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Biomedical subjects

P Yip

Publications and source records attributed to P Yip.

At least 19 recordsLinked to original sources
PubMed2006

Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury.

Chondroitin sulfate proteoglycans (CSPGs) are inhibitory extracellular matrix molecules that are upregulated after CNS injury. Degradation of CSPGs using the enzyme chondroitinase ABC (ChABC) can promote functional recovery after spinal cord injury. However, the mechanisms underlying this recovery are not clear. Here we investigated the effects of ChABC treatment on promoting plasticity within the spinal cord. We found robust sprouting of both injured (corticospinal) and intact (serotonergic) descending projections as well as uninjured primary afferents after a cervical dorsal column injury and ChABC treatment. Sprouting fibers were observed in aberrant locations in degenerating white matter proximal to the injury in regions where CSPGs had been degraded. Corticospinal and serotonergic sprouting fibers were also observed in spinal gray matter at and below the level of the lesion, indicating increased innervation in the terminal regions of descending projections important for locomotion. Spinal-injured animals treated with a vehicle solution showed no significant sprouting. Interestingly, ChABC treatment in uninjured animals did not induce sprouting in any system. Thus, both denervation and CSPG degradation were required to promote sprouting within the spinal cord. We also examined potential detrimental effects of ChABC-induced plasticity. However, although primary afferent sprouting was observed after lumbar dorsal column lesions and ChABC treatment, there was no increased connectivity of nociceptive neurons or development of mechanical allodynia or thermal hyperalgesia. Thus, CSPG digestion promotes robust sprouting of spinal projections in degenerating and denervated areas of the spinal cord; compensatory sprouting of descending systems could be a key mechanism underlying functional recovery.

Animals↗
PubMed2005

Comparison of forced-air warming and radiant heating during transurethral prostatic resection under spinal anaesthesia.

Forced-air warming is commonly used to warm patients intraoperatively, but may not achieve normothermia during a short procedure. Comparative trials of a new radiant warming device in general anaesthesia (Suntouch, Fisher and Paykel, Auckland, New Zealand) have had conflicting results. We conducted a randomized controlled trial to compare the efficacy and thermal comfort of the Suntouch radiant warmer and forced-air warming in patients at high risk of hypothermia during neuraxial blockade. With ethics committee approval, 60 patients having transurethral resection of the prostate under spinal were randomized to either radiant warming or forced-air warming. All intravenous and irrigation fluids were warmed but pre-warming was not used. The final intraoperative rectal temperatures for the radiant warming and forced-air warming groups were 36.1 degrees C and 36.4 degrees C respectively (P= 0.03). A large proportion of patients in both groups (46% and 33% respectively, P=0.3) were hypothermic (<36 degrees C) on arrival in the post-anaesthesia care unit. No other patient variables were significantly different. Neither warming device reliably prevented hypothermia, although forced-air warming was slightly superior.

Aged↗
PubMed2001

Mechanisms for intragenic complementation at the human argininosuccinate lyase locus.

Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the reversible cleavage of argininosuccinate to arginine and fumarate. Deficiencies in the enzyme result in the autosomal, recessive disorder argininosuccinic aciduria. Considerable clinical and genetic heterogeneity is associated with this disorder, which is thought to be a consequence of the extensive intragenic complementation identified in patient strains. Our ability to predict genotype-phenotype relationships is hampered by the current lack of understanding of the mechanisms by which complementation can occur. The 3-dimensional structure of wild-type ASL has enabled us to propose that the complementation between two ASL active site mutant subunits, Q286R and D87G, occurs through a regeneration of functional active sites in the heteromutant protein. We have reconstructed this complementation event, both in vivo and in vitro, using recombinant proteins and have confirmed this hypothesis. The complementation events between Q286R and two nonactive site mutants, M360T and A398D, have also been characterized. The M360T and A398D substitutions have adverse effects on the thermodynamic stability of the protein. Complementation between either the M360T or the A398D mutant and the stable Q286R mutant occurs through the formation of a more stable heteromeric protein with partial recovery of catalytic activity. The detection and characterization of a novel complementation event between the A398D and D87G mutants has shown how complementation in patients with argininosuccinic aciduria may correlate with the clinical phenotype.

Alanine↗
PubMed2001

High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

We describe here a system for the rapid identification, assay development, and characterization of gene-based single nucleotide polymorphisms (SNPs). This system couples informatics tools that mine candidate SNPs from public expressed sequence tag resources and automatically designs assay reagents with detection by a chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. As a proof of concept of this system, a genomewide collection of reagents for 9,115 gene-based SNP genetic markers was rapidly developed and validated. These data provide preliminary insights into patterns of polymorphism in a genomewide collection of gene-based polymorphisms.

Alleles↗
PubMed2000

Mortality of twins and singletons by gestational age: a varying-coefficient approach.

This study used data from the Swedish Medical Birth Registry between 1982 and 1995 to address the question of whether there is higher mortality in twins in relation to singletons of the same gestational age and to examine the optimal gestational age range for twins. A "varying-coefficient approach" was adopted to estimate the gestational age-specific relative and absolute risks of mortality in twins and singletons, adjusting for size at birth and risk factors of short gestational duration. The models showed that twins born between 29 and 37 weeks of gestation had lower mortality than did singletons of the same gestational age. Twins born at older gestational age had higher mortality than did their singleton counterparts, because longer gestational duration was more advantageous to singletons than to twins. Without adjustment for size at birth, there was an upturn of mortality in twins born after 38 weeks. It is postulated that twins have better health than singletons initially, but they could not enjoy the benefit of a longer gestational duration as much as singletons could. The optimal gestational age for twins appeared to be 37-39 weeks according to neonatal and infant mortality.

Age Distribution↗
PubMed2000

Mass spectrometry of single-stranded restriction fragments captured by an undigested complementary sequence.

In this report, we describe a simple and accurate method to analyze restriction fragments using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The two complementary strands of restriction fragments are separated through hybridization to a capture probe, which is a single-stranded undigested fragment. Using the biotin-streptavidin linkage, the hybrid is immobilized on streptavidin-coated magnetic beads. After conditioning the captured restriction fragments, they are eluted from the probe and their molecular weights are determined. The proposed method greatly improves the quality, and reduces the complexity of the mass spectrum by analyzing only one of the complementary strands of restriction fragments.

Biotinylation↗
PubMed2000

Crystal structure of a class I alpha1,2-mannosidase involved in N-glycan processing and endoplasmic reticulum quality control.

Mannose trimming is not only essential for N-glycan maturation in mammalian cells but also triggers degradation of misfolded glycoproteins. The crystal structure of the class I alpha1, 2-mannosidase that trims Man(9)GlcNAc(2) to Man(8)GlcNAc(2 )isomer B in the endoplasmic reticulum of Saccharomyces cerevisiae reveals a novel (alphaalpha)(7)-barrel in which an N-glycan from one molecule extends into the barrel of an adjacent molecule, interacting with the essential acidic residues and calcium ion. The observed protein-carbohydrate interactions provide the first insight into the catalytic mechanism and specificity of this eukaryotic enzyme family and may be used to design inhibitors that prevent degradation of misfolded glycoproteins in genetic diseases.

Carbohydrate Sequence↗
PubMed1999

Anticonvulsant activity of a metabotropic glutamate receptor 8 preferential agonist, (R,S)-4-phosphonophenylglycine.

Agonists at group III glutamate metabotropic receptors, such as L-serine-O-phosphate, have pro- and anti-convulsant activities in rodent models. We have used intracerebroventricular administration to test a novel group III agonist, (R,S)-4-phosphonophenylglycine (PPG), that is preferential for mglu(8), against sound-induced seizures in DBA/2 mice. Tonic and clonic seizures are abolished at 15 min (ED(50s) 0.14 [0.04-0.4] nmol, and 3.4 [2.1-5.6] nmol, respectively). The protection against tonic and clonic seizures by 20 nmol PPG is complete for 4 h, diminished by 6 h, and absent by 10 h. In contrast, L-Serine-O-phosphate gives only partial protection against sound-induced clonic seizures for 15-30 min (ED(50) 79 [45-139] nmol) in DBA/2 mice. In genetically epilepsy prone rats sound-induced seizures were blocked 5-60 min after the bilateral administration of PPG, 5-10 nmol, into the inferior colliculus. These data suggest that the mglu(8) receptor is a potential target for novel antiepileptic drugs.

Animals↗
PubMed1999

New features and enhancements in the X-PLOR computer program.

This article describes new methods for X-ray crystallographic refinement and nuclear magnetic resonance (NMR) structure determination that are available in the recent release of the X-PLOR software, X-PLOR 98.0. The major new features of the X-PLOR 98.0 software are: (i) the introduction of maximum likelihood methods (Pannu and Read, Acta Crystallogr 1996;A52:659-668) for X-ray crystallographic refinement with structure factor amplitude, intensity and phase probability targets, (ii) the addition of the Andersen thermal coupling method for temperature control during simulated annealing refinements, (iii) a new utility function for converting reflection data in to the X-PLOR format, (iv) validated scripts and performance enhancements for structure determination from NMR distance restraints using torsion angle dynamics, (v) fast code for direct nuclear Oberhauser effect (NOE) refinement using matrix doubling and gaussian quadratures, (vi) methodologies for using ambiguous restraint information to perform automated iterative peak assignment and structure determination (Nilges et al., J Mol Biol 1997;269: 408-422). Additional developments in methodology for refining crystal structures from poor initial models include the implementation of a fast adaptive bulk solvent scattering correction and an energy minimization routine that makes use of second derivative information. Trial crystallographic refinements with an energy minimization protocol that includes these enhancements indicate significantly improved convergence. The quality of the resulting models appears comparable to models obtained from refinement protocols that incorporate torsion angle dynamics. Test applications of the new energy minimizer to NMR structure refinement with using NOE calculations also show improved convergence, leading to more optimized final models.

Crystallography, X-Ray↗
PubMed1999

Long-term depot-medroxyprogesterone acetate and bone mineral density.

The association between long-term use of depot-medroxyprogesterone acetate (DMPA) and bone mineral density (BMD) has been controversial, as seen in three case-control studies in New Zealand, Thailand, and the United Kingdom. In the present case-controlled study of BMD, a group of 67 Chinese women who had used DMPA from 5-15 years was compared with 218 women of the same age range who had not used any steroidal hormones. DMPA users were found to have a significantly lower BMD at lumbar vertebra (L2-4) (0.93 g/cm2), neck of femur (0.69 g/cm2), trochanter (0.59 g/cm2), and Ward's triangle (0.58 g/cm2), as compared with the control group, whose corresponding BMD values were 1.03 g/cm2, 0.83 g/cm2, 0.71 g/cm2, and 0.78 g/cm2, respectively (p < 0.001). The average percentage of bone loss per year was estimated to be 1.1% in L2-4, 2.3% in neck of femur, 2.4% in trochanter, and 3.5% in Ward's triangle. The percentage of bone loss in L2-4 was found to be more pronounced with age. This study provided information that the use of DMPA in a Chinese group for > 5 years in associated with bone loss, and a prospective study is needed to confirm these data, which are different from two case-control studies.

Absorptiometry, Photon↗
PubMed1997

Seasonal variation in suicides re-examined: no sex difference in Hong Kong and Taiwan.

The seasonal variation in suicides in Hong Kong and Taiwan during the period 1981 to 1993 was examined using harmonic analysis. A single cycle per year with lowest incidence in the winter months was found in both locations and for both sexes. Despite the regional differences in ascertainment procedures and preferred suicide methods, the absence of a biseasonal distribution of female suicides was consistently observed. This finding was contrary to that reported in many Western countries. A non-shared psychosocial process underlying the cross-cultural differences in the seasonality of female suicide is suggested.

Cross-Cultural Comparison↗
PubMed1993

Structural characterization of a homophilic binding site in the neural cell adhesion molecule.

We have previously used synthetic peptides to identify a homophilic binding site between Lys-243 and Glu-252 (KYSFNYDGSE) in the third immunoglobulin-like domain of the chick neural cell adhesion molecule (NCAM). In this report, we show that the deletion of this decapeptide sequence from chick NCAM or the scrambling of the first 5 amino acid residues led to the abolition of the homophilic binding activity of NCAM, thus confirming the role of this sequence in NCAM-NCAM binding. To investigate the involvement of individual residues of this decapeptide in NCAM binding, competition experiments were carried out using peptide analogues with various amino acid substitutions. Substitution of both Lys-243 and Asp-249 with Ala or of the 3 aromatic residues with Ala led to a total loss of activity, highlighting the importance of these residues in NCAM binding. Site-directed mutagenesis was then employed to substitute individual amino acids within the decapeptide sequence with Ala. The homophilic binding activity of mutant NCAMs transiently expressed in COS-1 cells was determined using the NCAM-Covasphere binding assay. Substitution of the charged residues with alanine decreased NCAM binding activity, implicating electrostatic interactions in NCAM binding activity. Substitution of the aromatic residues Tyr-244 and Phe-246 with Ala abolished NCAM binding activity, suggesting that hydrophobic and/or aromatic interactions may play an important role in NCAM homophilic binding. Substitution of amino acids in the predicted beta-strand portion of the decapeptide with Pro, which would tend to disrupt beta-strand conformation, led to a substantial loss of activity. Thus, NCAM-NCAM binding may also depend on the beta-backbone structure of this site. These results are consistent with the involvement of multiple amino acids within the decapeptide sequence in NCAM homophilic interaction.

Amino Acid Sequence↗
PubMed1993

Estimating selective advantage of two alleles in discrete time.

A class of estimators for the selective advantage, s, in a Wright-Fisher model with two alleles, variable population size, and genic selection is derived via martingale theory. Explicit expressions are given for these estimators which only involve simple computation. The optimal estimate among this class of estimators is obtained. Asymptotic results are readily established by an application of a martingale central limit theorem. The performance of this optimal estimator is compared to known estimators by means of a simulation study.

Alleles↗
PubMed1993

Further acceptability evaluation of RU486 and ONO 802 as abortifacient agents in a Chinese population.

Of 144 consecutive women who requested early induced abortion, 99 (68.7%) and 45 (31.3%) women chose RU486 combined with ONO 802 (medical method) and suction evacuation (surgical method), respectively. Logistic regression analysis of covariates showed that age and marital status were significantly correlated with the acceptability and hence the choice of the medical method. There were also more working women in this medical group. Previous experience of induced abortion had no influence on the current choice of the abortion method. This group of women appeared to have a tendency of treating their disease with medication rather than with surgery if the condition would allow. They expressed fear about surgery. The long induction-abortion interval of three days will have to be tolerated, but the duration of bleeding should be minimised in order to improve the acceptability of the drug. RU486 is an alternative abortion method which should be made widely available.

Abortifacient Agents, Nonsteroidal↗
PubMed1992

Estimation of the dynamics and rate of transmission of classical swine fever (hog cholera) in wild pigs.

Infectious diseases establish in a population of wildlife hosts when the number of secondary infections is greater than or equal to one. To estimate whether establishment will occur requires extensive experience or a mathematical model of disease dynamics and estimates of the parameters of the disease model. The latter approach is explored here. Methods for estimating key model parameters, the transmission coefficient (beta) and the basic reproductive rate (RDRS), are described using classical swine fever (hog cholera) in wild pigs as an example. The tentative results indicate that an acute infection of classical swine fever will establish in a small population of wild pigs. Data required for estimation of disease transmission rates are reviewed and sources of bias and alternative methods discussed. A comprehensive evaluation of the biases and efficiencies of the methods is needed.

Animals↗
PubMed1992

The largest subunit of RNA polymerase II in Dictyostelium: conservation of the unique tail domain and gene expression.

cDNAs encoding the largest subunit of RNA polymerase II were isolated from a Dictyostelium cDNA library. A total of 2.9 kilobases (kb) of cDNA was sequenced and the amino acid sequence of the carboxyl-terminal half of the protein was deduced. Similar to other eukaryotic RNA polymerases II, the largest subunit of Dictyostelium RNA polymerase II contains a unique repetitive tail domain at its carboxyl-terminal region. It consists of 24 highly conserved heptapeptide repeats, with a consensus sequence of Tyr-Ser-Pro-Thr-Ser-Pro-Ser. In addition to the tail domain, five segments of the deduced primary structure show > 50% sequence identity with either yeast or mouse protein. RNA blots show that cDNA probes hybridized with a single mRNA species of approximately 6 kb and immunoblots using a monoclonal antibody raised against the tail domain lighted up a single protein band of 200 kilodaltons. Interestingly, expression of the largest subunit of RNA polymerase II appears to be under developmental regulation. The accumulation of its mRNA showed a 60% increase during the first 3 h of development, followed by a steady decrease during the next 6 h. Cells began to accumulate a higher level of the RNA polymerase II mRNA after 9 h of development. When cells were treated with low concentrations of cAMP pulses to stimulate the developmental process, the pattern of mRNA accumulation moved 3 h ahead, but otherwise remained similar to that of control cells.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of cDNA encoding a second cellular retinoic acid-binding protein.

The vitamin A derivative retinoic acid is known to be a potent agent for control of differentiation and proliferation of epithelial cells and to exert profound effects on pattern formation during embryogenesis. Its action at the molecular level appears to be mediated by two distinct classes of proteins: a family of nuclear receptors that regulates gene transcription in a ligand-dependent fashion and a small cellular retinoic acid-binding protein (CRABP) for which a precise function remains to be elucidated. In this report, we describe the identification (by molecular cloning of its cDNA) of an isoform of CRABP, referred to as CRABP-II, expressed at high levels during mouse embryogenesis and in adult skin. We also show that CRABP-II mRNA levels are induced by at least 50-fold upon treatment of F9 teratocarcinoma cells with retinoic acid. The up-regulation of the gene encoding CRABP-II by its ligand suggests that CRABP-II might be involved in a feedback regulatory role in the mechanism of action of retinoic acid on cellular differentiation.

Amino Acid Sequence↗