Biomedical subjects

James J Lu

Publications and source records attributed to James J Lu.

7 recordsLinked to original sources

PubMed2007

Cervical laminectomy: technique.

Spinal canal decompression via cervical laminectomy with or without foraminotomy is a mainstay of treatment of cervical spondylotic myelopathy and myeloradiculopathy. The goal of this surgery is to expand the cervical canal dorsally by removing the spinous processes, laminae, ligamentum flavum, and bony hypertrophy that are contributing to the canal stenosis. In selecting this particular approach to decompression, the surgeon must take into account the spinal geometry and the primary pathology of the patient: an "effective" cervical kyphosis is a contraindication to a dorsal approach, and spinal canal compromise secondary to ventral compression is best addressed through a ventral or a combined ventral and dorsal approach. This technique is technically facile and versatile in application. Complications with this procedure are relatively rare, with postoperative spinal instability being the primary concern. With proper patient selection and attention to surgical technique, laminectomy is a safe and effective approach to the management of cervical myelopathy in selected patients.

Cervical Vertebrae↗

PubMed2005

Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung.

High-molecular-mass polyethylenimines (PEIs) are widely used vectors for nucleic acid delivery. We found that removal of the residual N-acyl moieties from commercial linear 25-kDa PEI enhanced its plasmid DNA delivery efficiency 21 times in vitro, as well as 10,000 times in mice with a concomitant 1,500-fold enhancement in lung specificity. Several additional linear PEIs were synthesized by acid-catalyzed hydrolysis of poly(2-ethyl-2-oxazoline), yielding the pure polycations. PEI87 and PEI217 exhibited the highest efficiency in vitro: 115-fold and 6-fold above those of the commercial and deacylated PEI25s, respectively; moreover, PEI87 delivered DNA to mouse lung as efficiently as the pure PEI25 but at a lower concentration and with a 200-fold lung specificity. These improvements stem from an increase in the number of protonatable nitrogens, which presumably results in a tighter condensation of plasmid DNA and a better endosomal escape of the PEI/DNA complexes. As a validation of the potential of such linear, fully deacylated PEIs in gene therapy for lung diseases, systemic delivery in mice of the complexes of a short interfering RNA (siRNA) against a model gene, firefly luciferase, and PEI25 or PEI87 afforded a 77% and 93% suppression of the gene expression in the lungs, respectively. Furthermore, a polyplex of a siRNA against the influenza viral nucleocapsid protein gene and PEI87 resulted in a 94% drop of virus titers in the lungs of influenza-infected animals.

Acylation↗

PubMed2005

Poly(ethylene glycol) (PEG) enhances dynamic surface activity of a bovine lipid extract surfactant (BLES).

Shortage or malfunction of pulmonary surfactant in alveolar space leads to a critical condition termed respiratory distress syndrome (RDS). Surfactant replacement therapy, the major method to treat RDS, is an expensive treatment. In this paper, the effect of poly(ethylene glycol) (PEG) to improve dynamic surface activity of a bovine lipid extract surfactant (BLES) was studied by axisymmetric drop shape analysis (ADSA) and a captive bubble method. The activity of BLES+PEG mixtures was compared to that of a natural surfactant containing surfactant proteins A and D. When PEG was added into BLES mixtures, the surface tension hysteresis of BLES films was minimized when the films were compressed by more than 50%. PEG also helps to quickly restore surfactant films after film collapse. Thus, as far as surface tension effects go, the findings suggest that PEG might be used as a substitute for surfactant-associated protein SP-A in therapeutic surfactant products, and might also be used to reduce the amount of BLES required in clinical applications.

Animals↗

PubMed2005

Cross-linked small polyethylenimines: while still nontoxic, deliver DNA efficiently to mammalian cells in vitro and in vivo.

PURPOSE: Polyethylenimine (PEI) is among the most efficient nonviral gene delivery vectors. Its efficiency and cytotoxicity depend on molecular weight, with the 25-kDa PEI being most efficient but cytotoxic. Smaller PEIs are noncytotoxic but less efficient. Enhancement in gene delivery efficiency with minimal cytotoxicity by cross-linking of small PEIs via potentially biodegradable linkages was explored herein. The hypothesis was that cross-linking would raise the polycation's effective molecular weight and hence the transfection efficiency, while biodegradable linkages would undergo the intracellular breakdown after DNA delivery and hence not lead to cytotoxicity. Toward this goal, we carried out cross-linking of branched 2-kDa PEI and its 1:1 (w/w) mixture with a linear 423-Da PEI via ester- and/or amide-bearing linkages; the in vitro and in vivo gene delivery efficiency, as well as toxicity to mammalian cells, of the resultant cross-linked polycations were investigated. METHODS: The efficiency of the cross-linked PEIs in delivering in vitro a plasmid containing beta-galactosidase gene and their cytotoxicity were investigated in monkey kidney cells (COS-7). Dynamic light scattering was used to compare the relative DNA condensation efficiency of the unmodified and cross-linked PEIs. In vivo gene delivery efficiency was evaluated by intratracheal delivery in mice of the complexes of a luciferase-encoding plasmid and the PEIs and estimating the luciferase expression in the lungs. RESULTS: Cross-linking boosted the gene delivery efficiency of the small PEIs by 40- to 550-fold in vitro; the efficiency of the most potent conjugates even exceeded by an order of magnitude that of the branched 25-kDa PEI. Effective condensation of DNA was evident from the fact that the mean diameter of the complexes of the cross-linked PEIs was some 300 nm with a narrow size distribution, while the complexes of the unmodified small PEIs exhibited a mean size of >700 nm with a very broad size distribution. At concentrations where the 25-kDa PEI resulted in >95% cell death, the conjugates afforded nearly full cell viability. The cross-linked PEIs were 17 to 80 times more efficient than the unmodified ones in vivo; furthermore, their efficiencies were up to twice that of the 25-kDa PEI. CONCLUSIONS: Cross-linking of small PEIs with judiciously designed amide- and ester-bearing linkers boosts their gene delivery efficiency both in vitro and in vivo without increasing the cytotoxicity. The high efficiency is dependent on the nature of the linkages and the PEIs used.

Animals↗

PubMed2005

Polycation-mediated delivery of siRNAs for prophylaxis and treatment of influenza virus infection.

Influenza A virus causes one of the most prevalent infections in humans. In a typical year, 10-20% of the population of the US is infected by influenza virus, resulting in up to 40,000 deaths and 200,000 hospitalisations. Vaccination is the most effective preventative measure that can protect 70-90% of healthy adults aged < 65; however, the protection rate is much lower in those most susceptible to infection, namely infants, the elderly and individuals with weakened immune systems. Although four drugs have been approved by the FDA for use as prophylaxis and/or treatment of influenza, concerns about their side effects and the emergence of drug-resistant viruses persist. RNA interference (RNAi), an emerging method of post transcriptional gene silencing, appears ideal for the prevention and treatment of influenza. RNAi in mammals can be mediated by short interfering RNAs (siRNAs) of approximately 21-27 nucleotides in length. The authors have previously shown that siRNAs specific for conserved regions of the influenza virus genome are potent inhibitors of influenza virus replication in both cell lines and chicken embryos. This review discusses the recent progress in the in vivo inhibition of influenza virus by the delivery of siRNAs mediated by non-viral vectors, and the prospects of this strategy for prophylaxis and treatment of influenza infection in humans.

Animals↗

PubMed2004

Poly(ethylene glycol) enhances the surface activity of a pulmonary surfactant.

The primary role of lung surfactant is to reduce surface tension at the air-liquid interface of alveoli during respiration. Axisymmetric drop shape analysis (ADSA) was used to study the effect of poly(ethylene glycol) (PEG) on the rate of surface film formation of a bovine lipid extract surfactant (BLES), a therapeutic lung surfactant preparation. PEG of molecular weights 3,350; 8,000; 10,000; 35,000; and 300,000 in combination with a BLES mixture of 0.5 mg/mL was studied. The adsorption rate of BLES alone at 0.5 mg/mL was much slower than that of a natural lung surfactant at the same concentration; more than 200 s are required to reach the equilibrium surface tension of 25 mJ/m(2). PEG, while not surface active itself, enhances the adsorption of BLES to an extent depending on its concentration and molecular weight. These findings suggest that depletion attraction induced by higher molecular weight PEG (in the range of 8,000 to 35,000) may be responsible for increasing the adsorption rate of BLES at low concentration. The results provide a basis for using PEG as an additive to BLES to reduce its required concentration in clinical treatment, thus reducing the cost for surfactant replacement therapy.

Animals↗

PubMed2004

Constrained sessile drop as a new configuration to measure low surface tension in lung surfactant systems.

Existing methodology for surface tension measurements based on drop shapes suffers from the shortcoming that it is not capable to function at very low surface tension if the liquid dispersion is opaque, such as therapeutic lung surfactants at clinically relevant concentrations. The novel configuration proposed here removes the two big restrictions, i.e., the film leakage problem that is encountered with such methods as the pulsating bubble surfactometer as well as the pendant drop arrangement, and the problem of the opaqueness of the liquid, as in the original captive bubble arrangement. A sharp knife edge is the key design feature in the constrained sessile drop that avoids film leakage at low surface tension. The use of the constrained sessile drop configuration in conjunction with axisymmetric drop shape analysis to measure surface tension allows complete automation of the setup. Dynamic studies with lung surfactant can be performed readily by changing the volume of a sessile drop, and thus the surface area, by means of a motor-driven syringe. To illustrate the validity of using this configuration, experiments were performed using an exogenous lung surfactant preparation, bovine lipid extract surfactant (BLES) at 5.0 mg/ml. A comparison of results obtained for BLES at low concentration between the constrained sessile drop and captive bubble arrangement shows excellent agreement between the two approaches. When the surface area of the BLES film (0.5 mg/ml) was compressed by about the same amount in both systems, the minimum surface tensions attained were identical within the 95% confidence limits.

Animals↗