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Biomedical subjects

Y Wei

Publications and source records attributed to Y Wei.

351 records · Page 20Linked to original sources
PubMed1989

Synthesis and P-388 antitumor properties of the four diastereomeric 1-hydroxy-3,4-diaminocyclohexane-Cl2PtII complexes.

Synthesis and antileukemic activity in vivo of the four diastereomeric 1-hydroxy-3,4-diaminocyclohexane-Cl2PtII complexes (Cl2PtII-3a-d) are described. Respective bis(phenylmethyl) (1 alpha,2 alpha,4 beta)-, (1 alpha,2 alpha,4 alpha)-, (1 alpha,2 beta,4 beta)-, and (1 alpha,2 beta,4 alpha)-(4-hydroxy-1,2-cyclohexanediyl)bis(carbamates) (5a, 5b, 7a, 7b) were prepared by hydroboration-oxidation of the bis(carbobenzoxyamino) derivatives (4,5) of cis- and trans-4,5-diaminocyclohexene. The relative stereochemistry of intermediates 5a and 5b was established by correlation with the alcohol obtained by NaBH4 reduction of bis(phenylmethyl) (1 alpha,2 alpha,3 alpha,4 alpha)-(3,4-epoxy-1,2-cyclohexanediyl)bis(carbamate) (8), the all-cis stereochemistry of which was unambiguously determined by X-ray crystallographic analysis. In the P-388 murine leukemia model these monohydroxycyclohexanediamine-PtII complexes were more effective than the PtII complexes of the related diol diamines 1a-e but were less active than the cisplatin positive control.

Animals↗
PubMed1988

Phosphohistidine is found in basic nuclear proteins of Physarum polycephalum.

Nuclear extracts of the true slime mold, Physarum polycephalum, show protein histidine kinase activity towards exogenous histones [(1985) J. Biol. Chem. 260, 16106-16113]. Physarum microplasmodia were labeled with [32P]phosphate in vivo and two basic proteins containing alkali-stable phosphate were detected. The labeled proteins comigrated with Physarum histones H1 (approximately) and H2A and phosphoamino acid analysis showed that each protein contained [32P]-phosphohistidine. The H2A-like protein was also labeled in isolated nuclei incubated with [35S]thio-ATP. We conclude that some Physarum nuclear proteins contain phosphohistidine.

Histidine↗
PubMedDate not supplied

Multiple rearrangements and activated expression of c-myc induced by woodchuck hepatitis virus integration in a primary liver tumour.

Woodchuck hepatitis virus (WHV) is a small, partially double-stranded DNA virus. Like the related human hepatitis B virus (HBV), WHV induces acute and chronic hepatitis and hepatocellular carcinoma (HCC) in its natural host. WHV DNA integration into c-myc and N-myc, resulting in deregulated expression of these genes, has been described previously in woodchuck HCC. We have analysed a woodchuck liver tumour in which WHV DNA was integrated in the c-myc gene. The virus insertion provoked multiple alterations in one c-myc allele, probably involving secondary deletions and mutations. Integrated viral DNA, including promotor and enhancer sequences, acted as an insertional mutagen, leading to enhanced expression of heterogenous c-myc transcripts ranging from 7.2 to 14 kb in size, strikingly longer than normal 2.3-kb c-myc RNA. These results provide an additional example in which the oncogenic activation of a myc gene by cis-acting effect of WHV insertion may play a critical role in virus-induced woodchuck HCC.

Animals↗
PubMedDate not supplied

Identification of a potent peptide deformylase inhibitor from a rationally designed combinatorial library.

Peptide deformylase catalyzes the removal of the N-terminal formyl group from nascent polypeptides during prokaryotic protein synthesis and maturation and is essential for bacterial survival. Its apparent absence from mammalian organisms makes it an attractive target for designing novel antibacterial agents. Based on the substrate specificity of peptide deformylase from Escherichia coli, a focused library of peptide thiols was synthesized on TentaGel resin using a disulfide linkage. Screening of the library against the purified deformylase was carried out in solution phase after the inhibitors were released from the resin with a reducing agent. A potent deformylase inhibitor was obtained from a 750-member library and was further optimized through rational modification into a low nanomolar inhibitor (KI = 15 nM against E. coli deformylase).

Amidohydrolases↗
PubMedDate not supplied

Extracellular matrix protein turnover during salamander limb regeneration.

After amputation of a salamander limb, the extracellular matrix undergoes remodeling. The extracellular matrix that maintains the differentiated state of limb tissues is broken down and replaced by an extracellular matrix essential for dedifferentiation and blastema formation. We used monoclonal antibodies in immunohistochemistry methods and riboprobes in in situ hybridization to evaluate the upregulation of tenascin, type XII collagen, fibronectin, and the MT5 antigen. The Stump 1 antigen, an extracellular matrix protein that is abundant in the normal limb, is downregulated during regeneration and reappears late in regeneration as differentiation occurs. In the embryo, the Stump 1 antigen is also absent from the early limb bud and first appears during differentiation stages. Tenascin and fibronectin are also upregulated in the limb bud of the embryo, and these two extracellular matrix proteins appear to function during limb regeneration in adults and limb development in embryos. However, type XII collagen and the MT5 antigen are not found in the limb bud, indicating that type XII collagen and the MT5 antigen have roles in the regenerating limb but not in the embryo limb bud.

Journal Article↗
PubMedDate not supplied

A rapid, novel strategy to induce tumor cell-specific cytotoxic T lymphocyte responses using instant dentritomas.

The generation of fused cells between dendritic cells (DC) and tumor cells is a very effective approach for tumor antigen presentation in cancer immunotherapy. However, the application of this approach in clinical studies is limited by the need for established tumor cell lines and the time-consuming procedures for selecting and expanding the fused cells. In the current study, the authors report a rapid, novel approach to produce fused cells between DCs and primary tumor cells from patients with malignant melanoma. Peripheral blood DCs and a primary tumor cell culture were generated from the same patients, labeled with fluorescent green and red dyes, respectively, and fused. The fused cells were isolated by fluorescence-activated cell sorting. Because the fused cells do not need to be expanded, these cell hybrids have been named instant dendritomas. Fluorescence-activated cell sorting analysis showed that instant dendritomas express the key molecules for antigen presentation (HLA-A, B, C; HLA-DR; CD80; and CD86). In vitro studies have shown that instant dendritomas effectively activated autologous CD8+ T lymphocytes to proliferate and secret interferon-gamma. More importantly, the activated CD8+ T lymphocytes effectively lysed the patients' primary tumor cells. This approach represents a practical clinical strategy for cancer immunotherapy.

Antigen Presentation↗