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Biomedical subjects

Y Gu

Publications and source records attributed to Y Gu.

At least 37 records · Page 2Linked to original sources
PubMed2005

Comparisons between oral pulse alfacalcidol therapy and daily therapy in maintenance hemodialysis patients with secondary hyperparathyroidism: a randomized, controlled, and multicenter study.

OBJECTIVE: To investigate the efficacy and safety of 1alpha-(OH)-D3 high-dose pulse therapy or daily low-dose therapy in secondary hyperthyroidism in maintenance hemodialysis patients in China. METHODS: Maintenance hemodialysis patients of both gender with intact parathyroid hormone (iPTH) level above 200 pg/mL were randomly divided into a pulse group and a daily group. They were treated for 20 weeks, with 2 microg oral Alfacalcidol twice weekly or thrice weekly in the pulse group, and 0.5 microg oral Alfacalcidol per day in the daily group. The therapeutic end point was parathyroid hormone level < 200 pg/ mL. The iPTH levels during the study were monitored, and parameters representative of calcium and phosphate metabolism and side effects were also observed. RESULTS: One hundred and fifty-eight patients were initially enrolled, 91 in the pulse therapy group and 67 in the daily therapy group. There was no significant difference in age, hemodialysis duration, proportion of diabetic nephropathy and systemic diseases, proportion of patients who had received active vitamin D therapy previously, mean initial iPTH level (pulse group 570.47 +/- 295.86 pg/mL; daily group 498.33 +/- 207.84 pg/mL), serum calcium, serum phosphate, alkaline phosphatase (AKP), and albumin between two groups. In the pulse therapy group there were more patients with iPTH levels of 500 to approximately 1,000 pg/mL and > 1,000 pg/mL, so stratified analysis according to iPTH level was used. In therapeutic end point, iPTH levels in both groups were significantly lower compared with those before therapy (pulse group 261.29 +/- 234.97 pg/mL, P < .01; daily group 262.17 +/- 274.82 pg/mL, P < .01). After 4 weeks, the ratio of reaching end point in the pulse group was 35.2%, which was significantly higher than that (19.4%) in the daily group (P < .05). More obvious change was seen in the 200 to approximately 500 pg/mL subgroup by stratified analysis (P < .05), whereas there was no significant difference between the 500 to approximately 1,000 pg/mL and > 1,000 pg/mL subgroup (P > .05). At therapeutic end point, the total ratio of reaching end point did not differ between the two groups, and there were no obvious differences between each subgroup. In the iPTH 200 to approximately 500 pg/mL subgroup, mean iPTH%/week in the pulse group was significantly higher than that in the daily group, and no obvious difference was seen in other subgroups. AKP levels decreased significantly in both groups at therapeutic end point (pulse group 98.42 +/- 54.52 vs. 74.21 +/- 30.68 IU/L, P < .01; daily group 103.3 +/- 68.04 vs. 75.40 +/- 34.12 IU/L, P < .01). On the 4th week, AKP level in pulse group (82.39 +/- 35.23 IU/L) was significantly lower than the initial level (98.42 +/- 54.52 IU/L, P < .05), whereas in the daily group there was no difference between each week. The mean serum calcium, phosphate, and [Ca2+] x [P3+] levels in both groups did not change greatly. Nine patients in the pulse group (9.9%) and 8 patients in the daily group (11.9%) suffered hypercalcemia at least once. Persistent hypercalcemia occurred in 8 patients in the pulse group (8.8%) and 9 patients in the daily group (13.4%), but the difference in proportion did not show statistical significance. The serum phosphate in the daily group was higher after the therapy (1.74 +/- 0.36 vs. 1.89 +/- 0.36 mmol/L, P < .05), whereas that in the pulse group remained unchanged. At therapeutic end point, [Ca2+] x [P3+] level in the daily group was higher than that before the therapy (48.04 +/- 11.71 vs. 55.46 +/- 12.66, P < .05), whereas in the pulse group there was no significant difference. Side effects for both groups were minimal and well tolerated. CONCLUSIONS: Alfacalcidol [1alpha-(OH)-D3] has good and safe effects on secondary hyperparathyroidism in maintenance hemodialysis patients. The efficacy and early effects of pulse therapy are superior to those of daily therapy in moderate hyperparathyroidism patients.

Administration, Oral↗
PubMed2004

Multi-state, 4-aminopyridine-sensitive ion channels in human spermatozoa.

Although ion channels are known to be pivotal to sperm function, the technical difficulty of applying electrophysiological techniques to spermatozoa has prevented significant progress in this area. This is due to the cell size and angular shape in combination with their motility. Using a refined technique, specifically for patch clamping spermatozoa, we have made recordings from human cells. This technique permitted approaches which enable functional analysis of sperm ion channels, including acquisition of inside-out patches, generation of averaged currents, and observation of the effects of pharmacological manipulation during prolonged recordings. As well as a low conductance (7 pS) channel and a 25-pS channel, the most striking finding was the presence of very high conductance, 4-aminopyridine-sensitive multistate channels resembling the non-selective cation channel of sea urchin and mouse spermatozoa. Application of 2 mM 4-aminopyridine (a dose sufficient to cause channel blockade) caused an instant and dramatic transition of motility in the sperm population increasing hyperactivated motility by more than 10-fold as assessed by computer-assisted semen analysis. Combined application of patch clamp and pharmacological investigation of mature sperm cells and will permit rapid advances in our understanding the role of ion channels in sperm function.

4-Aminopyridine↗
PubMed2004

Quantitative fluorescence resonance energy transfer (FRET) measurement with acceptor photobleaching and spectral unmixing.

Fluorescence resonance energy transfer (FRET) by acceptor photobleaching is a simple but effective tool for measurements of protein-protein interactions. Until recently, it has been restricted to qualitative or relative assessments owing to the spectral bleed-through contamination resulting from fluorescence overlap between the donor and the acceptor. In this paper, we report a quantitative algorithm that combines the spectral unmixing technique with FRET by acceptor photobleaching. By spectrally unmixing the emissions before and after photobleaching, it is possible to resolve the spectral bleed-through and retrieve the FRET efficiency/interaction distance quantitatively. Using a human keratinocyte cell line transfected with cyan fluorescent protein (CFP)- and yellow fluorescent protein (YFP)-tagged Cx26 connexins as an example, FRET information at homotypic gap junctions is measured and compared with well-established methods. Results indicate that the new approach is sensitive, flexible, instrument independent and solely FRET dependent. It can achieve FRET estimations similar to that from a sensitized emission FRET method. This approach has a great advantage in providing the relative concentrations of the donor and the acceptor; this is, for example, very important in the comparative study of cell populations with variable expression levels.

Algorithms↗
PubMed2003

Construction and characterization of a half million clone BAC library of durum wheat ( Triticum turgidum ssp. durum).

Durum wheat ( Triticum turgidum ssp. durum, 2 n = 4 x = 28, genomes AB) is an economically important cereal used as the raw material to make pasta and semolina. In this paper we present the construction and characterization of a bacterial artificial chromosome (BAC) library of tetraploid durum wheat cv. Langdon. This variety was selected because of the availability of substitution lines that facilitate the assignment of BACs to the A and B genome. The selected Langdon line has a 30-cM segment of chromosome 6BS from T. turgidum ssp. dicoccoides carrying a gene for high grain protein content, the target of a positional cloning effort in our laboratory. A total of 516,096 clones were organized in 1,344 384-well plates and blotted on 28 high-density filters. Ninety-eight percent of these clones had wheat DNA inserts (0.3% chloroplast DNA, 1.4% empty clones and 0.3% empty wells). The average insert size of 500 randomly selected BAC clones was 131 kb, resulting in a coverage of 5.1-fold genome equivalents for each of the two genomes, and a 99.4% probability of recovering any gene from each of the two genomes of durum wheat. Six known copy-number probes were used to validate this theoretical coverage and gave an estimated coverage of 5.8-fold genome equivalents. Screening of the library with 11 probes related to grain storage proteins and starch biosynthesis showed that the library contains several clones for each of these genes, confirming the value of the library in characterizing the organization of these important gene families. In addition, characterization of fingerprints from colinear BACs from the A and B genomes showed a large differentiation between the A and B genomes. This library will be a useful tool for evolutionary studies in one of the best characterized polyploid systems and a source of valuable genes for wheat. Clones and high-density filters can be requested at http://agronomy.ucdavis.edu/Dubcovsky/BAC-library/BAC_Langdon.htm

Chromosomes, Artificial, Bacterial↗
PubMed2003

Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons: a strategy to increase opioid antinociception.

To develop a genetic approach for the treatment of pain, we introduced a recombinant adeno-associated viral (rAAV) vector containing the cDNA for the mu-opioid receptor (muOR) into primary afferent neurons in dorsal root ganglia (DRGs) of rats, which resulted in a long-lasting (>6 months) increase in muOR expression in DRG neurons. The increase greatly potentiated the antinociceptive effects of morphine in rAAV-muOR-infected rats with and without inflammation. Perforated patch recordings indicated that the efficacy and potency of opioid inhibition of voltage-dependent Ca(2+) channels were enhanced in infected neurons, which may underlie the increase in opiate efficacy. These data suggest that transfer of opioid receptor genes into DRG cells with rAAV vectors may offer a new therapeutic strategy for pain management.

Animals↗
PubMed2003

Synthesis and SAR of bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors.

Potent and selective bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors were synthesized by a novel convergent route. Selectivity and efficacy versus MMPs and TACE could be controlled by appropriate substitution on the scaffolds and by variation of the P1' group. Select compounds were found to be effective in in vivo models of arthritis.

ADAM Proteins↗
PubMed2003

Fourier-transform Raman and infrared spectroscopic analysis of 2-nitro-tetraphenylporphyrin and metallo-2-nitro-tetraphenylporphyrins.

The Fourier-transform Raman (FT-Raman) and infrared (FT-IR) spectra of 2-nitro-tetraphenylporphyrin (2-NO(2)-TPP), nickel-2-nitro-tetraphenylporphyrin (Ni-2-NO(2)-TPP), zinc-2-nitro-tetraphenylporphyrin (Zn-2-NO(2)-TPP) and copper-2-nitro-tetraphenylporphyrin (Cu-2-NO(2)-TPP) were acquired for the first time and carefully assigned and discussed. The effects of a beta-NO(2) group and the influence of the central metal on the molecular symmetry and vibrational spectra of the porphyrin macrocycle were also examined. The bands at 1323-1339, 1516-1526 and 961-971 cm(-1) were attributed to the symmetric and asymmetric stretching vibration of the NO(2) group and to the stretching vibration of the C(beta)-N bond, respectively, which connects the NO(2) group with the beta-carbon of the porphyrin macrocycle. These bands can act as a marker to distinguish beta-NO(2) TPPs from other beta-substituent TPPs. Cu-2-NO(2)-TPP has a C(4nu) molecular symmetry, which is different from those of Ni-2-NO(2)-TPP and Zn-2-NO(2)-TPP, i.e. D(4h).

Organometallic Compounds↗
PubMed2003

In vivo high-efficiency transcoronary gene delivery and Cre-LoxP gene switching in the adult mouse heart.

High-efficiency somatic gene transfer in adult mouse heart has not yet been achieved in vivo. Here, we demonstrate high-efficiency in vivo transcoronary gene delivery to the adult murine myocardium using a catheter-based technique with recombinant adenovirus (AdV) and adeno-associated virus (AAV) vectors in normal and genetically engineered mice. The method involves immersion hypothermia followed by transient aortic and pulmonary artery occlusion with proximal intra-aortic segmental injection of cardioplegic solution containing substance P and viral vectors. Gene expression measured using a LacZ marker gene was observed throughout both ventricles. The expression efficiency of a cytoplasmic LacZ marker gene in the left ventricular myocardium was 56.4+/-14.5% (mean+/-s.d.) at 4 days with an AdV vector, and with an AAV vector it was 81.0+/-5.9% at 4 weeks. Following AAV gene transfer, no gene expression was found in kidney, brain, lung, and spleen, but there was slight expression in liver. In addition, we demonstrate temporally controlled genetic manipulation in the heart with an efficiency of 54.6+/-5.2%, by transferring an AdV vector carrying Cre recombinase in ROSA26 flox-LacZ reporter mice. Procedure-related mortality was 16% for AdV and zero for AAV transfer. Thus, this method provides efficient, relatively homogeneous gene expression in both ventricles of the adult mouse heart, and offers a novel approach for conditional gene rescue or ablation in genetically engineered mouse models.

Adenoviridae↗
PubMed2003

Photodynamic therapy of esophageal varices: experimental studies in animal veins, and first clinical cases.

BACKGROUND AND STUDY AIMS: Endoscopic injection sclerotherapy and endoscopic variceal ligation have been found to have shortcomings in the treatment of esophageal varices. In this study the effectiveness of photodynamic therapy (PDT) in the obliteration of veins was investigated to evaluate its potential in the treatment of esophageal varices. METHODS: Auricular margin veins of rabbits were irradiated by copper vapor laser after intravenous injection of 10 mg/kg of hematoporphyrin monomethyl ether (which is a hematoporphyrin derivative) into the rabbits. Control groups included rabbits that received irradiation only, that received injection of photosensitizer only, and that received injection sclerotherapy (using sodium morrhuate). The treated areas were observed macroscopically and also identified using with ultrasonic miniprobe. Biopsies were performed and the specimens were examined microscopically after hematoxylin-eosin staining and Victoria blue staining. In addition, two patients with newly visible veins within the esophageal wall after endoscopic injection sclerotherapy underwent PDT. Intravenous injection of 5 mg/kg of hematoporphyrin monomethyl ether was given, and the newly visible veins were endoscopically irradiated by copper vapor laser. Endoscopic re-examination was performed 1 month later to evaluate the therapeutic effect. RESULTS: Thrombi of the auricular margin vein were formed and blood flow was obstructed after PDT. Thrombus formation and diffused necrosis of adjacent tissue was found after injection of sodium morrhuate. On ultrasonic examination, the lumina of the veins showed a slightly higher echo after PDT compared with a lower echo before treatment, which was another sign of thrombus formation. The rabbit ears showed a diffused low echo after injection of sodium morrhuate, indicating diffuse necrosis. On microscopic observation, destruction of the endothelium and formation of thrombus was seen after PDT. Further observation of specimens stained with Victoria blue showed that the layer of elastic fiber was intact. After injection of sodium morrhuate, extensive necrosis of tissue was seen microscopically. No macroscopic, ultrasonic, or microscopic change was found in the rabbits that received irradiation only or injection of photosensitizer only. The rate of thrombus formation in rabbits that received PDT was significantly higher than that in the rabbits that received irradiation only or injection of photosensitizor only ( P = 0.015, P = 0.015), and comparable to that in the rabbits that received sclerotherapy ( P = 0.467). In the clinical study, at endoscopy 1 month after PDT both the number and the "red sign" of newly visible veins were found to have decreased. No adverse effect was found. CONCLUSION: PDT can destroy the endothelium of the vein, result in thrombus formation, and eventually obliterate the vein. It is potentially a new method for the treatment of esophageal varices.

Animals↗
PubMed2003

FMR2 function: insight from a mouse knockout model.

The FMR2 gene is dysregulated by the fragile X E triplet repeat expansion in patients with FRAXE mental retardation syndrome. A CCG triplet, located in the 5' untranslated region of the FRAXE gene undergoes expansion and methylation in these patients, eliminating detectable gene transcription. FRAXE syndrome is distinct from fragile X syndrome, a more common genetic form of mental retardation caused by expansion and methylation of a similar repeat in the FMR1 gene located 600 kb proximal to FRAXE. FRAXE syndrome is rare, and patients' phenotypes are highly variable, leading to difficulties with predicting specific FMR2 functions based on the human disease. Recently, Lilliputian(Lilli), a Drosophila FMR2 orthologue, was identified; this gene has been linked with several signal transduction pathways, including the transforming growth factor-beta (TGF-beta) pathway, the Raf/MEK/MAP kinase (MAPK) pathway, and the P13K/PKB pathway. Mutation of Lilli shows defects in germinal band extension, cytoskeletal structure, cell growth, and organ development. The Lilli gene suggests possible functions for FMR2 (and related genes) in humans and mice, but cannot predict specific functions. Modeling FMR2 mutation in the mouse will be useful to understand specific functions of this gene in vertebrates. This review presents what has been learned thus far from the FMR2 knockout mouse model and suggests future studies on this model in order to compare it with the human FRAXE mental retardation disorder, Lilli mutants in Drosophila and other mouse models of genes in this family.

Amino Acid Sequence↗
PubMed2002

Identification of the anterior and posterior portions of the lateral pedicle cortex by roentgenograms in pedicle screw fixation.

Forty lumbar pedicles and pedicle screws in four cadavers were used to identify the anterior and posterior portions of the lumbar pedicle cortex by roentgenograms in order to evaluate the penetration of the pedicle cortex by pedicle screws intraoperatively. Firstly, the transverse pedicle angles were measured on roentgenograms. Three roentgenograms were taken on each pedicle in three different directions: (1). medial to the pedicle axis; (2). pedicle axis; (3). lateral to the pedicle axis. They revealed that the anterior portion of the lateral pedicle cortex was demonstrated by the pedicle lateral outline on the roentgenogram medial to the pedicle axis, and the posterior portion by the pedicle lateral outline on the roentgenogram lateral to the pedicle axis. Wire markers were used to confirm these data. Finally, anterior and/or posterior penetrations on the lateral pedicle cortex in pedicle screw fixation were studied by roentgenograms in these cadavers and showed that anterior penetration of lateral cortex was demonstrated by the view medial to the pedicle axis, and posterior penetration by the view lateral to the pedicle axis. It is concluded that projections medical and lateral to the pedicle axis are necessary to identify lateral screw penetration intraoperatively when X-ray checking is used.

Aged↗
PubMed2002

Statistics of level spacing of geometric resonances in random binary composites.

We study the statistics of level spacing of geometric resonances in the disordered binary networks. For a definite concentration p within the interval [0.2,0.7], numerical calculations indicate that the unfolded level spacing distribution P(t) and level number variance Sigma(2)(L) have general features. It is also shown that the short-range fluctuation P(t) and long-range spectral correlation Sigma(2)(L) lie between the profiles of the Poisson ensemble and Gaussion orthogonal ensemble. At the percolation threshold p(c), crossover behavior of functions P(t) and Sigma(2)(L) is obtained, giving the finite size scaling of mean level spacing delta and mean level number n, which obey the scaling laws, delta=1.032L(-1.952) and n=0.911L(1.970).

Journal Article↗
PubMed2002

The NMDA type glutamate receptors expressed by primary rat osteoblasts have the same electrophysiological characteristics as neuronal receptors.

Cells of mammalian bone express glutamate receptors. Functional N-methyl-D-aspartate (NMDA) receptors have been demonstrated in human, osteoblastic MG-63 cells, but currents in these cells, unlike those of mammalian neurons, are blocked by Mg(2+) in a voltage-insensitive manner. Differences between the characteristics of NMDA currents in bone cells and in neurons may reflect molecular variation of the receptors or associated molecules, with implications for the role(s) of glutamate in these different tissues and for targeting of ligands/antagonists. To determine whether NMDA receptors in primary bone cells are functional, and whether the currents carried by these receptors resemble those of MG-63 cells or those of mammalian neurons, we have applied the whole cell patch clamp technique to primary cultures of rat osteoblasts. In 0-Mg(2+) saline, 25% of cells showed a slowly developing inward current in response to bath perfusion with 1 mM or 100 microM NMDA. Antibodies against NMDA receptors stained approximately 26% of cells. When NMDA was applied by rapid superfusion, kinetics of the currents were similar to those of neuronal NMDA currents, reaching a peak within 20-30 ms. 1 mM Mg(2+) reduced current amplitude at negative holding potentials and caused the I-V relationship of the currents to adopt a 'J' shape rather than the linear relationship seen in the absence of added Mg(2+). Co-application of glycine (20 microM) with NMDA increased current amplitude by only 18%, suggesting that glycine is released from cells within the cultures. Currents were blocked by (+)-MK-801 and DL-2-amino-5-phosphonovaleric acid. Fluorimetric monitoring of [Ca(2+)](i) using fura-2 showed that, in Mg(2+)-free medium, NMDA caused a sustained rise in [Ca(2+)](i) that could be reversed by subsequent application of MK-801. We conclude that rat femoral osteoblasts express functional NMDA receptors and that these receptors differ from those previously identified in MG-63 cells. NMDA receptors of primary osteoblasts show a 'classical' voltage-sensitive Mg(2+) block, similar to that seen in neuronal NMDA receptors, and will therefore function as detectors of coincident receptor activation and membrane depolarization.

2-Amino-5-phosphonovalerate↗
PubMed2001

A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia.

KChIP2, a gene encoding three auxiliary subunits of Kv4.2 and Kv4.3, is preferentially expressed in the adult heart, and its expression is downregulated in cardiac hypertrophy. Mice deficient for KChIP2 exhibit normal cardiac structure and function but display a prolonged elevation in the ST segment on the electrocardiogram. The KChIP2(-/-) mice are highly susceptible to the induction of cardiac arrhythmias. Single-cell analysis revealed a substrate for arrhythmogenesis, including a complete absence of transient outward potassium current, I(to), and a marked increase in action potential duration. These studies demonstrate that a defect in KChIP2 is sufficient to confer a marked genetic susceptibility to arrhythmias, establishing a novel genetic pathway for ventricular tachycardia via a loss of the transmural gradient of I(to).

Action Potentials↗
PubMed2001

Crystallization and preliminary X-ray diffraction analysis of shikimate kinase from Mycobacterium tuberculosis in complex with MgADP.

Shikimate kinase (SK) from Mycobacterium tuberculosis (Mt) was overexpressed in Escherichia coli, purified and cocrystallized with MgADP in hanging drops using the vapor-diffusion procedure with PEG 4000 and 2-propanol as precipitants at pH 7.5. The crystal of MtSK-MgADP, which diffracted to 2.2 A resolution, belonged to space group P3(2)21 or P3(1)21, with unit-cell parameters a = b = 64.01, c = 92.41 A. There was one MtSK molecule in the asymmetric unit. Molecular-replacement trials with the crystal structure of SK from Erwinia chrysanthemi (PDB code 1shk) and adenylate kinase (PDB code 1ake) as search models were not successful. Heavy-atom derivative screening is in progress.

Adenosine Diphosphate↗