immunoreactive spines. The young group also showed a trend toward an estrogen-induced increase in immunoreactive spines in the dentate gyrus outer molecular layer, but this effect was not statistically significant (P =.097). We conclude that spine number in the rhesus monkey hippocampus is highly responsive to estrogen, yet, unlike the female rat, aged female rhesus monkeys retain the capacity for spine induction in response to estrogen. These data have important implications for cognitive effects of estrogen replacement in postmenopausal women and demonstrate that an estrogen replacement protocol that mimics normal physiological cycles with timed, intermittent peaks can have profound neurobiological effects.

Age Factors↗

Marked loss of myelinated nerve fibers in the human brain with age.

The white matter is the structure of the brain that declines most with age-almost 30%, but little is known about the age-effect on the fibers that constitute the white matter. In the present study, the total length of myelinated fibers was measured with a newly developed stereologic method. Specimens came from 36 normal Danes (18 males and 18 females) with an age ranging between 18 and 93 years. Samples were taken systematically and randomly from the white matter, and the biopsy specimens were randomly rotated before sectioning to avoid bias due to the anisotropic nature of nerve fibers. The fibers were counted at light microscopic level at approximately 10,000x magnification, and the diameter of each counted fiber was measured to get the diameter distribution. Males were found to have a total myelinated fiber length of 176,000 km at the age of 20 and 97,200 km at the age of 80, whereas the total length in females was 149,000 km at the age of 20 and 82,000 km at the age of 80. This finding corresponds to a 10% decrease per decade or a total decrease of 45% from the age of 20 to 80 years, and a sex difference of 16%. The fiber diameter distribution showed that primarily the thinner fibers were lost with a relative preservation of the thicker ones. The marked loss of myelinated nerve fibers with age could explain some of the cognitive decline seen in the elderly.

Adult↗

Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 transcriptional activator Rta is an oligomeric DNA-binding protein that interacts with tandem arrays of phased A/T-trinucleotide motifs.

Kaposi's sarcoma associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) encodes an immediate early transcriptional activator, Rta, which mediates viral reactivation from latency and lytic viral replication. Here we report the purification and characterizations of HHV-8 Rta and its interaction with Rta-responsive DNA elements. The Rta response element (RtaRE) in the promoter of the KSHV/HHV-8 K8 open reading frame was mapped to a 47-bp sequence (RtaRE1) and a 60-bp sequence (RtaRE2) upstream of the TATA motif. A comparison of the K8 RtaREs with other viral RtaREs revealed a pattern of multiple A/T triplets spaced with a periodicity of 10 or 20 bp. Substitutions of the in-phase A/T trinucleotides of the RtaRE1 with G/C bases greatly diminished Rta responsiveness and Rta binding. By contrast, base substitutions in an out-of-phase A/T-trinucleotide sequence had no effect. Importantly, multimers of (A/T)(3)N(7) and N(5)(A/T)(5)N(6)(A/T)(4) motifs supported a strong Rta response in a copy number-dependent manner. No specific sequence motifs in the spacer regions could be discerned. Potent Rta response, however, was obtained with phased A/T trinucleotides with 7-bp spacers of arbitrary sequences with high G/C content. Lengthening of the phased A/T motifs or lowering of the G/C content of the spacers resulted in a reduction in Rta response. Finally, Escherichia coli-derived Rta is an oligomer of 440 kDa in molecular size and binds RtaRE as an oligomer. These results support a model of Rta transactivation wherein the subunits of the Rta oligomer make multiple contacts with a tandem array of phased A/T triplets in the configuration of (A/T)(3)(G/C)(7) repeats.

Base Sequence↗

K-bZIP of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) binds KSHV/HHV-8 Rta and represses Rta-mediated transactivation.

The regulatory circuit for Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) gene expression bears resemblance to that of Epstein-Barr virus (EBV), but with interesting differences. Based on protein sequence similarities and synteny to their EBV counterparts, two KSHV/HHV-8 viral regulatory factors, HHV-8 Rta and K-bZIP, encoded by open reading frame (ORF) 50 and ORF K8, respectively, have been identified. Rta is an immediate early transcriptional activator that activates lytic viral replication and mediates viral reactivation from latency, while ORF K8 is an early gene activated by Rta. Extensive splicing of ORF K8 mRNA leads to the production of K-bZIP, a protein of the basic domain-leucine zipper (bZIP) family. The role of K-bZIP in viral replication, however, remains unresolved. Here, we report that K-bZIP is a nuclear protein that binds Rta directly both in vivo and in vitro and represses Rta-mediated transactivation of the K-bZIP promoter. We further demonstrate that the leucine zipper domain of K-bZIP is required for Rta binding and a K-bZIP mutant lacking the leucine zipper does not repress Rta activity. Finally, the K-bZIP-mediated repression of Rta transactivation cannot be restored by overexpression of the transcriptional coactivator p300 or the p300-CBP-associated factor, P/CAF. Our results suggest that K-bZIP is involved in a feedback circuit to turn off its own expression and possibly the expression of other early genes activated by Rta.

Basic-Leucine Zipper Transcription Factors↗

[Using scar tissue flap to repair secondary nasal deformities of unilateral cleft lip].

OBJECTIVE: To introduce the clinical application of the upper lip scar tissue flap in correcting secondary nasal deformities of unilateral cleft lip. METHODS: Two types of the upper lip scar tissue flap were developed in correcting nasal deformities with Millard's technique. RESULTS: The procedure was performed on 51 patients. All the scar tissue flaps survived completely. The deformities were better corrected than before. CONCLUSION: The scar tissue flap has adequate blood supply. This procedure is routinely combined with other commonly used techniques to correct secondary deformities of cleft lip. It is particularly applicable for repairing the nasal deformity when usable tissue is not enough.

Child↗

[Study on serum vascular endothelial growth factor level in ovarian malignant tumors].

OBJECTIVE: To explore the diagnostic value of serum vascular endothelial growth factor (VEGF) level in patients with ovarian carcinomas, and to evaluate the correlation between serum VEGF level and prognosis of ovarian cancer. METHOD: Serum VEGF level in patients with ovarian neoplasms (120 cases of ovarian carcinomas, 25 cases of benign tumors) and 90 healthy women as controls was determined by enzyme linked immunosorbent assay (ELISA), also the change of preoperative and postoperative serum VEGF level of 25 cases of epithelial ovarian cancer was observed. RESULTS: (1)The preoperative serum VEGF levels were (766 +/- 1237) mg/L in malignant groups, and there was a significant difference compared with normal controls (55 +/- 19) mg/L or patients with benign tumor (56 +/- 23) mg/L (P < 0.05). As a cut-off at 100 mg/L, sensitivity and specificity of preoperative serum VEGF levels for diagnosing ovarian cancer was 77% and 87% respectively. (2) Serum VEGF level were significantly elevated in advanced stage (955 +/- 1716) mg/L and poorly differentiated (991 +/- 1349) mg/L compared with early stage (198 +/- 287) mg/L and well differentiated (280 +/- 552) mg/L (P < 0.05), but there is no significant difference between the VEGF level and pathological types (P > 0.05). (3) The postoperative serum VEGF levels (118 +/- 110) mg/L were significantly lower than that in preoperative (1074 +/- 1211) mg/L. (4) The average total survival-time in patients with VEGF(+) was 28 months, but it in patients with VEGF(-) was 35 months (P < 0.05). CONCLUSION: Serum VEGF values were higher in malignant tumors and preoperative serum VEGF level has a potential as a marker for diagnosing and monitoring in ovarian neoplasms.

Adult↗

[Penile reconstruction by using a scapular free flap].

OBJECTIVE: To evaluate the scapular free flap for penile reconstruction. METHODS: Six patients with penile loss were reconstructed by transferring a scapular free flap with implanting a Malleable penile prosthesis. RESULTS: All of the flaps survived completely. With the follow-ups from six to twelve months, the reconstructed penile had excellent configuration and good function. CONCLUSION: The above mentioned technique could be a good method for penile reconstruction.

Follow-Up Studies↗

[Establishment of whole pancreaticoduodenal allotransplantation model with jejunum drainage and portal venous drainage in pigs].

OBJECTIVE: To establish a pig model of pancreaticoduodenal transplantation with jejunum drainage and portal venous drainage. METHODS: Forty pigs were randomly divided into the donor group and recipient group. University of Wisconsin (UW) solution was used for both in situ flush and storage of all organs under cold storage conditions. Whole pancreaticoduodenal graft was harvested with segments of abdominal aorta and portal vein and shaped under cold UW solution. Then, the end-to-end anastomosis was performed with the donor iliac artery bifurcation Y graft to the recipient superior mesenteric arteries and celiac artery. Furthermore, type I diabetes model was made by removal of the recipient pancreas The venous anastomosis was reconstructed between the donor portal vein and the recipient superior mesenteric vein. Meanwhile, the end-to-side anastomosis was performed with the donor common iliac artery bifurcation Y graft to the recipient abdomial aorta, and the side-to-side intestinal anastomosis between the donor duodenum and the recipient jejunum was performed. RESULTS: Twenty piges were subjected to pancreaticoduodenal transplantation, in which 1 died from respiratory depression because of anesthesia, and 2 had thrombus and infarction in the pancreatic graft after transplantation. 17 cases showed normal blood sugar in peripheral circulation 24 hours after operation, the mean survival of the graft was 18.6 +/- 2.6 days. CONCLUSION: The technique of duodenal transplantation with jejunum drainage and portal venous drainage may pave the way for the further development of pancreas transplantation in clinical practice. It can be utilized in basic research of pancreas transplantation.

Anastomosis, Surgical↗

[Repair of eyelid defect with a prefabricated flap].

OBJECTIVE: To introduce a new method for repair of eyelid defects. METHODS: Eyelid reconstruction was performed using a prefabricated island flap with an expanded forehead myocutaneous flap and hard palate mucoperiosteal graft. RESULTS: Five patients with congenital or acquired eyelid defects were successfully treated with this method. CONCLUSION: The introduced method is rational and practical for clinical applications.

Eyelids↗

[Repair of facial defect with expanded skin flap from medial upper arm].

OBJECTIVE: To investigate the blood supply of the expanded skin flap from medial upper arm and its application on the reparation of facial defect due to scar resection. METHODS: The operation was carried out for three steps: 1) The expander was embed under the superior proper fascia. 2) The skin flap from medial upper arm was created with superior ulnar collateral artery as blood supply and attributive branches of basilic and axillary veins as blood collection and was grafted onto the facial defect. 3). After being separated from donor site, the skin flap was employed to cover the facial defect with maximal area of 15 x 10 cm(2). RESULTS: Seven patients in all with facial scar and defects were managed with the skin flap. All the grafted skin flaps survived at last with nearly normal skin color, texture and contour. And the scar in donor sites seemed to be neglectable. CONCLUSION: Reparation of facial defects with medial upper arm skin flap after expanding could be recommended. But longer treatment time and some obsessive action of upper limbs and head might be disadvantages.

Adult↗

[Regeneration in gaps of the middle-mountain moist evergreen broad-leaved forest of Ailao mountains].

On the basis of investigation on gaps in the middle-mountain moist evergreen broad-leaved forest of Ailao Mountains Natural Reserve, Yunnan Province, tree seedlings (H < or = 50 cm) composition were compared in the gaps and the non-gap stand. The results showed that the dominant tree species of the forest were not preponderated over others in the gaps. The composition of tree seedlings in the gaps differed from those in the non-gap stand. The species diversity of tree seedlings in the gaps(H = 2.73, D = 0.89) were higher than those in the non-gap stand (H = 2.25, D = 0.82), and the Jaccard correlative coefficient were only 0.6. The density of tree seedlings in the gaps (38,636 N.hm-2) was much higher than that in the non-gap stand (17,323 N.hm-2), of which many species were only found in the gaps. The dominant height of the tree seedling in the gaps and the non-gap stand were also 11-20 cm, but the percentage of the tree seedlings higher than 20 cm in the gaps was significantly higher than that in the non-gap stand. The gap sizes had important impact on the tree seedling germination, and different species of tree seedling dominated in different size classes of gap.

Conservation of Natural Resources↗

Sidearm effect: improvement of the enantiomeric excess in the asymmetric Michael addition of indoles to alkylidene malonates.

A pseudo-C3-trisoxazoline was designed and synthesized. The improvement of the traditional bisoxazoline into a novel trisoxazoline by a sidearm approach resulted in highly catalytic enantioselective Michael addition of indoles to alkylidene malonates. Excellent catalytic reactivity and enantioselectivity (up to 99% yield and 93% ee) were achieved.

Journal Article↗

Crystal structure of earthworm fibrinolytic enzyme component a: revealing the structural determinants of its dual fibrinolytic activity.

Earthworm fibrinolytic enzyme component A (EFEa) from Eisenia fetida is a strong fibrinolytic enzyme that not only directly degrades fibrin, but also activates plasminogen. Proteolytic assays further revealed that it cleaved behind various P1 residue types. The crystal structure of EFEa was determined using the MIR method and refined to 2.3A resolution. The enzyme, showing the overall polypeptide fold of chymotrypsin-like serine proteases, possesses essential S1 specificity determinants characteristic of elastase. However, the beta strand at the west rim of the S1 specificity pocket is significantly elongated by a unique four-residue insertion (Ser-Ser-Gly-Leu) after Val217, which not only provides additional substrate hydrogen binding sites for distal P residues, but also causes extension of the S1 pocket at the south rim. The S2 subsite of the enzyme was partially occluded by the bulky side-chain of residue Tyr99. Structure-based inhibitor modeling demonstrated that EFEa's S1 specificity pocket was preferable for elastase-specific small hydrophobic P1 residues, while its accommodation of long and/or bulky P1 residues was also feasible if enhanced binding of the substrate and induced fit of the S1 pocket were achieved. EFEa is thereby endowed with relatively broad substrate specificity, including the dual fibrinolysis. The presence of Tyr99 at the S2 subsite indicates a preference for P2-Gly, while an induced fit of Tyr99 was also suggested for accommodation of bigger P2 residues. This structure is the first reported for an earthworm fibrinolytic enzyme component and serine protease originating from annelid worms.

Amino Acid Sequence↗

Unexpected catalyst for Wittig-type and dehalogenation reactions.

A novel catalyst 2 for Wittig-type and dehalogenation reactions was developed. In the presence of triphenyl phosphite, a wide variety of aldehydes could react with alpha-bromoacetates to afford alpha,beta-unsaturated esters or ketones in high yields with excellent E-stereoselectivity when 1-2 mol % of compound 2 was used. Compound 2 was also an effective catalyst for reductive dehalogenation of alpha-bromocarbonyl compounds. The mechanisms for the above reactions were also proposed.

Journal Article↗

Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology.

Neurofibromatosis type 2 is an autosomal dominant disorder characterized by tumors, predominantly schwannomas, in the nervous system. It is caused by mutations in the gene NF2, encoding the growth regulator schwannomin (also known as merlin). Mutations occur throughout the 17-exon gene, with most resulting in protein truncation and undetectable amounts of schwannomin protein. Pathogenic mutations that result in production of defective schwannomin include in-frame deletions of exon 2 and three independent missense mutations within this same exon. Mice with conditional deletion of exon 2 in Schwann cells develop schwannomas, which confirms the crucial nature of exon 2 for growth control. Here we report that the molecular adaptor paxillin binds directly to schwannomin at residues 50-70, which are encoded by exon 2. This interaction mediates the membrane localization of schwannomin to the plasma membrane, where it associates with beta 1 integrin and erbB2. It defines a pathogenic mechanism for the development of NF2 in humans with mutations in exon 2 of NF2.

Animals↗