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Biomedical subjects

J M Wan

Publications and source records attributed to J M Wan.

At least 19 recordsLinked to original sources
PubMed2006

QTL analysis for rice grain length and fine mapping of an identified QTL with stable and major effects.

Grain length in rice plays an important role in determining rice appearance, milling, cooking and eating quality. In this study, the genetic basis of grain length was dissected into six main-effect quantitative trait loci (QTLs) and twelve pairs of epistatic QTLs. The stability of these QTLs was evaluated in four environments using an F7 recombinant inbred line (RIL) population derived from the cross between a Japonica variety, Asominori, and an Indica variety, IR24. Moreover, chromosome segment substitution lines (CSSLs) harboring each of the six main-effect QTLs were used to evaluate gene action of QTLs across eight environments. A major QTL denoted as qGL-3a, was found to express stably not only in the isogenic background of Asominori but also in the recombinant background of Asominori and IR24 under multiple environments. The IR24 allele at qGL-3a has a positive effect on grain length. Based on the test of advanced backcross progenies, qGL-3a was dissected as a single Mendelian factor, i.e., long rice grain was controlled by a recessive gene gl-3. High-resolution genetic and physical maps were further constructed for fine mapping gl-3 by using 11 simple sequence repeat (SSR) markers designed using sequence information from seven BAC/PAC clones and a BC4F2 population consisting of 2,068 individuals. Consequently, the gl-3 gene was narrowed down to a candidate genomic region of 87.5 kb long defined by SSR markers RMw357 and RMw353 on chromosome 3, which provides a basis for map-based cloning of this gene and for marker-aided QTL pyramiding in rice quality breeding.

Alleles↗
PubMed2005

Stability of QTLs for rice grain dimension and endosperm chalkiness characteristics across eight environments.

Rice appearance quality, including traits specifying grain dimension and endosperm chalkiness, represents a major problem in many rice-producing areas of the world. In this study, the genetic basis of six appearance quality traits of milled rice was dissected into quantitative trait loci (QTL) main effects, and the stability of these QTLs was assessed in a population of 66 chromosome segment substitution lines (CSSLs) across eight environments. The CSSLs showed transgressive segregation for many of the traits, and significant correlations were detected among most of the traits. Twenty-two QTLs were identified on eight chromosomes, and numerous QTLs affecting related traits were mapped in the same regions, probably reflecting pleiotropic effects. Nine QTLs, namely qGL-1,qGL-3, qGW-5,qLWR-3, qLWR-5,qPGWC-8, qPGWC-9, qACE-8, and qDEC-8, were consistently detected across the eight environments. The additive main effect and multiplicative interaction (AMMI) analysis showed that genotype (G) x environment (E) interaction was significant for all six traits, with the first three iPCA terms accounting for over 80% of the G x E variance. Both D(I) values and the iPCA1-iPCA2 biplots showed that the CSSLs harboring the nine QTL alleles were more stable than those carrying any of the additional 13 QTL alleles, thereby confirming their environmental stability and pointing to their appropriateness as targets for marker-assisted selection for high-quality rice varieties.

Analysis of Variance↗
PubMed2004

QTL detection for eating quality of cooked rice in a population of chromosome segment substitution lines.

The genetic mechanism underlying six palatability properties of cooked rice and three physico-chemical traits was dissected in 66 BC(3)F(2) chromosome segment substitution lines (CSSLs), using a complete linkage map in three successive years. The CSSLs showed transgressive segregation for all traits studied. Significant correlation was detected among most palatability traits. A total of 25 QTLs for the nine traits were identified on nine chromosomes, and many QTLs affecting different quality traits were mapped in the same regions. Six QTLs--qLT-8 for luster, qTD-6 and qTD-8 for tenderness, qIVOE-6 and qIVOE-8 for integrated value of organoleptic evaluation, and qAC-8 for amylose content--were repeatedly detected across the 3 years. Phenotypic values were significantly different between the recurrent parent, cultivar Asominori, and the CSSLs harboring any of the six QTL alleles across the three environments, indicating that these six QTLs were non-environment-specific and could be used for marker-assisted selection in rice quality improvement.

Chromosome Mapping↗
PubMed2001

Eicosapentaenoic acid modulates cyclin expression and arrests cell cycle progression in human leukemic K-562 cells.

Eicosapentaenoic acid (EPA) is a polyunsaturated fatty acid (20:5omega3) found primarily in aquatic organisms. We have shown previously that EPA inhibits the growth but is not toxic to human leukemic K-562 cells. In this study, the anti-proliferative effect of EPA on the leukemic cells was further determined and its impacts on cell cycle progression and cyclin expression were investigated. EPA inhibited proliferation of K-562 cells, which was associated with accumulation of G0/G1 cells and down-regulation of cyclin E expression. Cyclin B1-expressing cells were also reduced showing that down-regulation of cyclin expression might be important in the anti-proliferation of EPA.

Apoptosis↗
PubMed2001

[Analysis of heading time genotype for a rice male sterile line Zhenshan 97A].

Zhenshan 97A, a rice male sterile, were applied widely since the release of hybrid rice in 1973 in China, but the genotype of heading time in this sterile line was still unknown. This definitely limited the further use of this sterile line in breeding practice and re-production of hybrid seeds. To solve this problem, we analyzed the segregation pattern of phenotype of heading time in progenies from crosses between Zhenshan 97A and four tester cultivars, Akihikari (e1e1e2e2e3e3 Se-1eSe-1e), Koshihikari (E1E1E2E2e3e3Se-1eSe-1e), Nipponbare (E1E1e2e2e3e3Se-1Se-1) and Hinohikari (E1E1E2E2e3e3Se-1Se-1), whose genotypes of heading time were already known. The results showed that the genotype of heading time in Zhenshan 97A was e1e1e2e2E3E3Se-1Se-1 and it also carried a recessive inhibitor i-Se-1 for phtoperiod-sensitivity. Meanwhile, a major photoperiod-sensitive dominant genes Se-1 and other modified photoperiod-sensitive genes: i-Se-1, E3, Hd3(En-Se-1), Hd5 and Hd6, were identified in Zhenshan 97A by crossing with QTL nearly isogenic lines: NIL (Hd1), NIL (Hd2), NIL(Hd3), NIL(Hd5) and NIL(Hd6).

Chromosome Mapping↗
PubMed2000

Induction of apoptosis by dietary polyunsaturated fatty acids in human leukemic cells is not associated with DNA fragmentation.

Apoptosis is important in anticancer strategy. In this study, bivariate annexin V/PI flow cytometry showed that dietary polyunsaturated fatty acids, arachidonic acid (AA) and eicosapentaenoic acid (EPA), induced apoptosis in human leukemic HL-60 but not K-562 cells. Results from DNA-PI flow cytometry and TUNEL flow cytometry illustrated that neither AA nor EPA induced DNA fragmentation in the leukemic cells. These findings suggested that the AA- and EPA-induced apoptosis might not associate with endonucleases activation, and DNA fragmentation could not be used as a sole criterion to identify apoptotic cells.

Apoptosis↗
PubMed1999

Induction of apoptosis in HL-60 cells by eicosapentaenoic acid (EPA) is associated with downregulation of bcl-2 expression.

Dietary polyunsaturated fatty acids (PUFAs) have been reported as a potential group of natural products which modulate tumor cell growth. In present study, eicosapentaenoic acid (EPA) was found to inhibit proliferation of human leukemic HL-60 and K-562 cells in vitro. EPA arrested cell cycle progression at G0/G1 phase, and induced necrosis in both HL-60 and K-562 cells. However, EPA induced apoptosis only in HL-60 but not K-562 cells. Also, bcl-2 protein expression was downregulated in much greater extent than that of bax showing that depression of bcl-2 might be an important step during the EPA-induced apoptosis in HL-60 cells.

Apoptosis↗
PubMed1995

Insulin-like growth factor-1 is not mitogenic for the Walker-256 carcinosarcoma.

This study was designed to determine whether intravenous infusion of recombinant human insulin-like growth factor 1 (IGF-1) stimulates tumor growth. In order to determine the potential interaction between nutrition and IGF-1 administration the study was conducted in fasting rats and during continuous feeding by total parenteral nutrition. Tumor cell cycle kinetics including labeling index, DNA synthesis time, cell cycle time in Go/G1, and G2/M in the total cell cycle, and potential doubling time were determined by flow cytometry after in vivo pulse labeling the rats bearing the Walker-256 Carcinosarcoma with 5'-bromo-2'-deoxyuridine (BrdUrd). The results show that IGF-1 treatment has no significant effects on the proliferative characteristics of the tumor model regardless of the feeding status of the animal. This study provides preliminary cell-cycle kinetics data on the short-term effect of IGF-1 on tumor growth. Failure to show a significant effect of IGF-1 on the proliferative characteristics of the tumor suggests that IGF-1 may be given to cancer patients in amounts sufficient to promote weight gain without deleterious stimulation of tumor proliferation.

Animals↗
PubMed1994

DNA replication time accounts for tumor growth variation induced by dietary fat in a breast carcinoma model.

Female Fischer rats were pair-fed on diets containing either safflower oil (SO) or fish oil (FO) for 6 weeks. Implanted breast 13762 MAT tumors had a doubling times of 35.4 and 55.5 h in SO and FO rats, respectively (P < 0.001). Proliferation kinetics were measured in vivo by bromedeoxyuridine (BrdUrd) labeling and bivariate DNA/BrdUrd analysis by flow cytometry. After 1 h of pulsing, the labeling index was similar in both groups. However, 6 h later, tumor cells from FO rats had significantly lower relative movement of BrdUrd-labeled cells (0.78 vs. 0.91, P < 0.001). These results reflected a significantly longer S phase duration (15.0 vs. 9.1 h, P < 0.001) in FO rats and accounted for all the difference in tumor growth rates. This mechanism, which has not previously been reported, implies a significant role for fatty acids in DNA replication.

Animals↗
PubMed1994

Influence of interleukin-2 infusion on cell cycle kinetics in the Walker-256 carcinosarcoma.

The effect of recombinant human interleukin-2 (IL-2) on tumor cell cycle kinetics was evaluated in rats bearing the Walker-256 carcinosarcoma. Seven days after implantation, tumor-bearing rats were infused intravenously with IL-2 at a dose of 500 mg/kg body weight or 5% dextrose for 6 h. Tumor cell mean DNA synthesis time (TDNA), labeling index, potential doubling time (Tpot), and growth fraction (GF) were determined in vivo by use of bromodeoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis using flow cytometry. IL-2 treatment significantly reduced the relative number of S-phase cells by 11.9% and increased the number of cells in the G0/G1 phase by 9.4%. The labeling index was reduced from 41.3 +/- 2.5% to 32.7 +/- 1.2% (P < .01). Estimates of TDNA derived from the change in BrdUrd movement relative to DNA content were not affected by IL-2 treatment. Based on these cytokinetic changes, IL-2 infusion significantly increased tumor Tpot from 15.3 +/- 0.3 h to 21.5 +/- 0.2 h (P < .001) and reduced GF from 1.01 +/- 0.07 to 0.83 +/- 0.01 (P < 0.001). The inhibitory effect of IL-2 infusion on tumor cell growth, which may be either direct or secondarily mediated by other factors, contrasts with other stimulatory effects of this cytokine on lymphoid cell proliferation.

Animals↗
PubMed1994

Effect of low and high amounts of a structured lipid containing fish oil on protein metabolism in enterally fed burned rats.

To determine the optimal fat intake and source in nutritional support, we measured the protein-sparing effects of a structured lipid (SL) derived from 60% medium-chain triglyceride (MCT) and 40% fish oil and a 50:50 soybean to safflower oil emulsion (long-chain triglyceride, LCT). Male Sprague-Dawley rats received an enteral diet for 7 d with either all nonprotein energy as dextrose (control diet) or 10% or 35% nonprotein energy as SL or LCT. The rats were burned on day 3. Indirect calorimetry and nitrogen balance were measured on day 2 (preburn) and days 4 and 6 (postburn). Respiratory quotient decreased postburn. There was a significant increase in total energy expenditure postburn, particularly with 35% LCT. Nitrogen balance was best without fat and 10% fat compared with 35% fat and with SL compared with LCT. These results confirm previous studies that fish oil-containing SLs possess protein-sparing effects in burn injury and that 10% SL seems optimal for nutritional support in burn injury.

Analysis of Variance↗
PubMed1993

Evaluation of antitumor effect of tumor necrosis factor in terms of protein metabolism and cell cycle kinetics.

To determine the significance of protein breakdown in regulating tumor growth and to better understand the antitumor mechanism of tumor necrosis factor in vivo, we measured the effects of a 6-h constant intravenous infusion of human recombinant tumor necrosis factor-alpha (rHuTNF) on tumor protein metabolism and cell cycle kinetics in rats bearing the Walker-256 carcinosarcoma. Protein metabolism was investigated with the use of [14C]leucine infusion; estimates of tumor cell cycle kinetics were obtained in vivo by use of 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis by flow cytometry. Reduction in tumor growth by rHuTNF was associated with a dose-dependent increase in tumor proteolysis but no change in tumor protein synthesis. At the cellular level, rHuTNF had a significant cytostatic effect on G2/M cells and caused a marked decrease in the fraction of cells capable of BrdUrd uptake. Release of BrdUrd, an indicator of cell death, was noted in only 7.5% of tumor cells labeled at the beginning of rHuTNF infusion. These results suggest that either tumor protein breakdown may influence cell cycle activity by regulating cytoplasmic protein mass or that tumor proteolysis may be a compensatory mechanism for limiting cytoplasmic size when cellular division is interrupted suddenly.

Animals↗
PubMed1992

Influence of omega-3 fatty acids on splanchnic blood flow and lactate metabolism in an endotoxemic rat model.

Alteration in regional blood flow is important in the pathogenesis of organ failure during endotoxemia and sepsis. In particular, intestinal ischemia is thought to enhance the translocation of bacteria into the systemic circulation. We used radioactive microspheres to measure the influence of two intravenous (IV) dietary fats (vegetable oil containing high levels of omega-6 fatty acids, and fish oil containing high levels of omega-3 fatty acids) on regional blood flow during low-dose Escherichia coli endotoxin infusion (0.1 mg/100 g body weight [BW]) in a rat model. Despite absence of changes in the cardiac output, blood flow rates to the small and large intestines, stomach, and pancreas, and also to the skin and skeletal muscle were significantly reduced after 18 hours of endotoxin infusion in the rats fed standard vegetable oil. Short-term IV feeding during a period of 40 hours with an isonitrogenous, isocaloric nutrient solution containing fish oil as the only lipid source normalized intestinal perfusion and increased blood flow to the liver and spleen. Low-dose endotoxin infusion also resulted in significant increases in glucose, lactate, and pyruvate concentrations. In comparison to standard vegetable fat emulsion, fish oil significantly reduced these parameters. A second experiment was conducted to measure lactate kinetics. Based on the dilution of U-14C-lactate, fish oil feeding was associated with higher lactate clearance than standard vegetable oil feeding during the endotoxin infusion. We conclude that short-term IV feeding with fish oil improves intestinal perfusion and portal blood flow, improves glucose tolerance, and increases lactate clearance in a low-dose endotoxin rat model.

Animals↗
PubMed1991

Comparative effects of omega-3 and omega-6 polyunsaturated fatty acids on protein metabolism in rats bearing the mammary adenocarcinoma.

The comparative effects of diets containing 20% (wt/wt) of either fish oil (FO) or safflower oil (SO) on protein synthesis and catabolism were determined in rats bearing the 7,12-dimethylbenz(a)anthracene (DMBA) 13762 mammary adenocarcinoma in vivo using a 6-hour constant infusion of L-(1-14C)-leucine. Tumor-bearing animals fed FO had significantly lower tumor growth rate (36 +/- 0.5 v 53 +/- 0.7%/d, P less than .05), total tumor protein synthesis (Ts) (1.25 +/- 0.1 v 1.85 +/- 0.1 mumol/h, P less than .05), and tumor protein concentration (12.0 +/- 0.5 v 14.0 +/- 0.7%/d, P less than 0.01). Tumor fractional synthetic rate and total protein breakdown rate of the tumor were unaffected by FO feeding. Both tumor-bearing and saline-control animals fed FO had significantly (P less than .01) lower liver fractional synthetic rate and total protein breakdown rate, and higher liver total protein compared with SO-fed rats. Muscle protein kinetics were unaffected by either treatment or diet. Whole body protein kinetics were not affected by dietary treatment, but the presence of tumor significantly (P less than .001) reduced whole body flux, synthesis, breakdown, and oxidation. Chronic FO feeding for 7 weeks significantly (P less than .001) lowered omega-6 polyunsaturated fatty acids (omega-6 PUFAs) and significantly elevated omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (P less than .001) in both plasma phospholipid and triglycerides. The present study indicates that dietary FO can modulate mammary tumor growth in a manner that reflects changes in protein metabolism in both host and tumor tissues.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Long-term feeding with structured lipid composed of medium-chain and N-3 fatty acids ameliorates endotoxic shock in guinea pigs.

The metabolic and physiologic responses to 7-hour endotoxin infusion (5.0 mg/kg h) were evaluated in guinea pigs following 6 weeks of dietary enrichment with diets containing either chemically structured lipid (SL) composed of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) in the form of N-3 polyunsaturated fatty acids (PUFAs), or safflower oil (SO), which is high in N-6 fatty acids. Plasma phospholipid fatty acid profiles, arterial blood pH, PCO2, PO2, HCO3, lactate, blood pressure, oxygen consumption, and energy expenditure were examined. Plasma phospholipid fatty acids profiles reflected dietary intake with SL-fed animals demonstrating a significantly higher N-3 to N-6 fatty acid ratio compared with SO-fed animals. SL-fed animals responded to endotoxemia with a mild metabolic acidosis with respiratory compensation, which was associated with moderate lactatemia (3 mmol/L). SO-fed animals developed a severe metabolic acidosis with acidemia and respiratory compensation, which was associated with hyperlactatemia (8 mmol/L, P less than .05 v SL). No differences were observed in blood pressure, oxygen consumption, energy expenditure, or respiratory quotient during endotoxemia between dietary groups compared with controls. We conclude that diets enriched with structured lipid composed of medium-chain and N-3 fatty acids can attenuate the sequelae of endotoxemia.

Animals↗
PubMed1989

Nutrition, immune function, and inflammation: an overview.

The collective evidence suggests that nutritional insult to both cell-mediated and humoral immunity in the presence of protein-energy malnutrition contributes to abnormalities of inflammation. The primary goal of nutritional support in inflammatory disease is to provide adequate energy and protein to meet endogenous requirements for tissue repair, IL-1 production, and restored cellular function, thus preventing secondary infection. Substrate provision should aim at improving the acute phase of injury while avoiding immune dysfunction. This goal may be achieved by altering the eicosanoid pathway toward a more regulated inflammatory state. In the context of allograft response, macrophages are central to the initiation of allosensitization by virtue of their ability to present antigen to T-cells. Activated T-cells may further modulate macrophage function by the secretion of lymphokines. Manipulation of macrophage eicosanoid production by dietary omega-3 PUFA may reduce cellular immune response. (table; see text) Nutritional support should also focus on providing essential micronutrients, with their potentially immunomodulating role, as adjunctive therapy in order to protect the host from toxic effects of free-radicals and chemicals released during inflammatory events. (Feeding regimens currently under investigation and development are presented in Table 4.) By integrating dietary immunotherapy with the use of recombinant hormones, monoclonal antibodies, and various available monokines, an optimal outcome for each patient may be achieved. However, effective application of immunotherapy to nutritional supplementation will require accurate monitoring of immune function in individual patients in order to avoid inappropriate treatment.

Animals↗
PubMed1987

Effect of dietary linoleate content on the metabolic response of rats to Escherichia coli endotoxin.

Dietary fat influences many aspects of immune function. Escherichia coli endotoxin is a potent stimulator of interleukin 1 production from macrophages. The present study examines the effect of feeding with fat diets rich (corn oil) and poor (coconut oil) in linoleate at high and low concentrations on responses to endotoxin. Spleen phosphatidylcholine linoleate contents were higher in the corn oil than in the coconut oil group and arachidonate concentrations were highest in the group fed a high concentration of corn oil. Coconut oil completely abolished the responses to endotoxin. The inhibitory effects of coconut oil could largely be due to reduced prostaglandin and leukotriene synthesis.

Animals↗