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Biomedical subjects

X Han

Publications and source records attributed to X Han.

At least 91 records · Page 5Linked to original sources

Characterization of tBid-induced cytochrome c release from mitochondria and liposomes.

tBid, the cleaved form of Bid, can induce cytochrome c (Cyt. c) release from rat heart mitochondria more efficiently and reproducibly than that from liver or brain mitochondria. Unlike Bax, such release was not prevented by cyclosphorin A, an inhibitor of the opening of permeability transition pore. Carbonyl-cyanide m-chlorophenyl-hydrazone or oligomycin also have no obvious effect on the release of Cyt. c. In contrast to ceramide, tBid-mediated Cyt. c release from mitochondria is independent of the redox state of Cyt. c. Furthermore, Bid or tBid can directly trigger the efflux of encapsulated Cyt. c or trypsin within liposomes without involvement of other protein factors.

Animals↗

Molecular modeling and site-directed mutagenesis of CCR5 reveal residues critical for chemokine binding and signal transduction.

The CC chemokine receptor CCR5 is the receptor for several chemokines and coreceptor for the entry of HIV-1. Whereas many studies focus on CCR5 interaction with HIV-1, residues in CCR5 important for chemokine binding and subsequent signal transduction remain poorly understood. Here we use an approach combining protein structure modeling and site-directed mutagenesis to probe the structure of CCR5 and its interactions with chemokine ligands and HIV-1. Structural models of CCR5 rationalize extensive biological data about the role of CCR5 in HIV-1 envelope glycoprotein gp120 binding and HIV-1 entry. Furthermore, we carry out site-directed mutagenesis guided by structural analysis of the complex of CCR5 and a chemokine. This leads to the novel observation that certain residues, such as Tyr10 and Lys26, in the N terminus of CCR5 play a critical structural role for ligand binding and signaling. Single glycine substitution of these residues significantly decreases chemokine binding and signal transduction. These results provide new insight into the structural basis for CCR5 receptor-ligand interaction and may guide the design of novel inhibitors.

Chemokines↗

IL-10 deficiency prevents IL-5 overproduction and eosinophilic inflammation in a murine model of asthma-like reaction.

Eosinophilic inflammation and bronchial mucus secretion are among the characteristic pathological changes in asthmatic reaction, which is mediated by Th2 type responses. Although it belongs to Th2 cytokines especially in the mouse, IL-10 is often considered an inhibitory cytokine for both Th1 and Th2 cells. In the present study, using a murine asthma model induced by ovalbumin (OVA), we demonstrated that endogenous IL-10 is critical for the development of asthma-like responses. Specifically, in comparison with wild-type controls, IL-10 gene knockout (KO) mice showed significantly reduced IL-5 production, eosinophilic inflammation and mucus production without notable changes in IL-4 and IgE responses following i. p. sensitization and subsequent intranasal challenge with OVA. In addition, Th1-related cytokine (IFN-gamma and IL-12) production in IL-10 KO mice was significantly higher than that in wild-type mice. The results suggest that endogenous IL-10 plays an important role in promoting pulmonary eosinophilic inflammatory reaction and mucus production during asthmatic reaction. The data also argue that IL-10 may be more influential in the development of IL-5-producing Th2 cells which differ from typical Th2 cells producing both IL-4 and IL-5.

Animals↗

Increased susceptibility to development of triggered activity in myocytes from mice with targeted disruption of endothelial nitric oxide synthase.

Nitric oxide generated by cardiac myocytes or delivered by drugs has been shown to regulate cardiac contractile function and has been implicated in suppressing some cardiac arrhythmias, although this remains controversial. We examined the ability of the soluble cardiac glycoside, ouabain, to trigger arrhythmic contractions in ventricular myocytes isolated from mice lacking a functional endothelial nitric oxide synthase gene (eNOS(null)). Arrhythmic activity, defined as aftercontractions, was induced with ouabain (50 micromol/L) and recorded using a video-motion detector in isolated, electrically driven single ventricular myocytes from adult eNOS(null)or from their wild-type (WT) littermates. The rate of ouabain-induced arrhythmic contractions was significantly higher in eNOS(null)myocytes than in WT myocytes. Application of the NO donor S-nitroso-acetylcysteine (SNAC) significantly diminished the frequency of arrhythmic contractions in eNOS(null)myocytes. The antiarrhythmic effect of NO, whether generated by eNOS in WT cells or by SNAC, could be partially reversed by 1H-[1,2,4]oxadiazolo-[4, 3-a]- quinoxalin-1-one (ODQ), a specific soluble guanylyl cyclase inhibitor. Ouabain significantly increased intracellular cGMP in WT but not eNOS(null)hearts, and this cGMP response was blocked by ODQ. Since cardiac glycoside- induced aftercontractions are activated by the transient inward current (I(ti)), the role of NO in ouabain (100 micromol/L)- induced I(ti)was examined using the nystatin-perforated patch-clamp technique. The frequency of ouabain-induced I(ti)was significantly higher in eNOS(null)myocytes than in WT myocytes, and this could be suppressed by SNAC. These data demonstrate that NO derived from myocyte eNOS activation suppresses ouabain-induced arrhythmic contractions by a mechanism that might involve activation of guanylyl cyclase and elevation of cGMP.

Acetylcysteine↗

The taurine transporter gene and its role in renal development.

This paper examines a unique hypothesis regarding an important role for taurine in renal development. Taurine-deficient neonatal kittens show renal developmental abnormalities, one of several lines of support for this speculation. Adaptive regulation of the taurine transporter gene is critical in mammalian species because maintenance of adequate tissue levels of taurine is essential to the normal development of the retina and the central nervous system. Observations of the remarkable phenotypic similarity that exists between children with deletion of bands p25-pter of chromosome 3 and taurine-deficient kits led us to hypothesize that deletion of the renal taurine transporter gene (TauT) might contribute to some features of the 3p-syndrome. Further, the renal taurine transporter gene is down-regulated by the tumor suppressor gene p53, and up-regulated by the Wilms tumor (WT-1) and early growth response-1 (EGR-1) genes. It has been demonstrated using WT-1 gene knockout mice that WT-1 is critical for normal renal development. In contrast, transgenic mice overexpressing the p53 gene have renal development defects, including hypoplasia similar to that observed in the taurine-deficient kitten. This paper reviews evidence that altered expression of the renal taurine transporter may result in reduced intracellular taurine content, which in turn may lead to abnormal cell volume regulation, cell death and, ultimately, defective renal development.

Animals↗

Viral fusion peptides: a tool set to disrupt and connect biological membranes.

The structure and function of viral fusion peptides are reviewed. The fusion peptides of influenza virus hemagglutinin and human immunodeficiency virus are used as paradigms. Fusion peptides associated with lipid bilayers are conformationally polymorphic. Current evidence suggests that the fusion-promoting state is the obliquely inserted alpha-helix. Fusion peptides also have a tendency to self-associate into beta-sheets at membrane surfaces. Although the conformational conversion between alpha- and beta-states is reversible under controlled conditions, its physiological relevance is not yet known. The energetics of peptide insertion and self-association could be measured recently using more soluble "second generation" fusion peptides. Fusion peptides have been reported to change membrane curvature and the state of hydration of membrane surfaces. The combined results are built into a model for the mechanism by which fusion peptides are proposed to assist in biological membrane fusion.

Amino Acid Sequence↗

[An experimental study of a new route for Acyclovir administration for anti-keratitis therapeutic treatment].

OBJECTIVE: To study the significance of a collagen shield made by centrifugal method that can deliver Acyclovir. METHODS: 28 white rabbits were divided into four groups for observing releasing of Acyclovir into aqueous at 0.5, 1, 3, 5 hours after adding drugs in two different administrative ways, that were putting drug loaded collagen shields on one eye of the rabbit and subconjunctival injection of drug in another eye of the rabbit as control. The drug concentrations in aqueous of rabbit at different times using different administrative routes were measured by high-performance liquid chromatography (HPLC). RESULTS: At 0.5 hr of drug administration, the Acyclovir concentrations in aqueous of subconjunctival injected rabbits were obviously higher than that in collagen shields loaded rabbits (t = 4.050, P <0.01), but it became not so notable at the time of 1 hr. (t =2.074, P>0.05). At the time of 3 hrs and 5 hrs, the drug concentrations in aqueous of collagen shield loaded eyes of the rabbits not only were higher than that of the subconjunctival injected rabbits (t=4.761, t=4.190, respectively, P <0.01), but also could sustain rather a long time. CONCLUSIONS: A drug delivering way using collagen shield made by centrifugal method can replace the subconjunctival injection.

Acyclovir↗

[Review on research of plant nutrient use efficiency].

The concept of nutrient use efficiency is the central to the understanding of ecosystem function. We reviewed the concept of nutrient use efficiency and resorption, its expression and calculation, affecting factors and biochemical basis, we also analyzed the current problems in the studies of nutrient use efficiency, and pointed out the directions for future research work of this field.

Absorption↗

[Stable carbon isotope characteristics of some woody plants in warm temperate zone].

It was found that the delta 13C values of the foliar, trunk, flower, and fruit of some woody plants in broad-leaved forest in warm temperate zone were affected by many factors, and showed a great interspecific difference and temporal and spatial heterogeneity. The intraspecific variation of delta 13C values was also great, with the order of Vitex negundo var. heterophylla 6.549@1000(-22.226@1000(-)-28.775@1000), Fraxinus rhynchophylla 5.706@1000(-23.687@1000(-)-29.393@1000), Jugans mandshurica 5.229@1000 (-26.146@1000-31.375@1000), Quercus liaotungensis 3.333@1000 (-24.324@1000(-)-27.657@1000), Syringa pekinensis 2.414@1000(-25.655@1000(-)-28.070@1000), and Prunus armeniaca var. ansu 2.296@1000 (-23.436@1000(-)-26.432@1000). Different organs of the same species had different delta 13C values: trunk and root barks had the low, while xylem had the highest delta 13C value. According to the relationship analysis between delta 13C value of Prunus armeniaca var. ansu xylem and environment factors, it was found that delta 13C value was strongly affected by annual mean temperature and followed by annual precipitation, mean temperature and precipitation in growth season.

Carbon Isotopes↗

Effect of 8-bromo-cyclic AMP on neuron specific enolase, heat shock protein, nitric oxide, nitric oxide synthase and nitric oxide synthase mRNA in human retinoblastoma HXO-Rb44 cells and cell differentiation.

OBJECTIVE: To study the effect of 8-bromo-cyclic AMP (8-Br-cAMP) on nitric oxide synthase (NOS) mRNA, NOS and nitric oxide (NO) product, heat shock protein (hsp) 70 and neuron specific enolase (NSE) in human retinoblastoma HXO-Rb44 cells and the effect related to cell differentiation. METHODS: Cultured human retinoblastoma HXO-Rb44 cells were divided into two aliquots. One was cultured with 2 x 10(-5) mol/L of 8-Br-cAMP for 24 hours as the experiment group; the other was treated with no 8-Br-cAMP as the control group. The cell suspensions in concentration of 1 x 10(7)/ml in both groups were dropped onto the nitrocellulose membrane (NCM). The NOS mRNA was detected with the biotin-labeled NOS cDNA probe by RNA dot blot. The NOS activity was detected by protein dot blot. The immunoreactivity (IR) of hsp70 and NSE was detected by protein dot blot. The NO was detected by nitrate reductase method. NCM specimens were analyzed by a TLC scanner for detection of the dot blot signal intensity. RESULTS: The signals of NOS mRNA, NOS activity, hsp70-IR, NSE-IR, and NO content in the experiment group were higher than those in the control group (P < 0.05-0.01). CONCLUSIONS: 8-Br-cAMP could increase NO product and the expression of NOS mRNA, NOS, NSE and hsp70. The results indicate that 8-Br-cAMP could facilitate synthesis of NO in the neuroblastoma HXO-Rb44 cells, which could have tendency toward neuron development, suggesting that the increased hsp70, NO and NOS may involve cell differentiation of the retinoblastoma HXO-Rb44.

8-Bromo Cyclic Adenosine Monophosphate↗

[Study on relationship between endometrium laminin expression and irregular uterine bleeding in Norplant users].

OBJECTIVE: To investigate the relationship between endometrium laminin (LN) expression and irregular uterine bleeding in Norplant users. METHODS: Eighteen endomerium samples obtained during day 10-14th from Norlant users for 1/2, 1 or > 2 years respectively with irregular bleeding were studied morphologically and immunohistochemically for LN expression. Six normal proliferative endometria and 18 connterpacts with regular bleeding were used as control. RESULTS: In Norplant users, endometrial glands decreased in numbers and asynchromized in appearance. The LN expression on basal lamina of glandular epithelium and vascular endothelium was lower in those with irregular bleeding as compared with regular bleeders (P < 0.05). CONCLUSION: The decline of LN expression may related to irregular bleeding in Norplant users.

Adult↗

[The role of Werner's syndrome gene in the genetic susceptibility to the type 2 diabetes in Chinese population].

OBJECTIVE: To test the hypothesis that Werner's syndrome gene (WRN) contributes to the genetic susceptibility to the type 2 diabetes in Chinese population. METHODS: Polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) method was used to test the distribution of a polymorphism (Cys1367Arg ) of the WRN gene in 241 type 2 diabetes patients and 108 normal control subjects. RESULTS: The frequency of "R" allele of the WRN gene in type 2 diabetes patients whose diagnosis age >/= 45 was significantly increased as compared with that in the control subjects (9.6% vs 4.6%, P = 0.04). CONCLUSION: The high frequency of allele "R" of the WRN gene in early onset Chinese type 2 diabetes patients suggests that the WRN gene may contribute to the genetic susceptibility of type 2 diabetes in Chinese population through either directly causing diabetes or interacting with the diabetogenic gene.

Adult↗

[Simultaneous pancreas-kidney transplantation for the treatment of type I diabetes with end-stage renal disease].

OBJECTIVE: To demonstrate whether simultaneous pancreas-kidney transplantation is practical for the treatment of Type I diabetes with end-stage renal disease. METHODS: Eight cases of combined pancreas-kidney transplantation were performed in our institute. The age ranged from 35 years to 48 years (average 43.46 years). All cases were diagnosed as type I diabetes with end-stage nephropathy, two cases with blindness due to retinopathy. The case history ranged from 2 years to 22 years. Pancreas allograft was placed in the right iliac fossa with pancreas exocrine drainage to bladder, whereas renal allograft the in left iliac fossa. Initial immunosuppression regimen is quadruple. RESULTS: Seven patient could be insulin free after transplantation, with normal fasting blood glucose. One patient received insulin treatment for 40 days after operation. One patient survived 1 year and 9 months after transplantation with normal functioning pancreas allograft and kidney allograft. Four patient survived 2 months with normal allograft function. Fasting blood glucose was between 4.5 and 6.2 mmol/L; Cr was between 53 and 106 micromol/L. Diet control was not necessary. Two patient died of encephalorrhagia, and 1 pancreatic vascular thrombosis and necrotic pancreatitis. CONCLUSIONS: Combined pancreas-kidney transplantation is feasible to treat type I diabetes with end-stage nephropathy. Functional pancreas allograft could be procured in the present condition. Pancreatic exocrine is drained to bladder. The diagnosis of acute rejection could be made earlier by detecting urine amylase. Heparin should be added in order to prevent pancreatic thrombosis.

Adult↗

[MMF and CyA in the prevention of early acute rejection after renal transplantation].

OBJECTIVE: To investigate the effect of MMF and low dose CyA on the prevention of early acute rejection after renal transplantation. METHODS: 146 patients with kidney transplantation were analyzed retrospectively from December 1997 to January 1999. These patients were divided into two groups according to the immunosuppressive regimen: Aza group (78 patients) and MMF group (68 patients). All patients met the following criteria: HLA mismatch </= 3 loci, lymphocytes toxicity test < 10%, PRA < 20% for second or third transplantation, warm ischemia time 5-11 minutes, and cold ischemia time 3-24 hours. RESULTS: There were 24 patients with acute rejection episodes (30.77%) in the Aza group; and 10 patients (14.71%) in the MMF group, (P < 0.05). The dosage of CyA and blood concentration of CyA were significantly different; 6.00 +/- 1.21 mg x kg(-1) x d(-1) and 286.00 +/- 20.02 microg/L in the Aza group; 4.00 +/- 1.14 mg x kg(-1) x d(-1) and 204.00 +/- 20.18 microg/L in the MMF group (P < 0.001). CONCLUSIONS: MMF with low dose CyA based triple regimen could prevent the acute rejection episodes effectively at the early period of post transplantation. This triple regimen can reduce the acute rejection episodes by 50%. To some extent, low dose CyA may avoid nephrotoxicity. The long-term effect of this regimen on allograft is still needed to observe.

Adolescent↗

[Changes of surfactant A and B in alveolar type II cells in hamster with elastase-induced emphysema].

OBJECTIVE: To observe the changes of surfactant A and B (SP-A and SP-B) in alveolar type II cells of lungs in hamsters with elastase-induced emphysema. METHODS: After intratracheal instilling of elastase, hamsters were killed at the 30th, 60th and 90th day of the experiment respectively. Slides of lung tissue were examined under light microscope and measured by calculating the mean linear intercepts. Then the slides were stained under immunohistochemistry procedures and measured by using a morphometric analysis system. Meanwhile, slides were also checked by electron microscopy. RESULTS: In comparison with the normal group, MLI of the elastase group was significantly increased (P < 0.01). Immunohistochemistry showed that the percentage of both SP-A and SP-B positive cells was significantly decreased 30 days after the intratracheal instilling of elastase (from 48.0% +/- 3.0% to 9.5% +/- 4.0% and from 28.0% +/- 4.0% to 13.3% +/- 4.1%, respectively; P < 0.01), however, a time-dependent recovery 90 days after instilling was seen. Electron microscopy showed a significantly decrease of the number of lamellae. CONCLUSION: The decrease of SP-A and SP-B in alveolar type II cells seems to play an important role in the development of emphysema.

Animals↗