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Biomedical subjects

Q Shen

Publications and source records attributed to Q Shen.

At least 19 recordsLinked to original sources
PubMed2001

Molecular structure and conformation of cyclopropylbenzene as determined by ab initio molecular orbital calculations, pulsed-jet fourier transform microwave spectroscopic, and gas-phase electron diffraction investigations.

Ab initio computational, microwave spectroscopic, and electron diffraction techniques have been used to study the gas-phase structure of cyclopropylbenzene. Theoretical calculations at the HF, B3LYP, and MP2 levels for basis sets 6-31G(d) and 6-311G(d) have been carried out. Both MP2 and B3LYP calculations showed the bisected form to be lower in energy (245/157 and 660/985 cal mol(-1), respectively, for basis sets 6-311G(d)/6-31G(d)). Rotational constants for the bisected form of the parent and eight singly substituted (13)C isotopic species were obtained. The selection rules of the observed rotational transitions and the facts that eight (rather than six) singly substituted (13)C isotopers are observed and assigned and that seven of the compound's nine carbon atoms lie in the molecule's symmetry plane required the molecule to exist in the bisected conformation. No transition from the perpendicular form was observed in the pulsed-jet microwave experiment. Gas-phase electron diffraction data were collected at a nozzle-tip temperature of 265 K. Least squares analyses were carried out using ED data alone and with the inclusion of microwave rotational constants. The principal structural results (r(g) and angle(alpha)) obtained from the combined ED/MW least-squares analysis are r(C-H)(av) = 1.093(6) A, r(C(7)-C(8))(v) = 1.514(20) A, r(C(8)-C(9))(d) = 1.507(26) A, r(C(7)-C(1)) = 1.520(25) A, r(C-C)(Ph) = 1.395(1) A, angleC(1)C(7)C(8) = 119.6(17) degrees, angleC(2)C(1)C(7) = 122.5(25) degrees, angleC(1)C(2)C(3) = 120.9(35) degrees, angleHC(8)C(9) = 116.7(20) degrees, angleHCC(Ph) = 120.0 degrees (assumed).

Journal Article↗
PubMed2001

Di-mu-phenylthio-bis[bis(eta5-methyl-cyclopentadienyl)(tetrahydrofuran)-lanthanum(III)] bis(tetrahydrofuran) solvate.

The title complex, [La(2)(C(6)H(7))(4)(C(6)H(5)S)(2)(C(4)H(8)O)(2)].2C(4)H(8)O, is a centrosymmetric dimer bridged through the S atoms of the benzenethiolate ligands. The bridging La(2)S(2) unit is completely planar, while the geometry around the nine-coordinate La atom is that of a distorted trigonal bipyramid. The La-S-La and S-La-S angles are 117.51 (4) and 62.5 (1) degrees, respectively, and the average La-S bond length is 2.9759 A. The crystals contain two tetrahydrofuran solvate molecules for every complex molecule.

Journal Article↗
PubMed2001

Excessive tumor-elaborated VEGF and its neutralization define a lethal paraneoplastic syndrome.

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and key regulator of both physiologic and pathologic (e.g., tumor) angiogenesis. In the course of studies designed to assess the ability of constitutive VEGF to block tumor regression in an inducible RAS melanoma model, mice implanted with VEGF-expressing tumors sustained high morbidity and mortality that were out of proportion to the tumor burden. Documented elevated serum levels of VEGF were associated with a lethal hepatic syndrome characterized by massive sinusoidal dilation and endothelial cell proliferation and apoptosis. Systemic levels of VEGF correlated with the severity of liver pathology and overall clinical compromise. A striking reversal of VEGF-induced liver pathology and prolonged survival were achieved by surgical excision of VEGF-secreting tumor or by systemic administration of a potent VEGF antagonist (VEGF-TRAP(R1R2)), thus defining a paraneoplastic syndrome caused by excessive VEGF activity. Moreover, this VEGF-induced syndrome resembles peliosis hepatis, a rare human condition that is encountered in the setting of advanced malignancies, high-dose androgen therapy, and Bartonella henselae infection. Thus, our findings in the mouse have suggested an etiologic role for VEGF in this disease and may lead to diagnostic and therapeutic options for this debilitating condition in humans.

Animals↗
PubMed2001

The stress- and abscisic acid-induced barley gene HVA22: developmental regulation and homologues in diverse organisms.

Abscisic acid (ABA) induces the expression of a battery of genes in mediating plant responses to environmental stresses. Here we report one of the early ABA-inducible genes in barley (Hordeum vulgare L.), HVA22, which shares little homology with other ABA-responsive genes such as LEA (late embryogenesis-abundant) and RAB (responsive to ABA) genes. In grains, the expression of HVA22 gene appears to be correlated with the dormancy status. The level of HVA22 mRNA increases during grain development, and declines to an undetectable level within 12 h after imbibition of non-dormant grains. In contrast, the HVA22 mRNA level remains high in dormant grains even after five days of imbibition. Treatment of dormant grains with gibberellin (GA) effectively breaks dormancy with a concomitant decline of the level of HVA22 mRNA. The expression of HVA22 appears to be tissue-specific with the level of its mRNA readily detectable in aleurone layers and embryos, yet undetectable in the starchy endosperm. The expression of HVA22 in vegetative tissues can be induced by ABA and environmental stresses, such as cold and drought. Apparent homologues of this barley gene are found in phylogenetically divergent eukaryotic organisms, including cereals, Arabidopsis, Caenorhabditis elegans, man, mouse and yeast, but not in any prokaryotes. Interestingly, similar to barley HVA22, the yeast homologue is also stress-inducible. These observations suggest that the HVA22 and its homologues encode a highly conserved stress-inducible protein which may play an important role in protecting cells from damage under stress conditions in many eukaryotic organisms.

Abscisic Acid↗
PubMed2001

Selective stimulation of smaller nerve fibers using biphasic rectangular pulses.

Based on the F-H model, a simulation system to study the excitation properties of myelinated nerve fibers was developed. In order to minimize electrochemical damage of nerve tissue, three selective stimulation methods employing biphasic rectangular pulses were studied, which use single, double and triple electrodes, respectively. The simulation results prove that all of the three methods are effective in selective stimulation of smaller nerve fibers in a compound nerve trunk under certain conditions. The feasibility of these methods is also verified by animal experiments on the sciatic nerve trunks of toads. The amplitude and delay of compound action potential and the results of collision experiments proved that the methods are valid. These methods will be very useful in functional neuromuscular stimulation.

Animals↗
PubMed2001

[Effect of Cordyceps militaris on the damage of rats induced by n-hexane].

Acutely inhaling n-hexane model was adopted to study the effect of Cordyceps militaris and the damage induced by n-hexane. The results showed that Cordyceps militaris was effective on the resisting lipid peroxidation. The results also showed that acutely inhaling n-hexane could lead to or enhance the damage reaction of oxygen free radicals, which could lead to injure of lipid peroxidation. That may be one of the mechanism of n-hexane toxicity effect on living things.

Administration, Inhalation↗
PubMed2000

Dimerization interfaces of v-erbA homodimers and heterodimers with retinoid X receptor alpha.

The oncoprotein v-ErbA, a member of the zinc finger transcription factor superfamily, is a mutated version of thyroid hormone receptor alpha1 that is virtually incapable of binding T3. v-ErbA and other members of this family can bind as homodimers and heterodimers with retinoid X receptors to specific DNA sequences arranged as direct, inverted, or everted repeats. At least two regions in the C-terminal domain, the I box (10 and 11 helices in v-ErbA and thyroid hormone receptors) and the 20-amino acid region are involved in dimerization. However, it has not been entirely understood how these receptors dimerize on differently oriented core motifs and whether the domain(s) responsible for homodimerization and heterodimerization are identical. Therefore, deletions of the entire 20-amino acid region, the 10 helix, the 11 helix, and point mutations within these regions of v-ErbA were made by site-directed mutagenesis. The mutant proteins were tested for their ability to form v-ErbA homodimers and heterodimers with retinoid X receptor alpha on differently oriented core motifs by electrophoretic mobility shift assay. Transient transfections were performed to determine the dominant negative activity of the v-ErbA mutants. The data indicate that different dimerization interfaces are used for v-ErbA homodimerization and heterodimerization with retinoid X receptor alpha, and different dimerization interfaces are used on differently oriented core motifs. The data are of general interest because the information improves our understanding of the role of these dimerization interfaces in the mechanism of action not only of v-ErbA but also of other members of the superfamily.

Amino Acid Sequence↗
PubMed2000

In vitro studies on L-771,688 (SNAP 6383), a new potent and selective alpha1A-adrenoceptor antagonist.

L-771,688 (SNAP 6383, methyl(4S)-4-(3, 4-difluorophenyl)-6-[(methyloxy)methyl]-2-oxo-3-[(¿3-[4-(2-pyridin yl)-1-piperidinyl]propyl¿amino)carbonyl]-1,2,3, 4-tetrahydro-5-pyrimidine carboxylate) had high affinity (Ki less than or = 1 nM) for [3H]prazosin binding to cloned human, rat and dog alpha1A-adrenoceptors and high selectivity (>500-fold) over alpha1B and alpha1D-adrenoceptors. [3H]Prazosin / (+/-)-beta-[125I]-4-hydroxy-phenyl)-ethyl-aminomethylteralone ([125I]HEAT) binding studies in human and animal tissues known to contain alpha1A and non-alpha1A-adrenoceptors further demonstrated the potency and alpha1A-subtype selectivity of L-771,688. [3H]L-771,688 binding studies at the cloned human alpha1A-adrenoceptors and in rat tissues indicated that specific [3H]L-771,688 binding was saturable and of high affinity (Kd=43-90 pM) and represented binding to the pharmacologically relevant alpha1A-adrenoceptors. L-771,688 antagonized norepinephrine-induced inositol-phosphate responses in cloned human alpha1A-adrenoceptors, as well as phenylephrine or A-61603 (N-[5-4,5-dihydro-1H-imidazol-2yl)-2-hydroxy-5,6,7, 8-terahydro-naphthlen-1-yl] methanesulfonamide hydrobromide) induced contraction in isolated rat, dog and human prostate, human and monkey bladder neck and rat caudal artery with apparent Kb values of 0.02-0.28 nM. In contrast, the contraction of rat aorta induced by norepinephrine was resistant to L-771,688. These data indicate that L-771,688 is a highly selective alpha1A-adrenoceptor antagonist.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2000

Synthesis and evaluation of furo[3,4-d]pyrimidinones as selective alpha1a-adrenergic receptor antagonists.

Furo[3,4-d]pyrimidinones were found to be metabolites of dihydropyrimidinones such as 1a-b that are subtype-selective antagonists of the alpha1a-adrenergic receptor. A versatile synthesis that provides access to furo[3,4-d]pyrimidinones in high yield and in enantiomerically pure forms is described along with structure-activity relationships in the series.

Adrenergic alpha-Antagonists↗
PubMed2000

Recognition and binding of the human selenocysteine insertion sequence by nucleolin.

Prokaryotic and eukaryotic cells cotranslationally incorporate the unusual amino acid selenocysteine at a UGA codon, which conventionally serves as a termination signal. Translation of selenoprotein gene transcripts in eukaryotes depends upon a "selenocysteine insertion sequence" in the 3'-untranslated region. We have previously shown that DNA-binding protein B specifically binds this sequence element. We now report the identification of nucleolin as a partner in the selenoprotein translation complex. In RNA electromobility shift assays, nucleolin binds the selenocysteine insertion sequence from the human cellular glutathione peroxidase gene, competes with binding activity from COS cells, and shows diminished affinity for probes with mutations in functionally important, conserved sequence elements. Antibody to nucleolin interferes with the gel shift activity of COS cell extract. Antibody to DNA-binding protein B co-extracts nucleolin from HeLa cell cytosol, and the two proteins co-sediment in glycerol gradient fractions of ribosomal high salt extracts. Thus, nucleolin appears to join DNA-binding protein B and possibly other partners to form a large complex that links the selenocysteine insertion sequence in the 3'-untranslated region to other elements in the coding region and ribosome to translate the UGA "stop" codon as selenocysteine.

Amino Acid Sequence↗
PubMed2000

Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy.

The present study investigates intracellular enzymatic pathways involved in the elimination of reactive oxygen species in the left ventricular myocardium of 10 individuals without heart failure and 12 patients with end-stage heart failure due to idiopathic dilated cardiomyopathy. Left ventricular enzyme activities, mRNA and protein levels of the hydrogen peroxide scavenging enzymes catalase (CAT) and glutathione peroxidase (GPX), and the superoxide anion scavenging enzymes mitochondrial (Mn-SOD) and cytosolic (Cu/Zn-SOD) superoxide dismutases were measured. In failing myocardium, there was a significant decrease in CAT activity (4.83+/-0.32 U/mg v 6.59+/-0.52, P<0.01) despite unchanged mRNA expression and protein levels. GPX, Mn-SOD and Cu/Zn-SOD were similar concerning activity, mRNA and protein levels. As indirect free radical markers, similar levels of the products of lipid peroxidation, malondialdehyde and 4-hydroxy-alkenals, and similar tissue nitrotyrosin content were measured. The decrease in CAT activity appears to be a post-transcriptional mechanism. A decreased myocardial capacity to scavenge hydrogen peroxide might lead to a shift in the intracellular redox balance which potentially results in activation of redox sensitive signalling pathways. Direct reactive oxygen species mediated damage was not detected by the methods applied.

Antioxidants↗
PubMed2000

Treatment services received by supplemental security income drug and alcoholic clients.

This study examined self reported problems and treatment services received by 237 recipients of Supplemental Security Income (SSI) benefits for "drug abusers and alcoholics" who had been assigned and entered into substance abuse treatment. All were administered the Treatment Services Review (TSR), a brief interview in which patients describe treatment services they have received during the past month and substance-related problems they are currently experiencing. In addition to describing serious alcohol and drug problems, SSI recipients reported a need for treatment for medical and psychiatric problems. The TSR data revealed that these clients primarily received drug and alcohol services and more limited medical, psychiatric, and employment services during treatment. There was relatively little indication of the provision of legal or family/social treatment services. The data are consistent with other findings that indicate that treatment for substance dependence provides only limited services other than those for alcohol and drug abuse.

Adult↗
PubMed2000

Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells.

Multipotent stem cells that generate both neurons and glia are widespread components of the early neuroepithelium. During CNS development, neurogenesis largely precedes gliogenesis: how is this timing achieved? Using clonal cell culture combined with long-term time-lapse video microscopy, we show that isolated stem cells from the embryonic mouse cerebral cortex exhibit a distinct order of cell-type production: neuroblasts first and glioblasts later. This is accompanied by changes in their capacity to make neurons versus glia and in their response to the mitogen EGF. Hence, multipotent stem cells alter their properties over time and undergo distinct phases of development that play a key role in scheduling production of diverse CNS cells.

Animals↗
PubMed2000

Liposome associated interferon-alpha-2b functions as an anti-fibrogenic factor in dermal wounds in the guinea pig.

We have previously reported that interferon-alpha-2b (IFN-alpha-2b) can be encapsulated in liposomes without compromising its anti-fibrogenic effects on dermal fibroblasts in vitro. This study was conducted to determine whether this preparation applied topically to guinea pig wounds can affect their healing. The rationale for this approach is that systemic administration of IFN-alpha-2b by injection for treatment of dermal fibrosis is uncomfortable, requires a large quantity of the cytokine and cannot be easily used in children. Liposomes are potentially useful vehicles for the topical delivery of drugs. Empty sonicated liposome vesicles were mixed with various concentrations of IFN-alpha-2b and then dried and rehydrated. An enzyme-linked immunosorbent assay (ELISA) was used to determine the efficiency of encapsulation and the stability of the preparation under experimental conditions. A total of 36 full thickness skin wounds (6/animal, 3 on each side) were made with an 8 mm disposable punch. Each wound on the right side received cream (100 mg/wound) containing 3000 units of liposome-encapsulated IFN-alpha-2b, while wounds on the left side received cream containing empty liposomes. There was a significant reduction in rate of contraction of wounds treated with IFN-alpha-2b as early as 5 days after wounding. This reduction remained significant up to 10 days. Northern analysis, used to evaluate the expression of mRNAs for type I and type III collagens in response to IFN-alpha-2b showed a marked reduction in abundance of the transcripts for the pro-alpha1(I) chain of type 1 collagen on days 11 and 14 after wounding. Similarly, the level of mRNA for type III procollagen was markedly reduced as early as day 7 and remained depressed up to day 14. These findings were consistent with results obtained for the total collagen content in tissue samples. Cellularity of the IFN-alpha-2b-treated wounds, assessed by vimentin content, was also markedly reduced at day 7 and remained depressed up to day 14. Liposome associated IFN-alpha-2b applied 5 days after completion of epithelialization reduced mRNA for the pro-alpha1(I) chain of type 1 collagen, confirming its transepidermal penetration and effectiveness. The activity of liposome-associated IFN-alpha-2b in vivo supports the concept of the topical use of this anti-fibrogenic agent for treatment of fibroproliferative disorders.

Administration, Cutaneous↗
PubMed2000

Human papillomavirus involvement in esophageal carcinogenesis in the high-incidence area of China. A study of 700 cases by screening and type-specific in situ hybridization.

BACKGROUND: Human papillomavirus (HPV) DNA has been identified in esophageal precancerous lesions and carcinomas. However, there are marked variations in the prevalence of HPV infection reported in different studies. Most previous studies on HPV and esophageal carcinomas have been based on a limited number of biopsy samples studied by different HPV detection methods with highly variable sensitivity and specificity, making systematic studies of larger series clearly warranted. METHODS: A series of 1876 surgical specimens (primary tumor, adjacent epithelium, regional lymph nodes, resection margins) from 700 patients surgically resected for an invasive squamous cell carcinoma of the esophagus in the high-incidence area of China was analyzed for the presence of HPV DNA with screening in situ hybridization (ISH) using biotinylated HPV DNA probes and followed by type-specific ISH for HPV 6, 11, 16, 18, 30, and 53. RESULTS: Of the 700 esophageal carcinomas, 118 (16.9%) were shown to contain HPV DNA sequences by screening ISH. Positive signals were most frequent in the cancer cells (16.6%), more rare in the surrounding hyperplastic and dysplastic epithelia (5.6%), and infrequently present in the resection margins (0.2%). HPV signals were also detected in cancer cells in 6.9% of the lymph node metastases. HPV types 6, 11, 16, 18, and 30 account for 39.8% of the HPV-positive lesions, of which the high-risk types HPV 16 and 18 were present in 27.1% (32 of 118). Notably, 60.2% of the HPV-positive lesions contained DNA sequences other than HPV types 6, 11, 16, 18, 30, and 53. CONCLUSIONS: This study reports the largest series of esophageal cancers ever analyzed for the presence of HPV DNA. Our results confirm the presence of common mucosal HPV types in esophageal carcinomas but also suggest the involvement of other (novel?) HPV types that are unusually detected in genital cancers in a significant proportion of these lesions. The results further indicate that HVP has an etiologic role in esophageal carcinogenesis, at least in the high-incidence area of northern China.

Biopsy↗
PubMed2000

Brainstem-evoked muscle potentials: their prognostic value in experimental spinal cord injury in the rat.

Recording myoelectric motor-evoked potentials is frequently used as an in vivo evaluation technique in experimental studies of spinal cord injury (SCI). The aim of the present study was to determine whether specific neuronal pathways conduct these potentials. Stainless steel screws were permanently implanted into the cranium of 18 rats for stimulation of brainstem-evoked muscle potentials (B-MPs). Twelve rats were subjected to spinal cord lesions that restricted the continuity of the spinal cord to different discrete sections of the lateral and/or ventral white matter (WM) of the left hemicord. Sham rats (n = 6) were subjected to laminectomy only. Left hind limb B-MPs and motor function (open field walking test) were recorded before surgery and weekly thereafter for six consecutive weeks. Motor function was severely affected by SCI in all rats but recovered significantly during the first 14 postoperative days. The degree of functional recovery depended not only on the amount of spared WM but also on the particular section of WM that had been spared. In contrast, B-MP amplitudes also were severely reduced by SCI, but did not recover during the survival period. Moreover, B-MP amplitudes correlated only weakly with the amount of sparedWM and were not influenced by which section ofWM had been spared. While functional recovery correlated significantly with the amount of spared WM, no correlation was found between B-MP amplitudes and functional recovery. B-MP conduction velocities were not affected by SCI. It is therefore believed that B-MPs have little prognostic value for experimental studies of SCI in the rat.

Analysis of Variance↗