Biomedical subjects
Publications and source records attributed to Xin Xu.
[reaction: see text] The asymmetric halo aldol reaction (AHA) using Evans oxazolidinones as chiral auxiliaries has been established for tandem I-C/C-C bond formations. The new asymmetric reaction provides a practical approach to a variety of halo aldols of a non-Evans type that cannot be easily synthesized by other methods. Excellent diastereoselectivity (>95%) and yields (80-93%) have been obtained for eight examples.
IL-12 is a heterodimer composed of p40 and p35 and is a key cytokine that functions to protect the host from viral and microbial infections. IL-12 links the innate immune system with the acquired immune system during infection, and induces differentiation of type 1 T cells that play an important role in the eradication of microbes. The induction of the IL-12 p40 gene is regulated by NF-kappaB in the presence of IFN-gamma. IFN-gamma induces IFN regulatory factor-1 (IRF-1), which in turn induces the transcription of the IL-12 p40 gene. However, the IRF-1 binding site in the promoter region of the IL-12 p40 gene has not yet been formally determined. In the present study, we demonstrated that IRF-1 directly binds to the IL-12 p40 gene promoter and identified its binding site. The IRF-1 binding site in the promoter region of the IL-12 p40 gene is shown to be in the -72 to -58 area of the 5'-upstream region. The -63 to -61 position is the critical site within this region for the binding of IRF-1 to the IL-12 p40 gene promoter. While IFN-gamma must be present for IL-12 p40 gene induction, the p35 gene is strongly induced by LPS, even in the absence of IFN-gamma, and therefore the induction of the p35 gene is IRF-1 independent.
A new asymmetric approach to chiral beta-iodo Baylis-Hillman hydroxy esters was developed via a tandem asymmetric I-C/C-C formation reaction. The reaction was conveniently carried out by slow addition of diethylaluminum iodide into a mixture of aldehyde and alpha,beta-acetylenic menthyl ester in dichloromethane at -23 degrees C. Excellent geometric selectivity, promising diastereoselectivity and modest to high yields (up to 91%) were obtained.
Ube2b (yeast Ubc2b/Rad6 homolog) null mice were described previously. Ube2b encodes the murine ubiquitin conjugating enzyme mHR6B. Ube2b(-/-) mice were shown to present male infertility and their sperm head shape anomalies suggested that Ube2b may be involved in the replacement of nuclear proteins during spermatid chromatin condensation. Apoptosis of spermatocytes suggested additional targets of Ube2b during spermatogenesis. Consistently, we found Ube2b transcription in both meiotic and postmeiotic stages by in situ hybridization. Immuno-electron microscopy revealed that transition proteins 1 and 2, protamines 1 and 2, and actin appear normally distributed during morphogenesis of Ube2b(-/-) spermatid heads. Surprisingly, electron microscopy revealed a particular sperm flagellum phenotype characterized by an abnormal distribution of periaxonemal structures. Flagellar anomalies of Ube2b null mice were previously described in infertile men indicating a possible genetic pathway for flagellar periaxonemal assembly in human.
Csnk2a2 encodes the CK2alpha'catalytic subunit of CK2 that is predominantly expressed in testis. Male mice in which Csnk2a2 has been disrupted were infertile and displayed oligozoospermia with an abnormal shape of the spermatid nucleus. In this study, Csnk2a2 null testes revealed extensive germ cell degenerative processes at all stages of spermatogenesis, including the first spermatogenesis wave. Nuclear envelope (NE) protrusions with loss of nuclear pores, swelling of the outer membrane, and disruption of the inner membrane were observed in cells ranging from spermatogonia to early spermatids. Most early round spermatids were depleted, and DNA-specific fluorescent dyes showed a large chromatin-free nuclear domain near the chromocenter. Spermatids that were not eliminated retained NE defects that could explain the acrosomal and nuclear abnormalities of Csnk2a2 null spermatozoa. Data suggest that CK2alpha' deficiency could impair the phosphorylation of nuclear proteins of male germ cells leading to a particular cell-death pathway characterized by NE protrusions and an unusual pattern of chromatin modifications in spermatids.
OBJECTIVE: To study the effects of progesterone (P) and 18-methyl levonorgestrel (LNG) on the expression of P receptors (PRA and PRB), c-fos, c-jun, and osteocalcin in the human osteosarcoma cell line MG-63 and human normal osteoblasts in order to understand the mechanism of progestin action on the proliferation and differentiation of osteoblasts. METHODS: Cell proliferation was tested by MTT assay. The expression of PR, c-fos, c-jun, and osteocalcin was measured by semi-quantitative RT-PCR, Western immunoblot or immunocytochemistry. RESULTS: Progesterone and LNG (10(-10)-10(-6)M) stimulated cell proliferation in a dose-dependent manner. Progesterone and LNG did not affect the expression of PRA and PRB mRNA and protein, but c-fos and c-jun mRNA and protein were upregulated in a dose-dependent manner. The expression of osteocalcin mRNA was also increased in human osteoblasts in a dose and time-dependent manner with greater effects of LNG than P, while the expression of osteocalcin mRNA in MG-63 cells was not changed by P or LNG. CONCLUSION: Progesterone and LNG promote osteocalcin gene transcription by stimulating the expression of c-fos and c-jun, and result in osteoblast proliferation and differentiation.
In this paper we propose a multivariate extension of family-based association tests based on generalized estimating equations. The test can be applied to multiple phenotypes and to phenotypic data obtained in longitudinal studies without making any distributional assumptions for the phenotypic observations. Methods for handling missing phenotypic information are discussed. Further, we compare the power of the multivariate test with permutation tests and with using separate tests for each outcome which are adjusted for multiple testing. Application of the proposed test to an asthma study illustrates the power of the approach.
A robust statistical method to detect linkage or association between a genetic marker and a set of distinct phenotypic traits is to combine univariate trait-specific test statistics for a more powerful overall test. This procedure does not need complex modeling assumptions, can easily handle the problem with partially missing trait values, and is applicable to the case with a mixture of qualitative and quantitative traits. In this note, we propose a simple test procedure along this line, and show its advantages over the standard combination tests for linkage or association in the literature through a data set from Genetic Analysis Workshop 12 (GAW12) and an extensive simulation study.
While a variety of methods have been developed to deal with incomplete parental genotype information in family-based association tests, sampling design issues with incomplete parental genotype data still have not received much attention. In this article, we present simulation studies with four genetic models and various sampling designs and evaluate power in family-based association studies. Efficiency depends heavily on disease prevalence. With rare diseases, sampling affecteds and their parents is preferred, and three sibs will be required to have close power if parents are unavailable. With more common diseases, sampling affecteds and two sibs will generally be more efficient than trios. When parents are unavailable, siblings need not be phenotyped if the disease is rare, but a loss of power will result with common diseases. Finally, for a class of complex traits where other genetic and environmental factors also cause phenotypic correlation among siblings, little loss of efficiency occurs to rare disease, but substantial loss of efficiency occurs to common disease.
Consider the case that individual phenotype and genotype observations were collected from a large or moderate number of pedigrees. Some of the pedigrees have multi-generation nuclear families. For each nuclear family, the phenotype trait value of each sibling is the time to onset for a specific event (e.g., disease). Often, this event time may be right censored, that is, an individual is event-free at the study examination time point. In this article, we propose a purely nonparametric test for testing if the distribution of a Haseman-Elston distance measure between two siblings' event times is independent of their mean genetic sharing identical by descent at a genetic marker based on such incomplete observations from all the nuclear families. The new test can be implemented easily and is illustrated with a data set from the Genetic Analysis Workshop 12. The validity of the new test is examined via a simulation study.
Previously, we described an APC-adenovirus (APC-Ad) FasL cell gene therapy method which could be used to deplete autoreactive T cells in vivo. FasL was toxic, however, and controlled regulation of FasL was not achieved. Here we describe an improved approach to delivering TNF-related apoptosis-inducing ligand (TRAIL) in vivo in which collagen II-induced (CII-induced) arthritis-susceptible (CIA-susceptible) DBA/1j mice were treated with CII-pulsed DCs that had been transfected with a novel Ad system. The Ad was engineered to exhibit inducible TRAIL under the control of the doxycycline-inducible (DOX-inducible) tetracycline response element (TRE). Four groups of mice were treated with CII-DC-AdTRAIL+DOX, CII-DC-AdTRAIL (no DOX), CII-DC-AdGFP+DOX, or DC-AdTRAIL+DOX (no CII), beginning 2 weeks after priming with CII in CFA. The incidence of arthritis and infiltration of T cells in the joint was significantly decreased in CII-DC-AdTRAIL+DOX-treated mice. The in vitro splenic T cell proliferative response and induction of IFN-gamma to bovine CII stimulation were also significantly reduced in mice treated with CII-DC-AdTRAIL+DOX. AdTRAIL+DOX was not toxic to DCs or mice but could induce activated T cells to undergo apoptosis in the spleen. Our results suggest that CII-DC-AdTRAIL+DOX cell gene therapy is a safe and effective method for inhibiting the development of CIA.
AIM: Our research attempted to evaluate the overall functional reserve of cirrhotic liver by combination of hepatic functional blood flow, liver volume, and Child-Pugh's classification, and to discuss its value of clinical application. METHODS: Ninety two patients with portal hypertension due to hepatic cirrhosis were investigated. All had a history of haematemesis and hematochezia, esophageal and gastric fundus varices, splenomegaly and hypersplenia. A 2-year follow-up was routinely performed and no one was lost. Twenty two healthy volunteers were used as control group. Blood and urine samples were collected 4 times before and after intravenous D-sorbitol infusion. The hepatic clearance (CL(H)) of D-sorbitol was then calculated according to enzymatic spectrophotometric method while the total blood flow (Q(TOTAL)) and intrahepatic shunt (R(INS)) were detected by multicolor Doppler ultrasound, and the liver volume was measured by spiral CT. Data were estimated by t-test, variance calculation and chi-squared test. The relationships between all these parameters and different groups were investigated according to Child-Pugh classification and postoperative complications respectively. RESULTS: Steady blood concentration was achieved 120 mins after D-sorbitol intravenous infusion, which was (0.358+/-0.064) mmol x L(-1) in cirrhotic group and (0.189+/-0.05) mmol x L(-1) in control group (P<0.01). CL(H) =(812.7+/-112.4) ml x min(-1), Q(TOTAL) =(1280.6+/-131.4) ml x min(-1), and R(INS) =(36.54+/-10.65) % in cirrhotic group and CL(H)=(1248.3+/-210.5) ml x min(-1), Q(TOTAL)=(1362.4+/-126.9) ml x min(-1), and R(INS)=(8.37+/-3.32) % in control group (P<0.01). The liver volume of cirrhotic group was 1057+/-249 cm(3), 851+/-148 cm(3) and 663+/-77 cm(3) in Child A, B and C group respectively with significant difference (P<0.001). The average volume of cirrhotic liver in Child B, C group was significantly reduced in comparison with that in control group (P<0.001). The patient, whose liver volume decreased by 40 % with the CLH below 600 ml x min(-1), would have a higher incidence of postoperative complications. There was no strict correspondent relationship between CL(H), liver volume and Child-Pugh's classification. CONCLUSION: The hepatic clearance of D-sorbitol, CT measured liver volume can be reliably used for the evaluation of hepatic functional blood flow and liver metabolic volume. Combined with the Child-Pugh's classification, it could be very useful for further understanding the liver functional reserve, therefore help determine reasonable therapeutic plan, choose surgical procedures and operating time.
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OBJECTIVE: To observe and compare the effects of using mGTR and venous autografts to repair the defect of facial nerve in rabbits. METHODS: mGTR and venous autografts were performed on three groups of rabbits. Then physical and histological examinations were carried out to get the results of these two repair methods. RESULTS: Both the two methods can induce regeneration of facial nerve. The mGTR is more effective and faster in repairing the nerve defect. Three months after operation, the distance of NCV between bilateral facial nerve in mGTR group was (2.10 +/- 1.2) m/s, (6.80 +/- 1.4) m/s in venous autografts, (2.16 +/- 1.6) m/s in nerve transplantation group. Histologically, the facial nerve fibers were arranged regularly and in continuity in mGTR, the facial nerve fibers were arranged irregularly with marked hyperplasia of connective tissues in venous autografts three months after repair. CONCLUSIONS: The mGTR is more effective than venous autografts in repair of facial nerve.
OBJECTIVE: To evaluate the clinical value of dental implants including Brånemark, Steri-oss and BLB systems. METHODS: The total 384 implants of different materials and shapes were inserted normally. According to the Chinese standard of dental implantation, the success rates of three types were compared. RESULTS: By following-up from one year to five years, the success rates of all implants were above 97%. CONCLUSION: The success rates of routine implants were mainly associated with indication, case selection, operation, rehabilitation and patients maintenance.
The study on the response of a mutant and a wild-type of Arabidopsis to 660 microliters.L-1 CO2 and ambient CO2 showed that under elevated CO2, the stomatal numbers of the mutant increased, while those of the wild-type decreased. The chlorophyll content and NR (nitrate reductase) activity of the mutant increased, but those of the wild-type had no obvious response. The mutant was not reproductively mature after the continuous exposure to increased CO2 for five months. The results provided evidence of plant response to the changes of atmospheric CO2 concentration, and the clues to related studies on other plants.
p63 is a recently identified homologue of the tumor suppressor gene TP53, which encodes multiple isotypes with transactivating, death-inducing and dominant-negative activities. p63 is expressed in basal cells of squamous epithelia and many kinds of tumors. To explore the penetrance of p63 in esophageal cancer, we analyzed p63 expression in squamous cell carcinomas, adjacent dysplasia and histologically normal mucosa of the esophagus by combination of immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the DeltaNp63 mRNA was easily detectable in all malignant and histologically normal tissues, whereas TAp63 presented extremely low or no expression. The p63 protein was highly expressed in 50 of 51 tumor tissues without significant difference in gender, age, stage and grade. Ten of 11 dysplasia exhibited strong p63 staining in all abnormal cells. Interestingly, p63 expression was observed in 96% (45/47) histologically normal epithelia adjacent to the cancerous tissues but only in 47% (14/30) mucosa far from tumors. Most of the epithelia far from tumors showed weaker staining than that adjacent to the cancerous tissues. In all the histologically normal epithelia with p63 expression, irrespective of the distance from the tumors, immunohistochemical reaction was restricted to the basal and suprabasal cell layers. Our data suggested that DeltaNp63 is the major isotype expressed in epithelia and tumors of the esophagus. Elevated expression of p63 is probably an early event in esophageal squamous cell carcinomas, which may play a significant role in the development of the disease.
In this paper, we present a detailed mechanism for the complete decomposition of NH3 to NHx(a) (x = 0-2). Our calculations show that the initial decomposition of NH3 to NH2(a) and H(a) is facile, with a transition-state energy 7.4 kcal mol-1 below the vacuum level. Further decomposition to N(a) or recombination-desorption to NH3(g) is hindered by a large barrier of approximately 46 kcal mol-1. There are two plausible NH2 decomposition pathways: 1) NH2(a) insertion into the surface Si-Si dimer bond, and 2) NH2(a) insertion into the Si-Si backbond. We find that pathway (1) leads to the formation of a surface Si = N unit, similar to a terminal Si = Nt pair in silicon nitride, Si3N4, while pathway (2) leads to the formation of a near-planar, subsurface Si3N unit, in analogy to a central nitrogen atom (Nc) bounded to three silicon atoms in the Si3N4 environment. Based on these results, a plausible microscopic mechanism for the nitridation of the Si(100)-(2 x 1) surface by NH3 is proposed.