Rescuing acute rejection of rat cardiac allografts with FTY720.
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Biomedical subjects
Publications and source records attributed to Y C Li.
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The effects of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on the N-acetyltransferase (NAT) activity and DNA adduct formation in PC-3 cells (human prostate tumor) was studied. PC-3 cells were placed into tissue culture flasks and grown in an incubator as cytosols and intact cells. The BHA or BHT were added to the cytosols and intact cells. The NAT activity in cytosol and intact PC-3 cells were measured by HPLC assaying exhibited for the amounts of N-acetyl-2-aminofluorene and N-acetyl-p-aminobenzoic acid, 2-aminofluorene and p-aminobenzoic acid. The NAT activity in PC-3 cells and cytosols were inhibited by BHA or BHT in a dose-dependent manner; that is, the higher the concentrations of BHA or BHT the higher inhibition of NAT activity. The NAT values of K(m) and V(max) from PC-3 cells were also decreased by BHA or BHT in both cytosols and intact cells. The data also demonstrated concomitant exposure to BHA or BHT decreased AF-DNA adduct formation which was seen in the PC-3 cells. In addition, the formation of DNA adduct was decreased after BHA or BHT exposure. These findings suggested the usefulness of using human cultured PC-3 cells for assessing arylamine-induced DNA adduct formation. Furthermore, the findings illustrate how effectively BHA or BHT reduce the adduct formation.
Computerized medical decision support systems have been a major research topic in recent years. Intelligent computer programs were implemented to aid physicians and other medical professionals in making difficult medical decisions. This report compares three different mathematical models for building a traumatic brain injury (TBI) medical decision support system (MDSS). These models were developed based on a large TBI patient database. This MDSS accepts a set of patient data such as the types of skull fracture, Glasgow Coma Scale (GCS), episode of convulsion and return the chance that a neurosurgeon would recommend an open-skull surgery for this patient. The three mathematical models described in this report including a logistic regression model, a multi-layer perceptron (MLP) neural network and a radial-basis-function (RBF) neural network. From the 12,640 patients selected from the database. A randomly drawn 9480 cases were used as the training group to develop/train our models. The other 3160 cases were in the validation group which we used to evaluate the performance of these models. We used sensitivity, specificity, areas under receiver-operating characteristics (ROC) curve and calibration curves as the indicator of how accurate these models are in predicting a neurosurgeon's decision on open-skull surgery. The results showed that, assuming equal importance of sensitivity and specificity, the logistic regression model had a (sensitivity, specificity) of (73%, 68%), compared to (80%, 80%) from the RBF model and (88%, 80%) from the MLP model. The resultant areas under ROC curve for logistic regression, RBF and MLP neural networks are 0.761, 0.880 and 0.897, respectively (P < 0.05). Among these models, the logistic regression has noticeably poorer calibration. This study demonstrated the feasibility of applying neural networks as the mechanism for TBI decision support systems based on clinical databases. The results also suggest that neural networks may be a better solution for complex, non-linear medical decision support systems than conventional statistical techniques such as logistic regression.
A number of repetitive DNA clones were generated from PCR amplifications of Indian muntjac genomic DNA using primer sequences derived from a white tailed deer satellite II DNA sequence. One clone (Mmv-0.7) was characterized and shown to be a cervid satellite II DNA clone. Multiple colored FISH studies with cervid satellite I (C5) and this satellite II clone (Mmv-0.7) to Chinese muntjac metaphase chromosomes localized both satellite DNAs at the pericentromeric regions of all chromosomes except for chromosome 3 and the Y chromosome, whereas chromosome 3 exhibited pericentromeric satellite II DNA only. Where distinguishable, the pericentromeric satellite II signals appeared terminally oriented with respect to satellite I. Six pairs of Chinese muntjac autosomes had interstitial satellite I sites with four of these autosomal pairs (chromosomes 1, 2 and two other smaller autosomal pairs) also exhibiting interstitial satellite II signals. An interstitial site on the X chromosome was found to have satellite II signals. For the Indian muntjac chromosomes, FISH studies revealed a pericentromeric hybridization for satellites I and II as well as 27 distinct interstitial hybridization sites, each having at least one of the satellite DNAs. These data were used to more precisely define the chromosome fusion-associated breakpoints that presumably led to the formation of the present-day Indian muntjac karyotype. It further hints at the possibility that the Indian muntjac karyotype may have evolved directly from a 2n = 70 ancestral karyotype rather than from an intermediate 2n = 46 Chinese muntjac-like karyotype.
Two stripe-rust resistance genes, YrH52 and Yr15, derived from the Israeli wild emmer wheat, Triticum dicoccoides, have been located on chromosome 1B. The main objectives of the present study were to increase marker density in the vicinity of YrH52 gene by means of AFLP, RAPD and microsatellite markers, to improve the map of another T dicoccoides-derived stripe-rust resistance gene Yr15 using microsatellite markers, and to preliminarily discriminate these two genes. Additional 26 marker loci comprising 20 AFLPs, three RAPDs, and three microsatellites were found to be linked to YrH52 gene. An updated genetic map consisting of 45 marker loci, in the region of YrH52 gene, was constructed with a total map length of 107.7 cm. The mean interval length was 0.96 cm in the region Xgwm359b-P55M53b carrying YrH52 gene. YrH52 was bracketed by Xgwm413 (Nor1 and UBC212a) and Xgwm273a (Xgwm273d) with map distance of 1.3 and 2.7 cm from either side, respectively. Eight additional microsatellite markers were found to be linked with Yr15, and the linkage map of Yr15 gene was thus obviously improved. In the YrH52-mapping population, no crossover was detected in the interval UBC212a (Xgwm413)-Yr15-Nor1, and YrH52 was located distally outside this interval. It may suggest that YrH52 is different from Yr15 even though both of them are derived from T. dicoccoides and are mapped on chromosome 1BS. The large number of molecular makers revealed in the present study would be helpful for the marker-assisted introgression of the T. dicoccoides-derived YrH52 and Yr15 stripe-rust resistance genes into elite cultivars of wheat, and the high-density map would accelerate the map-based cloning of the two genes.
Ras1 GTPase is the Schizosaccharomyces pombe homolog of the mammalian Ha-Ras proto-oncoprotein. Ras1 interacts with Scd1 (aka Ral1), a presumptive guanine nucleotide exchange factor for Cdc42sp, to control organization of the cytoskeleton. In this study, we demonstrated that the scd1 deletion (scd1Delta) induced hypersensitivity to microtubule destabilizing drugs and instability of the minichromosome. Overexpression of scd1 induced formation of abnormal spindles and chromosome missegregation. The scd1 deletion worsened the defects of spindle formation in tubulin mutants; by contrast, it did not induce lethality in mutants defective in the spindle pole bodies. These genetic data suggest that Scd1 can interact with tubulin with substantial specificity to affect proper spindle formation and chromosome segregation. Subcellular localization data further illustrated that a GFP-Scd1 fusion protein can associate with the spindle. Finally, we showed that unlike ras1Delta and scd1Delta, byr2Delta (affecting the Ras1 effector for mating) is not synthetically lethal with the tubulin mutations. These data collectively suggest that the Ras1 pathway can impinge upon microtubules through Scd1, but not Byr2, to affect proper spindle formation and chromosome segregation.
Arginine methylation in RNA-binding proteins containing arginine- and glycine-rich RGG motifs is catalyzed by specific protein arginine N-methyltransferase in cells. We previously showed that lymphoblastoid cells grown in the presence of an indirect methyltransferase inhibitor, adenosine dialdehyde (AdOx), accumulated high level of hypomethylated protein substrates for the endogenous protein methyltransferases or recombinant yeast arginine methyltransferase [Li, C. et al. (1998) Arch. Biochem. Biophys. 351, 53-59]. In this study we fractionated the lymphoblastoid cells to locate the methyltransferases and the substrates in cells. Different sets of hypomethylated methyl-accepting polypeptides with wide range of molecular masses were present in cytosolic, ribosomal, and nucleus fractions. The methylated amino acid residues of the methyl-accepting proteins in these fractions were determined. In all three fractions, dimethylarginine was the most abundant methylated amino acid. The protein-arginine methyltransferase activities in the three fractions were analyzed using recombinant fibrillarin (a nucleolar RGG protein) as the methyl-accepting substrate. Fibrillarin methylation was strongest in the presence of the cytosolic fraction, followed by the ribosomal and then the nucleus fractions. The results demonstrated that protein-arginine methyltransferases as well as their methyl-accepting substrates were widely distributed in different subcellular fractions of lymphoblastoid cells.
Three trials were conducted to evaluate the effect of moniliformin (M) on performance and immune function in chicks. Day-old chicks were randomly assigned to four dietary treatments (0, 50, 75, or 100 mg M/kg diet). In Trial 1, chicks were placed on treatments for 3 wk and were injected intravenously with 4.6 x 10(6) Escherichia coli on Day 21. Blood samples were collected at 60, 120, and 180 min after inoculation, and liver, spleen, and lung were collected at 180 min postinjection. Compared with control chicks, chicks fed 75 and 100 mg M/ kg diet had higher (P < 0.05) numbers of E. coli colonies in the circulation, liver, and spleen. In Trial 2, chicks were placed on diets for 4 wk and were injected with 0.5 mL Newcastle disease virus (NDV) vaccine intramuscularly on Weeks 2 and 3 of the experiment. The primary and secondary anti-NDV antibody titers were measured 7 d after each injection. Chicks fed 100 mg M/kg diet had lower (P < 0.05) secondary antibody titers than did control chicks. In Trial 3, lymphocyte proliferation in chicks exposed to M in vivo and in vitro was determined. Results of the in vivo study showed that cell proliferation in response to mitogens from control- and M-fed chicks did not differ (P > 0.05). For the in vitro study, lymphocyte proliferation decreased linearly (P < 0.01) with increased concentrations of M. In all three trials, chicks fed 100 mg M/kg diet had lower (P < 0.05) feed intake and weight gain than did control chicks. Data from the current study suggested that M decreased performance and immune response in chicks at the level of 75 mg/kg diet.
In vivo and in vitro experiments were conducted to determine whether P in a low-phytate corn (LPC) containing the lpa 1-1 allele is more available than P in a near-isogenic wild-type corn hybrid (NC). The LPC was analyzed to contain 0.18% nonphytate P and 0.26% total P (TP), whereas NC contained 0.05% nonphytate P and 0.25% TP. For these studies, nonphytate P was considered to be available P (AP). In the in vivo study, 150 1-d-old male chicks were randomly assigned to five treatments (six pens of five chicks each) for 21 d. The dietary treatments included: A) a diet containing 60% NC, 0.2% AP, and 0.8% Ca; B) a diet containing 60% LPC, 0.28% AP, and 0.8% Ca; C) an NC diet similar to Diet A, but with KH2PO4 added to increase the AP to 0.28% to match the AP in Diet B; D) an LPC diet containing 0.45% AP and 1% Ca; and E) an NC diet supplemented with KH2PO4 to provide 0.45% AP and 1% Ca. Diets A, B, and C were semipurified diets, with corn being the sole source of phytate. The only differences between Diets A and B were the source of corn and the amount of AP present in the diets. The levels of AP in these diets were deficient in order to measure the animal response to the different levels of AP. Diets D and E were typical corn-soybean meal diets, and were formulated to contain an optimal level of AP. Performance and bone ash were similar (P > 0.05) in chicks fed Diets B and C and in chicks fed Diets D and E. Chicks fed LPC diets (B and D) retained more P (P < 0.05) than chicks fed NC diets (C and E). Chicks fed Diet B had significantly higher (P < 0.05) Ca retention compared with chicks fed Diet A. An in vitro digestion procedure that simulated the physiological conditions of the gastrointestinal tract of broilers was used to determine P release from LPC and NC. Results showed that 65% (1,420 mg/kg) of the TP in LPC was released, compared with 23% (543 mg/kg) from NC. Results of these experiments indicate that the P in LPC is more available than the P in NC, and reducing the phytate content did not compromise the nutritional value of LPC. The increased P retention in chicks fed LPC suggests that substituting LPC for NC leads to a reduction in manure P. Also, the in vitro procedure accurately predicted differences in in vivo P availability between the two corns.
Effects of feeding diets containing fumonisin B1 (FB1) and moniliformin (M), singly or in combination, on performance and immune response were evaluated in poults. Day-old poults were randomly assigned to one of four dietary treatments with four replicates of four poults each. Dietary treatments were 1) control; 2) 200 mg FB1, 0 mg M/kg diet; 3) 0 mg FB1, 100 mg M/kg diet; and 4) 200 mg FB1, 100 mg M/kg diet. In Experiment 1, poults were injected with 0.25 mL Newcastle disease virus (NDV) vaccine on Weeks 2 and 3 of the experiment, and anti-NDV antibody titers were measured 7 d after each injection. Compared with controls, poults fed FB1 had significantly lower (P < 0.05) secondary antibody response. Poults fed M and the combination of FB1 and M had significantly lower (P < 0.05) primary and secondary antibody response. Lower relative thymus weights were observed in poults fed diets containing FB1 or M. Decreased relative bursa and spleen weights were observed in poults fed M. In Experiment 2, poults were placed on dietary treatments for 3 wk. On Day 21, 2 x 10(6) peripheral lymphocytes were incubated with mitogens. Poults fed diets containing FB1 had a significantly lower (P < 0.05) proliferative response to mitogens in comparison to controls. In Experiment 3, poults were placed on the diets for 3 wk and were injected with 4.4 x 10(7) E. coli/kg body weight on Day 21. Significantly higher (P < 0.05) numbers of E. coli colonies were observed in the blood and tissue homogenates of poults fed M. In all three experiments, feed intake and body weight gains were significantly lower (P < 0.05) in turkeys fed diets containing M. Data from the present study suggest that FB1 and M are immunosuppressive in poults and that M not only suppresses immune response but also performance. However, neither synergistic nor additive effects between FB1 and M were observed for any of the parameters measured.
The main objectives of the study reported here were to construct a molecular map of wild emmer wheat, Triticum dicoccoides, to characterize the marker-related anatomy of the genome, and to evaluate segregation and recombination patterns upon crossing T. dicoccoides with its domesticated descendant Triticum durum (cultivar Langdon). The total map length exceeded 3000 cM and possibly covered the entire tetraploid genome (AABB). Clusters of molecular markers were observed on most of the 14 chromosomes. AFLP (amplified fragment length polymorphism) markers manifested a random distribution among homologous groups, but not among genomes and chromosomes. Genetic differentiation between T. dicoccoides and T. durum was attributed mainly to the B genome as revealed by AFLP markers. The segregation-distorted markers were mainly clustered on 4A, 5A, and 5B chromosomes. Homeoalleles, differentially conferring the vigor of gametes, might be responsible for the distortion on 5A and 5B chromosomes. Quasilinkage, deviation from free recombination between markers of nonhomologous chromosomes, was discovered. Massive negative interference was observed in most of the chromosomes (an excess of double crossovers in adjacent intervals relative to the expected rates on the assumption of no interference). The general pattern of distribution of islands of negative interference included near-centromeric location, spanning the centromere, and median/subterminal location. [An appendix describing the molecular marker loci is available as an online supplement at http://www.genome.org.]
Several repetitive DNA fragments were generated from PCR amplifications of caribou DNA using primer sequences derived from the white-tailed deer satellite II DNA clone OvDII. Two fragments, designated Rt-0.5 and Rt-0.7, were sequenced and found to have 96% sequence similarity. These caribou clones also had 85% sequence similarity with OvDII. Multiple-colored fluorescence in situ hybridization (FISH) studies with satellite I and satellite II DNA probes to caribou metaphase chromosomes and extended chromatin fibers provided direct visualization of the genomic organization of these two satellite DNA families, with the following findings: (1) Cervid satellite I DNA is confined to the centromeric regions of the acrocentric autosomes, whereas satellite II DNA is found at the centromeric regions of all chromosomes except for the Y. (2) For most acrocentric chromosomes, the satellite I signal appeared to be medially located at the primary constriction, in contrast to that of satellite II, which appeared to be oriented toward the lateral sides as two separate fluorescent dots. (3) The satellite II clone Rt-0.7 appeared to be enriched in the centromeric region of the caribou X chromosome, a pair of biarmed autosomes, and a number of other acrocentric autosomes. (4) Fiber-FISH demonstrated that the satellite I and satellite II arrays were juxtaposed. On highly extended chromatin fibers, the total length of the hybridization signals for the two satellite DNA arrays often reached 300-400 microm. The length of a given satellite II array usually reached 200 microm, corresponding to 2 x 10(3) kb of DNA in a given centromere.
Three new lignans, ficusal (1) and ficusesquilignans A (2), B (3) and one new gamma-lactone, ficusolide diacetate (4), were isolated from the wood of Ficus microcarpa L.f. Their structures were determined by spectral evidence.
Developers of consumer health information (CHI) websites and pages in Taiwan have included: 1) individuals; 2) general hospitals; 3) disease-oriented associations; 4) government health administrative agencies; and 5) commercial corporations. General hospitals have developed the largest number of sites, but the quality of these sites differs widely. The unprecedented impact of health-oriented websites on medical care and the health of the public in general necessitates the establishment of credible instruments for the evaluation and rating of the quality of such websites and pages. In this paper, we describe the current status of CHI websites and pages in Taiwan. Suggestions for improving the content of CHI websites and pages are also proposed.
OBJECTIVE: To explore the pharmacological action and optimal concentration of borneol in treating suppurative otitis media. METHOD: Aspergillus niger separated from the secretion in external auditory canal of the patient and the fungus strains kept in the laboratory were used to determine the minimum fungus inhibiting concentration (MIC) and minimum fungus killing concentration (MFC) of borne. The change of cell ultrastructure after borneol taking effect was observed under electron microscope. RESULT: Borneol MIC and MFC turned out to be 5% and 10% respectively. The cell wall of Aspergillus niger became thicker and blurred with vacuoles. In the cytoplasm various materials were found deep dyed and agglutinated with many fat drops. The electron density increased and the ridge arrangement was in disorder. Some organelles were destroyed, and many areas of electron blank appeared. Some cells became warped and deformed and lost their original structure. CONCLUSION: Borneol can destroy the structure of fungus cells, make fungus dissolve and dieout and thus features a fungus inhibiting and killing function. The optimal inhibiting concentration is 5% and killing concentration 10%.
In fission yeast, Scd1/Ral1 is a putative guanine nucleotide exchange factor for Cdc42sp and also acts as a Ras1 effector necessary for the regulation of cytoskeleton organization. In this study, we have characterized a protein, Moe1, that binds directly to Scd1. A moe1 null (Delta) mutant exhibits numerous phenotypes indicative of abnormal microtubule functioning, including an abnormality in the spindle. moe1Delta mutants are resistant to microtubule destabilizing agents; moreover, moe1Delta rescued the growth defects of tubulin mutants containing unstable microtubules. These results suggest that Moe1 induces instability in microtubules. Biochemical and subcellular localization studies suggest that Moe1 and Scd1 colocalize in the nucleus. Furthermore, loss of function in Scd1 or Ras1 also induced abnormality in the spindle and is synthetically lethal with moe1Delta producing cells that lack a detectable spindle. These data demonstrate that Moe1 is a component of the Ras1 pathway necessary for proper spindle formation in the nucleus. Human and nematode Moe1 both can substitute for yeast Moe1, indicating that the function of Moe1 in spindle formation has been conserved substantially during evolution.
This paper describes our experience with a one-semester course on how to build a medically-related homepage on the Internet, designed for fourth-year medical students. Based on the assumption of limited technical knowledge of the Internet, this class taught students Internet-exploring skills, multimedia authoring and HTML (Hypertext Markup Language) in the first eight-week period. Students were then divided into four-person teams and asked to select a topic for a homepage. These teams were then asked to collect the necessary resources for the development of the homepage both through individual work and, consultation with an advisor. Each group project for building medically-related homepage was accomplished and presented in the remaining four-week period. The resultant projects of these fourth-year medical students were of surprisingly good content and high quality. Medical students rapidly learned to use the software tools, and through proper instruction and provision of equipment, they were able to build significant medical resources on the Internet that can potentially be useful in education, clinical applications and research.
Lifting tasks that involve twisting have been repeatedly implicated as contributing to the onset of occupational back injuries in epidemiological studies. The objective of this work was to quantify the three directional external moments acting on the spine during a sagittally symmetric and two asymmetric lifting tasks. A total of 15 subjects participated in the three lifting tasks. All tasks were performed at two qualitatively defined lifting speeds, 'slow' and 'fast', and with two load magnitudes: 10 and 20% of the subject's body weight. The mid-sagittal plane lifts were performed using two horizontal reach distances: 40 and 60 cm. A four-camera, two-forceplate motion and force measurement system were used to obtain the kinematic and kinetic data as the lifts were performed. A dynamic link-segment biomechanical model was used to quantify the reaction forces and moments at the ankle, knee, and hip and L5/S1 joints. Results from all tasks showed increased sagittal plane (forward bending) spine moments with the heavier load and at the faster lifting speed (p < 0.001). Spine lateral bending and twisting moments increased during the mid-sagittal plane lifts with the greater reach distance and the faster lifting speed, respectively. The twisting moments on the spine were greatest as subjects lifted from in front and placed the load to the side but were dependent upon the lifting speed and the load magnitude. The lateral bending moments increased during this same task with the heavier load. However, the spine lateral bending moments were greatest when lifting from one side to the other.