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Biomedical subjects

Y Qu

Publications and source records attributed to Y Qu.

135 records · Page 8Linked to original sources
PubMed1986

A model study on mode of bonding of cisplatin with DNA.

The interaction of cis-[Pt(NH3)2Cl2] with nucleosides, as constituents of DNA, was studied by spectrophotometric, 13C NMR and CNDO/2 methods. The apparent stability constants of the complexes formed and the initial rate of formation were determined. The sites of binding of nucleoside (or nucleotide) with Cisplatin were ascertained and the electronic structure of the model coordination compounds of Cisplatin and guanine was calculated by MO approach. On the basis of the obtained results, the mechanism of the antitumour action of Cisplatin was discussed, and a new possible mode of bonding of Cisplatin with DNA was proposed.

Binding Sites↗
PubMedDate not supplied

Platelet I1-imidazoline binding sites are elevated in depression but not generalized anxiety disorder.

Depressed patients have been reported to have a higher than normal density of platelet binding sites for 3H-clonidine, an alpha 2-adrenoceptor agonist. Paradoxically, other studies using 3H-alpha 2, antagonists have found no differences from controls. Because 3H-clonidine interacts with platelet alpha 2-adrenoceptors to form G-protein complexes, whereas 3H-alpha 2-antagonists bind with uncoupled receptors, an elevation in G-protein coupling might explain this paradox. Another possibility is that depression might be associated with increased non-adrenergic I1-imidazoline binding sites, which are also clonidine sensitive. To distinguish these possibilities, we utilized p125I-clonidine to measure density (Bmax) and affinity (KD) of platelet G-protein coupled alpha 2-adrenoceptors as well as platelet I1 binding sites, and compared diagnostic groups of major depressive disorder (MDD), generalized anxiety disorder (GAD) and healthy subjects. Specific inhibition of binding by norepinephrine (NE = 10 microM) was used to selectively quantify alpha 2-adrenoceptors, whereas inhibition by 10 microM moxonidine (a > 100-fold selective I1 ligand) quantified I1 binding sites under a NE mask. I1 sites were found to be markedly elevated by, on average, +136% in MDD patients (p = .0007), whereas there was only a marginal increase in alpha 2-adrenoceptor Bmax values in MDD patients (p = .08; GAD and healthy subjects did not differ). Treatment of MDD patients for 6-8 weeks with desipramine downregulated I1 sites as well as alpha 2-adrenoceptors. Positive correlations were also noted for both sites: (a) between Bmax values and the severity of depression (using the Hamilton Depression Rating Scale); and (b) between end-of-treatment plasma desipramine concentrations and the extent of downregulation in Bmax values when subject groups were pooled. None of the binding parameters was associated with plasma catecholamine concentrations. The results suggest that an increased density of platelet I1 binding sites may partially explain the utility of radiolabeled clonidine as a potential biological marker for depressive illness, although an additional increase in G-protein coupling cannot be excluded.

Adult↗
PubMedDate not supplied

Platelet I1-imidazoline binding sites are decreased by two dissimilar antidepressant agents in depressed patients.

Previous studies have indicated that there may be a dysregulation of alpha 2-adrenoceptors and imidazoline receptors in depression. This study compares the effects of chronic antidepressant treatment with a serotonin reuptake inhibitor (fluoxetine) versus a noradrenaline reuptake inhibitor (desipramine) on the binding parameters of the platelet imidazoline binding site (subtype I1) and of the platelet alpha 2-adrenoceptor in depressed patients. After 6 weeks of treatment with either antidepressant, platelet I1 binding sites became normalized (i.e. downregulated). A negative correlation was obtained between plasma epinephrine concentrations and platelet alpha 2-adrenoceptor Bmax values within the samples, but no correlation was obtained between any plasma catecholamine and a platelet I1 binding parameter. An additional finding was the increased affinity of alpha 2-adrenoceptors for p125I-clonidine in untreated depressed patients compared to healthy subjects. Because of the density of platelet I1 binding sites was downregulated by both of the antidepressants, we postulate that a decrease in platelet I1 binding site density may be related to an improved state from depression that these antidepressants produce.

Adrenergic Uptake Inhibitors↗
PubMedDate not supplied

Technical pitfalls encountered in PCR quantification using microsatellites.

Quantitative PCR has proved useful for different purposes, including the detection of particular genetic changes, such as deletions and duplications in several inherited disorders. Using patients with the known duplication mutation for Charcot-Marie-Tooth disease Type 1A as examples, the importance of selecting informative microsatellite loci and proper electrophoretic conditions so as to eliminate potential sources of error in quantitative PCR studies is discussed.

Alleles↗
PubMedDate not supplied

Arylsulfatase A pseudodeficiency: altered kinetic and heat-inactivation properties.

Arylsulfatase A (ASA) pseudodeficiency (PD) was described in clinically healthy individuals with ASA-deficient activity. To confirm that the PD individual in the present study is homozygous for the PD allele without any other mutations, direct solid-phase sequencing was done and the two A-to-G transitions--one at the third N-glycosylation site (N350S) and the other at the first polyadenylation signal (ATTAAC to AGTAAC)--were identified. No other mutations were detected in the entire coding region nor in the intron-exon boundary region of the ASA gene in the PD cells. Kinetic studies to compare the partially purified ASA from controls to that from a homozygote (PD allele) were carried out using p-nitrocatechol sulfate (p-NCS) as a substrate. The apparent Km for the control ASA was 0.6 mM and for the PD enzyme 2.0 mM (p < 0.01). The heat inactivation at 60 degrees C revealed 50% inactivation within 90 min for control ASA and 28 min for PD ASA. At 65 degrees C, the 50% inactivation was reached at 18 min for the control and at 8.5 min for the PD. These results document the decreased affinity of ASA toward p-NCS and increased heat inactivation from a PD individual. Western blot analysis following SDS-PAGE and isoelectric focusing revealed differences in both the molecular weight and the isoelectric point between the control ASA and that of the PD allele. To the best of our knowledge, this is the first report showing the altered properties of ASA from a PD homozygote.

Alleles↗
PubMedDate not supplied

3D MRI of the cervical spine: low flip angle FISP vs. Gd-DTPA TurboFLASH in degenerative disk disease.

The authors undertook this study to compare bright and dark CSF three-dimensional (3D) gradient-echo (GE) MR techniques to answer the following questions: Could a single Gd-DTPA enhanced T1-weighted GE volume sequence (with multiplanar reformats) be diagnostically equivalent for degenerative cervical disk disease to a standard sequence consisting of sagittal T1-weighted spin echo and axial low flip angle volume GE images (with reformatted images)? Does performing oblique coronal reformats perpendicular to the course of exiting cervical nerve roots improve diagnostic confidence over axial images alone? Thirty-one consecutive patients received a "routine" MR examination consisting of a sagittal T1-weighted spin echo and axial low flip angle volume sequence (FISP) [(35/7/5), 64 slices, 2 mm slice thickness, 192 x 256 matrix, 7.2 min]. Each patient was then given 0.1 mmol/kg Gd-DTPA intravenously, and reimaged with a T1-weighted volume GE sequence [(13/6/12), acquired as 128-1.2 mm coronal partitions, 192 x 256 matrix, 5.5 min]. Sequences were reconstructed on the standard diagnostic console in 1 mm increments. Sets of examinations (routine vs T1-weighted volume) were independently interpreted by three neuroradiologists for location, type, and severity of extradural degenerative disease. There was no strong or consistent trend for increased detection of disease by one imaging sequence over the other. For lateral disk disease, only 3% of the observations were in discordance. For disk disease, there was close agreement in the severity scores. All readers indicated that additional information was provided by the reformatted images more frequently with TurboFLASH (fast low angle shot) than with FISP. All readers indicated that increased confidence was provided by the reformatted images more frequently with TurboFLASH than with FISP. A single 3D contrast-enhanced TurboFLASH sequence is diagnostically equivalent to a set of two-dimensional T1-weighted sagittal spin echo and 3D axial low flip angle sequences for assessing the location and degree of cervical extradural degenerative disease. A screening examination of the cervical spine could be performed with a single contrast-enhanced 5.2 min study, and then relying on computer postprocessing to provide additional imaging planes.

Cervical Vertebrae↗