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J Huang

Publications and source records attributed to J Huang.

At least 163 records · Page 9Linked to original sources
PubMed2001

Comparison of 'model-free' and 'model-based' linkage statistics in the presence of locus heterogeneity: single data set and multiple data set applications.

Earlier work [Knapp et al.: Hum Hered 1994;44:44-51] focusing on affected sib pair (ASP) data established the equivalence between the mean test and a test based on a simple recessive lod score, as well as equivalences between certain forms of the maximum likelihood score (MLS) statistic [Risch: Am J Hum Genet 1990;46:242-253] and particular forms of the lod score. Here we extend the results of Knapp et al. [1994] by reconsidering these equivalences for ASP data, but in the presence of locus heterogeneity. We show that Risch's MLS statistic under the possible triangle constraints [Holmans: Am J Hum Genet 1993;52:362-374] is locally equivalent to the ordinary heterogeneity lod score assuming a simple recessive model (HLOD/R); while the one-parameter MLS assuming no dominance variance is locally equivalent to the (homogeneity) recessive lod. The companion paper (this issue, pp 199-208) showed that when considering multiple data sets in the presence of locus heterogeneity, the HLOD can suffer appreciable losses in power. We show here that in ASP data, these equivalences ensure that this same loss in power is incurred by both forms of the MLS statistic as well. The companion paper also introduced an adaptation of the lod, the compound lod score (HLOD/C). We confirm that the HLOD/C maintains higher power than these 'model-free' methods when applied to multiple heterogeneous data sets, even when it is calculated assuming the wrong genetic model.

Chromosome Mapping↗
PubMed2001

The score statistic of the LD-lod analysis: detecting linkage adaptive to linkage disequilibrium.

We study the properties of a modified lod score method for testing linkage that incorporates linkage disequilibrium (LD-lod). By examination of its score statistic, we show that the LD-lod score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. We also consider the connection between the LD-lod score method and the transmission-disequilibrium test (TDT) for triad data and the mean test for affected sib pair (ASP) data. We show that, for triad data, the recessive LD-lod test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-lod score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models considered in this report. Therefore, the LD-lod score method is an interesting approach for detecting linkage when the extent of LD is unknown, such as in a genome-wide screen with a dense set of genetic markers.

Genetic Linkage↗
PubMed2001

The null distribution of the heterogeneity lod score does depend on the assumed genetic model for the trait.

It is well known that the asymptotic null distribution of the homogeneity lod score (LOD) does not depend on the genetic model specified in the analysis. When appropriately rescaled, the LOD is asymptotically distributed as 0.5 chi(2)(0) + 0.5 chi(2)(1), regardless of the assumed trait model. However, because locus heterogeneity is a common phenomenon, the heterogeneity lod score (HLOD), rather than the LOD itself, is often used in gene mapping studies. We show here that, in contrast with the LOD, the asymptotic null distribution of the HLOD does depend upon the genetic model assumed in the analysis. In affected sib pair (ASP) data, this distribution can be worked out explicitly as (0.5 - c)chi(2)(0) + 0.5chi(2)(1) + cchi(2)(2), where c depends on the assumed trait model. E.g., for a simple dominant model (HLOD/D), c is a function of the disease allele frequency p: for p = 0.01, c = 0.0006; while for p = 0.1, c = 0.059. For a simple recessive model (HLOD/R), c = 0.098 independently of p. This latter (recessive) distribution turns out to be the same as the asymptotic distribution of the MLS statistic under the possible triangle constraint, which is asymptotically equivalent to the HLOD/R. The null distribution of the HLOD/D is close to that of the LOD, because the weight c on the chi(2)(2) component is small. These results mean that the cutoff value for a test of size alpha will tend to be smaller for the HLOD/D than the HLOD/R. For example, the alpha = 0.0001 cutoff (on the lod scale) for the HLOD/D with p = 0.05 is 3.01, while for the LOD it is 3.00, and for the HLOD/R it is 3.27. For general pedigrees, explicit analytical expression of the null HLOD distribution does not appear possible, but it will still depend on the assumed genetic model.

Chromosome Mapping↗
PubMed2001

Effects of adenosine on thrombosis and thrombolysis in a canine experimental preparation.

Intracoronary infusion of adenosine is reported to inhibit cyclic flow variations after coronary artery injury and stenosis. This study was performed in the anesthetized dog to determine if adenosine prevents arterial thrombosis and/or reocclusion after thrombolysis. Carotid and coronary arteries were instrumented with Doppler(TM) flow probes, a critical stenosis, infusion line and an anodal electrode. Two protocols were employed. In the thrombosis protocol, intracarotid infusion of adenosine (20 microg/kg/min for 3 h) did not alter cyclic flow variations or patency during induction of vessel wall injury. In the second protocol, occlusive arterial thrombi were induced by anodal current injury and lysed with local application of tissue plasminogen activator. Whereas adenosine prolonged the time to arterial occlusion, it did not affect cyclic flow variations or time to reocclusion after thrombolysis.

Adenosine↗
PubMed2001

Chronic endothelin-1 treatment leads to heterologous desensitization of insulin signaling in 3T3-L1 adipocytes.

We recently reported that insulin and endothelin-1 (ET-1) can stimulate GLUT4 translocation via the heterotrimeric G protein G alpha q/11 and through PI3-kinase--mediated pathways in 3T3-L1 adipocytes. Because both hormones stimulate glucose transport through a common downstream pathway, we determined whether chronic ET-1 pretreatment would desensitize these cells to acute insulin signaling. We found that ET-1 pretreatment substantially inhibited insulin-stimulated 2-deoxyglucose uptake and GLUT4 translocation. Cotreatment with the ETA receptor antagonist BQ 610 prevented these effects, whereas inhibitors of G alpha i or G beta gamma were without effect. Chronic ET-1 treatment inhibited insulin-stimulated tyrosine phosphorylation of G alpha q/11 and IRS-1, as well as their association with PI3-kinase and blocked the activation of PI3-kinase activity and phosphorylation of AKT: In addition, chronic ET-1 treatment caused IRS-1 degradation, which could be blocked by inhibitors of PI3-kinase or p70 S6-kinase. Similarly, expression of a constitutively active G alpha q mutant, but not the wild-type G alpha q, led to IRS-1 degradation and inhibited insulin-stimulated phosphorylation of IRS-1, suggesting that the ET-1-induced decrease in IRS-1 depends on G alpha q/11 and PI3-kinase. Insulin-stimulated tyrosine phosphorylation of SHC was also reduced in ET-1 treated cells, resulting in inhibition of the MAPK pathway. In conclusion, chronic ET-1 treatment of 3T3-L1 adipocytes leads to heterologous desensitization of metabolic and mitogenic actions of insulin, most likely through the decreased tyrosine phosphorylation of the insulin receptor substrates IRS-1, SHC, and G alpha q/11.

3T3 Cells↗
PubMed2001

Latifolosides I and J, two new triterpenoid saponins from the bark of Ilex latifolia.

Two new triterpenoid saponins, latifoloside I (1), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl 3beta,21alpha,28-trihydroxy-urs-12-ene 21-O-beta-D-glucopyranoside; latifoloside J (2), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-3beta,21alpha-dihydroxy-ursolic acid 21-O-beta-D-glucopyranoside, along with two known compounds, latifoloside C (3) and latifoloside E (4), were isolated from the bark of Ilex latifolia THUNB. Structure assignments were established on the basis of spectroscopic data and chemical evidence.

Carbohydrate Conformation↗
PubMed2001

Latifolosides K and L, two new triterpenoid saponins from the bark of Llex latifolia.

Two new triterpenoid saponins, latifoloside K (1), 3-O-beta-D-glucopyranosyl-(1-->3)-[alpha-L-rhamnopyranosyl-(1-->2)-]-alpha-L-arabinopyranosyl 3beta-hydroxy-urs-12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester and latifoloside L (2), 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->3)-[alpha-L-rhamnopyranosyl-(1-->2)-]-alpha-L-arabinopyranosyl 3beta,19alpha-dihydroxyursolic acid, were isolated from the bark of Ilex latifolia Thunb. Also isolated were two known compounds, ilekudinoside A (3) and kudinoside G (4). Structural assignments were established on the basis of spectroscopic data and chemical evidence.

Carbohydrate Conformation↗
PubMed2001

Two new podophyllotoxin glucosides from Sinopodophyllum emodi (Wall.) Ying.

Two new aryltetralin-type lignans, isopodophyllotoxin 7'-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (1) and 4-demethyl-picropodophyllotoxin 7'-O-beta-D-glucopyranoside (2), along with eight known podophyllotoxin derivatives: 4-demethyl-podophyllotoxin 7'-O-beta-D-glucopyranoside (3), podophyllotoxin 7'-O-beta-D-glucopyranoside (4), deoxypodophyllotoxin (5), picropodophyllotoxin (6), podophyllotoxin (7), 4-demethyl-picropodophyllotoxin (8), 4-demethyl-podophyllotoxin (9), and 4-demethyl-deoxypodophyllotoxin (10), were isolated from the roots and rhizomes of Sinopodophyllum emodi (Wall.) Ying (Berberidaceae). Their structures were identified based on NMR spectral data and chemical evidence.

Glucosides↗
PubMed2001

Clinical trial of arotinolol in the treatment of hypertension: dippers vs. non-dippers.

To compare the effects of an alpha, beta blocker, arotinolol, in the treatment of essential hypertension between patients with a dipper and those with a non-dipper profile by means of 24-h ambulatory blood pressure monitoring (ABPM), a multicenter single blind parallel trial was carried out in five clinical centers. After a one-week single blind placebo run-in period, the patients underwent ABPM if their clinic diastolic blood pressure (DBP) ranged from 90-109 mmHg and their clinic systolic blood pressure (SBP) was <180 mmHg. They were divided into two groups according to the absence (non-dipper group, 24 cases) or presence (dipper group, 23 cases) of nocturnal BP reduction > or =10% of daytime BP. ABPM was measured again at the end of the active treatment phase. All patients were given Arotinolol 10-20 mg twice daily for 4 weeks. Twenty four-hour systolic and diastolic average BPs (MSBP, MDBP), 24-h systolic and diastolic blood pressure load (LS BP, LDBP), daytime systolic and diastolic average BPs (dMSBP, dMDBP), daytime systolic and diastolic blood pressure load (dLSBP, dLDBP), nighttime systolic and diastolic average BPs (nMSBP, nMDBP) and nighttime systolic and diastolic blood pressure load (nLSBP, nLDBP) were calculated. Arotinolol was effective in 78.2% of dippers and 54.2% of non-dippers, but the difference in effectiveness between these groups was not statistically significant. After treatment, SBP and DBP-including 24-h, daytime and nighttime systolic and diastolic BPs- were significantly reduced in both groups. During the daytime period, the systolic and diastolic blood pressures were significantly reduced in both dippers and non-dippers, while nighttime systolic and diastolic blood pressures were significantly reduced only in the non-dipper group. No significant changes were found in the dipper group over this period. In conclusion, Arotinolol, which can be dosed twice daily, is an effective antihypertensive agent which effectively lowers blood pressure during the day while reducing nighttime blood pressure more in non-dippers than in dippers, without excessive lowering blood pressure in the latter.

Adrenergic beta-Antagonists↗
PubMed2001

New supports for enzyme immobilization based on copolymers of vinylene carbonate and acrylamide.

In this study, a series of beadlike and hydrophilic supports containing reactive cyclic carbonate groups for enzyme immobilization were prepared via reverse-phase suspension copolymerization of the aqueous solutions of vinylene carbonate (VCA), acrylamide (AA), and N,N'-methylene bisacrylamide in paraffin oil. The supports were used as a matrix for immobilization of trypsin and showed a considerable capacity to couple with trypsin and reasonable retention of activity for the immobilized trypsin, depending on the immobilization conditions, such as the content of VCA structural units, reaction time, and pH of the medium.

Acrylamide↗
PubMed2001

Quantitative detection of Chlamydia spp. by fluorescent PCR in the LightCycler.

Quantitative detection of intracellular bacteria of the genus Chlamydia by the standard cell culture method is cumbersome and operator dependent. As an alternative, we adapted hot-start PCR to the glass capillary quantitative PCR format of the LightCycler. The optimized PCR was consistently more efficient than commercially available pre-assembled PCRs. Detection by quantitative PCR of as few as single copies of DNA of Chlamydia spp. was accomplished by SYBR Green fluorescence of the dsDNA product and by fluorescence resonance energy transfer (FRET) hybridization probes. The PCRs were 15-fold more sensitive than the cell culture quantitative assay of C. psittaci B577 infectious stock. The number of chlamydial genomes detected by C. psittaci B577 FRET PCR correlated well with cell culture determination of inclusion forming units (IFUs) (r = 0.96, P < 0.0008). When infected tissue samples were analyzed by cell culture and PCR, the correlation coefficient between IFUs and chlamydial genomes was higher with C. psittaci B577 FRET PCR (r = 0.90, P < 0.0004) than with Chlamydia omp1 SYBR Green PCR (r = 0.85, P < 0.002).

Bacterial Outer Membrane Proteins↗
PubMed2001

Mutagenesis of the rapamycin producer Streptomyces hygroscopicus FC904.

Rapamycin (RPM) is produced by Streptomyces hygroscopicus FC904 isolated from soil in Fuzhou, China. It is a triene macrolide antibiotic with potential application as an immunosuppressant and drug for human gene therapy. In an attempt to improve rapamycin production, mutation and screening of the parent culture have been carried out. Thousands of survivors were obtained after mutagenesis by NTG (3 mg/ml) and UV (30 W, 15 cm, 30 seconds) of spore suspensions. None showed improved production of RPM. We determined the susceptibility to antibiotics of S. hygroscopicus FC904 by two fold dilutions of antibiotics in oatmeal agar plates. It was found that the strain was resistant to penicillin, erythromycin, RPM, tetracycline and chloramphenicol, but susceptible to mitomycin C (MIC, 10 microg/ml) and aminoglycosides such as gentamicin (MIC, 0.1 microg/ml), kanamycin (MIC, 0.1 microg/ml) and streptomycin (MIC, 0.3 microg/ml). Protoplasts of strain FC904 were prepared after finding the best conditions for their formation. They were treated with gentamicin, erythromycin, mitomycin C and NTG. Surprisingly, gentamicin was especially effective for obtaining higher RPM-producing mutants. Mutant C14 was selected by exposing the protoplasts of the parent strain FC904 to 1 microg/ml of gentamicin at 28 degrees C for 2 hours. A higher RPM-producing mutant (C14-1) was obtained from the protoplasts of mutant C14 treated with gentamicin, and its titer was 60% higher than that of the parent strain FC904 by HPLC analysis. Another improved mutant (C14-2) was obtained from the spores of mutant C 14 treated with 1 microg/ml of gentamicin plus 2 mg/ml of NTG at 28 degrees C for 2 hours. Mutant C14-2 had a titer 124% higher than FC904. The possible mechanism for the effect of gentamicin by using protoplasts or spore suspensions will be discussed, i.e. the possibility of gentamicin being a mutagen or a selective agent.

Anti-Bacterial Agents↗
PubMed2001

Future space. A new blueprint for business architecture.

Although the Internet is an essential conduit for many business activities, it isn't rendering the physical world any less important, as the failures of many Web merchants demonstrate. People need social and sensual contact. The companies that succeed will be those best able to integrate the physical and the virtual. But that requires a new kind of business architecture--a new approach to designing stores, offices, factories, and other spaces where business is conducted. The author, a faculty member at Harvard Graduate School of Design, provides practical guidelines to help managers and entrepreneurs think creatively about the structures in which their businesses operate. He outlines four challenges facing designers of such "convergent" structures, so-called because they function in both physical and virtual space: matching form to function, allowing visitors to visualize the presence of others, personalizing spaces, and choreographing connectivity. Using numerous examples, from a fashion retailer that wants to sell in stores as well as through a Web site to a radically new kind of consulate, the author shows how businesses can meet each challenge. For instance, allowing customers to visualize the presence of others means that visitors to a Web site should be given a sense of other site visitors. Personalizing physical and virtual spaces involves using databases to enable those spaces to adapt quickly to user preferences. The success of companies attempting to merge on-line and traditional operations will depend on many factors. But without a well-designed convergent architecture, no company will fully reap the synergies of physical space and Internet technology.

Architecture↗
PubMed2001

Frequent inactivation of the TP53 gene in esophageal squamous cell carcinoma from a high-risk population in China.

Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal cancers worldwide, and north central China has some of the highest rates in the world. Previous studies from tumors in this area of China have shown high frequencies of allelic loss on chromosome 17p13-11, which includes the region where the TP53 gene is found. We examined 56 ESCC patients using single-strand conformation polymorphism and DNA sequencing to assess the frequency and spectrum of TP53 mutation and the association between allelic loss at microsatellite marker TP53 and TP53 mutations. Ninety-six % of cases were found to have at least one genetic alteration, including TP53 mutation (77%), allelic loss within the TP53 gene (73%), and/or loss of heterozygosity at the TP53 microsatellite marker (80%); 75% had two or more such alterations, including 59% with both a point mutation and an intragenic allelic loss ("two hits"). The majority of mutations observed were in exon 5, where the most common type of nucleotide substitution was a G:C-->A:T or C:G-->T:A transition, including half that occurred at CpG sites. Allelic loss was most commonly found in exon 4 but was very common in exon 5 as well. Taken together, the multiple genetic alterations of TP53 in this population at high risk for ESCC indicate that there is a very high degree of genetic instability in these tumors, that TP53 is a primary target for inactivation, and that this tumor suppressor gene plays a critical role in the carcinogenesis process for ESCC.

Adult↗
PubMed2001

Control of chromatin accessibility for V(D)J recombination by interleukin-7.

IL-7 is a key factor for lymphoid development, and it contributes to V(D)J recombination at multiple loci in immune-receptor genes. IL-7 signal transduction, involving gamma(c) and Jak3, is required for successful recombination at the TCR-gamma locus. IL-7 signaling controls the initiation phase of V(D)J recombination by controlling access of the V(D)J recombinase to the locus. In the absence of IL-7, the TCR-gamma locus is methylated and packaged in a repressed form of chromatin consisting of hypoacetylated histones. IL-7 signaling likely increases the acetylation state of the nucleosomal core histones resulting in an "open" form of chromatin. This opening leads to a higher accessibility for the transcription machinery and increased accessibility of the Rag heterodimer that performs the cleavage of DNA.

Acetylation↗
PubMed2001

[Cloning and high level expression of mosquito detoxifying gene].

The full-length cDNA of mosquito esterase B1 had been isolated, and subcloned into pBV220. The recombinant vector pBV220B1 was constructed and transformed into E. coli DH5 alpha. A 60 kD protein was induced by 42 degrees C and its expression was temperature-dependent. After 6 h induction, the target protein occupied 50% of the total protein. The expressed product existed in both inclusion body and soluble proteins in the cells. The amount of the soluble detoxifying enzyme increased along with the induction time. The data of detoxifying experiments indicated that the detoxifying enzyme in expression strain of E. coli can detoxified toxicity of organophosphate insecticides, it showed a clear detoxifying affect on hens poisoned by organophosphate insecticides.

Animals↗