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D G Liu

Publications and source records attributed to D G Liu.

At least 19 recordsLinked to original sources
PubMed2001

Phosphoryltyrosyl mimetics in the design of peptide-based signal transduction inhibitors.

The central roles played by protein-tyrosine kinase (PTK)-dependent signal transduction in normal cellular regulation and homeostasis have made inappropriate or aberrant functions of certain of these pathways contributing factors to a variety of diseases, including several cancers. For this reason, development of PTK signaling inhibitors has evolved into an important approach toward new therapeutics. Since in these pathways phosphotyrosyl (pTyr) residues provide unique and defining functions either by their creation under the catalysis of PTKs, their recognition and binding by protein modules such as SH2 and phosphotyrosyl binding (PTB) domains, or their destruction by protein-tyrosine phosphatases, pTyr mimetics provide useful general starting points for inhibitor design. Important considerations in the development of such pTyr mimetics include enzymatic stability (particularly toward PTPs), high affinity recognition by target pTyr binding proteins, and good cellular bioavailability. Although small molecule, nonpeptide inhibitors may be ultimate objectives of inhibitor development, peptides frequently serve as display platforms for pTyr mimetics, which afford useful and conceptually straightforward starting points in the development process. Reported herein is a limited overview of pTyr mimetic development as it relates to peptide-based agents. Of particular interest are recent findings that highlight potential limitations of peptides as display platforms for the identification of small molecule leads. One conclusion that results from this work is that while peptide-based approaches toward small molecule inhibitor design are often intellectually satisfying from a structure-based perspective, extrapolation of negative findings to small molecule, nonpeptide contexts should be undertaken with extreme caution.

Binding Sites↗
PubMed2000

An efficient and convenient approach to the total synthesis of sphingofungin.

As a new member of the sphingofungin family, sphingofungin F exhibits interesting physiological activities with a structural unit of an alpha-substituted alanine. Described herein is an efficient and convenient stereoselective synthesis of sphingofungin F from L-(+)-tartaric acid, which utilizes Sharpless asymmetric epoxidation of allylic alcohol and Lewis acid-catalyzed intramolecular epoxide-opening reaction with an N-nucleophile, to introduce the other two desired stereogenic centers. Side chain functionality was incorporated into the chiral segment using a Wittig reaction.

Amino Acids↗
PubMed2000

Three-hybrid strategy reveals a peptide segment that specifically binds to the 3'-untranslated region of NF-IL6 mRNA.

The 3'UTR of eukaryotic mRNA is an important regulation region, on which many trans factors act. In recent years, a series of 3'UTRs were shown to have tumor suppressor function, including the 3'UTR of the human nuclear factor for interleukin-6 (NF-IL6 3'UTR). To understand molecular basis for this function, we have tried to isolate genes encoding protein factors acting on the RNA of NF-IL6 3'UTR. Here we show that, by using a yeast three-hybrid system, a cDNA fragment was successfully isolated. This cDNA was allowed to express in E. coli, and its expression product, a polypeptide of ca. 70 amino acids long, was shown to specifically bind to the NF-IL6 3'UTR RNA. A search in GenBank did not reveal homologous sequences. Therefore, this cDNA fragment may be a part of the gene of a novel NF-IL6 3'UTR specific binding protein.

Amino Acid Sequence↗
PubMed2000

Pilocytic astrocytomas do not show most of the genetic changes commonly seen in diffuse astrocytomas.

AIMS: While it is well known that pilocytic astrocytomas are clinically distinct from diffuse astrocytomas, few comprehensive studies have focused on their genetic differences. The aim of this study was to examine pilocytic astrocytomas for genetic alterations that are commonly seen in diffuse astrocytomas. METHODS AND RESULTS: By using molecular genetic and immunohistochemical techniques, we evaluated p16, p53, CDK4 and PTEN genes in 29 pilocytic astrocytomas. Mutation screening of p53 and PTEN was performed by single strand conformation polymorphism analysis followed by direct sequencing. Loss of heterozygosity (LOH) of p53, p16 and 10q23-25 loci was performed with microsatellite markers and genomic microsatellite instability (MSI) was also screened. Protein expression of p16, p53, CDK4 and PTEN was examined by immunohistochemistry. Five tumours were found to have single genetic alterations, which included a p53 mutation, a PTEN mutation, MSI at a single microsatellite marker of the p16 locus, and one single LOH at each p16 and 10q23 loci. Protein expressions of p16, CDK4 and PTEN were detected in 73%, 61% and 38% of tumours, respectively. Significantly and in sharp contrast to diffuse astrocytomas, no pilocytic astrocytoma in our series stained for p53 protein. CONCLUSION: Pilocytic astrocytomas have neither MSI phenotype nor recurrent alterations of the p53 and p116 genes. However, altered expression of PTEN may be important in the genesis of pilocytic astrocytomas. We conclude that pilocytic astrocytomas are genetically distinct from diffuse astrocytomas. Lack of p53 mutation/immunostaining may serve as a diagnostic adjunct for differentiating pilocytic astrocytomas from diffuse astrocytomas in small neurosurgical biopsies.

Adolescent↗
PubMed2000

[Effects of modified SD therapy on Bell's palsy].

OBJECTIVE: To investigate the effects of a modified SD therapy (intravenous high dose hydrocortisone and low molecular dextran) on Bell's palsy(BP), and to avoid the severe side-effects such as hepatic and renal disorders during the treatment. METHOD: Seventy-one BP patients were treated with modified SD method (modified group), thirty-two BP patients took prednisone (control group), and the curative rates of two therapies were compared, in the meanwhile recorded the side effects in detail. RESULT: Curative rate in modified group was 95.8% (House-Brakmsnn I-II) and in control group was 81.2% (P < 0.05). In modified group, the curative rate (I grade) in the patients were treated within 24 hours following onset was 75.0%, and the curative rate in other three subgroups were treated within 24-48 hours, 2-3 day and 3-5 day following onset was 43.8%, 26.7%, 18.8% respectively. Modified group had not shown hepatic and renal disorders or gastric ulcer. CONCLUSION: Modified SD method may increase recoverable rate and can avoid significant side effects for BP, and emphasizes the importance of the administration of SD therapy in the early stage of the disease.

Adult↗
PubMed1997

Expression of exogenous NF-IL6 induces apoptosis in Sp2/0-Ag14 myeloma cells.

NF-IL6 (or C/EBP beta) is a multifunctional transcription factor of the C/EBP family. To study the effects of exogenous expression of NF-IL6 on the growth of cells of hematopoietic tumors, we infected SP2/0-Ag14 myeloma cells with pLXSN recombinant retrovirus harboring the NF-IL6 cDNA. We found that the transfected cells revealed changes typical of the apoptosis and finally died. The expression of NF-IL6 protein was shown by a "supershift" assay in the NF-IL6-transfected cells. In controls, where cells were infected by the retroviral vector with a mutant NF-IL6 coding region as well as the vector without insert, no sign for expression of NF-IL6 and apoptosis was observed. Therefore, our work shows that the apoptosis of this myeloma cell line was induced by the exogenous NF-IL6 expression. This is significantly different from the apparent effects of NF-IL6 in leukemia cells and in fibroblasts. These facts indicate that NF-IL6 exerts different functions in different cell types. We discuss possible mechanisms for the NF-IL6-induced apoptosis.

Animals↗
PubMed1994

Functional status of pancreatic islet in acute leukemia.

Using enzymatic assay and radioimmunoassay, we studied the functional status of pancreatic islet in 50 patients with acute leukemia. Oral glucose tolerance test and insulin and C peptide release were made in 40 patients before and after treatment. 14 patients who revealed diabetic curve and delayed insulin and C peptide release before treatment showed normal values in 6 after therapy. Five patients with impaired glucose tolerance and decreased insulin and C peptide release before treatment showed normalization of these parameters following therapy. Five patients with normal pretreatment values disclosed abnormal post-treatment results. The remaining 16 patients displayed normal results both before and after therapy. Anti-insulin antibodies were negative, and glucagon level was normal in all the 50 patients. The red cell insulin receptor binding rate analysed in 47 patients was significantly higher than in controls (P < 0.001). We considered that the disturbed glucose metabolism in acute leukemia was not uncommon mainly due to the dysfunction of pancreatic islet beta cells as a result of islet damage by leukemic cells, the effect of corticosteroid and chemotherapy and the preexisting diabetes. Impaired glucose metabolism had no influence on therapeutic effect.

Adolescent↗
PubMed1993

[Immunohistochemical and ultrastructural study of plurihormonal pituitary adenomas].

38 cases of plurihormornal pituitary adenomas containing growth hormone were detected by PAP technique for GH, PRL, ACTH, TSH and GnH. Plurihormonal pituitary adenomas were classified according to their hormonal content and pattern of hormonal combinations. Under the transmission electron microscopy, the plurihormonal pituitary adenomas might be monomorphous or multimorphous, thus, one morphologic cell type could elaborate several hormones. Using immunoelectron microscopical colloidal gold double labelling technique, we found 3 kinds of hormonal distribution in plurihormonal pituitary adenomas: different cells containing different hormones; one cell with plural hormones, even one secretory granule with two hormones; combination the former two. Even in the normal pituitary anterior lobe, we found there were cells secreting one type of hormone and also cells secreting plural hormones. Plurihormonal pituitary adenomas might derive from multiple cell type, from one cell type, or from both cell containing one type of hormone and cell containing plural hormones.

Adenoma↗
PubMed1992

A cDNA clone with anti-oncogene activity.

A cDNA clone, p14-6, which has an anti-oncogene activity on the v-Ki-Ras oncogene-transformed malignant cell line DT, was found. This clone was recovered from the revertant R14 cells, which had been isolated by transfections of DT cells with a normal human fibroblast cDNA library cloned in pcD2, an Okayama-Berg vector. When transfected into DT cells, p14-6 clone gave rise to phenotypical flat reversion in 5-15% of DT transfectant colonies. The p14-6-transfected flat cell line, RR, was proven to be a true revertant with significantly reduced malignancy by in vitro and in vivo malignancy tests. All other clones recovered from R14 cells were unable to cause this reversion. Molecular hybridizations showed that the p14-6 was inserted into RR genome as tandem repeats, and no structural change was found in the v-Ki-Ras oncogene in RR genome. These facts suggest that the anti-oncogene activity of the p14-6 clone on the DT cells may be exerted through expression of the cDNA contained in this clone.

Animals↗
PubMed1990

Gastroesophageal anastomotic leakage following resection of carcinoma of the esophagus and gastric cardia: analysis of ten cases.

Postoperative anastomotic leakage is one of the most dangerous and, unfortunately, most frequent complications. Many methods have been tried to prevent such leakage. The incidence of leakage has decreased to 3.84% in our hospital in recent years. Ten cases of gastroesophageal anastomotic leakage following resection of carcinoma of the esophagus and gastric cardia are analyzed and a new tool, the three-leaf clamp, which reduced the anastomotic leakage, is introduced.

Anastomosis, Surgical↗
PubMed1990

Laboratory and clinical diagnosis of human cytomegalovirus infection after transplantation.

Urine and blood specimens from 32 recipients of allograft organ transplant were investigated for human cytomegalovirus (HCMV) by conventional cell culture, indirect immunofluorescent assay subsequent to the rapid cell culture and DNA-DNA hybridization. The results showed that the rapid cell culture technique might be the best method for rapid detection of active HCMV infection after transplantation because it possesses the advantages of simplicity, speediness, sensitiveness, and high reliability of detecting productive HCMV infection. The major symptoms were prolonged or intermittent fever unresponsive to antibiotics, dysfunction or loss of function of the transplanted organ, pulmonary infiltrates and leukopenia. As our results suggested, reactivation of a latent infection appears to be the most probable etiologic factor contributing to HCMV infection after transplantation.

Cytomegalovirus↗