Biomedical subjects

Q Ding

Publications and source records attributed to Q Ding.

At least 37 records · Page 2Linked to original sources

PubMed2000

Extracellular FGF-1 inhibits cytoskeletal organization and promotes fibroblast motility.

Previous efforts from this laboratory have established that acidic fibroblast growth factor (FGF-1), either added exogenously or secreted as a biologically active protein, induces a transformed phenotype in primary murine fibroblasts. Experimental studies described here demonstrate that constitutive exposure to extracellular FGF-I results in reduced cell attachment to multiple ligands, inhibition of cytoskeletal organization, and reduced collagen contraction, despite no detectable change in integrin cell surface expression. In addition, FGF-1-transduced fibroblasts demonstrated a > 10-fold increase in migration, an observation correlated with increased tyrosine phosphorylation of p125FAK and p130CAS. Collectively, these results suggest that FGF-1-induced fibroblast transformation includes the involvement of specific FGF receptor-mediated signal transduction cascades targeted to cytoskeletal and focal adhesion structures.

Animals↗

PubMed2000

Synthesis and antitumor cytotoxicity evaluation of pyrido[4,3,2-de]quinolines and isoquinolino[6,5,4,3-cde]quinolines.

A series of novel pyrido[4,3,2-de]quinoline and isoquinolino[6,5,4,3-cde] quinoline compounds was synthesized and evaluated for cytotoxicity in the National Cancer Institute developmental therapeutics program. The tricyclic compound 7 was synthesized by the cyclization of 3,4-diamino-1,2dimethoxybenzene with diethyl 1,3-acetonedicarboxylate. Oxidation of monochloropyrido[4,3,2-de]quinoline 8 selectively produced 2,3-diketopyrido[4,3,2-de]quinoline 9 as deep violet crystals. Compound 9, when treated with acetone or acetophenone, affords the tetracyclic isoquinolino[6,5,4,3-cde]quinolines 13 and 14, respectively. 2,3-Diketopyrido[4,3,2-de]quinolines 9 and 10 exhibit higher cytotoxic potency than isoquinolino[6,5,4,3-cdelquinolines 13, 14, 15 and 16. Compound 9 selectively affects the cell growth against leukemia CCRF-CEM and HL-60 cell lines, the non-small cell lung cancer HOP-92 cell line, and breast cancer MDA-MB231/ ATCC and MDA-MB- 435 cell lines with GI(50) values of <2.0 microM. Modification of compound 9 with an ester group at the N-1 position afforded compound 10, which exhibits a wide spectrum of anticancer activities with a mean graph midpoint value of 1.8 microM against the 60 cancer cell lines.

Antineoplastic Agents↗

PubMed2000

[Transurethral electrovaporization-ablation of superficial bladder carcinoma].

OBJECTIVE: To observe short-term curative effect of transurethral electrovaporization-ablation of superficial bladder carcinoma. METHODS: 82 cases of superficial bladder carcinoma were treated using transurethral electrovaporization-ablation. RESULTS: The mean operative time was 36 min. One patient was complicated with extraperitoneal bladder perforation. No patients experienced TUR syndrome and severe hemorrhage. During the follow up for 2-18 months, 3 patients had recurrence respectively at 7, 8 and 10 months after the operation. CONCLUSIONS: Cut-electrode had vaporization and ablation with smooth surface of the wound and speed. The advantage includes safety, few complication, evident efficacy, and short hospitalization.

Adult↗

PubMed2000

[Measurement of T and DHT contents in normal and diseased human prostate tissues].

OBJECTIVE: To measure T and DHT contents in normal and diseased human prostate tissues. METHODS: Serum and prostatic T and DHT levels were measured in patients with normal, benign prostatic hyperplasia and prostate cancer. RESULTS: A decline was observed in serum T level, but no change in DHT concentration with aging. There were no significant differences in both blood T and DHT levels between the patients with BPH or PCA and normal controls. Serum T level remained constant. There were excessive accumulation of DHT in BPH, and cancerous prostate tissues were responsible for the pathogenesis of BPH and PCA. Finasteride treatment did not produce a reduction in prostatic DHT content. CONCLUSION: More than one form of 5a-reductases is responsible for the high level of DHT in the gland.

Adult↗

PubMed1999

Mouse suppressor of fused is a negative regulator of sonic hedgehog signaling and alters the subcellular distribution of Gli1.

The Hedgehog (Hh) signaling pathway has critical functions during embryogenesis of both invertebrate and vertebrate species [1]; defects in this pathway in humans can cause developmental disorders as well as neoplasia [2]. Although the Gli1, Gli2, and Gli3 zinc finger proteins are known to be effectors of Hh signaling in vertebrates, the mechanisms regulating activity of these transcription factors remain poorly understood [3] [4]. In Drosophila, activity of the Gli homolog Cubitus interruptus (Ci) is likely to be modulated by its interaction with a cytoplasmic complex containing several other proteins [5] [6], including Costal2, Fused (Fu), and Suppressor of fused (Su(fu)), the last of which has been shown to interact directly with Ci [7]. We have cloned mouse Suppressor of fused (mSu(fu)) and detected its 4.5 kb transcript throughout embryogenesis and in several adult tissues. In cultured cells, mSu(fu) overexpression inhibited transcriptional activation mediated by Sonic hedgehog (Shh), Gli1 and Gli2. Co-immunoprecipitation of epitope-tagged proteins indicated that mSu(fu) interacts with Gli1, Gli2, and Gli3, and that the inhibitory effects of mSu(fu) on Gli1's transcriptional activity were mediated through interactions with both amino- and carboxy-terminal regions of Gli1. Gli1 was localized primarily to the nucleus of both HeLa cells and the Shh-responsive cell line MNS-70; co-expression with mSu(fu) resulted in a striking increase in cytoplasmic Gli1 immunostaining. Our findings indicate that mSu(fu) can function as a negative regulator of Shh signaling and suggest that this effect is mediated by interaction with Gli transcription factors.

Amino Acid Sequence↗

PubMed1999

Enterocyte-like differentiation of the Caco-2 intestinal cell line is associated with increases in AP-1 protein binding.

The nuclear factor AP-1, a large family of transcription factors composed of the Jun and Fos protein families, plays a role in the differentiation of various cells; the role of the AP-1 factors in intestinal differentiation is not known. Members of the AP-1 family can be activated by the Ras pathway and, in addition, Ras appears to be important for gut differentiation. The purpose of this study was to determine whether AP-1 activity is altered in the Caco-2 cell line, which spontaneously differentiates to a small bowel phenotype after confluency, and the Caco-2-ras cell line, which exhibits differentiated properties regardless of culture conditions. AP-1 binding activity, consisting of c-Jun, JunD, c-Fos and Fra-2 proteins, was increased in Caco-2 cells at 3 days postconfluency, a time point associated with G1 block and cessation of proliferation. Steady state levels of JunD were increased at day 3 postconfluency as determined by Western blot. Furthermore, AP-1 binding was increased in preconfluent Caco-2-ras cells compared with parental Caco-2 cells, suggesting that AP-1 induction may be mediated by the Ras pathway. The early induction of AP-1 binding activity suggests a role for these proteins in the differentiation of the Caco-2 intestinal cell line.

Binding, Competitive↗

PubMed1999

Embryonic Stem Cells in vitro - Prospects for Cell and Developmental Biology, Embryotoxicology and Cell Therapy.

Embryonic stem (ES) cells are able to differentiate in vitro via embryo-like aggregates, so-called "embryoid bodies", into derivatives of the endodermal, ectodermal and mesodermal lineage. We established standardised protocols for cardiogenesis, myogenesis, neurogenesis and vascular smooth muscle cell differentiation in vitro. The developmentally controlled expression of tissue-specific genes, proteins, ion channels and receptors during ES cell differentiation is the basis of several in vitro approaches: (1) "Loss of function" assays with ES cells containing homozygous mutations of specific genes, (2) "Gain of function" assays with ES cells overexpressing exogenous genes, (3) Developmental analysis of teratogenic/embryotoxic compounds in vitro, (4) Pharmacological assays and the establishment of model systems for pathological cell functions, and (5) The application of differentiation and growth factors for induction of selectively differentiated cells which, in the future, may be used as a source for tissue grafts. We propose the ES cell technology as valuable in vitro system to substitute and reduce the use of animals in basic and applied research.

Journal Article↗

PubMed1999

[Nonpalpable testicular masses incidentally discovered by ultrasound].

OBJECTIVE: To determine the diagnosis and management of impalpable testicular masses detected sonographically. METHODS: We analyzed retrospectively the sonographic findings and pathologic results of such cases and reviewed related literature. RESULTS: In over 600 patients receiving scrotal ultrasound, 14 aged on average 42.4 years (14 to 71 years) had 16 impalpable testicular masses, with a diameter of 5 to 30 mm (mean 12.1 mm). All masses were predominantly hypoechoic except for one appeared hyperechoic and calcified. Pathological examination showed 2 seminomas, 2 lymphomas, 2 testicular tuberculoses and cysts respectively. The other six were embryonal cell carcinoma, metastatic adenocarcinoma, testicular fibrosis, partial infarction, testis abscess, and hematoma. Malignant lesions accounted for 42.86% (6/14). In 13 of 14 patients, the affected testis was resected, while in 1 the testis spared for frozen sectioning revealed a benign cystic lesion. CONCLUSIONS: Ultrasound findings can not differentiate malignant from benign in the impalpable lesions, and clinical history should be considered. All patients with indefinite diagnosis should undergo inguinal exploration and the testis can be spared if intraoperative frozen section diagnosis is negative. Ultrasound follow-up should be used only if there is a strong evidence of infection or trauma.

Adolescent↗

PubMed1999

[Detection of telomerase activity in prostate needle-biopsy samples].

OBJECTIVE: To detect telomerase activity inprostate needle-biopsy samples and its role in diagnosis and prognosis of prostate cancer. METHODS: 20 tissue samples of prostate cancer tissues and 16 samples of adjacent tissues were obtained by needle-biopsy guided by transrectal B ultrasonography. 16 samples of benign prostatic hyperplasia tissues were obtained by prostatectomy and were confirmed pathologically. Telomerase activity was revealed by modified PCR-based telomeric repeat amplication protocol (TRAP)-silver staining assay. RESULTS: Telomerase activity was revealed in 18 cases of prostate cancer. In tissues adjacent to prostate cancer, telomerase activity was found in 7 of 11 cases of prostatic intraepithelial neoplasia (PIN), and in 2 of 5 cases of BPH. None of tissue samples from patients with BPH showed telomerase activity. CONCLUSIONS: Telomerase activity in prostate needle-biopsy samples might be an useful marker for detecting prostate cancer and biological malignancy.

Adenocarcinoma↗

PubMed1999

[Purity analysis of cephalosporins with capillary zone electrophoresis].

A capillary zone electrophoresis method is proposed for the purity determination of nine cephalosporin drugs. A background electrolyte comprising of either 20 mmol/L pH 9.20 borate buffer or 20 mmol/L pH 6.86 phosphate buffer was used for most drugs studied except for cefaloridine which formed neutral molecules at these pH values. For it 50 mmol/L pH 2.05 phosphate buffer was used instead. Internal normalization method was employed for quantitation. The method is simple, rapid and versatile. Analysis was completed within 8 min. The merits and limitations of the method were also discussed.

Cefazolin↗

PubMed1999

Pyrroloquinoline and pyridoacridine alkaloids from marine sources.

Marine organisms are a rich source for natural products. Pyrrolo[4,3, 2-de]quinolines and pyrido[4,3,2-mn]acridines are of major interest as metabolites in sponges and ascidians. Many of these compounds have generated interest both as challenging problems for structure elucidation and synthesis as well as for their cytotoxicities. The isolation, structure proof, biological activities, chemical properties and synthesis have attracted the attention of chemists, biologists and pharmacists. The principal structural feature of these alkaloids is the core of a planar iminoquinone moiety which can intercalate into DNA and cleave the DNA double helix or inhibit the action of topoisomerase II. Of the makaluvamines, makaluvamine F and A are the most cytotoxic to the HCT 116 cell line. The enhanced toxicity of the makaluvamines towards xrs-6 cells shows that all of the makaluvamines, except makaluvamine B, act like m-AMSA and etoposide in inhibiting topo iso merases via cleavable complex formation, or via the direct induction of DNA double-strand breaks. They are also amongst the most potent inhibitors of topoisomerase II. Both makaluvamine A and C can decrease tumor size in a solid human tumor model. Discorhabdin A and C in contrast are of high cytotoxicity, but they exhibit no inhibition of topoisomerase II. As representatives of the derivatives of pyrido[4,3,2-mn]acridine, cystodytins, kuanoniamines and diplamine are the most potent to inhibit HCT replication. Eilatin, as a 1,10-phenanthroline derivative, can form complexes with metal ions. It has been shown that these metal complexes can bind to DNA by intercalation. The new members of the pyrrolo[4,3,2-de]quinolines and pyrido[4,3, 2-mn]acridines, such as veiutamine, discorhabdin G, tsitsikammamines, epinartins, arnoamines as well as sagitol are reviewed. Some successful syntheses of pyrrolo[4,3,2-de]quinoline ring system and pyrido[4,3,2-mn]acridine ring system are also reviewed in this article.

Acridines↗

PubMed1998

Genetic algorithm-based wavelength selection for the near-infrared determination of glucose in biological matrixes: initialization strategies and effects of spectral resolution.

An improved genetic algorithm (GA)-based wavelength selection procedure is developed to optimize both the near-infrared wavelengths used and the number of latent variables employed in building partial least-squares (PLS) calibration models. This GA-based wavelength selection algorithm is applied to the determination of glucose in two different biological matrixes. With random selection of a small number of initial wavelengths, a dramatic reduction in the number of wavelengths required for building the PLS calibration models is observed. The fitness function used to guide the GA, the method of recombination used, and the effect of spectral resolution on the wavelength selection are also studied. In the resolution study, the original data with a point spacing of 2 cm-1 are deresolved to 4-, 8-, and 16-cm-1 point spacings by truncating the collected interferograms before applying the Fourier processing step. The use of lower resolution spectra is found to reduce further the number of final wavelengths selected by the GA, and the performance of the optimal calibration models obtained with the original spectra is maintained with the lower resolution spectra of both 4- and 8-cm-1 point spacing. Degradation in performance is observed with the spectra computed with a point spacing of 16 cm-1, however.

Algorithms↗

PubMed1998

Glutathione depletion associated with the HIV-1 TAT protein mediates the extracellular appearance of acidic fibroblast growth factor.

Primary murine embryonic fibroblasts transfected with HIV-1 TAT demonstrated decreased levels of high energy phosphates (ATP, GTP, UTP/CTP), adenine nucleotides (ATP, ADP, AMP), and both NAD+/NADH redox pairs, resulting in a substantial loss of redox poise. A greater than 50% decrease in intracellular reduced glutathione (GSH) concentration was accompanied by the extracellular appearance of acidic fibroblast growth factor (FGF-1). Addition of either N-acetyl-L-cysteine or glutathione ester (GSE), but not L-2-oxothiazolidine 4-carboxylate, partially restored intracellular GSH levels and resulted in loss of extracellular FGF-1. Treatment of FGF-1-transduced cells with buthionine sulfoximine (BSO) resulted in a time- and dose-dependent decrease in total cellular GSH concentration that was accompanied by the extracellular appearance of FGF-1. Inclusion of GSE during BSO treatment eliminated the extracellular appearance of FGF-1. BSO treatment of cells transfected with a mutant form of FGF-1, in which all three cysteine residues were replaced with serines, also decreased total cellular GSH concentration but failed to induce the extracellular appearance of FGF-1. Collectively, these results suggest that HIV-1 TAT induces a condition of oxidative stress, which mediates cellular secretion of FGF-1, an observation relevant to the pathophysiologic development and progression of AIDS-associated Kaposi's sarcoma.

Acetylcysteine↗

PubMed1998

Essential function of Gli2 and Gli3 in the formation of lung, trachea and oesophagus.

Foregut malformations (oesophageal atresia, tracheo-oesophageal fistula, lung anomalies and congenital stenosis of the oesophagus and trachea) are relatively common anomalies occurring in 1 in 2,000-5,000 live births, although their aetiology is poorly understood. The secreted glycoprotein Sonic hedgehog (Shh) has been suggested to act as an endodermal signal that controls hindgut patterning and lung growth. In mice, three zinc-finger transcription factors, Gli1, Gli2 and Gli3, have been implicated in the transduction of Shh signal. We report here that mutant mice lacking Gli2 function exhibit foregut defects, including stenosis of the oesophagus and trachea, as well as hypoplasia and lobulation defects of the lung. A reduction of 50% in the gene dosage of Gli3 in a Gli2-/- background resulted in oesophageal atresia with tracheo-oesophageal fistula and a severe lung phenotype. Mutant mice lacking both Gli2 and Gli3 function did not form oesophagus, trachea and lung. These results indicate that Gli2 and Gli3 possess specific and overlapping functions in Shh signalling during foregut development, and suggest that mutations in GLI genes may be involved in human foregut malformations.

Animals↗

PubMed1998

The clinical characteristics of possession disorder among 20 Chinese patients in the Hebei province of China.

OBJECTIVE: This paper describes the clinical characteristics of 20 hospitalized psychiatric patients in the Hebei province of China who believed they were possessed. METHODS: A structured interview focused on clinical characteristics associated with possession phenomena was developed and administered to 20 patients at eight hospitals in the province. All patients had been given the Chinese diagnosis of yi-ping (hysteria) by Chinese physicians before being recruited for the study. RESULTS: The subjects' mean age was 37 years. Most were women from rural areas with little education. Major events reported to precede possession included interpersonal conflicts, subjectively meaningful circumstances, illness, and death of an individual or dreaming of a deceased individual. Possessing agents were thought to be spirits of deceased individuals, deities, animals, and devils. Twenty percent of subjects reported multiple possessions. The initial experience of possession typically came on acutely and often became a chronic relapsing illness. Almost all subjects manifested the two symptoms of loss of control over their actions and acting differently. They frequently showed loss of awareness of surroundings, loss of personal identity, inability to distinguish reality from fantasy, change in tone of voice, and loss of perceived sensitivity to pain. CONCLUSIONS: Preliminary findings indicate that the disorder is a syndrome with distinct clinical characteristics that adheres most closely to the DSM-IV diagnosis of dissociative trance disorder under the category of dissociative disorder not otherwise specified.

Adult↗

PubMed1998

Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice.

Floor plate cells at the midline of the neural tube are specified by high-level activity of Sonic hedgehog (Shh) secreted by notochord, whereas motor neurons are thought to be specified by a lower level activity of Shh secreted in turn by floor plate cells. In Drosophila, the Gli zinc finger protein Cubitus interruptus functions as a transcription factor activating Hedgehog-responsive genes. We report that the expression of known Shh-responsive genes such as Ptc and Gli1 is downregulated in mutant mice lacking Gli2 function. Gli2 mutants fail to develop a floor plate yet still develop motor neurons, which occupy the ventral midline of the neural tube. Our results imply that Gli2 is required to mediate high level but not low level Shh activity and show that the development of motor neurons can occur in the absence of floor plate induction.

Animals↗

PubMed1997

Immunolocalization of acidic fibroblast growth factor and receptors in the tubulointerstitial compartment of chronically rejected human renal allografts.

Tubular damage and loss associated with interstitial inflammation and fibrosis may be the most important determinants in chronic renal allograft rejection. To elucidate potential pathophysiologic mechanisms associated with tubulointerstitial lesions, we examined the expression of a fibrogenic cytokine, acidic fibroblast growth factor (FGF-1) and its high-affinity receptors, in both relevant renal transplant controls (n=5) and tissue from patients (n=19) who underwent nephrectomy after graft loss, secondary to chronic rejection. In situ hybridization and immunohistochemical analyses demonstrated minimal expression of FGF-1 mRNA and protein in the tubulointerstitial compartment of the normal human kidney. In contrast, tubulointerstitial lesions in kidney allografts experiencing chronic rejection demonstrated the exaggerated appearance of both FGF-1 protein and mRNA in resident inflammatory and tubular epithelial cells. Patterns of staining were consistent throughout tubular compartments and did not appear to be localized to any particular region. The tubulointerstitium in kidneys with findings of chronic rejection also exhibited increased immunodetection of proliferating cell nuclear antigen in the tubular epithelium, inflammatory cell infiltrate, and neovascular structures. The enhanced appearance of FGF-1 and readily detectable fibroblast growth factor receptors suggests that this polypeptide mitogen may serve as an important mediator of growth and repair responses, associated with development of angiogenesis and tubulointerstitial lesions during chronic rejection of human renal allografts.

Biomarkers↗

PubMed1997

Vibrio harveyi NADPH:FMN oxidoreductase: preparation and characterization of the apoenzyme and monomer-dimer equilibrium.

A rapid chromatography method was developed for the preparation of apoenzyme of Vibrio harveyi NADPH:FMN oxidoreductase with > or =80% yields. The apoenzyme bound one FMN per enzyme monomer with a dissociation constant of 0.2 microM at 23 degrees C. The reconstituted holoenzyme was catalytically as active as the native enzyme. FMN binding resulted in 87 and 92% of quenching of protein and flavin fluorescence, respectively, indicating a conformational difference between the apoprotein and the holoenzyme. Neither riboflavin nor FAD showed any appreciable binding to the cofactor site of the apoenzyme but both flavins were active substrates for the FMN-containing holoenzyme. 2-ThioFMN bound to the cofactor site of the apoenzyme with an affinity similar to that for FMN binding. The holoenzyme reconstituted with 2-thioFMN showed a 509-nm absorption peak, which represents a 19-nm red shift from the corresponding peak of the free flavin, and was catalytically active in using either FMN or 2-thioFMN as a substrate. The holoenzyme showed a concentration dependence in molecular sieve chromatography corresponding to higher apparent molecular weights at higher concentrations. Both the holoenzyme and the apoenzyme was shown at 4 degrees C by equilibrium ultracentrifugation to undergo dimerization with dissociation constants of 1.8 and 3.3 microM, respectively.

Apoenzymes↗