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Biomedical subjects

S Xu

Publications and source records attributed to S Xu.

At least 289 records · Page 16Linked to original sources

Mapping quantitative trait loci for ordered categorical traits in four-way crosses.

Many quantitative traits of economical importance are ordinal in nature. Although methods of mapping quantitative trait loci (QTLs) for continuous quantitative characters are well developed, such methods for ordinal characters are generally lacking. In this paper, we develop a method based on the framework of a generalized linear model using four-way cross populations. The method estimates and tests the average effects of a gene substitution in the parents. All markers in the same linkage group are simultaneously used to infer the allelic transmission of a putative QTL. General results of the method are demonstrated by a few simulation experiments. We discuss extensions of the method to QTL mapping in full-sib families.

Animals↗

Studies on dammarane-type saponins in the flower-buds of Panax ginseng C.A. Meyer.

From the dried flower-buds of Panax ginseng C.A. Meyer, a new minor dammarane-type triterpene saponin named ginsenoside III together with nine known saponins was isolated. On the basis of spectral and chemical evidence, the structure of the new saponin was elucidated as 3-O-[beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-beta- D-glucopyranosyl-3 beta,12 beta,20(S)-trihydroxy-dammar-25-en-24-one.

Magnetic Resonance Spectroscopy↗

Neutralization of syncytium-inducing primary isolates by sera from human immunodeficiency virus (HIV)-uninfected recipients of candidate HIV vaccines.

Most candidate human immunodeficiency virus (HIV)-1 vaccines induce antibodies that neutralize T cell line-adapted HIV-1 strains. Until recently, however, no neutralizing activity against primary HIV-1 isolates had been demonstrated in sera from human vaccinees. Since most candidate HIV-1 vaccines have been constructed from T cell line-adapted syncytium-inducing (SI) strains, experiments were done to test whether sera from recipients of SI-based vaccines could preferentially neutralize SI primary HIV-1 isolates. Various neutralization assays were performed with sera from volunteers receiving ALVACgp160MN and/or rgp120SF2. Neutralizing activity was detected against 4 of 8 SI primary isolates but against none of 5 non-SI primary isolates. The data suggest that, for the induction of neutralizing antibodies to a broad array of HIV-1 primary isolates, a polyvalent vaccine will be needed containing representatives of more than a single category of viruses.

AIDS Vaccines↗

Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. NIAID AIDS Vaccine Evaluation Group.

A safety and immunogenicity trial was conducted in vaccinia-immune and vaccinia-naive human immunodeficiency virus (HIV)-uninfected adults who were randomized to receive 10(6) or 10(7) TCID50 of canarypox (ALVAC) vector expressing HIV-1MN gp160 or 10(5.5) TCID50 of ALVAC-rabies virus glycoprotein control at 0 and 1 or 2 months and ALVAC-gp160 or 50 microg of HIV-1SF2 recombinant (r) gp120 in microfluidized emulsion at 9 and 12 months; others received rgp120 at 0, 1, 6, and 12 months. All vaccines were well-tolerated. Neither vaccinia-immune status before vaccination nor ALVAC dose affected HIV immune responses. HIV-1MN and HIV-1SF2 neutralizing antibodies were detected more often (100%) in ALVAC-gp160/rgp120 recipients than in recipients of ALVAC-gp160 (<65%) or rgp120 (89%) alone. ALVAC-gp160/rgp120 also elicited more frequent HIV V3-specific and fusion-inhibition antibodies, antibody-dependent cellular cytotoxicity, lymphoproliferation, and cytotoxic CD8+ T cell activity than did either vaccine alone. Trials with ALVAC expressing additional HIV components and rgp120 are underway.

AIDS Vaccines↗

Mapping quantitative trait loci using multiple families of line crosses.

To avoid a loss in statistical power as a result of homozygous individuals being selected as parents of a mapping population, one can use multiple families of line crosses for quantitative trait genetic linkage analysis. Two strategies of combining data are investigated: the fixed-model and the random-model strategies. The fixed-model approach estimates and tests the average effect of gene substitution for each parent, while the random-model approach treats each effect of gene substitution as a random variable and directly estimates and tests the variance of gene substitution. Extensive Monte Carlo simulations verify that the two strategies perform equally well, although the random model is preferable in combining data from a large number of families. Simulations also show that there may be an optimal sampling strategy (number of families vs. number of individuals per family) in which QTL mapping reaches its maximum power and minimum estimation error. Deviation from the optimal strategy reduces the efficiency of the method.

Chromosome Mapping↗

Combining different line crosses for mapping quantitative trait loci using the identical by descent-based variance component method.

Mapping quantitative trait loci (QTLs) is usually conducted with a single line cross. The power of such QTL mapping depends highly on the two parental lines. If the two lines are fixed for the same allele at a putative QTL, the QTL is undetectable. On the other hand, if a QTL is segregating in the line cross and is detected, the estimated variance of the QTL cannot be extrapolated beyond the statistical inference space of the two parental lines. To reduce the likelihood of missing a QTL and to increase the statistical inference space of the estimated QTL variance, we present a consensus QTL mapping strategy. We adopt the identical by descent (IBD)-based variance component method originally applied to human linkage analysis by combining multiple line crosses as independent families. We explore the properties of consensus QTL mapping and demonstrate the method with F2, backcross (BC), and full-sib (FS) families. In addition, we examine the effects of the QTL heritability, marker informativeness, QTL position, the number of families, and family size. We show that F2 families notably outperform BC and FS families in detecting a QTL. There is a substantial reduction in the standard deviation of the estimated QTL position and the separation of the QTL and polygenic variance. Finally, we show that the power to detect a QTL is greater when using a small number of large families than a large number of small families.

Chromosome Mapping↗

Endothelins: effect on matrix biosynthesis and proliferation in normal and scleroderma fibroblasts.

We investigated the effect of endothelin-1 (ET-1) in normal and systemic sclerosis (SSc) dermal fibroblasts. Collagen type I, collagen type III, and MMP-1 levels in culture supernatants were measured by competition ELISA and cellular mRNA expression was examined by Northern blotting. Mitogenic responses to ET-1 were assessed by [3H]TdR incorporation. ET receptor mRNA expression was examined by RT-PCR analysis of fibroblast RNA and with surface binding studies using radiolabeled ET receptor ligands and specific receptor antagonists. ET-1 enhanced release of collagen types I and III by control and SSc fibroblast strains, but the effects were significantly greater for control cells (p < 0.05). This effect appeared to involve both ETA and ETB receptor subtypes. SSc fibroblasts demonstrated lower constitutive MMP-1 production than control fibroblasts (p < 0.01), but ET-1 treatment decreased MMP-1 in normal fibroblasts to levels observed in SSc. Mitogenic response (percent control [3H]TdR incorporation) to ET-1 for SSc fibroblasts was 130 +/- 34, significantly less (p < 0.01) than that for normal fibroblasts strains (290 +/- 25). This response appeared to be predominantly mediated via the ETA receptor subtype. Surface binding studies suggested a significantly lower level of ETA binding sites in SSc compared with normal fibroblasts (p < 0.05). These data suggest that ET-1 induces a fibrogenic phenotype in normal dermal fibroblasts that resembles that seen in fibroblasts grown from lesional SSc skin. Moreover, SSc cells appear to be refractory to these effects, and this reduced responsiveness is associated with an altered ratio of ETA:ETB receptor expression, supporting a role for ET-1 in the fibrotic pathology of SSc.

Cell Division↗

Induction of neutralizing antibodies to T-cell line-adapted and primary human immunodeficiency virus type 1 isolates with a prime-boost vaccine regimen in chimpanzees.

Five chimpanzees were immunized by administration of one or more intranasal priming doses of one to three recombinant adenoviruses containing a gp160 insert from human immunodeficiency virus type 1 (HIV-1) MN (HIV-1MN) followed by one or more boosts of recombinant HIV-1SF2 gp120 delivered intramuscularly with MF59 adjuvant. This regimen resulted in humoral immune responses in three of five animals. Humoral responses included immunochemically active anti-H1V-1 antibodies (Abs) directed to recombinant gp120 and neutralizing Abs reactive with T-cell-line-adapted HIV-1MN and HIV-1SF2. In addition, neutralizing activity was detected to the two homologous primary isolates and to two of three heterologous primary isolates which, like the immunizing strains, can use CXCR4 as a coreceptor for infection. The three animals with detectable neutralizing Abs and a fourth exhibiting the best cytotoxic T-lymphocyte response were protected from a low-dose intravenous challenge with a cell-free HIV-1SF2 primary isolate administered 4 weeks after the last boost. Animals were rested for 46 weeks and then rechallenged, without a boost, with an eightfold-higher challenge dose of HIV-1SF2. The three animals with persistent neutralizing Abs were again protected. These data show that a strong, long-lived protective Ab response can be induced with a prime-boost regimen in chimpanzees. The data suggest that in chimpanzees, the presence of neutralizing Abs correlates with protection for animals challenged intravenously with a high dose of a homologous strain of HIV-1, and they demonstrate for the first time the induction of neutralizing Abs to homologous and heterologous primary isolates.

Animals↗

Neutralization profiles of primary human immunodeficiency virus type 1 isolates in the context of coreceptor usage.

Most strains of human immunodeficiency virus type 1 (HIV-1) which have only been carried in vitro in peripheral blood mononuclear cells (primary isolates) can be neutralized by antibodies, but their sensitivity to neutralization varies considerably. To study the parameters that contribute to the differential neutralization sensitivity of primary HIV-1 isolates, we developed a neutralization assay with a panel of genetically engineered cell lines (GHOST cells) that express CD4, one of eight chemokine receptors which function as HIV-1 coreceptors, and a Tat-dependent green fluorescent protein reporter cassette which permits the evaluation and quantitation of HIV-1 infection by flow cytometry. All 21 primary isolates from several clades could grow in the various GHOST cell lines, and their use of one or more coreceptors could easily be defined by flow cytometric analysis. Ten of these primary isolates, three that were CXCR4 (X4)-tropic, three that were CCR5 (R5)-tropic, and four that were dual- or polytropic were chosen for study of their sensitivity to neutralization by human monoclonal and polyclonal antibodies. Viruses from the X4-tropic category of viruses were first tested since they have generally been considered to be particularly neutralization sensitive. It was found that the X4-tropic virus group contained both neutralization-sensitive and neutralization-resistant viruses. Similar results were obtained with R5-tropic viruses and with dual- or polytropic viruses. Within each category of viruses, neutralization sensitivity and resistance could be observed. Therefore, sensitivity to neutralization appears to be the consequence of factors that influence the antibody-virus interaction and its sequelae rather than coreceptor usage. Neutralization of various viruses by the V3-specific monoclonal antibody, 447-52D, was shown to be dependent not only on the presence of the relevant epitope but also on its presentation. An epitope within the envelope of a particular virus is not sufficient to render a virus sensitive to neutralization by an antibody that recognizes that epitope. Moreover, conformation-dependent factors may overcome the need for absolute fidelity in the match between an antibody and its core epitope, permitting sufficient affinity between the viral envelope protein and the antibody to neutralize the virus. The studies indicate that the neutralization sensitivity of HIV-1 primary isolates is a consequence of the complex interaction between virus, antibody, and target cell.

Cell Line↗

Active and inhibitory components of the insulin-like growth factor binding protein-3 protease system in adult serum, interstitial, and synovial fluid.

Circulating insulin-like growth factor binding protein-3 (IGFBP-3) proteolytic activity is normally low but increases in serum from pregnant women and from patients with various pathologies. In contrast, we have recently reported that outside the circulation, such activity is normally high but decreases in various pathologies. We have now compared components of the IGFBP-3 proteolytic system revealed after size fractionation of serum and extravascular fluids with different intrinsic levels of such activity. Normal serum, serum from pregnant women, and synovial fluid from patients with rheumatoid arthritis revealed high and low molecular weight (MW) areas of activity. However, only the low MW activity was apparent in interstitial fluid from normal skin (N Inst F) or psoriatic lesions (P Inst F) and in synovial fluid from normal volunteers (N Syn F) or patients with osteoarthritis (OA Syn F). Addition of inhibitors revealed both areas to comprise more than one enzyme, including serine proteases and metalloproteinases; both could also be inhibited by P Inst F, NS, RA Syn F, and inhibitory fractions from the separation of the latter two. These findings demonstrate low and high MW regions of proteolytic activity, which may contribute to the IGFBP-3 protease system, the former always present, whereas the latter seems to be retained within the circulation apart from inflammatory conditions. The variations apparent in IGFBP-3 protease activity in the intact samples related to the presence of an inhibitor, which may protect IGFBP-3 from proteolysis, rather than to changes in the component proteases.

Adult↗

The effect of ruminal bypass lysine and methionine on milk yield and composition of lactating cows.

Fifty-six multiparous Holstein cows were assigned at 3 wk prepartum to rations based on grass silage with 1) corn distillers grains to provide 86 and 90% of estimated required metabolizable Lys and Met, respectively; 2) a blend of blood meal, fish meal, and meat and bone meal as amino acid (AA) sources to provide 112 and 103% of required metabolizable Lys and Met, respectively; 3) ruminally protected Lys and Met added as a top-dressing to ration 1 to provide 27 g/d of Lys and 8 g/d of Met as available AA at the duodenum postpartum; and 4) ruminally protected AA for 8 wk postpartum as a top-dressing to ration 1 to provide 40 g/d of Lys and 13 g/d of Met as available AA at the duodenum. Cows fed rations 3 and 4 were offered 13.5 g/d of duodenally available Lys and 4 g/d of duodenally available Met for 3 wk prepartum. The total length of the study was 43 wk. Cows fed ration 4 consumed 3 to 4 kg more dry matter than did cows fed the other three rations, and milk yield and the percentage of milk protein and fat were significantly increased during the first 8 wk of lactation. In early lactation, cows fed ration 3 had a greater milk fat percentage but similar dry matter intake, protein percentage, and yield of 4% fat-corrected milk compared with cows fed ration 2. The concentrations of blood serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, triglyceride, and nonesterified fatty acids were lower for cows fed ration 4 during the first 8 wk of lactation than they were for cows fed the other three rations. The mammary arteriovenous difference of whole blood AA indicated that Met along with His and Arg may be the most limiting AA for milk yield.

Amino Acids↗

N-ras mutations in 43 Chinese cases of acute myeloid leukemia.

OBJECTIVE: To detect 3 kinds of N-ras mutations in Chinese patients with acute myeloid leukemia (AML). METHODS: In vitro DNA amplification followed by oligonucleotide dot analysis were used to study N-ras gene mutations in 43 cases of acute myeloid leukemia (AML). 25 healthy people were used as controls. Patients were selected in the Beijing district and consisted of 19 males and 24 females. The average age was 37. The controls were healthy individuals with the average age of 36.5 from the same region. 3 oligonucleotide probes were artificially synthesized to detect mutations in codon 12 and 13 of N-ras. RESULTS: Five out of 43 AML samples have been found contain G-->A mutation in codon 12.2 have G-->T mutation in codon 12. One has G-->A mutation in codon 13. The mutation rate was 18.6%. None of the controls presented these mutations. The frequency of mutation of N-ras in the AML samples showed statistical differences with that of the controls. CONCLUSION: Analysis of the results suggests the N-ras mutations may have some relationship with the etiology of acute myeloid leukemia.

Adult↗

Anti-Sa antibody in Chinese rheumatoid arthritis.

OBJECTIVE: To test anti-Sa antibody in different autoimmune connective tissue diseases and analyze the relationship between Sa antibody and clinical manifestations and laboratory tests in rheumatoid arthritis. METHOD: Sa antigen was extracted from human placenta. Anti-Sa antibody was tested in 40 normal people and 478 connective tissue disease (CTD) patients using Western Blotting (WB). RESULTS: Sa antigen was a protein with molecular weights of 50 kD and 55 kD. Anti-Sa antibody was positive in 31.9% (61/191) rheumatoid arthritis (RA), 3.0% (2/67) Sjögren's syndrome (SS), 4.3% (2/46) systemic lupus erythmatosus (SLE) and 0% (0/66) Behcet's disease, 0% (0/60) polymyositis/dermatomyositis (PM/DM), 0% (0/66) other CTD and 0% (0/40) normal controls. Anti-Sa antibody was different from other auto-antibodies in RA. In rheumatoid arthritis its sensitivity, specificity, positive prediction rate, negative prediction rate were 31.9%, 98.6%, 93.8% and 68.5% respectively. Anti-Sa antibody positive patients were significantly different from anti-Sa antibody negative patients in moming stiffness, ESR, ANA and X-ray grade. CONCLUSION: Anti-Sa antibody was a new auto-antibody for the diagnosis of RA. Anti-Sa antibody positive patients seem to have more serious inflammation and more advanced disease process.

Adult↗

[The responses of fibroblasts from three parts of keloids and normal skin to interleukin-1 beta and interleukin-6].

OBJECTIVE: The purpose of this study was to explore the responses of fibroblasts from keloids and normal skin to interleukin-1 beta and interleukin-6. METHODS: Six samples of keloids and 6 samples of normal skin were collected as the experimental and control group respectively. The means of cell culture was used to investigate the responses of fibroblasts from three different parts of keloids and normal skin to interleukin-1 beta (200 U/ml) and interleukin-6 (100 U/ml). RESULTS: Interleukin-1 beta could inhibit the growth of fibroblasts from the proliferative part of keloids but stimulate growth of those from normal skin, while it did not affect the growth of those from other parts of keloids. Fibroblasts from different parts of keloids and normal skin were all inhibited by interleukin-6. CONCLUSION: The responses of fibroblasts from three parts of keloids and normal skin to interleukin-1 beta and interleukin-6 were not much similar.

Adult↗

[Study on in situ expression of type I and III procollagen mRNAs in different parts of keloid and normal skin].

OBJECTIVE: Based on the histomorphologic differences of three parts of keloid, i.e., invasive, proliferative and senile regions, the study was carried out to explore the differences of expression of type I and type III procollagen mRNAs in the three different parts of keloid and normal skin. METHOD: Four samples of keloid from four patients and two samples of normal skin were collected. The expression of pro alpha 1 (I) and pro alpha 1 (III) procollagen mRNAs in keloid and normal skin was investigated by in situ hybridization techniques. RESULT: Both type I and III procollagen mRNAs levels increased in keloid, especially type I, resulting in elevated ratios of type I to III procollagen mRNA. In keloid, expressive intention of type I and type III procollagen mRNAs was higher in the papillary layer than in the reticular layer. Also the expressive intention of type I and type III in keloid was higher in invasive and proliferative regions than in the senile region. However, expressive intention of type I and type III procollagen mRNAs in the invasive region of keloid was similar to that in the proliferative region. CONCLUSION: The differences of expression of type I and type III procollagen mRNAs in different pathological regions of keloid and normal skin is one cause of forming different pathological regions in keloid.

Adult↗

A clinical study on bing gan ling oral liquid for treatment of hepatitis C.

Based on the principles of cooling the blood to expel the pathogenic toxins and regulating the function of liver and activating the spleen in traditional Chinese medicine, 60 cases of chronic hepatitis C were treated with Bing Gan Ling (BGL), an oral liquid, which is composed mainly of Shuiniujiao (Cornu Bubali), Huzhang (Rhizoma Polygoni Cuspidati), Chishao (Radix Paeoniae Rubra), and Huangqi (Radix Astragali), etc. The total effective rate was 86.7%, which is considerably better than that of the control group (P < 0.01). The animal experiments and pathological studies suggest that the above-mentioned prescription has marked action of protecting the liver and lowering the activity of enzymes; and that it can ameliorate the acute liver injury induced by D-galactosamine.

Adult↗

[A study on the anti-metastatic effects of CD3Ak cells in nude mice].

OBJECTIVE: To investigate whether cancer draining lymph node lymphocytes activated by CD3 McAB in vitro have anti-tumor effects in vivo. METHODS: Nude mice with highly metastatic human ovarian cancer were treated with CD3 McAB activated killer cells (CD3AK) from human ovarian cancer draining lymph node lymphocytes. 31 experimental nude mice were divided into 4 groups; the cisplatin group (7 mice), the CD3AK cells group (7 mice), the combined treatment group (7 mice), and control group (10 mice). Treatment began on the 10th day after tumor transplantation for a total of 80 days. RESULTS: The transplanted tumors disappeared in 1 mouse of CD3AK group, significant difference in the anti-metastatic effect was found between the CD3AK group (2/7 mice with metastasis) and the control group (8/10 mice with metastasis). Significant difference in average tumor volume was found between the CD3AK group (0.5788 +/- 0.2549) and the control group (1.5685 +/- 0.283). The tumor growth inhibition rate reached 63.1% in the CD3AK group. Significant difference in the serum level of progesterone was found between the CD3AK group (3.3843 +/- 0.5314) and the control group (6.3480 +/- 0.7615). Significant difference in the histiocyte increase in the lymph node sinuses was found between the CD3AK group (59/69) and the control group (55/94). CONCLUSION: These results suggest that CD3AK cells appear to be effective in tumor growth inhibition, anti-metastasis and enhancing host immunologic function.

Animals↗