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Biomedical subjects

S Li

Publications and source records attributed to S Li.

At least 73 records · Page 4Linked to original sources
PubMed2005

Impact of bond order loss on surface and nanosolid mechanics.

An analytical solution shows that a competition between bond order loss and the associated bond strength gain of the lower coordinated atoms near the edge of a surface dictates the mechanics of the surface and, hence, a nanosolid. Bond order loss lowers the activation energy for atomic dislocation, whereas bond strength gain enhances the energy density or mechanical strength in the region near the surface. Therefore, the surface is harder than the bulk interior at temperatures far below the melting point (T(m)), and the surface becomes softer at temperatures close to the surface T(m) that drops because of bond order loss. Matching predictions to measurements reveals that a transition happens to the Hall-Petch relationship for a nanosolid when the effect of bond order loss becomes dominant, and the critical size of the Hall-Petch transition depends intrinsically on the bond nature of the specimen and the ratio of T/T(m), where T is the temperature of operation.

Journal Article↗
PubMed2005

Dose volume histogram comparison between ADAC Pinnacle and Nomos Corvus systems for IMRT.

This paper compares dose volume histograms (DVHs) generated by the ADAC Pinnacle and the Nomos Corvus planning systems. Seven prostate cases and seven head and neck cases were selected for review. Plans computed on both systems possessed exactly the same anatomical contours and IMRT segments. The Pinnacle system used the collapsed cone convolution superposition, while Corvus employed a finite size pencil beam (FSPB) convolution. Prostate DVH results demonstrated similar DVH curves from both systems. For each structure, the ratio of Pinnacle dose value divided by Corvus value was calculated. The high dose structures (which might contain tumour) had ratios close to unity, while the low dose structures (the critical organs) had ratios farther away from unity. Almost all ratios were less than unity, indicating a systematic difference that Pinnacle calculated doses were lower than Corvus ones. Head and neck data provided similar findings. A possible cause for this discrepancy could be the beam modelling. The difference in DVH parameters that we discovered between the two systems was about the same order of magnitude as the measurement-computation difference. When low dose is critical, such difference may affect the clinical planning decision.

Algorithms↗
PubMed2005

Successful islet transplantation from a single pancreas harvested from a young, low-BMI, non-heart-beating cadaver.

BACKGROUND: Young donors, donors with low body mass index (BMI), and non-heart-beating (NHB) donors are considered nonideal for islet transplantation. In this report, we successfully used a pancreas from a young, low-BMI, NHB donor for islet transplantation. METHODS: The donor was a 15-year-old adolescent boy whose cause of death was rupture of a primary brain tumor. According to Japanese regulations, his pancreas was procured after cardiac arrest. Warm ischemic time was 3 minutes and cold ischemic time was 300 minutes. The pancreas was digested by the automated method of Ricordi, followed by purification using continuous Euro-Ficoll gradients on a Cobe 2991 device. The recipient was a 35-year-old woman with unstable type 1 diabetes mellitus. Her pretransplant C-peptide level was null. She suffered frequent hypoglycemic unawareness. Her pretransplant M value, which is a good marker for glucose instability, was 125. Islet yield was 252,816 IEQ. There were no signs of contamination. Viability of islets assessed by FDA/PI staining was 83%. Stimulation index was 2.7. RESULTS: The patient received 5160 IEQ/kg of islets via the portal vein under local anesthesia. There were no transplant-related complications. Although she required minimal exogenous insulin, her C-peptide level increased to 0.7 ng/mL at postoperative day (POD) 14. Her M value at POD 15 to 19 decreased dramatically to 23.6, indicating good glycemic control. At 3 months posttransplant, episodes of hypoglycemia disappeared. CONCLUSIONS: Although an additional transplant is mandatory to wean patients from insulin, this case shows the possibility of using marginal donors, such as a young, low-BMI, NHB donor, for pancreas islet transplantation.

Adolescent↗
PubMed2005

Stable transduction of myogenic cells with lentiviral vectors expressing a minidystrophin.

Gene therapy for Duchenne muscular dystrophy (DMD) will require sustained expression of therapeutic dystrophins in striated muscles. Lentiviral vectors have a relatively large transgene carrying capacity and can integrate into nondividing cells. We therefore explored the use of lentiviral vectors for transferring genes into mouse skeletal muscle cells. These vectors successfully transferred a minidystrophin expression cassette into mdx muscles, and minidystrophin expression persisted and prevented subsequent muscle fiber degeneration for at least 6 months. However, only low to moderate levels of skeletal muscle transduction could be obtained by intramuscular injection of the highest currently available lentiviral doses. Using cultured cells, the lentiviral vectors effectively transduced proliferating and terminally differentiated muscle cells, indicating that cell cycling is not essential for transduction of myogenic cells. We further showed that lentiviral vectors efficiently transduced both primary myoblasts and multipotent adult progenitor cells (MAPCs) in vitro, and the cells persistently expressed transgenes without any obvious toxicity. When mdx primary myoblasts were genetically modified with minidystrophin vectors and transplanted into mdx skeletal muscles, significant numbers of dystrophin-expressing myofibers formed. Finally, we showed that a short, highly active CK6 regulatory cassette directed muscle-specific activity in the context of the lentiviral vectors. The ability of lentiviral vectors to transduce myogenic progenitors using a minidystrophin cassette regulated by a muscle-specific promoter suggests that this system could be useful for ex vivo gene therapy of muscular dystrophy.

Animals↗
PubMed2005

Infrared up-converting phosphors for bioassays.

The development of up-converting phosphor reporter particles has added a powerful tool to modern detection technologies. Carefully constructed phosphor reporters have core-shell structures with surface functional groups suitable for standard bio-conjugations. These reporters are chemically stable, possess the unique property of infrared up-conversion, and are readily detected. In contrast to conventional fluorescent reporters, up-converting phosphor particles do not bleach and allow permanent excitation with simultaneous signal integration. A large anti-Stokes shift (up to 500 nm) separates discrete emission peaks from the infrared excitation source. Along with the unmatched contrast in biological specimens due to the absence of autofluorescence upon infrared excitation, up-converting phosphor technology (UPT) has unique properties for highly-sensitive particle-based assays. The production and characteristics of UPT reporter particles as well as their application in various bioassays is reviewed.

Biological Assay↗
PubMed2005

Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial.

BACKGROUND: Psoriasis is a chronic disease that significantly diminishes the health-related quality of life (HRQOL). Infliximab is a chimeric, tumour necrosis factor alpha monoclonal antibody that has been shown to improve the signs and symptoms of plaque psoriasis. OBJECTIVES: The objective of this study was to evaluate the effect of infliximab induction therapy on the HRQOL of patients with severe plaque psoriasis. METHODS: In this double-blind, placebo-controlled trial, 249 patients were randomly assigned to receive intravenous infusions of 3 or 5 mg kg(-1) of infliximab or placebo and were treated at weeks 0, 2 and 6. Patients completed the Dermatology Life Quality Index (DLQI) at baseline and week 10. RESULTS: Infliximab induction therapy resulted in a substantial improvement in HRQOL. At week 10, patients in the infliximab 3- and 5-mg kg(-1) groups showed a median percentage improvement in DLQI scores of 84.0% and 91.0%, respectively, compared with 0% in the placebo group (P < 0.001). The median decrease from baseline in DLQI score at week 10 was 8.0 and 10.0 for the 3 and 5 mg kg(-1) infliximab groups, respectively, compared with 0 in the placebo group (P < 0.001). Thirty-three per cent and 40% of patients in the 3 and 5 mg kg(-1) infliximab groups, respectively, had a DLQI score of 0 at week 10, compared with 2% in the placebo group (P < 0.001). There was a strong correlation between the percentage change from baseline at week 10 in Psoriasis Area and Severity Index (PASI) scores and the percentage change in DLQI scores during the same period (Spearman's correlation, 0.61, P < 0.001). When the infliximab and placebo treatment groups were combined, patients with at least 75% improvement in PASI scores between baseline and week 10 had a greater mean improvement in DLQI scores (81%) than those with 50-75% improvement in PASI during the same period (60%). CONCLUSIONS: Infliximab induction therapy resulted in significant improvement in HRQOL in patients with severe psoriasis.

Adult↗
PubMed2005

Age- and sex-specific body composition of Chinese children.

UNLABELLED: We examined age- and sex-specific body compositions of Chinese children by the bioelectrical impedance method. The subjects were a total of 587 children aged 6-14 y who had normal relative weight. In all ages, boys had larger fat-free mass and lower percent body fat (%BF) than girls did. Even in the subjects with BMI <20 kg/m2, more than one quarter of them had high %BF. CONCLUSION: Chinese children may have higher %BF than that predicted by BMI.

Adolescent↗
PubMed2005

Complement component c5a is integral to the febrile response of mice to lipopolysaccharide.

OBJECTIVES: The complement system is critical to the febrile response of mice to intraperitoneally administered lipopolysaccharide (LPS). We previously identified C3 and C5 as two components potentially involved in this response. This study was designed to examine whether the complement system is also pivotal in the response of mice to intravenously or intracerebroventricularly injected LPS, to distinguish between C3 and C5 and their cognate derivatives as the essential mediator(s), and to determine whether the failure of complement-deficient mice to develop a fever could be due to their possible inability to secrete pyrogenic cytokines. METHODS: Wild-type (WT; C57BL/6J) mice, hypocomplemented or not by intravenously injected cobra venom factor (10 U/mouse), and C3-, CR3- and C5-sufficient and -deficient mice were intravenously challenged with LPS (0.25 mug/mouse); WT and C3-/- mice pretreated with a C5a receptor antagonist (C5aRa) were similarly challenged. In addition, the serum levels of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-6 were compared in LPS-treated C5+/+ and C5-/- mice. RESULTS: LPS induced a 1 degrees C rise in core temperature in all the mice, except C5-/- mice and those pretreated with C5aRa. C5+/+ and C5-/- mice challenged intracerebroventricularly with LPS exhibited identical febrile responses. LPS induced similar increases in the serum levels of IL-1beta, TNFalpha and IL-6 in C5+/+ and C5-/- mice. CONCLUSIONS: C5a is crucial for the development of febrile responses to LPS in mice; its site of action is peripheral, not central. The possibility that an inability to produce cytokines could account for the failure of C5-/- mice to develop a fever is not supported.

Animals↗
PubMed2005

Fabrication using a rapid prototyping system and in vitro characterization of PEG-PCL-PLA scaffolds for tissue engineering.

In the field of tissue engineering new polymers are needed to fabricate scaffolds with specific properties depending on the targeted tissue. This work aimed at designing and developing a 3D scaffold with variable mechanical strength, fully interconnected porous network, controllable hydrophilicity and degradability. For this, a desktop-robot-based melt-extrusion rapid prototyping technique was applied to a novel tri-block co-polymer, namely poly(ethylene glycol)-block-poly(epsilon-caprolactone)-block-poly(DL-lactide), PEG-PCL-P(DL)LA. This co-polymer was melted by electrical heating and directly extruded out using computer-controlled rapid prototyping by means of compressed purified air to build porous scaffolds. Various lay-down patterns (0/30/60/90/120/150 degrees, 0/45/90/135 degrees, 0/60/120 degrees and 0/90 degrees) were produced by using appropriate positioning of the robotic control system. Scanning electron microscopy and micro-computed tomography were used to show that 3D scaffold architectures were honeycomb-like with completely interconnected and controlled channel characteristics. Compression tests were performed and the data obtained agreed well with the typical behavior of a porous material undergoing deformation. Preliminary cell response to the as-fabricated scaffolds has been studied with primary human fibroblasts. The results demonstrated the suitability of the process and the cell biocompatibility of the polymer, two important properties among the many required for effective clinical use and efficient tissue-engineering scaffolding.

Adult↗
PubMed2004

Postmortem mu-opioid receptor binding in suicide victims and controls.

BACKGROUND: Endogenous opiates may reinforce self-injurious behavior in animal and human subjects. Higher postmortem mu-opioid receptor binding is reported in some brain regions in young compared with older suicide victims. The present study compared opioid receptor binding kinetics in postmortem brains of young suicide victims and matched controls in two brain areas. METHODS: The density (Bmax) and affinity (K(D)) of the mu-opioid receptors were assayed postmortem using [3H] DAGO in prefrontal cortex (PFC) and pre-post central gyri (PPCG) in 9 suicide victims and 10 controls, matched for age and gender ratio. RESULTS: Binding indices did not differ between suicide victims and controls in either brain area and did not correlate with age. PFC Bmax was higher than PPCG Bmax (F=8.030; df=1,16; p=.012) for the combined sample. There was no brain region difference in K(D) between PFC and PPCG, but the interaction between K(D) and group was significant (F = 5.890; df = 1,16; p = .027). The K(D) in the suicide victims was lower than controls in the PFC and higher than controls in the PPCG. CONCLUSION: Our study demonstrated more mu-opioid receptors in PFC compared with PPCG binding regardless of suicide status. The region-dependent differences in binding affinity in suicide victims may reflect regionally different opiate transmission.

Adult↗
PubMed2004

Structural genomics of Caenorhabditis elegans: structure of the BAG domain.

Binding of the BAG domain to the eukaryotic chaperone heat-shock protein (Hsp70) promotes ATP-dependent release of the protein substrate from Hsp70. Although the murine and human BAG domains have been shown to form an antiparallel three-helix bundle, the Caenorhabditis elegans BAG domain is formed by two antiparallel helices, while the third helix is extended away and stabilized by crystal-packing interactions. A small beta-sheet between helices 2 and 3 interferes with formation of the intramolecular three-helix bundle. However, intermolecular three-helix bundles are observed throughout the crystal packing and suggest that stable functional dimers and tetramers can be formed in solution. The structure may represent a new folding type of the BAG domain.

Animals↗
PubMed2004

Localization of 20alpha-hydroxysteroid dehydrogenase mRNA in mouse brain by in situ hybridization.

The enzyme 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) catalyzes the conversion of progesterone into its inactive form, 20alpha-hydroxyprogesterone. We studied the expression of 20alpha-HSD mRNA in mouse brain by in situ hybridization. 20alpha-HSD mRNA was exclusively found in neurons in cortex and hippocampus. In the cortex, the labelled cells were concentrated in the external granular layer, the external pyramidal layer and the inner granular layer. In the hippocampus, the labelling was mostly located over pyramidal cells of the CA1 layer. These results suggest that progesterone can be inactivated by 20alpha-HSD in some specific brain areas.

20-alpha-Hydroxysteroid Dehydrogenase↗
PubMed2004

Preferential expression of hPGFS in primary SCCHN and tumour cell lines derived from respiratory and digestive organs.

Identifying overexpressed genes in tumours is a critical step for tumour diagnosis, prognosis, and treatment. Using differential display polymerase chain reaction, sequence analysis, and gene Blast searches, we discovered that human prostaglandin F synthase (hPGFS) was upregulated in squamous cell carcinoma of the head and neck (SCCHN). Northern blot analysis indicated that up to a 16-fold increase in the level of hPGFS expression was detected in 40.5% (15 out of 37) of SCCHN primary tumours. The increased expression of hPGFS in SCCHN was primarily detected in SCC of larynx and hypopharynx (59%, P<0.05). Using the same primary tissue samples, increased levels of epidermal growth factor receptor (EGFR) expression were detected in only 32% of tumour tissues, suggesting hPGFS may have the potential to become a drug target or molecular marker for SCCHN. To determine if the increased level of hPGFS expression came from tumour cells, we determined the level of hPGFS expression in SCCHN tumour cell lines. A high level of hPGFS expression was detected in four out of five tumour SCCHN cell lines. To determine if upregulation of hPGFS is SCCHN-specific, hPGFS expression was analysed in 59 tumour cell lines derived from different types of tumours. The expression of hPGFS was increased from two- to 500-fold in a large portion of cell lines derived from lung (five out of nine), colon (five out of seven) as well as head and neck cancer (four out of five). These data link hPGFS expression to tumours located in the respiratory and digestive organs.

Biomarkers, Tumor↗
PubMed2004

Design, synthesis, and evaluation of metabolism-based analogues of haloperidol incapable of forming MPP+-like species.

The long-term, irreversible, Parkinsonism-like side effects of haloperidol have been speculated to involve several mechanisms. More recently, it has been speculated that the metabolic transformation to MPP+-like species may contribute to the Parkinsonism-like side effects. Because BCPP+ and its reduced analogue have been shown to possess the potential to destroy dopamine receptors in the nigrostriatum, we have designed new analogues of haloperidol lacking the structural features necessary to form neurotoxic quaternary species but retaining their dopamine-binding capacity. The most potent agent at the D2 receptor, the homopiperidine analogue 11, was found to be equipotent to haloperidol. It was also of interest to identify analogues with DA binding profiles similar to that of clozapine at the dopamine receptor subtypes. Evaluation of the proposed agents shows that the ratio of D2 to D4 (2) binding of clozapine was mimicked by 7 [K(i)(D2) = 33, K(i)(D3) = 200, K(i)(D4) = 11 nM; K(i)(D2)/K(i)(D4) = 3] and 9 [K(i)(D2) = 44, K(i)(D3) = 170, K(i)(D4) = 24 nM; K(i)(D2)/K(i)(D4) = 2]. A preliminary in-vivo testing of compound 7 shows that its behavioral profile is similar to that of clozapine. This profile suggests that there is a need for further evaluation of these two synthetic agents and their enantiomers for efficacy and lack of catalepsy in animal models.

Animals↗
PubMed2004

Polymorphisms in the taste receptor gene (Tas1r3) region are associated with saccharin preference in 30 mouse strains.

The results of recent studies suggest that the mouse Sac (saccharin preference) locus is identical to the Tas1r3 (taste receptor) gene. The goal of this study was to identify Tas1r3 sequence variants associated with saccharin preference in a large number of inbred mouse strains. Initially, we sequenced approximately 6.7 kb of the Tas1r3 gene and its flanking regions from six inbred mouse strains with high and low saccharin preference, including the strains in which the Sac alleles were described originally (C57BL/6J, Sac(b); DBA/2J, Sac(d)). Of the 89 sequence variants detected among these six strains, eight polymorphic sites were significantly associated with preferences for 1.6 mm saccharin. Next, each of these eight variant sites were genotyped in 24 additional mouse strains. Analysis of the genotype-phenotype associations in all 30 strains showed the strongest association with saccharin preference at three sites: nucleotide (nt) -791 (3 bp insertion/deletion), nt +135 (Ser45Ser), and nt +179 (Ile60Thr). We measured Tas1r3 gene expression, transcript size, and T1R3 immunoreactivity in the taste tissue of two inbred mouse strains with different Tas1r3 haplotypes and saccharin preferences. The results of these experiments suggest that the polymorphisms associated with saccharin preference do not act by blocking gene expression, changing alternative splicing, or interfering with protein translation in taste tissue. The amino acid substitution (Ile60Thr) may influence the ability of the protein to form dimers or bind sweeteners. Here, we present data for future studies directed to experimentally confirm the function of these polymorphisms and highlight some of the difficulties of identifying specific DNA sequence variants that underlie quantitative trait loci.

Animals↗
PubMed2004

Impact of neuropathic pain on the gene expression and activity of cytochrome P450side-chain-cleavage in sensory neural networks.

Development of efficient therapy against chronic and stubborn pains requires fundamental identification of adequate cellular and molecular targets. This study combined cellular, molecular and biochemical approaches to investigate the gene expression and enzymatic activity of cytochrome P450side-chain-cleavage (P450scc) in spinal neural networks under normal and neuropathic pain states. P450scc is the key onset enzyme for steroidogenesis in endocrine glands and for neurosteroid biosynthesis in nerve cells. The P450scc gene was over-expressed in spinal and supra-spinal networks during neuropathic pain provoked by sciatic nerve ligature. Plasticity was observed in P450scc cellular distribution in pain circuits and its activity also increased inducing in vivo, hyper-secretion of pregnenolone and allopregnanolone which strongly stimulates type A receptors for g-aminobutyric acid, a pivotal neurotransmitter involved in pain modulation. These results, by establishing a direct link between neuropathic pain and neuroactive steroid formation in the nervous system, open new perspectives for chronic-pain modulation by endogenous neurosteroids.

Animals↗