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Biomedical subjects

Hong Xu

Publications and source records attributed to Hong Xu.

At least 91 records · Page 5Linked to original sources

Production of donor T cells is critical for induction of donor-specific tolerance and maintenance of chimerism.

Nonmyeloablative conditioning has significantly reduced the morbidity associated with bone marrow transplantation. The donor hemopoietic cell lineage(s) responsible for the induction and maintenance of tolerance in nonmyeloablatively conditioned recipients is not defined. In the present studies we evaluated which hemopoietic stem cell-derived components are critical to the induction of tolerance in a total body irradiation-based model. Recipient B10 mice were pretreated with mAbs and transplanted with allogeneic B10.BR bone marrow after conditioning with 100-300 cGy total body irradiation. The proportion of recipients engrafting increased in a dose-dependent fashion. All chimeric recipients exhibited multilineage donor cell production. However, induction of tolerance correlated strictly with early production of donor T cells. The chimeras without donor T cells rejected donor skin grafts and demonstrated strong antidonor reactivity in vitro, while possessing high levels of donor chimerism. These animals lost chimerism within 8 mo. Differentiation into T cells was aborted at a prethymic stage in recipients that did not produce donor T cells. Moreover, donor Ag-driven clonal deletion of recipient T cells occurred only in chimeras with donor T cells. These results demonstrate that donor T cell production is critical in the induction of transplantation tolerance and the maintenance of durable chimerism. In addition, donor T cell production directly correlates with the deletion of potentially alloreactive cells.

Animals↗

Ras induces mediator complex exchange on C/EBP beta.

C/EBPbeta is an intrinsically repressed transcription factor that regulates genes involved in differentiation, proliferation, tumorigenesis, and apoptosis. C/EBPbeta acts as a repressor that is turned into an activator by the Ras oncoprotein through phosphorylation of a MAPK site. C/EBPbeta activation is accompanied by a conformational change. Active and repressive C/EBPbeta interacts with multisubunit Mediator complexes through the CRSP130/Sur2 subunit. The CRSP130/Sur2 subunit is common to two distinct types of Mediator complexes, characterized by CRSP70 and CDK8 proteins as transcriptionally active and inactive Mediator, respectively. Knockdown of CRSP130/Sur2 prevents Mediator binding and transactivation through C/EBPbeta. Oncogenic Ras signaling or activating mutations in C/EBPbeta selects the transcriptionally active Mediator complex that also associates with RNA polymerase II. These results show that a Ras-induced structural alteration of C/EBPbeta determines differential gene activation through selective interaction with distinct Mediator complexes.

Apoptosis↗

Identification of protein complexes required for efficient sister chromatid cohesion.

Ctf8p is a component of Ctf18-RFC, an alternative replication factor C-like complex required for efficient sister chromatid cohesion in Saccharomyces cerevisiae. We performed synthetic genetic array (SGA) analysis with a ctf8 deletion strain as a primary screen to identify other nonessential genes required for efficient sister chromatid cohesion. We then assessed proficiency of cohesion at three chromosomal loci in strains containing deletions of the genes identified in the ctf8 SGA screen. Deletion of seven genes (CHL1, CSM3, BIM1, KAR3, TOF1, CTF4, and VIK1) resulted in defective sister chromatid cohesion. Mass spectrometric analysis of immunoprecipitated complexes identified a physical association between Kar3p and Vik1p and an interaction between Csm3p and Tof1p that we confirmed by coimmunoprecipitation from cell extracts. These data indicate that synthetic genetic array analysis coupled with specific secondary screens can effectively identify protein complexes functionally related to a reference gene. Furthermore, we find that genes involved in mitotic spindle integrity and positioning have a previously unrecognized role in sister chromatid cohesion.

Chromatids↗

Effects of naloxone on the long-term potentiation of EPSPs from the pathway of Schaffer collateral to CA1 region of hippocampus in aged rats with declined memory.

Morris water maze (MWM) was employed to distinguish the aged rats with declined memory to investigate the effect of naloxone on the synaptic plasticity of hippocampus in declined memory aged rats. After administration with naloxone for 7 days, LTP of excitatory post-synaptic potentials (EPSPs) from Schaffer collateral to CA1 region was recorded. The results showed that the maintenance of LTP of EPSPs from Schaffer collateral to CA1 subfield in isolate hippocampal brain slice was prolonged by naloxone with improved Morris water maze performance and reduced threshold of EPSPs. It is suggested that naloxone can improve learning and memory through enhancement of the synaptic plasticity of hippocampus in aged rats with declined memory.

Aging↗

Biomechanical properties of skin in vitro for different expansion methods.

OBJECTIVE: In plastic surgery, clinicians are interested in replacing conventional expansion by rapid expansion, because the expansion period could be shortened greatly. Also people are concerned that skin properties after rapid expansion might not approach those after conventional expansion. DESIGN: Biomechanical testing of skin for different expansion methods. BACKGROUND: It would be useful to know how much the mechanical properties of skin have been altered during rapid and conventional expansion and during different maintaining times. METHODS: Tensile strength, stress-strain relationship, stress relaxation, and creep were measured by a material testing machine. RESULT: The biomechanical properties of experimental specimens differ significantly from those of their controls immediately after expansion, however, the difference is reduced with time. With the same maintaining period, the biomechanical properties of rapidly expanded skin are similar to conventionally expanded skin. CONCLUSION: Rapid skin expansion did not demonstrate any deleterious effect when compared with the conventional expansion. Extension of the maintaining period can improve the biomechanical properties of expanded skin. Therefore, rapid expansion with an extended maintaining period is acceptable in clinical practice.

Animals↗

Effects of the substitution positions of Br group in intercalative ligand on the DNA-binding behaviors of Ru(II) polypyridyl complexes.

Two new polypyridyl ligands containing substituent Br at different positions in the phenyl ring, PBIP [PBIP=2-(4-bromophenyl)imidazo[4,5-f]1,10-phenanthroline], OBIP [OBIP=2-(2-bromophenyl)imidazo[4,5-f]1,10-phenanthroline] and their Ru(II) complexes, [Ru(phen)2PBIP]2+ 1, [Ru(phen)2OBIP]2+ 2 (phen=1,10-phenanthroline), have been synthesized and characterized. The binding strength of the two complexes to calf thymus DNA (CT DNA) was investigated with spectrophotometric methods, viscosity measurements, as well as equilibrium dialysis and circular dichroism spectroscopy. The theoretical calculations for these two complexes were also carried out applying the density functional theory (DFT) method. The experimental results show that the Br group substituting H at different positions of the phenyl ring in the intercalated ligand has significant effects on the spectral properties and the DNA-binding behaviors of Ru(II) complexes. Both the complexes can bind to CT DNA in intercalative mode and interact with CT DNA enantioselectively. Moreover, complex 1 can bind to CT DNA more strongly than complex 2, and complex 2 can become a much better candidate as an enantioselective binder to CT DNA than complex 1. The theoretical calculations show that both intercalative ligands, PBIP and OBIP, in these two complexes are essentially planar, and the obtained electronic structures of the complexes can be used to explain reasonably some of their experimental regularities or trends. Such experimental and theoretical information will be useful in design of novel probes of nucleic acid structures.

Animals↗

One- and two-dimensional solid-state magic angle spinning NMR studies on the hydration process of layered sodium disilicate SKS-6.

Three different kinds of silanols, which include isolated silanol, silanol I (with the hydroxyl proton bonded to an oxygen atom in the adjacent layer) and silanol II (with the hydroxyl proton bonded to the non-bridging oxygen at the same silicon atom), are generated during the hydration process of SKS-6 (delta-Na2Si2O5). 1H-1H nuclear Overhauser enhancement spectroscopy reveals that the proton of silanol I has an effective chemical exchange or spin diffusion with the proton of hydrogen-bonded water, while the proton of silanol II is likely far away from the other proton-containing species. 29Si magic angle spinning, 1H-->29Si CP/MAS NMR and 1H-29Si phase-modulated Lee-Goldburg decoupled correlation experiments demonstrate that the local environments of the silicon sites in the final hydrated sample are mainly composed of Q2 [(SiO)2Si(OH)O(-)Na+], Q3 [(SiO)3Si(OH) and (SiO)3SiO(-)Na+] and Q4 [Si(OSi)4] groups.

Journal Article↗

The three-dimensional structure and X-ray sequence reveal that trichomaglin is a novel S-like ribonuclease.

Trichomaglin is a protein isolated from root tuber of the plant Maganlin (Trichosanthes Lepiniate, Cucurbitaceae). The crystal structure of trichomaglin has been determined by multiple-isomorphous replacement and refined at 2.2 A resolution. The X-ray sequence was established, based on electron density combined with the experimentally determined N-terminal sequence, and the sequence information derived from mass spectroscopic analysis. X-ray sequence-based homolog search and the three-dimensional structure reveal that trichomaglin is a novel S-like RNase, which was confirmed by biological assay. Trichomaglin molecule contains an additional beta sheet in the HV(b) region, compared with the known plant RNase structures. Fourteen cystein residues form seven disulfide bridges, more than those in the other known structures of S- and S-like RNases. His43 and His105 are expected to be the catalytic acid and base, respectively. Four hydrosulfate ions are bound in the active site pocket, three of them mimicking the substrate binding sites.

Amino Acid Sequence↗

Endoscopic sealing of pancreatic fistula by using N-butyl-2-cyanoacrylate.

BACKGROUND: The treatment of pancreatic fistula can be difficult. A novel endoscopic approach to sealing pancreatic fistulas by using N-butyl-2-cyanoacrylate is described. METHODS: Twelve patients with pancreatic fistulas underwent endoscopic injection of N-butyl-2-cyanoacrylate into the fistulous tract, in addition to endoscopic drainage. RESULTS: Fistulas were closed successfully in 8 of 12 patients. A single treatment session was successful in 7 patients; a second session was required in one patient. In two patients, closure was temporary, and, in one patient, the treatment failed. One patient died 24 hours after treatment. He developed a pulmonary thromboembolism from a left popliteal vein thrombosis and died from complications of surgical thromboembolectomy. At autopsy, a pulmonary embolus was found, but there was no evidence of N-butyl-2-cyanoacrylate in the lungs. No procedure-related complication occurred over a median follow-up of 20.7 months (range 9-51 months). CONCLUSIONS: In this preliminary study, occlusion of pancreatic fistulas by using N-butyl-2-cyanoacrylate glue was safe and effective, and obviated the need for surgery in a substantial proportion of patients. Further studies of the use of N-butyl-2-cyanoacrylate for closure of pancreatic fistula are warranted.

Adult↗

Radial distributions of temperature pressure and velocities for pulsatile blood flow in an axisymmetrical stiff tube.

Using perturbation theory with the assumption that the pulsatile blood flow in an axisymmetrical stiff tube is the first-order term to solve the linear equations of continuity, motion and heat conduction, the equations of the pulsatile flow, including temperature, are derived, and the instantaneous radial distribution of temperature, pressure and velocities for one frequency component are obtained. Using the published geometrical and physiological parameters of a large artery, a numerical analysis of the distribution relationship between the axial velocity and temperature is carried out. The primary studies show that the amplitude of temperature fluctuation in the tube is inversely proportional to the pulsatile frequency, the temperature and velocities gradients are mainly restricted in the near-wall layers with the increase of pulsatile frequency, and there is a close similarity of the radial pulsating distribution between temperature and axial velocity, which indicates that the blood flux in the artery as well as the motion function of heart can be indirectly described by the measurement of temperature fluctuation.

Animals↗

Cinnamomin--a versatile type II ribosome-inactivating protein.

Ribosome-inactivating proteins (RIPs) are a group of toxic proteins that can specifically act on the universally conserved sarcin/ricin domain (S/R domain) of the largest RNA in ribosome and thus irreversibly inactivate ribosome for protein synthesis. Cinnamomin is a multifunctional type II RIP isolated in our laboratory from the mature seeds of the camphor tree. This protein has been extensively studied with regard to its purification, characteristics, structure and function, genetic expression, enzymatic mechanism, physiological role in seed cell and toxicity to cancer cells and insect larvae. The research results of cinnamomin obtained in our laboratory are summarized in this review. Understanding of cinnamomin and the relative new proteins will help expand our knowledge of RIPs and may accelerate theoretical study and the development of their potential applications.

Algal Proteins↗

Mrc1 is required for sister chromatid cohesion to aid in recombination repair of spontaneous damage.

The SRS2 gene of Saccharomyces cerevisiae encoding a 3'-->5' DNA helicase is part of the postreplication repair pathway and functions to ensure proper repair of DNA damage arising during DNA replication through pathways that do not involve homologous recombination. Through a synthetic gene array analysis, genes that are essential when Srs2 is absent have been identified. Among these are MRC1, TOF1, and CSM3, which mediate the intra-S checkpoint response. srs2 Delta mrc1 Delta synthetic lethality is due to inappropriate recombination, as the lethality can be suppressed by genetic elimination of homologous recombination. srs2 Delta mrc1 Delta synthetic lethality is dependent on the role of Mrc1 in DNA replication but independent of the role of Mrc1 in a DNA damage checkpoint response. mrc1 Delta, tof1 Delta and csm3 Delta mutants have sister chromatid cohesion defects, implicating sister chromatid cohesion established at the replication fork as an important factor in promoting repair of stalled replication forks through gap repair.

Cell Cycle Proteins↗

Fermentable dietary fiber potentiates the localization of immune cells in the rat large intestinal crypts.

Intestinal crypts are composed of a well-defined hierarchy of epithelial cells, and proliferating epithelial cells reside close to the bottom of the crypts-even in the large intestine. We investigated whether CD8(+)and CD4(+)intraepithelial lymphocytes (IELs) and CD161(+) natural killer (NK) cells localized in proliferating or differentiated epithelial region of cecum and colon. Both proliferating epithelial layer cells and the immune cells along the longitudinal crypt axis of the large intestine were measured histochemically. Dietary intervention revealed that the physiological localization of the immune cells in the longitudinal crypt axis depended on the immune cell type. CD8(+) IELs were preferentially located among differentiated epithelial cells. In contrast, CD161(+) NK cells were located adjacent to the epithelial cells at the bottom of crypt. Cecal crypts contained significantly larger numbers of CD8(+) IELs than did colonic crypts. However, there was only a minor population of CD4(+) IEL in the cecal and colonic epithelia. Some dietary fibers increased the densities of CD8(+) IELs and CD161(+) NK cells in the cecum, with the magnitude of response varying among the types of fiber. There was a significant relationship between SCFA and the localization of immune cells, especially CD8(+) IEL and CD161(+) NK cells, which are considered to be involved in the maintenance of epithelial homeostasis.

Animals↗

CD45 congenic bone marrow transplantation: evidence for T cell-mediated immunity.

CD45 congenic mice have been used to study stem cell engraftment in the absence of alloreactivity. Recently, impaired engraftment was reported in this model and attributed to weak immune reactivity. We have confirmed that there is indeed low-level reactivity mediated by CD8(+) cells and alpha beta-TCR(+) T cells. B6 (CD45.2) recipients were conditioned with total body irradiation (TBI) and transplanted with increasing doses of B6 (CD45.1) bone marrow cells (BMCs). Although chimerism was present at 1 month in all recipients, durable engraftment did not occur with <150 cGy of TBI, emphasizing the importance of long-term follow-up in evaluating nonmyeloablative conditioning approaches. A single dose of cyclophosphamide on day 2 also significantly enhanced engraftment. When B6 TCR beta(-/-), TCR delta(-/-), or TCR beta(-/-)/delta(-/-) (CD45.2) mice were transplanted with CD45.1 bone marrow, significantly enhanced engraftment occurred in recipients lacking alpha beta-TCR(+) T cells (p < .00005). Similarly, removal of alpha beta-TCR(+) host T cells in wild-type recipients resulted in enhanced engraftment. Engraftment was also significantly increased in CD8(-/-) and CD4(-/-)/8(-/-) recipients (p < .0005). Taken together, these results demonstrate that alpha beta-TCR(+) and CD8(+) T cells play a critical role in regulating engraftment of CD45 congenic marrow and suggest that these cells are the main effector cells in low-level alloreactivity to the CD45 disparity.

Animals↗

Comparative study of interaction of two type II ribosome-inactivating proteins and their A-chains with model membrane.

Both cinnamomin and ricin are type II ribosome-inactivating proteins. Cinnamomin is less cytotoxic compared with ricin. In order to clarify the mechanism of their different cytotoxicities, the interaction of cinnamomin and its A-chain with model membrane was investigated and compared with that of ricin and its A-chain. It was revealed that cinnamomin is less effective than ricin in interacting with model membrane. Cinnamomin A-chain interacts with model membrane much less violently than ricin A-chain. The differences in the interaction of cinnamomin, ricin or their A-chains with model membrane might at least in part indicate the different cytotoxicity between cinnamomin and ricin.

Algal Proteins↗

Flt3-ligand treatment prevents diabetes in NOD mice.

The mechanism by which mixed chimerism reverses autoimmunity in type 1 diabetes has not been defined. NOD mice have a well-characterized defect in the production of myeloid progenitors that is believed to contribute significantly to the autoimmune process. We therefore investigated whether chimerism induces a correction of this defect. Mixed chimerism restored production of myeloid progenitors in NOD mice to normal levels. Notably, NOD bone marrow cells as well as donor bone marrow cells produced the mature myeloid progeny, and the level of donor chimerism was not correlated with the degree of restoration of the defect. Moreover, NOD bone marrow cells cultured with Flt3-ligand developed a heat-stable antigen-positive/Ly6C+ population comprised primarily of mature myeloid dendritic cells, suggesting that the underlying abnormality is not cell intrinsic but rather due to a block in development of mature myeloid progeny, including myeloid dendritic cells. Strikingly, treatment of NOD mice with Flt3-ligand significantly decreased insulitis and progression to diabetes and was associated with a significant increase in myeloid dendritic cells and in vivo induction of CD4+/CD25+ cells in the pancreatic lymph node. Therefore, Flt3-ligand treatment and/or the establishment of mixed chimerism in prediabetic candidates may provide a benign and novel approach to treat diabetes.

Adjuvants, Immunologic↗

[Epidemiologic characteristics of influenza in China, from 2001 to 2003].

OBJECTIVE: To understand the epidemiologic characters of influenza in China from 2001 to 2003. METHODS: Data of outpatient visits for influenza-like illness (ILI) each week and outbreaks of influenza were collected through National Influenza Surveillance Network, which includes 11 northern and 12 southern provinces of China. Samples were collected in the outpatients of ILI from 2001 to 2003 and influenza viruses were isolated and identified. RESULTS: Epidemiological and laboratory surveillance data showed that the annual seasonality of influenza epidemic was clear. The peak of epidemic of influenza in northern areas was in winter season, during December to January. However, there were three peaks distributed to Spring (Apr.-May.), Summer (Jun.-Aug.) and Winter (Dec.-Jan.) seasons in the southern areas. In the peak months, the number of ILI visits per day and per surveillance hospital had increased two-fold in northern and by 37% in southern China. The baseline of percentages for ILI visits, which calculated with 75th percentiles (P75), was 13.68% in the north and 13.08% in southern China. The age distribution of ILI was related to seasonal types of influenza. When the predominated strain of the season was influenza B virus, the ratio of the ILI visits younger than 15 year-old, increased obviously. When the predominated stains became influenza A virus, the ratio of patient visits for ILI aged over 25 year-old increased. Of 63 outbreaks of influenza, 92% of them occurred at primary and middle schools and usually occurred in May (32%). The type of strains usually changed around June. CONCLUSION: The quality of national influenza surveillance system is reliable since it was matched between percentages of ILI visits and rates of influenza virus isolation. The different epidemiologic characteristics in north and south of China was noticed. Peak in spring was shown in southern area and which called for more analysis. The change of the types of strains in the outbreaks during April to June in the southern China could provide data for better understanding on the trend of epidemics in the next season.

Adolescent↗

Theories and practice in prevention and treatment principles in relation to Chinese herbal medicine and bone loss.

Osteoporosis is a world wide problem that is increasing in significance as the global population both increases and ages. While osteoporosis has been extensively studied in recent years, the utilization of Traditional Chinese Herbal Medicine for the prevention and treatment of this condition have seldom been examined in the Western world. This paper reviews the theories and the literature that relate to prevention and treatment of bone loss at the time of menopause according to the principles of Traditional Chinese Herbal Medicine. Practical developments in these areas are also illustrated in this paper based on the authors' research findings in recent studies.

Aged↗