Biomedical subjects

C Gu

Publications and source records attributed to C Gu.

At least 55 records · Page 3Linked to original sources

PubMed1999

Assays of ligand-human serum albumin binding using pulsed ultrafiltration and liquid chromatography-mass spectrometry.

Two approaches were utilized to increase the throughput of pulsed ultrafiltration assays of ligand binding to human serum albumin, reducing the volume of the ultrafiltration chamber and combining pulsed ultrafiltration with high performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-MS). Affinity constants for binding of ligands to human serum albumin were determined using pulsed ultrafiltration with ultraviolet absorbance detection. The first affinity constants (Ka1) were measured for the binding of dansylsarcosine, dansylamide, 7-anilinocoumarin-4-acetic acid and warfarin, and were determined to be 1.8 x 105, 5 x 104, 8 x 104, and 2.0 x 105 M-1, respectively. The throughput of pulsed ultrafiltration analyses was tripled compared to previous pulsed ultrafiltration measurements by reducing the volume of the chamber. In addition, the use of LC-MS with pulsed ultrafiltration permitted the simultaneous comparison and rank ordering of ligand mixtures for binding to serum albumin. For example, the throughput of these pulsed ultrafiltration measurements was tripled by analyzing three ligands as a mixture.

Chromatography, Liquid↗

PubMed1999

[The expression of Mdm2 protein and p53 mutation in lung squamous cell carcinomas and their clinicopathological significance].

OBJECTIVE: In order to study the interrelation between p53 mutation, Mdm2 overexpression and pulmonary squamous cell carcinomas. METHODS: Forty-five pulmonary squamous cell carcinomas were investigated for expression of Mdm2 protein and p53 mutation using immunohistochemical techniques and PCR-SSCP. The findings were correlated with the clinicopathological features of carcinomas. RESULTS: (1) Mdm2 protein overexpression (62%, 28/45) and p53 mutation (51%, 23/45) are a common event in pulmonary squamous cell carcinomas (P < 0.05). (2) Statistical analysis revealed a strong correlation between Mdm2/p53 coexpression and lymph metastases (66%, 10/15) was observed (P < 0.05). CONCLUSIONS: The coexistence of Mdm2 protein and p53 aberration in a subset of pulmonary carcinomas may be indicative of a gain of function phenotype with more aggressive characteristic.

Carcinoma, Squamous Cell↗

PubMed1999

[Cardiac metal foreign body: analysis of 21 cases].

OBJECTIVE: To improve early diagnosis and clinical treatment of metal foreign body in the heart. METHODS: In 21 patients, case history, clinical manifestation, chest X-ray film, and echocardiograph were reviewed. 20 patients received operation: emergency exploration (13) and elective operation (7). Four patients were subjected to cardiopulmonary bypass. The other one was not operated on because of absence of symptoms and small foreign body. Foreign bodies mostly bullets, were usually located in the right ventricle. Ventricular fibrillation occurred in 3 patients during operation, two of them were resuscitated. RESULTS: 20 patients but one recovered, a mortality rate of 5%. CONCLUSIONS: Early diagnosis, rapid management, and localization of foreign body are essential to the selection of treatment.

Adolescent↗

PubMed1999

[The clinical characters of myopatic pharyngoparalysis and laryngoparalysis with 3 cases report].

OBJECTIVE: To improve the level of diagnosis and treatment about myopathic pharyngoparalysis and laryngoparalysis (MPL). METHOD: 3 cases of MPL were diagnosed by clinical inaterials, electromyogram, serokinase and muscle biopsy. The clinical characters are dysphagia, phonasthenia, abnormal electromyogram and high CPK et al. They were all treated with glucocorticoid. RESULT: The effect of treatment on all 3 cases was good. CONCLUSION: It is important to distinguish MPL with neuropathic pharyngoparalysis and laryngoparalysis. An appropriate glucocorticoid treatment is also impontant.

Adolescent↗

PubMed1998

Testing causal hypotheses in multivariate linkage analysis of quantitative traits: general formulation and application to sibpair data.

We provide a general framework for the development of model-free methods for the linkage analysis of multivariate phenotypic data. It is possible within this framework to test both for linkage of a set of phenotypes to one or more markers and for the presence of structural relations among the phenotypes themselves. This report presents the general model, paying special attention to the assumptions that enter its formulation, and outlines the estimation procedures that may be used.

Chromosome Mapping↗

PubMed1998

Meta-analysis methodology for combining non-parametric sibpair linkage results: genetic homogeneity and identical markers.

Meta-analysis methodology is developed for combining sibpair linkage results across multiple studies employing different study designs, some employing quantitative traits (e.g., blood pressure) and some employing qualitative traits (e.g., clinical hypertension), under the assumption that the underlying (disease) trait loci are the same. Pooling results based on three commonly used sibpair methods is considered: the affected sibpair method for dichotomous traits and, for quantitative traits, the Haseman-Elston regression method and the Risch-Zhang extremely discordant sibpair method. The proportion of genes shared identical by descent (IBD) by a sibpair of certain trait outcomes is chosen as a common effect to be pooled across studies. Variation in the observed IBD proportions among individual studies is modeled using a random effects model. A heterogeneity test is provided to assess the variability among individual studies. When results from all three types of studies are available, we derive pooled estimates of IBD proportions both for sibpairs with extremely concordant trait values and for sibpairs with extremely discordant trait values, and construct a combined test of linkage based on the difference of the two estimates. Simulation studies demonstrate the need for and the advantage of meta-analysis of linkage results. We also present some guidelines for reporting linkage studies bearing potential future meta-analysis in mind.

Chromosome Mapping↗

PubMed1998

BRE: a modulator of TNF-alpha action.

A stress-responsive gene highly expressed in brain and reproductive organs (BRE) is down-regulated after UV irradiation, DNA damaging agents, or retinoic acid treatment. The human BRE gene encodes a mRNA of 1.9 kb, which gives rise to a protein of 383 amino acids with a molecular size of 44 kilodaltons. BRE is not homologous to any known gene and its function has not been defined. Here we report that BRE was identified multiple times in a yeast two-hybrid screen of a murine cerebellar cDNA library, using the juxtamembrane domain of the p55 tumor necrosis factor alpha (TNF) receptor. The interaction between the p55 receptor and BRE was verified by an in vitro biochemical assay by using recombinant fusion proteins and by co-immunoprecipitation of transfected mammalian cells. In the yeast two-hybrid assay, BRE specifically interacted with p55 TNF receptor but not with other TNF family members such as the Fas receptor, the p75 TNF receptor, and p75 neurotrophin receptor. Overexpression of BRE inhibited TNF-induced NFkappaB activation, indicating that the interaction of BRE protein with the cytoplasmic region of p55 TNF receptor may modulate signal transduction by TNF-alpha.

Animals↗

PubMed1998

Temporal and spatial relationship of pylorus to antroduodenal motility in functional dyspepsia.

OBJECTIVE: To investigate the temporal and spatial relationship of pylorus to antroduodenal motility in functional dyspepsia (FD). METHODS: Eleven healthy subjects (HS) and 14 patients with FD were studied. Antral-pyloro-duodenal manometry was performed for 3 hours fasting and 2 hours after 80 Kcal of solid test meal. RESULTS: (1) The incidence of phase III was 7/11 in HS and 3/14 in FD in antrum (P < 0.05), 8/11 and 4/14 in pylorus (P < 0.05), 10/11 and 6/14 in duodenum (P < 0.05), respectively. (2) The percentage of antropyloroduodenal coordinations during phase II of MMC was 58.5% in HS and 18.5% in FD (P < 0.001). (3) The pyloroduodenal coordination was 78.2% and 38.9% (P < 0.01) at 60 minutes after meal and 77.1% and 54.0% (P < 0.01) at 120 minutes postprandially in HS and in FD. (4) The percentage of isolated pyloric pressure waves (IPPWs) was 4.8%, 29.7% (P < 0.001) at 60 minutes, and 9.3%, 25.1% (P < 0.01) at 120 minutes in HS and FD. CONCLUSIONS: There were abnormalities of gastro-pyloro-duodenal motility in both interdigestive and digestive stages; the higher incidence of IPPWs and disordered temporal and spatial relationship of pylorus to antroduodenal motility may result in a delayed gastric emptying in FD. The possible mechanism may be involved in abnormal neural control.

Adolescent↗

PubMed1998

Familial resemblance for resting blood pressure with particular reference to racial differences: preliminary analyses from the HERITAGE Family Study.

Resting blood pressure in both white and black families participating in the HERITAGE Family Study was analyzed using a simple familial correlation model to assess familial influences. The two samples of black and white families were analyzed separately and together, providing an opportunity to test for heterogeneity in the familial resemblance. Maximal heritability was 46% for systolic blood pressure (SBP) and 31% for diastolic blood pressure (DBP) in the pooled sample. Noticeably higher heritabilities were found in the black sample (68% for SBP and 56% for DBP) than in the white sample (43% for SBP and 24% for DBP). The patterns of familial correlations were similar in blacks and whites, with the exception that spouse resemblance was significant in white families but not in black families. These results along with the finding that the magnitude of the familial correlations was higher in the black sample than in the white sample suggest that the effects of host and familial environmental factors differ between the races.

Adolescent↗

PubMed1997

Using smoothing spline anova to examine the relation of risk factors to the incidence and progression of diabetic retinopathy.

Smoothing spline ANOVA (ANalysis Of VAriance) methods provide a flexible alternative to the standard parametric GLIM (generalized linear models) methods for analysing the relationship of predictor variables to outcomes with data from large epidemiologic studies. These methods allow the visualization of relationships not readily fit by simple GLIM models, and provide for the ability to visualize interactions between the variables. At the same time, they reduce to GLIM models if the data suggest that the added flexibility is unwarranted. Using this method, we investigate risk factors for incidence and progression of diabetic retinopathy in a group of patients with older onset diabetes from the Wisconsin Epidemiological Study of Diabetic Retinopathy. We carry out four analyses to illustrate various properties of this class of methods. Some of the results confirm previous findings with use of standard methods, while others allow the visualization of more complex relationships not evident from the application of parametric methods.

Adult↗

PubMed1997

Genome screening using extremely discordant and extremely concordant sib pairs.

We applied extreme sib-pair methods in two ways to the GAW10 Problem 2A data sets to detect susceptible quantitative trait loci using extremely discordant sib pairs only, and combining them with the available extremely concordant sib pairs as suggested by the authors elsewhere. Ten successive original replicates were combined into one sampling pool so as to get the necessary number of extreme sib pairs. A total of 100 replicates were used to produce 10 such data sets for both initial detection and confirmations. Strong signals were found with markers D5G15 for Q1, D8G27-28 for Q4, and D9G7-9 for Q5.

Chromosome Mapping↗

PubMed1997

Probabilities of identity-by-descent patterns in sibships when the parents are not genotyped.

An assumption-free algorithm has been applied to compute the probabilities of all possible identity-by-descent (IBD) configurations when the parents have not been genotyped. These probabilities can be used to determine the amount of information that a particular sibship will bring to a nonparametric linkage analysis. It is shown that the number of possible configurations can be extremely large even when the markers are closely spaced and are rather polymorphic. Further, it is not always possible to reduce this number to a manageable one simply by consideration of the relative probabilities of the configurations.

Algorithms↗

PubMed1997

Responses of plasma fibronectin to the changes of dietary protein levels in rats.

In this study, the plasma fibronectin was evaluated as a nutritional marker in protein- and protein-energy malnourished rats in comparison with plasma prealbumin, albumin, and total protein. The plasma fibronectin was determined by nephelometric assay based on the interaction of an antigen and antibody. The rats were subjected to three diets, containing 20, 5, and 0% casein, respectively, for 5 wk except in the last 2 wk, the rats on the 0% casein diet were re-fed on a 20% casein diet. The results showed that in the rats on a 5% casein diet (protein malnourished), the plasma fibronectin concentration rose significantly in the early stage and normalized thereafter. In the rats subjected to a 0% casein diet (protein-energy malnourished), the plasma fibronectin concentration did not decline quickly in response to protein depletion, compared with the plasma prealbumin, albumin, and total protein concentrations. Following the re-feeding of a 20% casein diet in the last 2 wk, the plasma fibronectin concentration was restored earlier than other plasma protein concentrations. No significant change in plasma fibronectin concentration was found in the rats receiving a 20% casein diet (control) over the 5 wk feeding period. It is concluded that plasma fibronectin may not be a suitable marker for protein or protein-energy malnutrition, though it is a sensitive index for nutritional rehabilitation.

Animals↗

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↗