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Biomedical subjects

W Song

Publications and source records attributed to W Song.

At least 19 recordsLinked to original sources

Drastic reduction of shot noise in semiconductor superlattices.

We have found experimentally that the shot noise of the tunneling current I through an undoped semiconductor superlattice is reduced with respect to the Poissonian noise value 2eI, and that the noise approaches 1/3 of that value in superlattices whose quantum wells are strongly coupled. On the other hand, when the coupling is weak or when a strong electric field is applied to the superlattice, the noise becomes Poissonian. Although our results are qualitatively consistent with existing theories for one-dimensional multibarrier structures, the theories cannot account for the dependence of the noise on superlattice parameters that we have observed.

Journal Article↗

Emergence of Escherichia coli isolates producing conjugative plasmid-mediated DHA-1 beta-lactamase in a Korean university hospital.

Seven isolates of cefoxitin-resistant Escherichia coli with an inducible phenotype were detected between November 2002 and July 2003 in a Korean hospital. Conjugations were tested by the filter mating method using azide-resistant E. coli J53 as the recipient. All isolates and their transconjugants were tested for broth microdilution minimum inhibitory concentrations, isoelectric focusing (IEF), polymerase chain reaction (PCR) for SHV, TEM, CTX-M and DHA-derived beta-lactamases, and DNA sequencing. XbaI-digested genomic DNA bands of the seven isolates were separated by pulsed-field gel electrophoresis (PFGE). IEF, PCR and sequence analysis revealed that all isolates possessed a blaTEM-1-like and a blaDHA-1 gene. Two isolates also carried the blaCTX-M-14 gene. Transfer of the resistance by conjugation experiments of all seven isolates was successful, suggesting that the blaDHA-1-containing plasmids in the E. coli isolates were self-transmissible. The isolates were recovered from patients in wards or an intensive care unit, all of which had been exposed to beta-lactams before isolation of the DHA-1 producers. Five patterns among the seven isolates were demonstrated by PFGE; sporadic infections with E. coli possessing an inducible beta-lactam resistance phenotype were found. DHA-1 encoded by conjugative plasmids conferred the resistance phenotype. The spread of the DHA-1 producers was due to both clonal spread and horizontal transfer of the resistance gene.

Adult↗

Effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia in Chinese population.

Therapy with losartan compared to irbesartan was performed in a Chinese sample of hypertensive patients with elevated serum uric acid (SUA) levels. After 1 week of screening and a 2 week single-blinded placebo baseline period, patients were treated for 4 weeks with losartan 50 mg or irbesartan 150 mg. After 4 weeks, patients with SiDBP <90 mmHg and SiSBP <140 mmHg continued the same dose regimen for another 4 weeks. If blood pressure was not controlled after 4 weeks of treatment, the dose of either regimen was doubled to losartan 100 mg and irbesartan 300 mg. There were 351 patients randomized (176 to losartan and 175 to irbesartan), and of these, 325 patients completed the study (162 in the losartan group and 163 in the irbesartan group). At baseline, the median SUA level in the losartan group was 422 and 420 micromol/l in the irbesartan group. At 8 weeks of therapy, SUA decreased by 63 mumol/l in the losartan group compared to 12 mumol/l in the irbesartan group (P < 0.0001). Blood pressure declined comparably in both groups from 151/92 mmHg at baseline to 137/83 and 135/83 (losartan and irbesartan, respectively, NS). No severe AEs were found for either treatment group. Therapy with losartan decreased SUA levels significantly more than irbesartan in Chinese patients with hypertension and elevated SUA levels, demonstrating the unique uricosuric effect of this ARB in this ethnic group.

Angiotensin II Type 1 Receptor Blockers↗

Urotensin II and renal function in the rat.

Urotensin II (UII) is a potent vasoactive hormone in mammals. However, despite its well-known effects on epithelial sodium transport in fish, little is known about its actions on the mammalian kidney. The aim of this study was to determine the effects of UII on renal function in the rat. Using standard clearance methods, the effects of rUII and the rat UII receptor (UT) antagonist, urantide, were studied. UII was measured in plasma and urine by radioimmunoassay. UII and UT were localized in the kidney by immunohistochemistry and mRNA expression quantified. Rat urinary [UII] was 1,650-fold higher than that in plasma. Immunoreactive-UII was localized to the proximal tubules, outer and inner medullary collecting ducts (IMCD); UT receptor was identified in glomerular arterioles, thin ascending limbs, and IMCD. UII and UT mRNA expression was greater in the medulla; expression was higher still in spontaneously hypertensive rats (SHRs) associated with raised plasma (UII). Injection of rUII induced reductions in glomerular filtration rate (GFR), urine flow, and sodium excretion. Urantide infusion resulted in increases in these variables. Endogenous UII appears to contribute to the regulation of GFR and renal sodium and water handling in the rat. While hemodynamic changes predominate, we cannot rule out the possibility of a direct tubular action of UII. Increased expression of UII and UT in the SHR suggests that UII plays a role in the pathophysiology of cardiovascular disease.

Animals↗

Interleukin 18 and human immunodeficiency virus type I infection in adolescents and adults.

Interleukin (IL)-18, a proinflammatory cytokine, has been recognized recently as an important factor in both treated and untreated patients with human immunodeficiency virus type 1 (HIV-1) infection. Consistent with all earlier reports, our quantification of serum IL-18 concentrations in 88 HIV-1 seropositive, North American adolescents (14-18 years old) revealed a positive correlation with cell-free HIV-1 viral load at two separate visits (Spearman's r = 0.31 and 0.50, respectively, P < 0.01 for both), along with a negative correlation with CD4+ T cell counts (r = -0.31 and -0.35, P < 0.01 for both). In additional analyses of 66 adults (21-58 years old) from Zambia, HIV-1 seroconversion was associated uniformly with elevated IL-18 production (P < 0.0001). These epidemiological relationships were independent of other population-related characteristics, including age, gender and ethnicity. In neither study population could serum IL-18 concentrations be associated with the IL-18 gene (IL18) promoter genotypes defined by five major single nucleotide polymorphisms. Collectively, these findings suggest that circulating IL-18 rather than the IL18 genotype may provide a useful biomarker for HIV-1-related events or outcomes.

ADP-ribosyl Cyclase 1↗

The membrane attack pathway of complement drives pathology in passively induced experimental autoimmune myasthenia gravis in mice.

The human neuromuscular disease myasthenia gravis (MG) is characterized by the generation of autoantibodies reactive with nicotinic acetylcholine receptors (AChR) that cause loss of AChR from the neuromuscular end-plate with resultant failure of neuromuscular transmission. A role for complement (C) in AChR loss has been suggested based upon morphological identification of C at the end-plate in MG and from the effects of C inhibition in murine models. Here we provide further evidence implicating C, and specifically the membrane attack complex (MAC), in a mouse model of MG. Mice deficient in the C regulators Daf1 and/or Cd59a were tested in the model. Wild-type mice were resistant to disease while mice deficient in Daf1 had mild disease symptoms with evidence of C activation and AChR loss at end-plates. Cd59a-deficient mice had very mild disease with some muscle inflammation and essentially undamaged end-plates. In contrast, mice deficient in both C regulators developed a severe paralytic disease with marked muscle inflammation and loss of end-plates. Inhibition of MAC assembly abrogated clinical disease in these double-deficient mice, demonstrating conclusively that MAC formation was driving pathology in the model. These findings provoke us to suggest that current anti-C therapeutics targeting MAC assembly will be beneficial in MG patients resistant to conventional therapies.

Animals↗

Rice endophyte Pantoea agglomerans YS19 promotes host plant growth and affects allocations of host photosynthates.

AIMS: The aims of the study were to identify the effects of rice endophyte Pantoea agglomerans YS19 on host plant growth and allocations of photosynthates. METHODS AND RESULTS: Endophytic diazotrophic YS19 showed nitrogen-fixing activity in N-free medium, and produced four categories of phytohormones which were indole-3-acetic acid, abscisic acid, gibberellic acid and cytokinin in Luria-Bertani medium. Inoculation of YS19 improved the biomass of the 12-day-cultivated host rice seedlings by 63.4% on N-free medium or by 18.7% on N-supplemented medium. Spraying of YS19 cell culture onto the rice plants at the premilk stage enhanced the transportation of the photosynthetic assimilation product from the source (flag leaves) to the sink (stachys) significantly. The formation of the plant sink was obviously inhibited when YS19 cell culture was applied at the late milk stage. CONCLUSIONS: This research suggests that endophyte YS19 promotes host rice plant growth and affects allocations of host photosynthates. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggested that YS19 possesses the potential for increasing rice production in field application. Meanwhile, a suitable plant growth stage must be selected for the foliar spraying of YS19 cell culture.

Biomass↗

Differentiating sex chromosomes of the dioecious Spinacia oleracea L. (spinach) by FISH of 45S rDNA.

Spinacia oleracea L. (spinach) is a dioecious species with both male and female plants having 2n = 2x = 12 chromosomes, consisting of two large metacentrics, two long subtelocentrics, two short subtelocentrics, two acrocentrics, and four submetacentrics. The location of 45S rDNA was investigated on metaphase chromosomes using fluorescence in situ hybridization (FISH). The numbers of 45S rDNA foci in diploid sets of chromosomes from females was six and from males was five. All the fluorescent foci lay in secondary constrictions and the satellites. Our results indicate that an XY-type sex chromosome system could be present in spinach where the Y chromosome lacks a 45S RNA focus.

Chromosomes, Plant↗

Activation of iCaspase-9 in neovessels inhibits oral tumor progression.

Tumors of the oral cavity are highly vascularized malignancies. Disruption of neovascular networks was shown to limit the access of nutrients and oxygen to tumor cells and inhibit tumor progression. Here, we evaluated the effect of the activation of an artificial death switch (iCaspase-9) expressed in neovascular endothelial cells on the progression of oral tumors. We used biodegradable scaffolds to co-implant human dermal microvascular endothelial cells stably expressing iCaspase-9 (HDMEC-iCasp9) with oral cancer cells expressing luciferase (OSCC3-luc or UM-SCC-17B-luc) in immunodeficient mice. Alternatively, untransduced HDMEC were co-implanted with oral cancer cells, and a transcriptionaly targeted adenovirus (Ad-VEGFR2-iCasp-9) was injected locally to deliver iCaspase-9 to neovascular endothelial cells. In vivo bioluminescence demonstrated that tumor progression was inhibited, and immunohistochemistry showed that microvessel density was decreased, when iCaspase-9 was activated in tumor-associated microvessels. We conclude that activation of iCaspase-9 in neovascular endothelial cells is sufficient to inhibit the progression of xenografted oral tumors.

Analysis of Variance↗

Microscopic and macroscopic characterization of organosilane-functionalized nanocrystalline NaZSM-5.

Nanocrystalline NaZSM-5 zeolites with systematically varied particle sizes (15, 60, and 200 nm) were functionalized with organosilanes. Through the systematic variation of particle size and therefore external surface area of NaZSM-5, the extent of functionalization and location of functional groups were spectroscopically verified. 29Si magic-angle spinning (MAS) NMR and Fourier transform infrared (FTIR) spectroscopy provided conclusive evidence that the silanol groups located on the external surface of NaZSM-5 were functionalized through reaction with the organosilanes. The 29Si NMR results provided quantitative information about the extent of functionalization on NaZSM-5. A nitroxide spin label was adsorbed on the external surface of NaZSM-5 to probe the surface properties by electron paramagnetic resonance (EPR) spectroscopy. The macroscopic and microscopic properties, such as the behavior of functionalized NaZSM-5 in different solvents, and the specific surface areas were also investigated. The hydrophobicity of the functionalized NaZSM-5 was found to increase relative to the parent NaZSM-5 as expected for an organic surface coating.

Journal Article↗

Dosimetric impact of image-guided 3D conformal radiation therapy of prostate cancer.

The goal of this work is to quantify the impact of image-guided conformal radiation therapy (CRT) on the dose distribution by correcting patient setup uncertainty and inter-fraction tumour motion. This was a retrospective analysis that used five randomly selected prostate cancer patients that underwent approximately 15 computed tomography (CT) scans during their radiation treatment course. The beam arrangement from the treatment plan was imported into each repeat CT study and the dose distribution was recalculated for the new beam setups. Various setup scenarios were then compared to assess the impact of image guidance on radiation treatment precision. These included (1) daily alignment to skin markers, thus representing a conventional beam setup without image guidance, (2) alignment to bony anatomy for correction of daily patient setup error, thus representing on-line portal image guidance, and (3) alignment to the 'CTV of the day' for correction of inter-fraction tumour motion, thus representing on-line CT or ultrasound image guidance. Treatment scenarios (1) and (3) were repeated with a reduced CTV to PTV margin, where the former represents a treatment using small margins without daily image guidance. Daily realignment of the treatment beams to the prostate showed an average increase in minimum tumour dose of 1.5 Gy, in all cases where tumour 'geographic miss' without image guidance was apparent. However, normal tissue sparing did not improve unless the PTV margin was reduced. Daily realignment to the tumour combined with reducing the margin size by a factor of 2 resulted in an average escalation in tumour dose of 9.0 Gy for all five static plans. However, the prescription dose could be escalated by 13.8 Gy when accounting for changes in anatomy by accumulating daily doses using nonlinear image registration techniques. These results provide quantitative information on the effectiveness of image-guided radiation treatment of prostate cancer and demonstrate that the dosimetric impact is patient dependent.

Artifacts↗

High yield method for nanocrystalline zeolite synthesis.

Nanocrystalline zeolites, such as silicalite-1 and zeolite Y, were synthesized in high yield by periodically removing nanocrystals from the synthesis solution and recycling the unused reagents, including the template and T-atom sources.

Journal Article↗

The EGFR mutation and its correlation with response of gefitinib in previously treated Chinese patients with advanced non-small-cell lung cancer.

BACKGROUND: The aim of the study was to evaluate the efficacy of gefitinib and the epidermal growth factor receptor (EGFR) mutation to gefitinib response in a series of Chinese patients with pretreated advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 98 patients who had failed at least one platinum-based regimen received gefitinib 250 mg once daily. The mutation analysis of the EGFR kinase domain was performed for 30 patients using paraffin-embedded tumor tissue. RESULTS: The response rate was 31.6% and the disease control rate was 67.3%. Objective response was correlated with adenocarcinoma, female gender and non-smokers. Median progress free survival (PFS) was 7.0 months, median overall survival (OS) was 12.0 months and 1-year survival was 53.1%. The median PFS and OS were improved among patients with adenocarcinoma, gefitinib responders and non-smokers. Active gene mutation was detected in 12 patients. Mutation rates were higher among gefitinib responders, non-smokers, patients with adenocarcinoma and female patients. OS was longer for patients with gene mutation than for patients without mutation. CONCLUSION: Gefitinib demonstrated significant antitumor activity with a favorable toxicity profile for pretreated Chinese patients with advanced NSCLC. The active mutation of the EGFR kinase domain was strongly associated with response to gefitinib and prolonged overall survival.

Adenocarcinoma↗

Antiangiogenic gene therapy: disruption of neovascular networks mediated by inducible caspase-9 delivered with a transcriptionally targeted adenoviral vector.

The activation of an inducible caspase (iCaspase-9) mediates apoptosis of neovascular endothelial cells, and overcomes the prosurvival effect of vascular endothelial growth factor or basic fibroblast growth factor. The potential utilization of direct activation of caspases as an antiangiogenic strategy for treatment of angiogenesis-dependent diseases (eg cancer) requires expression of the inducible caspase primarily in the tumor endothelium. The objective of this work was to develop and characterize a transcriptionally targeted adenoviral vector that mediates expression of iCaspase-9 specifically in neovascular endothelial cells. We observed that adenoviral vectors containing the human VEGFR2 promoter induced reporter gene expression primarily in proliferating human dermal microvascular endothelial cells (HDMEC). HDMEC transduced with recombinant adenoviral vectors containing iCaspase-9 under regulation of the VEGFR2 promoter (Ad-hVEGFR2-iCaspase-9) and exposed to a cell-permeable dimerizer drug (AP20187), presented higher caspase-3 activity and apoptosis than controls (P < or = 0.05). Using the SCID Mouse Model of Human Angiogenesis, we observed that local delivery of Ad-hVEGFR2-iCaspase-9 followed by intraperitoneal injection of AP20187 resulted in endothelial cell apoptosis and local ablation of microvessels. We believe that this constitutes the first report of a transcriptionally targeted antiangiogenic adenoviral vector that mediates neovascular disruption upon activation of a caspase-based artificial death switch.

Adenoviridae↗

Urotensin II: ancient hormone with new functions in vertebrate body fluid regulation.

Urotensin II (UII), described in many fish species, is secreted by the caudal neurosecretory system, a unique fish neuroendocrine structure. We have examined UII secretion and its control in euryhaline fish, supporting a proposed role in osmoregulation. However, it is now apparent that UII is present in other vertebrates, including mammals. The 12-amino-acid peptide has been highly conserved and the key cyclic region is common from fish to humans. Our UII radioimmunoassay for flounder, directed to this cyclic region, has shown circulating UII levels in humans and rats comparable with those in fish. In mammals, UII cardiovascular effects vary between species, with vasoconstriction only evident in specific vascular beds. The kidney expresses UII receptors and responds to UII administration by a reduction in glomerular filtration rate, urine flow, and excretion of the major ions. Interestingly, plasma levels of UII are chronically elevated in rat models of hypertension. These observations imply an unforeseen role for this ancient fish hormone in the physiological and perhaps pathophysiological regulation of body fluids in higher vertebrates, including humans.

Animals↗

Oxidative stress potentiates BACE1 gene expression and Abeta generation.

Alzheimer's Disease (AD) is the most common neurodegenerative disorder leading to dementia and its prevalence increases with age. The pathological features of AD are characterized by the beta-amyloid protein (A(beta)) deposits in the core of neuritic plaques and abnormal neurofibrillary tangles in the brain of AD patients. BACE1 is the major beta-secretase to cleave the beta-amyloid precursor protein (APP) to generate A(beta). Oxidative stress has been shown to affect A(beta) generation in the AD pathogenesis and the mechanism of such effect is unknown. In this report we generated a novel promoterless enhanced green fluorescent protein (EGFP) reporter gene cloning vector and cloned a 1.9-kb BACE1 gene promoter fragment in this vector. The BACE1 promoter fragment can efficiently activate EGFP or luciferase gene transcription. Oxidative stress induced by hydrogen peroxide resulted in significant increase in the BACE1 promoter activity. Furthermore, hydrogen peroxide treatment facilitated beta-secretase activity and A(beta) generation. Thus, upregulation of BACE1 transcription by oxidative stress may contribute to the pathogenesis of Alzheimer's disease.

Amyloid Precursor Protein Secretases↗

Synthesis, characterization, and adsorption properties of nanocrystalline ZSM-5.

Nanocrystalline ZSM-5 with a Si/Al ratio of 20 was synthesized using clear solutions and a hydrothermal synthesis procedure. The resulting ZSM-5 materials were characterized by powder X-ray diffraction, scanning electron microscopy (SEM), nitrogen adsorption isotherms, solid-state nuclear magnetic resonance, and toluene adsorption. A commercial ZSM-5 sample was similarly characterized for comparison with the synthesized materials. The particle sizes of the synthesized ZSM-5 samples were calculated using the measured external surface areas and were determined to be 15 and 60 nm. SEM images indicated that the ZSM-5 samples consist of agglomerated and possibly intergrown particles. Toluene adsorption measurements showed that the ZSM-5 sample with a particle size of 15 nm adsorbed approximately 50% more toluene than the other ZSM-5 samples, most likely due to the adsorption of toluene on the external surface. For the toluene adsorbed on the internal zeolite surface, approximately one toluene molecule was adsorbed per channel intersection for each of the ZSM-5 samples.

Adsorption↗