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Biomedical subjects

B Hu

Publications and source records attributed to B Hu.

At least 19 recordsLinked to original sources

An essential role for CCAAT/enhancer binding protein beta in bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is characterized by inflammation, genesis of myofibroblasts, and abnormal tissue repair. Despite extensive research, its pathogenesis remains incompletely understood. Previously, the transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) was found to be a key regulator of myofibroblast differentiation in vitro, and to be involved in the acute phase and inflammatory responses. In an attempt to test the role of C/EBPbeta in the development of pulmonary fibrosis, experiments using C/EBPbeta null mice and their wild-type littermates were conducted. Our findings indicated that, compared to wild-type mice, animals deficient in C/EBPbeta showed significantly reduced fibrotic lesions and collagen deposition in the lung upon endotracheal injection of bleomycin. Further studies on the mechanisms by which C/EBPbeta regulates fibrosis indicated that knockout of C/EBPbeta attenuates inflammatory cytokine expression in bleomycin-treated mice. The reduced alpha-smooth muscle actin gene expression in either isolated lung fibroblasts or lung tissue from bleomycin or saline-treated C/EBPbeta deficient mice suggests that C/EBPbeta regulates myofibroblast differentiation during fibrosis. Consistent with this finding, cells from C/EBPbeta deficient mice exhibited higher proliferative rates than those from wild-type mice. These data suggest that C/EBPbeta plays an essential role in pulmonary fibrosis and that this role appears to be multifactorial with respect to cytokine expression, cell differentiation, and proliferation.

Actins↗

Axonal and somatic filtering of antidromically evoked cortical excitation by simulated deep brain stimulation in rat brain.

Antidromic cortical excitation has been implicated as a contributing mechanism for high-frequency deep brain stimulation (DBS). Here, we examined the reliability of antidromic responses of type 2 corticofugal fibres in rat over a stimulation frequency range compatible to the DBS used in humans. We activated antidromically individual layer V neurones by stimulating their two subcortical axonal branches. We found that antidromic cortical excitation is not as reliable as generally assumed. Whereas the fast conducting branches of a type 2 axon in the highly myelinated brainstem region follow high-frequency stimulation, the slower conducting fibres in the poorly myelinated thalamic region function as low-pass filters. These fibres fail to transmit consecutive antidromic spikes at the beginning of high-frequency stimulation, but are able to maintain a steady low-frequency (6-12 Hz) spike output during the stimulation. In addition, antidromic responses evoked from both branches are rarely present in cortical neurones with a more hyperpolarized membrane potential. Our data indicate that axon-mediated antidromic excitation in the cortex is strongly influenced by the myelo-architecture of the stimulation site and the excitability of individual cortical neurones.

Action Potentials↗

Rapid eye movement sleep deprivation selectively impairs recall of fear extinction in hippocampus-independent tasks in rats.

Previous studies have shown that rapid eye movement (REM) sleep deprivation (RSD) exerts a detrimental effect on some memory tasks. However, whether post-learning RSD impairs memory for fear extinction, an important model of inhibitory learning, remains to be elucidated. The present study examined the effects of post-extinction RSD from 0 to 6 h and 6 to 12 h on recall of fear extinction tested 24 h after extinction training. We found that RSD from 0 to 6 h significantly increased freezing when recall of extinction of cued fear was tested in the context in which rats received extinction training whereas RSD from 6 to 12 h had no effect (experiments 1 and 2, two hippocampus-independent memory tasks). RSD at either time point had no effect on freezing when recall of extinction of cued fear was tested in the context different from that in which extinction training occurred (experiment 3, a hippocampus-dependent memory task). Additionally, we observed no effect of RSD at either time point on freezing during recall test for extinction of contextual fear (experiment 4, a hippocampus-dependent memory task). These results suggest that the effects of post-extinction RSD on memory for fear extinction are complex. RSD impairs recall of fear extinction in hippocampus-independent tasks, but does not affect recall of fear extinction in hippocampus-dependent tasks. Our findings extend previous research on the effects of RSD on learning and memory and support the notion that REM sleep is involved in memory process of certain tasks.

Acoustic Stimulation↗

A new expression plasmid in Bifidobacterium longum as a delivery system of endostatin for cancer gene therapy.

To utilize Bifidobacterium longum (B. longum) as a safe and stable delivery system for endostatin in cancer gene therapy, we constructed pBV22210 vector combining a chloramphenicol-resistance gene (Cm(r)) from pBCSK(+) plasmid, a cryptic plasmid pMB1 from B. longum strain with pBV222. Endostatin was cloned directly downstream of an N terminal His6-tag sequence in the pBV22210, so that the endostatin protein expressed in B. longum could be purified with Ni-binding resin. The results indicated that the plasmid electroporated into B. longum was maintained stably in the absence of selective antibiotics and did not significantly affect biological characteristics of B. longum. In addition, the plasmid in B. longum showed a strong inhibitory effect on the growth of mouse solid liver tumor in vivo. These results suggested that this new plasmid may be a stable vector in B. longum for transporting anti-cancer genes in cancer gene therapy.

Animals↗

Electrical property of Mo-doped VO2 nanowire array film by melting-quenching sol-gel method.

Mo-doped VO(2) nanowire array film with good thermochromic properties was prepared by melting-quenching followed by heat treatment in a vacuum. The formation of the new microstructure is related to the cleavage of the oxide lamella along (001) and (100) plane with large interplanar spacing. Mo doping results in the loss of V(4+)-V(4+) pairs and destabilizes the semiconductor phase and consequently lowers the semiconductor-to-metal transition temperature T(c) from 64 to 42 degrees C. Because of enhancement of the electron concentration due to the presence of Mo donors, the Fermi level shifts toward the conduction band, resulting in the decrease of activation energy E(a), hence, temperature coefficient of resistance.

Letter↗

Synthesis and electrical transport of single-crystal NH4V3O8 nanobelts.

Monoclinic NH(4)V(3)O(8) single-crystalline nanobelts with widths of 80-180 nm, thicknesses of 50-100 nm, and lengths up to tens of micrometers have been synthesized at large scale in an ammonium metavanadate solution by a templates/catalysts-free route. Such nanobelts grow along the direction of [010]. The individual NH(4)V(3)O(8) nanobelt exhibits nonlinear, symmetric current/voltage (I/V) characteristics, with a conductivity of 0.1-1 S/cm at room temperature and a dielectric constant of approximately 130. The dominant conduction mechanism is based on small polaron hopping due to ohmic mechanism at low electric field below 249 V/cm due to Schottky emission at medium electric field between 249 and 600 V/cm and due to the Poole-Frenkel emission mechanism at high field above 600 V/cm.

Catalysis↗

Extended quasimodes within nominally localized random waveguides.

We have measured the spatial and spectral dependence of the microwave field inside an open absorbing waveguide filled with randomly juxtaposed dielectric slabs in the spectral region in which the average level spacing exceeds the typical level width. Whenever lines overlap in the spectrum, the field exhibits multiple peaks within the sample. Only then is substantial energy found beyond the first half of the sample. When the spectrum throughout the sample is decomposed into a sum of Lorentzian lines plus a broad background, their central frequencies and widths are found to be essentially independent of position. Thus, this decomposition provides the electromagnetic quasimodes underlying the extended field in nominally localized samples. These quasimodes may exhibit multiple peaks in space when they overlap spectrally.

Journal Article↗

The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous end-joining.

Mammalian Hus1 plays an important role in maintaining genomic integrity. Cells lacking mouse Hus1 are hypersensitive to DNA damage inducers including UV and camptothecin (CPT). By using clonogenic assay, we show here that Hus1 deficient mouse cells are hypersensitive to ionizing radiation (IR) compared with their Hus1-positive counterparts. However, these cells show similar induction levels and similar rejoining rates of DNA double strand breaks (DSBs) following IR, indicating that the effect of Hus1 on cell radiosensitivity is independent of nonhomologous end-joining (NHEJ). By combining an I-SceI-induced-DNA DSBs system and a siRNA approach, we also show that knocking down Hus1 decreases the efficiency of homologous recombination repair (HRR), which is associated with the cellular sensitivity to IR-induced killing. Together, these results indicate that the role of Hus1 affecting the sensitivity of cells to IR-induced killing is independent of NHEJ but might be linked to HRR.

Animals↗

Role of Smad3 in the regulation of rat telomerase reverse transcriptase by TGFbeta.

Telomerase is induced in certain pathological conditions such as cancer and tissue injury and repair. This induction in fibroblasts from injured lung is repressed by transforming growth factor beta (TGFbeta) via yet unknown mechanisms. In this study, the role of Smad3 in the inhibition of telomerase reverse transcriptase (TERT) gene transcription by TGFbeta was investigated. The rat TERT (rTERT) gene promoter was cloned by PCR amplification and fused with a luciferase reporter gene. This construct was used to analyse regulation of promoter activity in fibroblasts isolated from bleomycin-injured lung with induced telomerase activity. The results showed that TGFbeta inhibited rTERT transcription while stimulating Smad3 expression. Interestingly, TGFbeta also inhibited the expression of c-myc. Cotransfection with a Smad3 expressing plasmid further repressed rTERT transcription and c-myc expression, while cotransfection with the corresponding antisense Smad3 construct had the opposite effect. Mutation of an E-box in the rTERT promoter suppressed its activity, which could be further reduced by TGFbeta treatment. In contrast, mutation at a Smad binding element enhanced promoter activity whose inhibition was impaired by TGFbeta treatment. Thus TGFbeta inhibition of rTERT gene expression was directly mediated by Smad3 via the Smad binding element, while c-myc appears to primarily regulate its constitutive or induced expression.

Animals↗

Transgastric endoscopic splenectomy: is it possible?

BACKGROUND: We have previously reported the feasibility of diagnostic and therapeutic peritoneoscopy including liver biopsy, gastrojejunostomy, and tubal ligation by an oral transgastric approach. We present results of per-oral transgastric splenectomy in a porcine model. The goal of this study was to determine the technical feasibility of per-oral transgastric splenectomy using a flexible endoscope. METHODS: We performed acute experiments on 50-kg pigs. All animals were fed liquids for 3 days prior to procedure. The procedures were performed under general anesthesia with endotracheal intubation. The flexible endoscope was passed per orally into the stomach and puncture of the gastric wall was performed with a needle knife. The puncture was extended to create a 1.5-cm incision using a pull-type sphincterotome, and a double-channel endoscope was advanced into the peritoneal cavity. The peritoneal cavity was insufflated with air through the endoscope. The spleen was visualized. The splenic vessels were ligated with endoscopic loops and clips, and then mesentery was dissected using electrocautery. RESULTS: Endoscopic splenectomy was performed on six pigs. There were no complications during gastric incision and entrance into the peritoneal cavity. Visualization of the spleen and other intraperitoneal organs was very good. Ligation of the splenic vessels and mobilization of the spleen were achieved using commercially available devices and endoscopic accessories. CONCLUSIONS: Transgastric endoscopic splenectomy in a porcine model appears technically feasible. Additional long-term survival experiments are planned.

Animals↗

Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not effective: a single-centre randomized study.

To investigate the efficacy of antepartum administration of three doses of hepatitis B immunoglobulin (HBIg), currently being used in China, 250 pregnant women who were seropositive for hepatitis B e antigen (HBeAg) were randomly divided into study (117 cases) and control groups (133 cases). Subjects in the study group received HBIg 400 IU intramuscularly once a month at the third, second and first month before delivery; subjects in the control group received no antepartum treatment. All neonates received passive-active immunization after birth. The maternal hepatitis B virus (HBV) markers, hepatitis B surface antigen (HBsAg) titres and HBV deoxyribonucleic acid (DNA) levels were measured at week 28 of gestation (before the antepartum treatment) and at labour; the neonatal serum HBV markers were detected at birth and at 12 months after birth. No side-effects were found in any of the women or their neonates. No statistical differences were seen between the maternal HBsAg and HBV DNA levels of the study and control groups at labour nor the protective efficacy rates of postnatal immunoprophylaxis at 12 months after birth (P > 0.05, respectively). To conclude, antepartum administration of three doses of HBIg for the HBeAg-positive women is inefficacious.

Adult↗

Bone marrow cells can give rise to ameloblast-like cells.

Post-eruptive loss of ameloblasts requires identification of alternative sources for these cells to realize tooth-tissue-engineering strategies. Recent reports showed that bone-marrow-derived cells can give rise to different types of epithelial cells, suggesting their potential to serve as a source for ameloblasts. To investigate this potential, we mixed c-Kit(+)-enriched bone marrow cells with embryonic dental epithelial cells and cultured them in re-association with dental mesenchyme. Non-dividing, polarized, and secretory ameloblast-like cells were achieved without cell fusion. Before basement membrane reconstitution, some bone marrow cells migrated to the mesenchyme, where they exhibited morphological, molecular, and functional characteristics of odontoblasts. These results show, for the first time, that bone-marrow-derived cells can be reprogrammed to give rise to ameloblast-like cells, offering novel possibilities for tooth-tissue engineering and the study of the simultaneous differentiation of one bone marrow cell subpopulation into cells of two different embryonic lineages.

Ameloblasts↗

Quasielastic 3He(e,e'p)2H reaction at Q2 = 1.5 GeV2 for recoil momenta up to 1 GeV/c.

We have studied the quasielastic 3He(e,e(')p)2H reaction in perpendicular coplanar kinematics, with the energy and the momentum transferred by the electron fixed at 840 MeV and 1502 MeV/c, respectively. The 3He(e,e(')p)2H cross section was measured for missing momenta up to 1000 MeV/c, while the A(TL) asymmetry was extracted for missing momenta up to 660 MeV/c. For missing momenta up to 150 MeV/c, the cross section is described by variational calculations using modern 3He wave functions. For missing momenta from 150 to 750 MeV/c, strong final-state interaction effects are observed. Near 1000 MeV/c, the experimental cross section is more than an order of magnitude larger than predicted by available theories. The A(TL) asymmetry displays characteristic features of broken factorization with a structure that is similar to that generated by available models.

Journal Article↗

Measurement of the 3He(e,e'p)pn reaction at high missing energies and momenta.

Results of the Jefferson Lab Hall A quasielastic 3He(e,e'p)pn measurements are presented. These measurements were performed at fixed transferred momentum and energy, q=1502 MeV/c and omega=840 MeV, respectively, for missing momenta p(m) up to 1 GeV/c and missing energies in the continuum region, up to pion threshold; this kinematic coverage is much more extensive than that of any previous experiment. The cross section data are presented along with the effective momentum density distribution and compared to theoretical models.

Journal Article↗

Transoral obesity surgery: endoluminal gastroplasty with an endoscopic suture device.

BACKGROUND AND STUDY AIMS: Surgical creation of a small gastric pouch with a restricted outlet is a well-established option for the treatment of morbid obesity. This report describes initial experience with endoscopic transoral stomach partition using a newly designed suturing apparatus. MATERIALS AND METHODS: A fresh porcine stomach was placed in the Erlangen model. A prototype suture device, incorporating a curved needle and an intracorporeal tightening mechanism, was used in this procedure. A long fishing line was first introduced into the stomach, with the two ends left outside. The suturing device, premounted outside a standard gastroscope, was inserted into the stomach and delivered several stitches attaching the fishing line to both the anterior and posterior walls along the line for the stomach to be partitioned. Five throws of half-hitches were tied onto the fishing line extracorporeally and separately pushed into place, creating a gastric pouch just below the esophagogastric junction. A flexible sheath of 8 cm long was then put on one side of the fishing line and pushed into the stomach. Additional extracorporeal knots were tied on the fishing line, forming a restrictive ring at the outlet of the pouch. The ring was then anchored to the stomach wall with similar endosutures. RESULTS: The proximal gastric pouch, with an estimated volume of approximately 100 ml, was successfully created with a restrictive band at its outlet. All of the stitches were securely sutured, with consistent penetration of the muscular layer of the stomach wall. CONCLUSIONS: In a bench model, it is technically possible to accomplish transoral gastroplasty endoscopically with an intraluminal suturing device. Further live animal studies will be needed in order to confirm the efficacy and safety of this procedure before clinical application.

Animals↗

Assessing the adequacy of endoscopically tied knots: a functional approach.

BACKGROUND AND STUDY AIMS: Endoscopic intracorporeal knots have potentially enormous applications in endoscopic surgery. We describe a method for testing the security of various types of endoscopically tied knots using a vessel perfusion manometer system. METHODS: A 4-cm segment of porcine splenic artery was placed on the mucosal surface of a pig stomach. The two ends of the vessel were brought out through the gastric wall and connected to a two-way manometer. One end was also joined to a pressure infusion bag. The stomach was mounted in an Erlangen training model. A long 3/0 nylon thread, previously introduced into the submucosal layer of the stomach and encircling the vessel, was brought out from the mouth. Three-throw square knots, Mayo knots, "surgeon's" knots and five-throw square knots were tied and pushed into place using a cap attached to a gastroscope. The pressure at the two ends of the artery was compared. If the pressure could be increased to over 200 mm Hg at one end without a change in the other, the knot was considered secure. RESULTS: Each type of knot was tested 12 times under endoscopic vision. The range for mean knotting time was 3.4 - 4.5 minutes. Five-throw knots took significantly longer to tie than three-throw knots (P < 0.005). There was one loose knot in each of the three-throw and Mayo groups, and three each in the "surgeon's" and five-throw groups (P > 0.05). CONCLUSIONS: This system is a reliable model for testing intracorporeal knots tied endoscopically. A three-half-hitches square knot with 3/0 nylon, tied using a flexible endoscope and knot-tightening cap, can withstand pressure up to 200 mm Hg.

Animals↗

Developing an animal model of massive ulcer bleeding for assessing endoscopic hemostatic devices.

BACKGROUND: Existing animal models of ulcerative bleeding are not suitable for endoscopic investigation. We describe a new porcine model of massive arterial bleeding in the stomach and its use for assessing a novel endoscopic suturing device. METHODS: Two animal models were investigated. In model 1, the short gastric artery (mean diameter 2 mm) was divided near its gastric end. A mucosal defect was created near the greater curve and the divided artery was brought into the lumen of the stomach through a submucosal tunnel. An inflatable plastic cuff was placed around the base of the artery. Cuff deflation led to massive bleeding. In model 2, the short gastric artery was carefully exposed along a segment of 2 cm on the side facing the stomach. It was then anchored to a small gastrostomy made at the posterior wall near the vessel. At endoscopy an ulcer-like lesion could be seen with a pulsatile vessel at the base and brisk bleeding could be started by cutting a hole in the artery using endoscissors. The pigs were heparinized by an intravenous bolus of 110-300 units per kilogram, in both models. A prototype suturing device, the Eagle Claw, was inserted using a gastroscope and the curved needle was driven around the bleeding artery. Extracorporeal knotting or intracorporeal ligation was done endoscopically. RESULTS: Pulsatile arterial bleeding was successfully created in four pigs using model 1, and in another four pigs using model 2. Model 2 was more reproducible and less time-consuming to create. Endoscopic suturing controlled arterial bleeding in five out of eight pigs with a single stitch and in another three pigs with an additional stitch. CONCLUSION: This animal model provides reproducible massive hemorrhage suitable for endoscopic studies. Control of gastric bleeding from large arteries by endoscopic suturing is possible.

Animals↗

Results from the ARTEMIS DISK Global Antifungal Surveillance Study: a 6.5-year analysis of susceptibilities of Candida and other yeast species to fluconazole and voriconazole by standardized disk diffusion testing.

Fluconazole in vitro susceptibility test results for 140,767 yeasts were collected from 127 participating investigators in 39 countries from June 1997 through December 2003. Data were collected on 79,343 yeast isolates tested with voriconazole from 2001 through 2003. All investigators tested clinical yeast isolates by the CLSI (formerly NCCLS) M44-A disk diffusion method. Test plates were automatically read and results were recorded with the BIOMIC Vision Image Analysis System. Species, drug, zone diameter, susceptibility category, and quality control results were collected quarterly via e-mail for analysis. Duplicate (the same patient, same species, and same susceptible-resistant biotype profile during any 7-day period) and uncontrolled test results were not analyzed. The 10 most common species of yeasts all showed less resistance to voriconazole than to fluconazole. Candida krusei showed the largest difference, with over 70% resistance to fluconazole and less than 8% to voriconazole. All species of yeasts tested were more susceptible to voriconazole than to fluconazole, assuming proposed interpretive breakpoints of > or =17 mm (susceptible) and < or =13 mm (resistant) for voriconazole. MICs reported in this study were determined from the zone diameter in millimeters from the continuous agar gradient around each disk, which was calibrated with MICs determined from the standard CLSI M27-A2 broth dilution method by balanced-weight regression analysis. The results from this investigation demonstrate the broad spectrum of the azoles for most of the opportunistic yeast pathogens but also highlight several areas where resistance may be progressing and/or where previously rare species may be "emerging."

Antifungal Agents↗