Biomedical subjects

F Sun

Publications and source records attributed to F Sun.

At least 73 records · Page 4Linked to original sources

PubMed1999

Using case-control designs for genome-wide screening for associations between genetic markers and disease susceptibility loci.

We used a case-control design to scan the genome for any associations between genetic markers and disease susceptibility loci using the first two replicates of the Mycenaean population from the GAW11 (Problem 2) data. Using a case-control approach, we constructed a series of 2-by-3 tables for each allele of every marker on all six chromosomes. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated for all alleles of every marker. We selected the one allele for which the estimated OR had the minimum p-value to plot in the graph. Among these selected ORs, we calculated 95% CI for those that had a p-value < or = adjusted alpha level. Significantly high ORs were taken to indicate an association between a marker locus and a suspected disease-susceptibility gene. For the Mycenaean population, the case-control design identified allele number 1 of marker 24 on chromosome 1 to be associated with a disease susceptibility gene, OR = 2.10 (95% CI 1.66-2.62). Our approach failed to show any other significant association between case-control status and genetic markers. Stratified analysis on the environmental risk factor (E1) provided no further evidence of significant association other than allele 1 of marker 24 on chromosome 1. These data indicate the absence of linkage disequilibrium for markers flanking loci A, B, and C. Finally, we examined the effect of gene x environment (G x E) interaction for the identified allele. Our results provided no evidence of G x E interaction, but suggested that the environmental exposure alone was a risk factor for the disease.

Alleles↗

PubMed1999

Whole genome association studies for genes affecting alcohol dependence.

We applied the transmission/disequilibrium test (TDT) for sibs (S-TDT) and for families with one parent (1-TDT), to the Collaborative Study on the Genetics of Alcoholism data set. The combined test is used to screen the whole genome to locate genes responsible for alcohol dependence. This analysis supports the previous finding that the region close to GABRB1 on chromosome 4 might be associated with alcohol dependence. The regions close to D6S474 and D11S1998 are also of particular interest. We found segregation distortion at the GR1K1 locus. The segregation distortion might be due to the binning method used in genotyping at this locus.

Alcoholism↗

PubMed1999

Association of genetic polymorphisms of alcohol-metabolizing enzymes with excessive alcohol consumption in Japanese men.

To evaluate the independent and interactive contributions of alcohol dehydrogenase-2 (ADH2), aldehyde dehydrogenase-2 (ALDH2) and ethanol-induced isozyme cytochrome P450-2E1 (CYP2E1) genes to alcohol consumption large enough to induce health problems, 643 healthy Japanese men aged between 23 and 64 years, recruited from two different occupational groups, were analyzed for genotype and drinking habits. The frequency of excessive alcohol consumers (EAC) who drank 90 ml or more alcohol more than 3 days a week was significantly higher in subjects possessing the ALDH2(1)/ALDH2(1) genotype than in those having ALDH2(1)/ALDH2(2) or ALDH2(2)/ALDH2(2) genotypes. A significant difference was also found in the different genotypes of CYP2E1. Moreover, a borderline significant interaction between the ALDH2 and CYP2E1 genotypes on excessive alcohol consumption was observed, i.e., the group of subjects having the c2 allele of CYP2E1 had a higher frequency of EAC than those having c1/c1 genotypes in the genotype subgroup ALDH2(1)/ALDH2(1), whereas these were not found in the heterozygote and homozygote subgroups of the ALDH2(2) allele. Neither the independent nor interactive genetic effect of ADH2 on excessive alcohol consumption was obvious. In conclusion, Japanese men with the ALDH2(1)/ALDH2(1) genotype and the c2 allele of CYP2E1 are at higher risk of showing excessive alcohol consumption.

Adult↗

PubMed1999

Genome-wide scanning for type 2 diabetes susceptibility in Canadian Oji-Cree, using 190 microsatellite markers.

We undertook a genome-wide scan using 190 markers with an average separation of 20 cM in 49 Canadian Oji-Cree sib pairs affected with type 2 diabetes. Four of these markers, one each on chromosomes 6, 8, 16, and 22, showed both suggestive linkage and suggestive association with type 2 diabetes in the Oji-Cree. None of these markers corresponded to any chromosomal region or marker that has so far been linked with type 2 diabetes in other populations. Thus, there might be several genetic loci that confer susceptibility to type 2 diabetes in this study sample. We are following up on these preliminary leads by increasing the density of the markers within these linked and associated regions, and also by increasing the number of study subjects. Also, we found instances in which there were wide disparities between the Oji-Cree and reference Caucasians with respect to marker heterozygosity. This suggests that a particular set of markers for genome-wide scanning will have different informativeness in different ethnic groups. Thus, different marker sets will likely be required for different ethnic groups in order to maximize their information content for linkage calculations.

Adult↗

PubMed1999

Modeling DNA shuffling.

In vitro evolution is a new, important laboratory method to evolve molecules with desired properties. It has been used in a variety of biological studies and drug development. In this paper, we study one important mutagenesis method used in in vitro evolution experiments called DNA shuffling. We construct a mathematical model for DNA shuffling and study the properties of molecules after DNA shuffling experiments based on this model. The model for DNA shuffling consists of two parts. First we apply the Lander-Waterman model for physical mapping by fingerprinting random clones to model the distribution of regions that can be reassembled through DNA shuffling. Then we present a model for recombination between different DNA species with different mutations. We compare our theoretical results with experimental data. Finally we propose novel applications of the theoretical results to the optimal design of DNA shuffling experiments and to physical mapping using DNA shuffling.

Base Sequence↗

PubMed1999

Miscarriage prevention tea affects plasma beta-endorphin concentrations in women with early threatened abortions.

Twenty threatened abortive patients in the 7-8th week of gestation were treated with a classical miscarriage prevention tea (Shou-Tai-Tang) combined with psychological consultation. All of the patients had a history of unexplained recurrent abortions. This treatment succeeded in sixteen out of 20 patients. The plasma concentrations of beta-endorphin (beta-EP), gonadotrophin releasing hormone (GnRH), human chorionic gonadotrophin (hCG), and progesterone (P4) were measured by radioimmunoassay before and after treatment. Compared to control subjects, beta-EP levels were significantly higher, while GnRH, hCG, and P4 were lower than before treatment. Concentrations of these peptides/hormones returned to normal ranges after successful treatment.

Abortion, Spontaneous↗

PubMed1999

Case-only design to measure gene-gene interaction.

The case-only design is an efficient and valid approach to screening for gene-environment interaction under the assumption of the independence between exposure and genotype in the population. In this paper, we show that the case-only design is also a valid and efficient approach to measuring gene-gene interaction under the assumption that the frequencies of genes are independent in the population. Just as the case-only design requires fewer cases than the case-control design to measure gene-environment interaction, it also requires fewer cases to measure gene-gene interactions.

Epidemiologic Studies↗

PubMed1999

[Effect of tiangui recipe on serum leptin and pituitary gonadotropin in androgen-sterilized rats].

OBJECTIVE: To explore the effect of Tiangui Recipe (TGR) on obesity and reproductive function in androgen-sterilized rats (ASR). METHODS: ASR model was established by subcutaneous injection of testosterone propionate to SD female rats of 9 days age. Change of serum leptin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in model rats of 115 days old before and after feeding TGR was measured by radioimmunoassay (RIA). Meanwhile, criteria of energy state, including diurnal food intake, retroperitoneal fat depot weight and body weight, were measured and evaluated. RESULTS: ASR had the characteristics of high metabolic rate, energy imbalance and obesity. Serum level of leptin increased and FSH, LH decreased significantly (P < 0.01) in model rats as compared with the normal rats. Significant positive correlation between leptin level and body weight (r = 0.8977, P < 0.001) was observed, and negative correlation was seen between FSH, LH and leptin (r = -0.7517, P < 0.001; r = -0.8444, P < 0.001, respectively). The endocrinous changes of ASR all returned to normal range after the TGR treatment. CONCLUSION: Obesity and concerned hypogonadotropic hypogonadal anovulation were expressed in ASR. TGR may play an important role in reducing weight and inducing ovulation.

Androgens↗

PubMed1999

[Effect of TCM on plasma beta-endorphin and placental endocrine in threatened abortion].

OBJECTIVE: To explore the effect of TCM on plasma beta-endorphin (beta-EP) and placental endocrine function in patients of threatened abortions (TA). METHODS: Changes of plasma beta-EP, gonadotrophin releasing hormone (GnRH), human chorionic gonadotrophin (HCG), progesterone (P4) levels were measured with RIA in 40 cases of TA with a history of recurrent spontaneous abortion treated with Chinese herbal medicine for reinforcing Kidney and Qi, hemostasis and antiabortion. And the results were compared with those of normal early pregnant women and patients with incomplete abortion as control. RESULTS: The plasma beta-EP level in TA was significantly higher than that in normal pregnant women, P < 0.01. On the contrary, plasma GnRH, HCG and P4 were obviously lower in TA as compared with those of the normal cases, P < 0.01. After treatment, 36 of the 40 patients succeeded in the continuity of pregnancy, their symptoms of TA disappeared, and the above-mentioned four criteria measured at 10-12th week of gestation were similar to those of normal cases, P > 0.05. CONCLUSION: TCM treatment can regulate plasma beta-EP and placental endocrine function in threatened abortion.

Abortion, Threatened↗

PubMed1999

[Location of the binary toxin gene of Bacillus sphaeriucs and some biological characteristics of its asprogenous mutants].

Location of the binary toxin gene of Bs C3-41 and some biological characteristics of its asporogenous mutants which obtained by DES treatment were studied in this paper. Mutant C4, L5 with blocked at the stage II of sporulation course were not possessed of any crystalline inclusion, but the binary toxin proteins were detected in their cells by SDS-PAGE analysis. Another mutant G5 which blocked at the stage III of sporulation course formed parasporal crystal in the cells, and its toxicity to larvae of Culex quinquefasciatus was about 50 times higher than those of mutant C4 and L5. The result of curing plasmid and Southern blot analysis confirm the binary toxin gene of Bs C3-41, Bs 1691 and Bs-10 locate on the chromosome.

Animals↗

PubMed1999

Change in tissue concentrations of lipid hydroperoxides, vitamin C and vitamin E in rats with streptozotocin-induced diabetes.

The tissue concentration of lipid hydroperoxides, which was determined by a specific method involving chemical derivatization and HPLC, increased significantly in the heart, liver, kidney and muscle of diabetic rats 8 weeks after the intraperitoneal injection of streptozotocin compared with that of the control group. These results demonstrate that an enhanced oxidative stress is caused in these tissues by diabetes. Vitamin C concentrations of the brain, heart, lung, liver, kidney and plasma of the diabetic rats decreased significantly after 8 weeks compared with those of the control group. Vitamin E concentrations of the brain, heart, liver, kidney, muscle and plasma of the diabetic rats increased significantly after 4 weeks compared with the control group. After 8 weeks, an elevation in vitamin E concentration was observed in the heart, liver, muscle and plasma of the diabetic rats.

Analysis of Variance↗

PubMed1998

The alternation of optokinetic responses driven by moving stimuli in humans.

When the two eyes were exposed dichoptically to two oppositely moving patterns, the alternating OKN was elicited, in which the eye movements tracked the two moving stimuli alternately. In the present experiment, two oppositely moving stimuli were periodically exchanged between the eyes, the results showed that the alternation of OKN direction was not affected by this exchange. It suggests that alternating OKN was not controlled by rivalry between the two eyes but between two perceived motion patterns.

Functional Laterality↗

PubMed1998

A new method for estimating the risk ratio in studies using case-parental control design.

The authors describe a new simple noniterative, yet efficient method to estimate the risk ratio in studies using case-parental control design. The new method is compared with two other noniterative methods, Khoury's method and Flanders and Khoury's method, and with a maximum likelihood-based method of Schaid and Sommer. The authors found that the variance of the new estimation method is usually smaller than that of Khoury's method or Flanders and Khoury's method and that it is slightly larger than that of the maximum likelihood-based method of Schaid and Sommer. Despite the slightly large variance of the new estimator compared with that of the maximum likelihood-based method, the simplicity of the new estimator and its variance makes the new method appealing. When genotypic information for only one parent is available, the authors also describe a method to estimate the risk ratio without assuming Hardy-Weinberg equilibrium or random mating. A simple formula for the variance of the estimator is given.

Alleles↗

PubMed1998

Higher T-wave amplitude associated with better prognosis in patients receiving thrombolytic therapy for acute myocardial infarction (a GUSTO-I substudy). Global Utilization of Streptokinase and Tissue plasminogen Activator for Occluded Coronary Arteries.

Increased T-wave amplitude is one of the earliest electrocardiographic (ECG) changes following coronary artery occlusion. Therefore, higher T waves in the presenting electrocardiogram should represent earlier time to treatment and thus be associated with lower mortality following thrombolytic therapy. However, T-wave amplitude has never been evaluated as a prognostic marker in this setting. We examined clinical outcomes in 3,317 patients with acute myocardial infarction (AMI) who underwent thrombolysis in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) Study. Patients were classified as either those with high T waves or those with low T waves. Higher T waves were defined as those >98th percentile of the upper limit of normal. T-wave amplitude was also evaluated as a continuous variable according to infarct location (maximum T-wave amplitude) and as the amount of excess T-wave amplitude above normal (excess T-wave amplitude). Patients with higher T waves had lower 30-day mortality than those without (5.2% vs 8.6%, p = 0.001) and were less likely to develop congestive heart failure (15% vs 24%, p <0.001) or cardiogenic shock (6.1% vs 8.6%, p = 0.023). Higher maximum T-wave amplitude and excess T-wave amplitude were predictive of lower 30-day mortality (chi-square = 67, p <0.001 and chi-square = 33, p <0.001, respectively). These differences remain significant after controlling for other prognostic baseline ECG variables. In addition, T-wave amplitude added prognostic significance after controlling for time to treatment. T-wave amplitude, an often-overlooked component of the electrocardiogram, can add significant prognostic information in initial evaluation of patients with AMI.

Aged↗

PubMed1998

Testing for contributions of mitochondrial DNA mutations to complex diseases.

Several complex disorders are suspected of being associated with mitochondrial DNA (mtDNA) mutations. We studied the statistical properties of a test based on proband-relative pairs to identify potential mtDNA mutation involvement in a complex disorder. The test compares the recurrence risk of relatives of probands along the mitochondrial lineage with that of relatives along the nonmitochondrial lineage. If mtDNA mutations are involved, the recurrence risk will be higher among relatives in the mitochondrial lineage. The form of the test is independent of the assumed models of inheritance and interaction of the nuclear autosomal mutations with mtDNA mutations. The power of the test, however, differs among the different models and by the type of proband-relative pairs used in the test. We considered heterogeneity models with and without phenocopies, a three-state heteroplasmic mtDNA transmission model, and a multiplicative epistasis model. Under the heterogeneity model, the power of the test increases as the relationship between the proband and the relative becomes more distant. Under the multiplicative epistasis model, the power of the test decreases as the relationship between the proband and the relative becomes more distant.

DNA, Mitochondrial↗

PubMed1998

Neural network mosaic model for pupillary responses to spatial stimuli.

A neural network mosaic model was developed to investigate the spatial-temporal properties of the human pupillary control system. It was based on the double-layer neural network model developed by Cannon and Robinson and the pupillary dual-path model developed by Sun and Stark. The neural network portion of the model received its input from a sensor array and consisted of a retina-like two-dimensional neuronal layer. The dual-path portion of the model was composed of interconnections of the neurons that formed a mosaic of AC transient and DC sustained paths. The spatial aggregates of the AC and DC signals were input to the AC and DC summing neurons, respectively. Finally, the weighted sum of the aggregate AC and DC signals provided the output for driving the pupillary response. An important property of the model was that it could adaptively learn from training samples by adjustment of the weights. The neural network mosaic model showed excellent performance in simulating both the traditional pupillary phenomena and the new spatial stimulation findings such as responses to change in stimulus pattern and shift of light spot. Moreover, the model could also be used for the diagnosis of clinical deficits and image processing in machine vision.

Brain Stem↗

PubMed1998

-6A promoter variant of angiotensinogen and blood pressure variation in Canadian Oji-Cree.

We previously reported significant associations between variation in the AGT gene at codon 235 and both systolic pressure and hypertension in Canadian Oji-Cree. Recently, Inoue et al suggested that the AGT T235 variant was not causative, but was rather in linkage disequilibrium with a variant in the AGT promoter, namely -6A, that was associated with increased in vitro expression of angiotensinogen and was thus a strong candidate to be the functional basis of the previously observed associations. We genotyped 518 adult Oji-Cree for the AGT promoter polymorphism and tested for its association with blood pressure and hypertension. We found that the frequency of the -6A variant was 0.85 in the Oji-Cree, which is much higher than the frequency observed in other human samples. We also found strong linkage disequilibrium between the AGT -6A and T235 variants. However, genetic variation of the AGT promoter was only marginally associated with variation in systolic pressure, with a trend to significantly higher systolic pressure seen in AGT -6A/A homozygotes than in subjects with other genotypes. In addition, genetic variation of the AGT promoter tended to be associated with a diagnosis of hypertension. Despite the very high prevalence of -6A, our native sample was essentially normotensive. Our findings are consistent with a marginally deleterious effect of the AGT -6A allele on blood pressure, but linkage disequilibrium with another causative variant cannot be ruled out in this sample of aboriginal Canadians.

Adult↗

PubMed1998

Seven new microcystins possessing two L-glutamic acid units, isolated from Anabaena sp. strain 186.

Electrospray ionization mass spectrometry has been applied to the structure assignment of seven new microcystins (1-7), obtained from cultured Anabaena sp. strain 186. The seven new microcystins contain the dehydroalanine (Dha) or L-Ser unit instead of the N-methyldehydroalanine unit and the L-Glu and/or its delta-methyl ester [E(OMe)] units at the two variable L-amino acid units, and the structures were assigned as [Dha7]microcystin-E(OMe)E(OMe) (1), [D-Asp3,Dha7]microcystin-E(OMe)E(OMe) (2), [L-Ser7]microcystin-E(OMe)E(OMe) (3), [D-Asp3,L-Ser7]microcystin-E(OMe)E(OMe) (4), [Dha7]microcystin-EE(OMe) (5), [D-Asp3,Dha7]microcystin-EE(OMe) (6), and [L-Ser7]microcystin-EE(OMe) (7). These microcystins are the first examples containing dicarboxylic amino acids at the two variable L-amino acid units in microcystins.

Anabaena↗