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C Gu

Publications and source records attributed to C Gu.

At least 73 records · Page 4Linked to original sources
PubMed1997

A linkage strategy for detection of human quantitative-trait loci. I. Generalized relative risk ratios and power of sib pairs with extreme trait values.

We generalize the concept of the relative risk ratio (lambda) to the case of quantitative traits, to take into account the various trait outcomes of a relative pair. Formulas are derived to express the expected proportions of genes shared identical by descent by a sib pair, in terms of the generalized lambda's for sib pairs (lambda S), parent-offspring pairs (lambda O), and monozygotic twins (lambda M) and in terms of the recombination fraction, with the assumption of no residual correlations. If residual correlations are nonzero among relative pairs, we assume that they are the same among sib pairs, parent-offspring pairs, and monozygotic twins, and we employ a slightly different definition for the generalized lambda so that the same set of formulas still hold. The power (or, the sample size necessary) to detect quantitative-trait loci (QTLs) by use of extreme sib pairs (ESPs) is shown to be a function of the three generalized lambda's. Since lambda M can be derived by use of values of lambda S and lambda O, estimates of the latter two lambda's will suffice for the analysis of power and the necessary sample sizes of ESPs, for a QTL linkage study.

Female↗
PubMed1997

A linkage strategy for detection of human quantitative-trait loci. II. Optimization of study designs based on extreme sib pairs and generalized relative risk ratios.

We are concerned here with practical issues in the application of extreme sib-pair (ESP) methods to quantitative traits. Two important factors-namely, the way extreme trait values are defined and the proportions in which different types of ESPs are pooled, in the analysis-are shown to determine the power and the cost effectiveness of a study design. We found that, in general, combining reasonable numbers of both extremely discordant and extremely concordant sib pairs that were available in the sample is more powerful and more cost effective than pursuing only a single type of ESP. We also found that dividing trait values with a less extreme threshold at one end or at both ends of the trait distribution leads to more cost-effective designs. The notion of generalized relative risk ratios (the lambda methods, as described in the first part of this series of two articles) is used to calculate the power and sample size for various choices of polychotomization of trait values and for the combination of different types of ESPs. A balance then can be struck among these choices, to attain an optimum design.

Female↗
PubMed1997

Differential ethanol sensitivity of subpopulations of GABAA synapses onto rat hippocampal CA1 pyramidal neurons.

The actions of ethanol on gamma-aminobutyric acid-A (GABAA) receptor-mediated synaptic transmission in rat hippocampal CA1 neurons remain controversial. Recent studies have reported that intoxicating concentrations of ethanol (10-100 mM) can potentiate, inhibit, or have no effect on GABAA receptor-mediated synaptic responses in this brain region. The essential determinants of ethanol sensitivity have not been defined; however, GABAA receptor subunit composition, as well as posttranslational modifications of these receptors, have been suggested as important factors in conferring ethanol sensitivity to the GABAA receptor complex. Multiple types of GABAA receptor-mediated synaptic responses have been described within individual hippocampal CA1 neurons. These responses have been shown to differ in some of their physiological and pharmacological properties. In the present study we tested hypothesis that some of the disparate findings concerning the effects of ethanol may have resulted from differences in the ethanol sensitivity of GABAA receptor-mediated synapses on single CA1 pyramidal cells. Electrical stimulation adjacent to the stratum pyramidale (proximal) and within the stratum lacunosum-moleculare (distal) activated nonoverlapping populations of GABAA receptors on rat hippocampal CA1 neurons. Proximal inhibitory postsynaptic currents (IPSCs) decayed with a single time constant and were significantly potentiated by ethanol at all concentrations tested (40, 80, and 160 mM). Distal IPSCs had slower decay rates that were often described better by the sum of two exponentials and were significantly less sensitive to ethanol at all concentrations tested. Three other allosteric modulators of GABAA receptor function with well-defined GABAA receptor subunit requirements, pentobarbital, flunitrazepam, and zolpidem, potentiated proximal and distal GABAA IPSCs to the same extent. These results demonstrate that the ethanol sensitivity of GABAA receptors can differ, not only between brain regions but within single neurons. These findings offer a possible explanation for the conflicting results of previous studies on ethanol modulation of GABAA receptor-mediated synaptic transmission in rat hippocampal CA1 neurons.

Animals↗
PubMed1997

[Coronary artery bypass graft with internal mammary artery in 53 cases].

Coronary bypass graft (CABG) with internal mammary artery was used (IMA) in 53 cases. They were treated medically but not effective. More than one time myocardial infarctions occurred 44 cases, and 16 of them had complicated ventricular aneurysm. All of them had moderate hypothermia cardiopulmonary bypass except one, who was only subjected to anastomosis of left IMA to left anterior descending branch without cardiopulmonary bypass. The mean grafts of this group were 4.28 (lift ventricular aneurysmectomy was performed simultaneously in 4 cases). Operative death was occurred in 4 cases. Of the 35 cases which had been followed for 6 months to 1 year, 30 were free of symptoms, 5 got better and had more physical exertion. It is suggested that CABG with IMA is satisfactory.

Adult↗
PubMed1996

A hierarchy of SSB protomers in replication protein A.

Replication Protein A (RPA) is a heterotrimeric single-stranded DNA-binding protein (SSB) found in all eukaryotic cells. RPA is known to be required for many of the same reactions catalyzed by the homotetrameric SSB of bacteria, but its origin, subunit functions, and mechanism of binding remain a mystery. Here we show that the three subunits of yeast RPA contain a total of four domains with weak sequence similarity to the Escherichia coli SSB protomer. We refer to these four regions as potential ssDNA-binding domains (SBDs). The p69 subunit, which is known to bind ssDNA on its own, contains two SBDs that together confer stable binding to ssDNA. The p36 and p13 subunits each contain a single SBD that does not bind stably, but corresponds to the minimal region required for viability in yeast. Photocross-linking of recombinant protein to ssDNA indicates that an SBD consists of approximately 120 amino acids with two centrally located aromatic residues. Mutation of these aromatic residues inactivates ssDNA binding and is a lethal event in three of the four domains. Finally, we present evidence that the p36 subunit binds ssDNA, as part of the RPA complex, in a salt-dependent reaction similar to the wrapping of ssDNA about E. coli SSB. The results are consistent with the notion that RPA arose by duplication of an ancestral SSB gene and that tetrameric ssDNA-binding domains and higher order binding are essential features of cellular SSBs.

Amino Acid Sequence↗
PubMed1996

Combining extremely concordant sibpairs with extremely discordant sibpairs provides a cost effective way to linkage analysis of quantitative trait loci.

Extremely discordant (ED) sibpairs have been shown to be very powerful for linkage analysis of human quantitative traits [Risch and Zhang (1995) Science 268: 1584-1589]. In many cases, the extremely concordant (EC) sibpairs collected in the process of screening for ED sibpairs carry valuable information for linkage. Therefore, it seems justifiable to investigate the advantages of genotyping and to include them with the ED sibpairs for linkage analysis. Herein we explore the distributions of EC as well as ED sibpairs under various genetic models and provide a basis for combining both types of sibpairs. A simple statistic testing means of genes shared identical by descent (IBD) in applied to combine both types of EC sibpairs (high-high and low-low) with the ED pairs. We show that when a decent number of EC pairs is added to the ED sample for analysis, the power is much enhanced, making it especially desirable when the number of available ED pairs is small. We show at the same time that combining EC pairs with ED pairs is more cost effective than pursuing ED sibpairs alone.

Costs and Cost Analysis↗
PubMed1996

[Surgical treatment of ventricular septal defect complicated by pulmonary hypertension: analysis of 24 cases].

Until now the most important factor affecting the surgical treatment of ventricular septal defect (VSD) is pulmonary hypertention. 307 patients with ventricular septal defect (VSD) were treated surgically from May 1989 to May 1995 with a mortality rate of 2.9%. Among the 307 patients, 24 were complicated by severe pulmonary hypertension (Pp/Ps > or = 80%) and the mortality rate was 20.8%. Perioperative therapy and operative indications were discussed. Catheterization data, physical examination, chest X-ray and electrocardiographic findings were also analysed by comparision with operative outcome.

Cardiac Surgical Procedures↗
PubMed1996

[Feedback regulation of acetylcholine (ACh) on ion channel activity in snake motor nerve terminals].

In the vertebrate motor nerve terminals, the fact that the ACh release was affected by various activators and blockers of ACh receptors suggests the existence of several types of feedback regulation. The regulatory effect of ACh on the various ion channels in the snake motor nerve terminals was investigated by using subendothelial recording technique. (1) Suppression of IK(Ca). Similar to that of 3 mmol/L TEA, IK(Ca) could also be reversibly suppressed by 2 mmol/L ACh. (2) Regulatory effect on ICa. The time course of ICa in the presence of 30 mmol/L TEA was decreased by perfusion of 2 mmol/L ACh, an effect being more clear in high [Ca2+]o (7 mmol/L). The Ca2+ plateau, revealed by further addition of 3,4-DAP (300 mumol/L) to block all K+ channels, was also inhibited. These inhibitory effects could be reversed by 2 mmol/L atropine. It is likely that the inhibition of IK,f and IK(Ca) by ACh is to improve ACh release in normal condition, suggesting the presence of a positive feedback mechanism, while under circumstances in which ICa is increased, ACh may inhibit ICa so as to suppress the release itself as a result of negative feedback mechanism.

Acetylcholine↗
PubMed1995

TDT with covariates and genomic screens with mod scores: their behavior on simulated data.

We describe an extension to the TDT (transmission/disequilibrium test) which allows for more than two marker alleles and for covariates measured on the parent or offspring. We also describe a systematic genomic search where the mod score (maximized lod score) is computed for each marker under constraints on the population prevalence or penetrances of a single locus.

Computer Simulation↗
PubMed1995

A chromosome-based method to infer IBD scores for missing and ambiguous markers.

We propose a probability model to impute missing identical-by-descent (IBD) vectors for linkage analysis, when adjacent marker loci are typed and interference is estimable. A chromosome-based IBD distribution, conditioned on available marker data, is computed using a fast algorithm to estimate the joint probability of genes IBD at several equally spaced linked loci. Weighted IBD vectors are then used in various test statistics for linkage analysis. As an example, we analyzed the 18 affected sib pairs in the GAW9 Problem 1 data set using Risch's lod-score test.

Algorithms↗
PubMed1995

[Reversible elimination of K+ and Na+ currents at motor nerve terminals by SM486, a derivative of artemisinin].

Some derivatives of Artemisinin have been used as malariacides. Artemisinin derivative SM486 is water-soluble and has been shown also to have local anesthesia action. Here we report the effect of SM486 on Na+ and K+ channels at motor nerve terminals. Experiments were performed on mouse triangularis sterni nerve-muscle preparations. Presynaptic currents were picked up with a microelectrode inserted into the subendothelial space of the superficial nerve bundle under visual control using a x400 magnification water immersion objective. The results showed: (1) Both IK and INa were depressed in a dose-dependent manner, although the minimal effective concentration of SM486 for IK was lower than that for INa; (2) The depression was reversible as shown by the fact that the nearly completely blocked INa and IK currents could be restored to the control by simply washing away the perfusate SM486. (3) The decrease of IK was progressive, while the change of INa always began after IK proceeded to decrease rapidly. The effects of procaine on INa and IK are similar to SM486 but the effective concentration was higher.

Anesthetics, Local↗
PubMed1995

[Two case of androgen-secreting ovary tumor].

Two cases of androgen-secreting ovary tumor were reported. patients' chief complaints were menoxemia and hirsutism; clitorism was found by physical examination. Their serum testosterone (T) were high (10.2-6.7nmol/L) and could not be suppressed to normal range by middle-dose dexamethasone inhibiting test. ACTH stimulating test could not stimulate the high serum T to raise futher, but HCG stimulating test could increase serum T to higher level. Pelvic examination, type B ultrasonic and CT scan confirmed a mass on one of the ovaries. Sertoli-Leydig cell tumor and gynandroblastoma were proved respectively by pathology. After removing the tumor, their serum T were returned to normal level.

Adult↗