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Biomedical subjects

Q Lin

Publications and source records attributed to Q Lin.

At least 163 records · Page 9Linked to original sources
PubMed1997

Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C.

Members of the myocyte enhancer factor-2 (MEF2) family of MADS (MCM1, agamous, deficiens, serum response factor)-box transcription factors bind an A-T-rich DNA sequence associated with muscle-specific genes. The murine MEF2C gene is expressed in heart precursor cells before formation of the linear heart tube. In mice homozygous for a null mutation of MEF2C, the heart tube did not undergo looping morphogenesis, the future right ventricle did not form, and a subset of cardiac muscle genes was not expressed. The absence of the right ventricular region of the mutant heart correlated with down-regulation of the dHAND gene, which encodes a basic helix-loop-helix transcription factor required for cardiac morphogenesis. Thus, MEF2C is an essential regulator of cardiac myogenesis and right ventricular development.

Acyltransferases↗
PubMed1997

Involvement of cGMP in nociceptive processing by and sensitization of spinothalamic neurons in primates.

Central sensitization of spinothalamic tract (STT) neurons in anesthetized monkeys after intradermal injection of capsaicin depends in part on disinhibition. Protein kinase C is suggested to participate in this process. The present study shows that the nitric oxide-cGMP (NO-cGMP) signal transduction system also contributes to sensitization of wide dynamic range (WDR) STT neurons located in the deep dorsal horn. The NO-cGMP system was activated by microdialysis administration into the dorsal horn of 8-bromo-cGMP, an analog of cGMP. Sensitization of STT cells by 8-bromo-cGMP increased the responses of deep WDR STT cells to both weak and strong mechanical stimulation of the skin and simultaneously attenuated the inhibition of the same neurons produced by stimulation in the periaqueductal gray (PAG). In contrast, WDR STT cells in the superficial dorsal horn and high-threshold (HT) STT cells in superficial or deep layers showed reduced responses to mechanical stimulation of the skin after infusion of 8-bromo-cGMP, and PAG inhibition of these neurons was unaffected. Sensitization of STT cells and the attenuation of PAG inhibition induced by intradermal injection of capsaicin were prevented by preteatment of the dorsal horn with a guanylate cyclase inhibitor, 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. The results support the hypothesis that activation of the NO-cGMP signal transduction system contributes to the sensitization of WDR STT neurons in the deep dorsal horn and helps explain why intradermal capsaicin injections often fail to sensitize superficial and HT STT cells. The results also support the idea that sensitization of STT cells is produced in part by disinhibition.

Animals↗
PubMed1997

Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis.

The zinc finger transcription factor GATA4 has been implicated in heart development based on its early expression in precardiogenic splanchnic mesoderm and its ability to activate the expression of a number of cardiac-specific genes. To determine the role of GATA4 in embryogenesis, we generated mice homozygous for a GATA4 null allele. Homozygous GATA4 null mice arrested in development between E7.0 and E9.5 because of severe developmental abnormalities. Mutant embryos most notably lacked a primitive heart tube and foregut and developed partially outside the yolk sac. In the mutants, the two bilaterally symmetric promyocardial primordia failed to migrate ventrally but instead remained lateral and generated two independent heart tubes that contained differentiated cardiomyocytes. We show that these deformities resulted from a general loss in lateral to ventral folding throughout the embryo. GATA4 is most highly expressed within the precardiogenic splanchnic mesoderm at the posterior lip of the anterior intestinal portal, corresponding to the region of the embryo that undergoes ventral fusion. We propose that GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AIP.

Animals↗
PubMed1997

Fluorescence studies on the interaction of a synthetic signal peptide and its analog with liposomes.

The N-terminal signal sequence of glucitol permease of Escherichia coli (Gut22: MIETITPGAVWFIGLFQKGGEC) and its analog (Gut22Ana: MIETITHGAEWFIGLFQKGGEC) were synthesized. The analog had a Pro residue substituted for the His at the 7th position of Gut22 and a Val residue substituted for the Glu at the 10th position. Previous studies indicated that due to its structural rigidity, the interaction of Gut22Ana with lipid bilayer was much weaker than that of Gut22 (Wang, Q.D., Cui, D.F. and Lin, Q.S. (1996) Science in China (Series C) 39, 395-405). To further probe the location of the tryptophan residues of the peptides in lipid bilayer, the membrane penetration depth of the tryptophan residue of Gut22 was measured using spin-labeled phospholipids, and fluorescence quenching of the peptides by iodide and acrylamide in the presence and absence of phosphatidylserine/phosphatidylcholine liposomes were also studied. Fluorescent labeling of the peptides enabled the study of their association with membrane by fluorospectrophotometry. In the presence of liposomes, the peptides were protected from reaction with chymotrypsin, indicating that the peptide incorporated into the membrane. However, dithionite, which acts external to the membrane, reacted with the peptide, showing that the peptides did not translocate across lipid bilayer spontaneously.

Acrylamide↗
PubMed1997

Human fetal astrocytes as an ex vivo gene therapy vehicle for delivering biologically active nerve growth factor.

The therapeutic use of neurotrophic factors for neurodegenerative diseases is promising, however, optimal methods for continuous delivery of these substances to the human central nervous system (CNS) remains problematic. One approach would be to graft genetically engineered human cells that continuously secrete high levels of a biologically produced and processed neurotrophic factor. This ex vivo gene therapy approach has worked well in animal models of neurodegenerative diseases using a variety of nonneuronal cell types to deliver the transgene. In our studies, we have been investigating the potential of astrocytes, a cell type normally present in the CNS, as a vehicle for ex vivo gene therapy. Here, we demonstrate that astrocytes in the human fetal cortex can be isolated and efficiently infected with an amphotropic retrovirus harboring mouse beta-nerve growth factor (NGF). These transduced astrocytes express high levels of NGF mRNA and secrete bioactive NGF protein as demonstrated by stimulation of neurite outgrowth from adrenal chromaffin cells. NGF ELISA showed that these astrocytes secrete NGF protein at a rate of 41 ng/day per 10(5) cells after 2 weeks in vitro, whereas NGF is undetectable in medium conditioned by normal astrocytes. These data suggest that human fetal astrocytes can be used for delivering biologically produced neurotrophic factors to the human CNS.

Astrocytes↗
PubMed1997

Dopaminergic neurons protected from degeneration by GDNF gene therapy.

Glial cell line-derived neurotrophic factor (GDNF) supports growth and survival of dopaminergic (DA) neurons. A replication-defective adenoviral (Ad) vector encoding human GDNF injected near the rat substantia nigra was found to protect DA neurons from the progressive degeneration induced by the neurotoxin 6-hydroxydopamine (6-OHDA) injected into the striatum. Ad GDNF gene therapy reduced loss of DA neurons approximately threefold 6 weeks after 6-OHDA lesion, as compared with no treatment or injection of Ad lacZ or Ad mGDNF (encoding a biologically inactive deletion mutant GDNF). These results suggest that Ad vector-mediated GDNF gene therapy may slow the DA neuronal cell loss in humans with Parkinson's disease.

Adenoviridae↗
PubMed1997

Improved heterologous expression of the white-rot fungal ligninase H8 by crossover linker mutagenesis.

Using the crossover-linker mutagenesis method, the 5' noncoding region of the lambda ML-1 cDNA, which encodes the ligninase H8 isozyme of the white-rot fungus, Phanerochaete chrysosporium, was deleted with the simultaneous insertion of the putative Spodoptera frugiperda ribosome-binding sequence (RBS) (TATAAAT) directly in front of the translation-initiation codon of this gene. A recombinant baculovirus, pVL-Mu-H8, carrying the ligninase-H8 gene was successfully constructed, as determined by both sequence analysis and dot blot hybridization. A more than 18-fold increase in the expression of ligninase H8, compared to the previous pEV11-1A.3 recombinant baculovirus, was detected in the Sf-21 insect cells. This enzyme was detected within 3 d postinfection and was biologically active, capable of oxidizing the model lignin compound, veratryl alcohol. The molecular weight of the overexpressed 42 kD protein was similar to that of the native fungal ligninase-H8 isozyme and it also reacted specifically with the anti-H8 monoclonal antibody (MAb 2D4.9) in Western blot analysis.

Animals↗
PubMed1997

Involvement of protein kinase C in responses of rat dorsal horn neurons to mechanical stimuli and periaqueductal gray descending inhibition.

The effects of a protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), on the activity and periaqueductal gray (PAG)-induced inhibition of rat dorsal horn neurons of the lumbar spinal cord were tested. A microdialysis fiber was placed through the dorsal horn for the purpose of local application of pharmacological agents. Extracellular single-unit recordings from dorsal horn neurons were made near the microdialysis fiber. TPA was tested on nociceptive dorsal horn cells. There was a significant increase in the background activity and responses to "brush", with no changes in responses to pressure and pinch stimuli. TPA also significantly blocked the PAG-induced inhibition of responses to brush, press, and pinch. These effects were eliminated by coadministration of the PKC inhibitor NPC-15437. The solvent, which contained dimethyl sulfoxide, was also tested for its effect on the responses to peripheral mechanical stimuli and PAG-induced inhibition of the dorsal horn neurons. There were no significant changes. This experiment suggests that activation of the PKC second messenger system might increase the activity of dorsal horn neurons and their responses to peripheral stimuli; in addition, the phorbol ester attenuated the PAG-induced descending inhibition of the dorsal horn neuron activity.

Animals↗
PubMed1997

Sustainable cutaneous gene delivery.

Durable gene delivery to human skin is necessary for lasting correction of human genetic skin disease. Current cutaneous gene-delivery strategies, however, have achieved only transient gene expression, often only within a small percentage of tissue cells. The recent inability to sustain phenotypic correction of human genetic skin disease due to loss of therapeutic gene expression in regenerated epidermal tissue has highlighted this current limitation. In an effort to surmount this problem, we have generated gene delivery vectors that produce more durable gene delivery in human skin tissue in vivo.

Animals↗
PubMed1997

Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND.

dHAND and eHAND are related basic helix-loop-helix (bHLH) transcription factors that are expressed in mesodermal and neural crest-derived structures of the developing heart. In contrast to their homogeneous expression during avian cardiogenesis, during mouse heart development we show that dHAND and eHAND are expressed in a complementary fashion and are restricted to segments of the heart tube fated to form the right and left ventricles, respectively. dHAND and eHAND represent the earliest cardiac chamber-specific transcription factors yet identified. Targeted gene deletion of dHAND in mouse embryos resulted in embryonic lethality at embryonic day 10.5 from heart failure. Our description of the cardiac phenotype of dHAND mutant embryos is the first demonstration of a single gene controlling the formation of the mesodermally derived right ventricle and the neural crest-derived aortic arches and reveals a novel cardiogenic subprogramme for right ventricular development.

Animals↗
PubMed1997

Phosphorylation of the Src substrate Sam68 by Cdc2 during mitosis.

Sam68 (Src-associated in mitosis) is an SH3 (Src-homology 3), SH2 (Src-homology 2), and RNA binding protein which associates with and is tyrosine phosphorylated by wild-type and activated forms of c-Src in a mitosis-specific manner. We now show that Sam68 immunoprecipitated from either HeLa S3 or NIH3T3 cells is phosphorylated on threonine residues exclusively during mitosis as well as on serine residues during both interphase and mitosis. Recombinant Sam68, expressed as a glutathione S-transferase (GST) fusion protein, was phosphorylated on threonine and serine residues after incubation with mitotic lysates several-fold more extensively than after incubation with unsynchronized lysates. Cdc2 was identified as the kinase responsible for the mitotic threonine phosphorylation by (1) immunodepletion of the mitotic Sam68 kinase from cell lysates with anti-Cdc2 antibodies, (2) inhibition of Sam68 phosphorylation in vitro and in vivo by the cyclin-dependent kinase inhibitor olomoucine and (3) phosphorylation of Sam68 by purified Cdc2. These data demonstrate that Sam68 is a direct target of Cdc2 and may therefore mediate some of its biological effects during mitosis.

3T3 Cells↗
PubMed1997

Interferons alpha/beta inhibit IL-7-induced proliferation of CD4- CD8- CD3- CD44+ CD25+ thymocytes, but do not inhibit that of CD4- CD8- CD3- CD44- CD25- thymocytes.

Type 1 interferons (IFN-alpha/beta) have recently been shown to inhibit interleukin-7 (IL-7)-induced growth and survival of early B-lineage cells. The CD3- CD4- CD8- (triple negative; TN) thymocytes from normal mice strongly proliferated upon stimulation with IL-7 in suspension, culture. Such an IL-7-induced proliferation was suppressed by the addition of IFN-alpha/beta, but a fraction of the TN thymocytes still showed proliferation. The IL-7-induced growth of TN thymocytes from acid mice, which lack the CD44- CD25- subpopulation, was completely inhibited by the addition of IFN-alpha/beta. The IL-7 induced proliferation of CD4- CD8- thymocytes from T-cell receptor (TCR) transgenic mice, the majority of which are CD3+ CD44- CD25-, was resistant to IFN-alpha/beta-mediated suppression. In fetal thymus organ cultures (FTOC), the addition of IL-7 greatly increased the population of CD4- CD8- CD44+ CD25+ thymocytes and IFN-alpha/beta inhibited this IL-7-driven expansion. In contrast, the addition of IL-7 markedly decreased the percentages of CD4- CD8- CD3- CD44- CD25- cells, and IFN-alpha/beta reversed the effect and increased the subpopulations of CD44- CD25+ and CD44- CD25-. Finally, IFN-beta mRNA was found to be expressed in the thymus. The data suggest that type I interferons inhibit IL-7-driven proliferation of TN thymocytes, but do not block the normal differentiation process.

Animals↗
PubMed1997

Impact of cognitive rehabilitation therapy on neuropsychological impairments as measured by brain perfusion SPECT: a longitudinal study.

Three patients, with known brain injury and neuropsychological impairments, are followed through an individualized cognitive rehabilitation programme and post discharge from the treatment programme. Single Photon Emission Computed Tomography (SPECT) of the brain was employed to evaluate resting relative cerebral blood flow (rCBF) during the process of recovery from brain injury. All patients experienced significant improvements on measures of neuropsychological functioning and improvements in rCBF during this longitudinal study. The specific changes in rCBF appear to be related to the location of the patient's brain injury and strategies particular to cognitive rehabilitation therapy. Continued improvements in rCBF, functional abilities, and cognitive skills were documented in these three cases up to 45 months post brain injury.

Adult↗
PubMed1997

Cerebral perfusion SPECT imaging in epileptic and nonepileptic seizures.

Patients with epileptic and nonepileptic seizures are commonly encountered in clinical practice, and they can pose a difficult diagnostic problem. We present two cases that show the difficult task of differentiating between true epileptic and nonepileptic or psychogenic seizures in some patients. The clinical presentations were complex and the use of video-monitored EEG alone was insufficient to make definitive diagnoses. Ictal and interictal Tc-99m HMPAO brain perfusion SPECT imaging examinations were used to help establish the correct diagnoses. This report describes the advantage of using the brain perfusion SPECT imaging examination. The injection of stabilized Tc-99m HMPAO during an ictal event followed by appropriate medical therapy provides a method of obtaining a reasonable image of relative perfusion (activity) during the seizure. These images can then be compared with interictal examinations and an epileptic or nonepileptic focus may be localized. The Tc-99m HMPAO brain perfusion SPECT imaging study was helpful in establishing the correct diagnosis in both cases.

Adult↗
PubMed1997

[The correlation between lung cancer lymph node metastasis and nm23-H1 gene mutation, mRNA expression].

OBJECTIVE: To examine the genomic status and the mRNA expression of the nm23-H1 gene, and to analyse the relationship between metastasis of non-small cell lung carcinomas and the gene abnormalities. METHOD: By using PCR-SSCP and semiquantitative RT-PCR, the nm23-H1 gene mutation and mRNA expression were studied in 31 cases of non-small cell lung cancer. The normal tissue adjacent to carcinoma and normal lung tissue were used as control. RESULT: None of the nm23-H1 gene mutation was found in all the lung cancer samples. Decreased expressions of this gene were found in 14 of 20 lung cancer cases with lymph node metastasis, the rate (14/20) of this was significantly higher than that (3/11) of the non-metastatic cancers (P < 0.05). CONCLUSION: These data indicate that nm23-H1 may be a putative metastasis suppressor gene which had shown reverse regulating activation in the metastatic progression of lung cancers, and the level of nm23-H1 mRNA may be considered as one of the pathological indicators in predicting metastatic potential of lung cancers.

Adult↗
PubMed1997

[Assay of terpenes in the leaves of Ginkgo biloba extract and its preparations by in situ fluorometric TLC].

A new TLC method for the assay of terpene lactones in Ginkgo biloba extract and its preparations has been established by means of optimized development condition and post-chromatographic thermal fluorescence derivatization. Satisfactory results can be obtained through polynomial regression calibration. The data obtained by this method have been proved ten times higher in sensitivity than those obtained by HPLC-refracto-detector.

Chromatography, High Pressure Liquid↗
PubMed1997

[High performance gel chromatographic behaviour of sodium alginate and determination of its molecular weight parameters].

The molecular weight parameters of sodium alginate were determined by high performance gel chromatography with Waters Bondagel E-High A column. The differences in high performance gel chromatographic behaviours between the sodium alginate and the non-polar standard Dextran T500 were compared. The influences of the sample concentration and the sample volume on the results were discussed. The high performance gel chromatographic behaviour of sodium alginate is different from that of Dextran T500, and is also different from those on Sepharose or Sephadex columns. The peak shifted toward full osmotic side under in crease of ionic strength. The elution volumn didn't tend toward stable, even though at the high concentration of 0.5mol/L NaCl. A change of the sample concentration at stable sample volume or the sample volume at stable sample concentration would cause tailing peaks. It was showed that the sample size of sodium alginate would be less than 25microg, and the relative standard deviations of Mn, Mw and d were 0.95%, 4.04% and 4.70%.

Alginates↗