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Biomedical subjects

C Liang

Publications and source records attributed to C Liang.

At least 19 recordsLinked to original sources
PubMed2006

Conformational differences in protein disulfide linkages between normal hair and hair from subjects with trichothiodystrophy: a quantitative analysis by Raman microspectroscopy.

Raman spectra of normal hair shafts and hair shafts from patients exhibiting trichothiodystrophy (TTD) were obtained using line focus laser illumination. Because hair from TTD patients has a significant decrease in the content of the sulfur-containing amino acids in comparison to normal hair, the 550-500 cm(-1) disulfide stretching mode region of the Raman spectrum was examined in detail. A quantitative spectral analysis demonstrates significant increases in the two energetically less favored gauche-gauche-trans (g-g-t) and trans-gauche-trans (t-g-t) forms. These observations suggest that the increased amounts of these less stable disulfide conformers are contributing factors to or associated with the hair brittleness observed for this congenital disorder. Structure-spectra correlations for the three dominant disulfide conformers are confirmed by quantum chemical calculations using modern density functional theory (DFT).

Biopolymers↗
PubMed2005

A third blind test of crystal structure prediction.

Following the interest generated by two previous blind tests of crystal structure prediction (CSP1999 and CSP2001), a third such collaborative project (CSP2004) was hosted by the Cambridge Crystallographic Data Centre. A range of methodologies used in searching for and ranking the likelihood of predicted crystal structures is represented amongst the 18 participating research groups, although most are based on the global minimization of the lattice energy. Initially the participants were given molecular diagrams of three molecules and asked to submit three predictions for the most likely crystal structure of each. Unlike earlier blind tests, no restriction was placed on the possible space group of the target crystal structures. Furthermore, Z' = 2 structures were allowed. Part-way through the test, a partial structure report was discovered for one of the molecules, which could no longer be considered a blind test. Hence, a second molecule from the same category (small, rigid with common atom types) was offered to the participants as a replacement. Success rates within the three submitted predictions were lower than in the previous tests - there was only one successful prediction for any of the three ;blind' molecules. For the ;simplest' rigid molecule, this lack of success is partly due to the observed structure crystallizing with two molecules in the asymmetric unit. As in the 2001 blind test, there was no success in predicting the structure of the flexible molecule. The results highlight the necessity for better energy models, capable of simultaneously describing conformational and packing energies with high accuracy. There is also a need for improvements in search procedures for crystals with more than one independent molecule, as well as for molecules with conformational flexibility. These are necessary requirements for the prediction of possible thermodynamically favoured polymorphs. Which of these are actually realised is also influenced by as yet insufficiently understood processes of nucleation and crystal growth.

Algorithms↗
PubMed2003

The influence of temperature and moisture contents regimes on the aerobic microbial activity of a biosolids composting blend.

To understand the relationships between temperature, moisture content, and microbial activity during the composting of biosolids (municipal wastewater treatment sludge), well-controlled incubation experiments were conducted using a 2-factor factorial design with six temperatures (22, 29, 36, 43, 50, and 57 degrees C) and five moisture contents (30, 40, 50, 60, and 70%). The microbial activity was measured as O2 uptake rate (mg g(-1) h(-1)) using a computer controlled respirometer. In this study, moisture content proved to be a dominant factor impacting aerobic microbial activity of the composting blend. Fifty percent moisture content appeared to be the minimal requirement for obtaining activities greater than 1.0 mg g(-1) h(-1). Temperature was also documented to be an important factor for biosolids composting. However, its effect was less influential than moisture content. Particularly, the enhancement of composting activities induced by temperature increment could be realized by increasing moisture content alone.

Bacteria, Aerobic↗
PubMed2003

Both stress experience and age determine the impairment or enhancement effect of stress on spatial memory retrieval.

It has been documented that stress or glucocorticoids have conflicting effects on memory under different conditions. However, it is not fully understood why stress can either impair or enhance memory. Here, we have examined the performance of six age groups of Wistar rats in a water maze spatial task to evaluate the effects of stress under different conditions. We found that the impairment or enhancement effect of an 'elevated platform' (EP) stress on memory was dependent on previous stress experience and on age. EP stress impaired memory retrieval in water maze naive animals, but enhanced rather than impaired memory retrieval in young water maze stress-experienced animals. Furthermore, exogenously applied corticosterone or foot shock stress before water maze training prevented the impairment of memory retrieval that should be induced by treatment with corticosterone or foot shock before the 'probe trial'. Again, memory retrieval was enhanced in young animals under these conditions, and this enhancement can be prevented by the glucocorticoid receptor antagonist RU 38486. Thus, glucocorticoid receptor activation not only induced impairment of memory but also increased the capacity of young animals to overcome a later stress. The present findings suggest that the effect of stress on memory can be switched from impairment to enhancement dependent on both stress experience and age.

Aging↗
PubMed2002

Near real time in vivo fibre optic confocal microscopy: sub-cellular structure resolved.

We have built a fibre optic confocal reflectance microscope capable of imaging biological tissue in near real time. The measured lateral resolution is 3 micro m and axial resolution is 6 micro m. Images of epithelial cells, excised tissue biopsies, and the human lip in vivo have been obtained at 15 frames s-1. Both cell morphology and tissue architecture can be appreciated from images obtained with this microscope. This device has the potential to enable reflected light confocal imaging of internal organs for in situ detection of pathology.

Animals↗
PubMed2001

Antioxidant vitamins attenuate oxidative stress and cardiac dysfunction in tachycardia-induced cardiomyopathy.

OBJECTIVES: We administered antioxidant vitamins to rabbits with pacing-induced cardiomyopathy to assess whether antioxidant therapy retards the progression of congestive heart failure (CHF). BACKGROUND: Although oxidative stress is increased in CHF, whether progression of heart failure could be prevented or reduced by antioxidants is not known. METHODS: Rabbits with chronic cardiac pacing and sham operation were randomized to receive a combination of beta-carotene, ascorbic acid and alpha-tocopherol, alpha-tocopherol alone or placebo over eight weeks. Echocardiography was used to measure cardiac function weekly. Resting hemodynamics and in vivo myocardial beta-adrenergic responsiveness were studied at week 8. Animals were then sacrificed for measuring myocardial beta-receptor density, norepinephrine (NE) uptake-1 site density, sympathetic neuronal marker profiles, tissue-reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and oxidative damage of mitochondrial DNA (mtDNA). RESULTS: Rapid cardiac pacing increased myocardial oxidative stress as evidenced by reduced myocardial GSH/GSSG ratio and increased oxidized mtDNA and produced cardiac dysfunction, beta-adrenergic subsensitivity, beta-receptor downregulation, diminished sympathetic neurotransmitter profiles and reduced NE uptake-1 carrier density. A combination of antioxidant vitamins reduced the myocardial oxidative stress, attenuated cardiac dysfunction and prevented myocardial beta-receptor downregulation and sympathetic nerve terminal dysfunction. Administration of alpha-tocopherol alone produced similar effects, but the effects were less marked than those produced by the three vitamins together. Vitamins produced no effects in sham-operated animals. CONCLUSIONS: Antioxidant vitamins reduced tissue oxidative stress in CHF and attenuated the associated cardiac dysfunction, beta-receptor downregulation and sympathetic nerve terminal abnormalities. The findings suggest that antioxidant therapy may be efficacious in human CHF.

Analysis of Variance↗
PubMed2001

HIV-1 nucleocapsid protein and the secondary structure of the binary complex formed between tRNA(Lys.3) and viral RNA template play different roles during initiation of (-) strand DNA reverse transcription.

In human immunodeficiency virus type 1 (HIV-1), the tRNA(Lys.3) primer and viral RNA template can form a specific complex that is characterized by extensive inter- and intramolecular interactions. Initiation of reverse transcription from this complex has been shown to be distinguished from subsequent elongation by early pausing events, such as at the +1 and +3 nucleotide positions. One major concern regarding the biological relevance of these results is that most kinetic studies of HIV-1 reverse transcription have been performed using tRNA(Lys.3)-viral (v) RNA complexes that were formed by heat annealing. In contrast, tRNA(Lys.3) in viruses is placed onto the primer binding site by nucleocapsid (NC) sequences of the Gag protein. In this study, we have further characterized the initiation features of reverse transcription in the presence of HIV-1 NC protein. In contrast to results obtained with a heat-annealed tRNA(Lys.3).vRNA complex, we found that polymerization reactions catalyzed by HIV-1 reverse transcriptase did not commonly pause at the +1 nucleotide position when a NC-annealed RNA complex was used, and that this was true regardless whether NC was actually still present during reverse transcription. This activity of NC required both zinc finger motifs, as demonstrated by experiments that employed zinc finger-mutated forms of NC protein (H23C NC and ddNC), supporting the involvement of the zinc fingers in the RNA chaperone activity of NC. However, NC was not able to help reverse transcriptase to escape the +3 pausing event. Mutagenesis of a stem structure within the tRNA(Lys.3). vRNA complex led to disappearance of the +3 pausing event as well as to significantly reduced rates of reverse transcription. Thus, this stem structure is essential for optimal reverse transcription, despite its role in promotion of the +3 pausing event.

Amino Acid Motifs↗
PubMed2001

Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle.

Cdc6p and the origin recognition complex (ORC) are essential for assembly of a pre-replicative complex (preRC) at origins of replication, before the initiation of DNA synthesis. In the absence of Cdc6p, cells fail to initiate DNA replication and undergo a "reductional" mitosis, in which the unreplicated chromosomes are randomly segregated to the spindle poles. We show here that the cells harboring a mutation in the essential Cdc6p Walker A-box arrest in late mitosis, probably at anaphase. This cell cycle block requires either the three Cdc28p phosphorylation sites within the N terminus of Cdc6p or a short region (aa 8-17) that contains a Cy (Cyclin) interaction sequence. These same two Cdc6p mutants that allow a reductional mitosis are defective in binding Cdc28p kinase. In addition to Cdc6p, ORC also binds to cyclin-dependent kinases (CDKs). Interestingly, Sic1p, a CDK inhibitor protein, blocked the S phase-specific Cdc28p-Clb5p kinase from interacting with ORC, but did not prevent the G(1)-specific Cdc28p-Cln2p kinase-ORC interaction. We suggest that ORC, Cdc6p, and Sic1p bind to different CDKs in a cell cycle-dependent manner to temporally regulate events that (i) allow preRC formation after mitosis, (ii) prevent mitosis before DNA replication can occur, and (iii) promote initiation of DNA replication.

Amino Acid Sequence↗
PubMed2001

[Distraction osteogenesis in correction of mandibular micrognathia accompanying obstructive sleep apnea syndrome].

OBJECTIVE: To evaluate the effect of distraction osteogenesis in correction of mandibular micrognathia accompanying obstructive sleep apnea syndrome (OSAS). METHODS: A total of 15 patients, aged 9 to 43 years, 11 males and 4 females, were treated. 7 patients suffered from bilateral ankylosis of temporo manclibular joint inducing severe mandibular micrognathia and accompanying severe OSAS. 3 cases suffered from unilateral TMJ ankylosis with OSAS. 3 patients suffered from congenital developmental micrognathia with OSAS. 2 cases were caused by trauma. Among the 15 patients, 12 were treated by synchronous bilateral mandibular distraction, 3 patients were distracted unilaterally. Every patient had been evaluated pre- and postoperatively with cephalometry and polysomnography. RESULTS: The minimum distance of distraction was 9 mm, the maximum was 30 mm, with a mean of 20.4 mm, in mandible of 15 patients with 27 sides. The distraction process was smooth in all the cases. The osteogenesis was good, without infection and other complications. Complete curative effect was achieved in 4 severe, 3 moderate, and 4 mild cases. The posterior airway space was increased from averaged 4.5 mm preoperatively to 12.4 mm. The increase of SNB angle was from preoperative 66 degrees to 75 degrees on average postoperatively. The vast majority of the patients had their subjective symptoms alleviated gradually or disappeared completely. The results were stable without relapse during a follow-up period of 12 months. CONCLUSION: The distraction osteogenesis can not only be used to effectively correct severe mandibular micrognathia deformity, but also can cure its accompanying OSAS. The procedure is simple, with low risk, high curative rate, low relapse rate, and stable result. Up to now, it is the most effective method in the treatment of this difficult and complicated kind of disorder.

Adolescent↗
PubMed2001

A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells.

Recent studies have indicated that the development of cyclin-dependent kinase (cdk)2 inhibitors that deregulate E2F are a plausible pharmacological strategy for novel antineoplastic agents. We show here that 3-[1-(3H-Imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), a novel 3-substituted indolinone compound, binds to and selectively inhibits the activity of cdk2. This inhibition results in a time-dependent decrease (4-64%) in the phosphorylation of the retinoblastoma protein pRb, an increase in caspase-3 activation (5-84%), and alterations in cell cycle resulting in either a G(0)-G(1) or a G(2)-M block. We also report here cell line differences in the cdk-dependent phosphorylation of pRb. These findings demonstrate that SU9516 is a selective cdk2 inhibitor and support the theory that compounds that inhibit cdk2 are viable resources in the development of new antineoplastic agents.

Adenocarcinoma↗
PubMed2001

Indolinone tyrosine kinase inhibitors block Kit activation and growth of small cell lung cancer cells.

Six indolinone tyrosine kinase inhibitors were characterized for their ability to inhibit Kit kinase and for their effects on the growth of small cell lung cancer (SCLC) cell lines. All of the six compounds were potent inhibitors of Kit kinase in a biochemical assay. A homology model of compound binding to the ATP binding site could account for the increased potency observed with the addition of a propionate moiety to the indolinone core but not the increase observed with addition of a chloride moiety. Although all of the compounds tested were potent in the biochemical assay, several exhibited significantly less potency in cellular kinase assays. Their effects on stem cell factor (SCF)-dependent Kit autophosphorylation and SCLC cell growth were also examined. Inhibition of SCF-stimulated Kit activation and cell growth in the H526 cell line was dose-dependent. At concentrations that inhibited SCF-stimulated H526 cell growth, there was little effect on insulin-like growth factor-1-stimulated growth, suggesting that these compounds exhibit reasonable selectivity for inhibition of Kit-mediated proliferation. Higher doses of the compounds were needed to inhibit serum-stimulated growth. Of the six compounds examined, SU5416 and SU6597 demonstrated the best cellular potency and, therefore, their effect on the growth of multiple SCLC cell lines in serum-containing media was examined. In addition to inhibiting proliferation, these compounds also induced significant cell death of several SCLC cell lines, but not of normal human diploid fibroblasts, in complete media. These observations suggest that Kit kinase inhibitors such as these may offer a new approach for inhibiting Kit-mediated proliferation of tumors such as SCLC, gastrointestinal stromal tumors, seminomas, and leukemias.

Animals↗
PubMed2001

Health effects of fluoride pollution caused by coal burning.

Recently a huge amount of fluoride in coal has been released into indoor environments by the combustion of coal and fluoride pollution seems to be increasing in some rural areas in China. Combustion of coal and coal bricks is the primary source of gaseous and aerosol fluoride and these forms of fluoride can easily enter exposed food products and the human respiratory tract. Major human fluoride exposure was caused by consumption of fluoride contaminated food, such as corn, chilies and potatoes. For each diagnostic syndrome of dental fluorosis, a log-normal distribution was observed on the logarithm of urinary fluoride concentration in students in China. Urinary fluoride content was found to be a primary health indicator of the prevalence of dental fluorosis in the community. In the fluorosis areas, osteosclerosis in skeletal fluorosis patients was observed with a high prevalence. A biochemical marker of bone resorption, urinary deoxypyridinoline content was much higher in residents in China than in residents in Japan. It was suggested that bone resorption was stimulated to a greater extent in residents in China and fluoride may stimulate both bone resorption and bone formation. Renal function especially glomerular filtration rate was very sensitive to fluoride exposure. Inorganic phosphate concentrations in urine were significantly lower in the residents in fluorosis areas in China than in non-fluorosis area in China and Japan. Since airborne fluoride from the combustion of coal pollutes extensively both the living environment and food, it is necessary to reduce fluoride pollution caused by coal burning.

Adult↗
PubMed2001

Pharmacokinetics of tetramethylpyrazine in rat blood and brain using microdialysis.

Since the central nervous acting agent, tetramethylpyrazine, is reported to have appreciable blood-brain barrier penetrability, a design allowing simultaneous and continual monitoring of drug concentrations in blood and brain was employed to study the distribution of intravenously administered tetramethylpyrazine (10 mg kg(-1)). The system consisted of two microdialysis probes, each optimally constructed for sampling of the respective body fluids, inserted into the right jugular vein and striatum of male Sprague--Dawley rats. The probes were perfused with appropriate media at rates optimized for recovery. Dialysates were automatically collected using a microfraction collector and drugs were analyzed by high performance liquid chromatography (HPLC) with ultra violet (UV) detection. Results indicate that both blood and brain pharmacokinetics of unbound tetramethylpyrazine fit best to a two-compartment model. The elimination half-life of tetramethylpyrazine in rat blood and brain were 82.1 and 184.6 min, respectively. Increasing brain/blood concentration ratios suggested that tetramethylpyrazine effectively penetrated the blood--brain barrier.

Animals↗
PubMed2001

A study of a new TSM bio-mimetic sensor using a molecularly imprinted polymer coating and its application for the determination of nicotine in human serum and urine.

A new bio-mimetic quartz crystal thickness-shear-mode (TSM) sensor, using an imprinted polymer coating as the sensitive material, has been fabricated and applied to the determination of nicotine (NIC) in human serum and urine. The molecularly imprinted polymer (MIP) was synthesized using NIC as the template molecule and methacrylic acid (MAA) as the functional monomer. The sensor showed high selectivity and a sensitive response to NIC in aqueous system. The linear response range of the sensor was between 5.0 x 10(-8) and 1.0 x 10(-4) M with a detection limit of 2.5 x 10(-8) M. The viscoelasticity of the coating in the air and in liquid has been studied by the impedance spectrum. The MIP sensor was stable and exhibited effective reproducibility. Satisfactory results were achieved in the detection of the real samples.

Biosensing Techniques↗
PubMed2001

Degeneration of neurons and glia in the Niemann-Pick C mouse is unrelated to the low-density lipoprotein receptor.

The BALB/c mouse model of Niemann-Pick type C disease exhibits similar neuropathological features to the human condition, including cerebral atrophy, demyelination of the corpus callosum, and degeneration of cerebellar Purkinje cells. The gene defect in Niemann-Pick C disease causes cholesterol to accumulate within the lysosomal compartment of neurons and glial cells. In order to determine whether cholesterol accumulation through the low-density lipoprotein receptor pathway plays an important role in the degenerative process, Niemann-Pick C mice were crossed with low-density lipoprotein receptor knockout mice. The purpose of the present study was to determine whether degeneration of neurons and glial cells is reduced in Niemann-Pick C animals lacking the low-density lipoprotein receptor. Using stereological counting methods, Purkinje cells were counted in the cerebellum and glial cell bodies were counted in the corpus callosum in mice at 3, 7.5 and 11 weeks of age. In the Niemann-Pick C animals, compared to wild-type control mice, there were 48% fewer glial cells at 3 weeks of age, and by 11 weeks of age there were 63% fewer glial cells. Purkinje cells were decreased in number by 13% at 3 weeks of age, and by 11 weeks of age there was a 96% loss. In the Niemann-Pick C animals lacking low-density lipoprotein receptors, there was no difference in the magnitude of glial cell or Purkinje cell loss compared to the Niemann-Pick C animals. These data indicate that both neurons and glia are vulnerable to degeneration in the Niemann-Pick C mouse, but that blocking the accumulation of cholesterol through the low-density lipoprotein receptor pathway does not alter the degenerative phenotype of Niemann-Pick C disease.

Animals↗
PubMed2001

Effects of cryoanalgesia on post-thoracotomy pain and on the structure of intercostal nerves: a human prospective randomized trial and a histological study.

OBJECTIVE: The choice of analgesia in the management of post-thoracotomy pain remains controversial. Although several alternative forms of post-thoracotomy analgesia exist, all have their disadvantages. Cryoanalgesia, localized freezing of intercostal nerves, has been reported to have variable effectiveness and an incidence of long-term cutaneous sensory changes. We carried out an animal study to assess the reversibility of histological changes induced by cryoanalgesia and a prospective randomized trial to compare the effectiveness of cryoanalgesia with conventional analgesia (parenteral opiates). METHODS: In six anaesthetized dogs, intercostal nerves were exposed to a varying duration of cryo-application (30, 60, 90 and 120 s). The nerves were biopsied and examined histologically at regular intervals over the following 6 months. In the clinical study, 200 consecutive patients undergoing thoracotomy were randomized to cryoanalgesia and conventional (parenteral opiates) analgesia groups. Postoperative pain scores, respiratory function tests and use of opiate analgesia were measured for the two groups. RESULTS: Following application of the cryoprobe, degeneration and fragmentation of the axons was evident with associated inflammatory changes. As the endoneurium remained intact, axonal regeneration took place after the resolution of axonal swelling. Over the course of weeks, recovery of the intercostal nerve occurred and was complete after 1 month for the 30 and 60 s groups. For nerves exposed to longer durations of cryoanalgesia, the time taken for complete recovery was proportionally increased. Clinically, there was a statistically significant (P<0.05) improvement in postoperative pain scores and use of opiate analgesia and an improvement (P>0.05) in respiratory function tests for patients in the cryoanalgesia group. The previously suggested cutaneous sensory changes resolved within 6 months with complete restoration of function. CONCLUSIONS: We suggest that cryoanalgesia be considered as a simple, inexpensive, long-term form of post-thoracotomy pain relief, which does not cause any long-term histological damage to intercostal nerves.

Adult↗
PubMed2001

Telepathology overview: from concept to implementation.

Telepathology is the practice of pathology at a distance by using video imaging and telecommunications. Significant progress has been made in telepathology. To date, 12 classes of telepathology systems have been engineered. Rapid and ultrarapid virtual slide processors may further expand the range of telepathology applications. Next-generation digital imaging light microscopes, such as miniaturized microscope arrays (MMA), may make virtual slide processing a routine laboratory tool. Diagnostic accuracy of telepathology is comparable with that of conventional light microscopy for most diagnoses. Current telepathology applications include intraoperative frozen sections services, routine surgical pathology services, second opinions, and subspecialty consultations. Three telepathology practice models are discussed: the subspecialty practice (SSP) model; the case triage practice (CTP) model; and the virtual group practice (VGP) model. Human factors influence performance with telepathology. Experience with 500 telepathology cases from multiple organs significantly reduces the video viewing time per case (P < .01). Many technology innovations can be represented as S-curves. After long incubation periods, technology use and/or efficiency may accelerate. Telepathology appears to be following an S-curve for a technical innovation.

Diffusion of Innovation↗