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Biomedical subjects

C Liang

Publications and source records attributed to C Liang.

At least 19 recordsLinked to original sources
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↗
PubMed2001

Implantation of silicon chip microphotodiode arrays into the cat subretinal space.

There are currently no therapies to restore vision to patients blinded by photoreceptor degeneration. This project concerns an experimental approach toward a semiconductor-based subretinal prosthetic designed to electrically stimulate the retina. The present study describes surgical techniques for implanting a silicon microphotodiode array in the cat subretinal space and subsequent studies of implant biocompatibility and durability. Using a single-port vitreoretinal approach, implants were placed into the subretinal space of the right eye of normal cats. Implanted retinas were evaluated post-operatively over a 10 to 27 month period using indirect ophthalmoscopy, fundus photography, electroretinography, and histology. Infrared stimulation was used to isolate the electrical response of the implant from that of the normal retina. Although implants continued to generate electrical current in response to light, the amplitude of the implant response decreased gradually due to dissolution of the implant's gold electrode. Electroretinograms recorded from implanted eyes had normal waveforms but were typically 10-15% smaller in amplitude than those in unimplanted left eyes. The nonpermeable silicon disks blocked choroidal nourishment to the retina, producing degeneration of the photoreceptors. The laminar structure of the inner retinal layers was preserved. Retinal areas located away from the implantation site appeared normal in all respects. These results demonstrate that silicon-chip microphotodiode-based implants can be successfully placed into the subretinal space. Gold electrode-based subretinal implants, however, appear to be unsuitable for long-term use due to electrode dissolution and subsequent decreased electrical activity.

Animals↗
PubMed2001

Hydrophobic amino acids in the human immunodeficiency virus type 1 p2 and nucleocapsid proteins can contribute to the rescue of deleted viral RNA packaging signals.

An RNA fragment of 75 nucleotides, which is located between the primer binding site and the 5' major splice donor site in human immunodeficiency virus type 1, has been shown to participate in specific encapsidation of viral RNA. Compensation studies have identified two second-site mutations, namely, MP2 (a T12I substitution in p2) and MNC (a T24I substitution in the nucleocapsid [NC] protein) that were involved in the rescue of various deletions in the aforementioned RNA region (i.e., BH-D1, BH-D2, and BH-LD3). To study whether the MP2 and MNC point mutations exert their compensatory effects in a cis manner, production of Gag proteins was blocked by insertion of stop codons into LD3, LD3-MP2-MNC, and wild-type BH10 such that the constructs generated, i.e., LD3-DG, LD3-MP2-MNC-DG, and BH-DG, only provided RNA transcripts for packaging. The results of cotransfection experiments showed that the LD3-MP2-MNC-DG viral RNA was packaged as inefficiently as LD3-DG; in contrast, BH-DG was efficiently packaged. Therefore, nucleotide substitutions in MP2 and MNC did not act in a cis manner to correct the packaging deficits in LD3. Next, we deliberately changed the T12 in p2 or the T24 in the NC to each of 19 other amino acids. We found that amino acids with long hydrophobic side chains, i.e., V, L, I, and M, were favored at either position 12 in p2 or at position 24 in NC to compensate for the above-mentioned deletions. Further studies showed that only a few amino acids could not be used at these two sites by the wild-type virus due to decreased RNA levels in the virion or abnormal Gag protein processing. In this case, W, D, and E could not substitute for T12 in p2, and S, D, and N could not substitute for T24 in NC, without affecting viral infectivity. Therefore, the long hydrophobic side chains of V, L, I, and M are necessary for these amino acids to rescue the BH-D1, BH-D2, and BH-LD3 mutated viruses.

Amino Acids↗
PubMed2001

Partial restoration of replication of simian immunodeficiency virus by point mutations in either the dimerization initiation site (DIS) or Gag region after deletion mutagenesis within the DIS.

We used the simian immunodeficiency virus (SIV) molecular clone SIVmac239 to generate a deletion construct, termed SD2, in which we eliminated 22 nucleotides at positions +398 to +418 within the putative dimerization initiation site (DIS) stem. This SD2 deletion severely impaired viral replication, due to adverse effects on the packaging of viral genomic RNA, the processing of Gag proteins, and viral protein patterns. However, long-term culture of SD2 in either C8166 or CEMx174 cells resulted in restoration of replication capacity, due to two different sets of three compensatory point mutations, located within both the DIS and Gag regions. In the case of C8166 cells, both a K197R and a E49K mutation were identified within the capsid (CA) protein and the p6 protein of Gag, respectively, while the other point mutation (A423G) was found within the putative DIS loop. In the case of CEMx174 cells, two compensatory mutations were present within the viral nucleocapsid (NC) protein, E18G and Q31K, in addition to the same A423G substitution as observed with C8166 cells. A set of all three mutations was required in each case for restoration of replication capacity, and either set of mutations could be substituted for the other in both the C8166 and CEMx174 cell lines.

Base Sequence↗
PubMed2001

An intact U5-leader stem is important for efficient replication of simian immunodeficiency virus.

Previous work has shown that four deletions in simian immunodeficiency virus (SIV), termed SD1a, SD1b, SD1c, and SD6, which eliminated sequences at nucleotide positions 322 to 362, 322 to 370, 322 to 379, and 371 to 379, respectively, located downstream of the primer binding site, impaired viral replication capacity to different extents. Long-term culturing of viruses containing the SD1a, SD1b, and SD6 deletions led to revertants that possessed wild-type replication kinetics. We now show that these revertants retained the original deletions in each case but that novel additional mutations were also present. These included a large deletion termed D1 (nt +216 to +237) within the U5 region that was shown to be biologically relevant to reversion of both the SD1a and SD1b constructs. In the case of SD6, two compensatory point mutations, i.e., A+369G, termed M1, located immediately upstream of the SD6 deletion, and C+201T, termed M2, within U5, were identified and could act either singly or in combination to restore viral replication. Secondary structure suggests that an intact U5-leader stem is important in SIV for infectiousness and that the additional mutants described played important roles in restoration of this motif.

Base Sequence↗
PubMed2001

Role for human immunodeficiency virus type 1 Tat protein in suppression of viral reverse transcriptase activity during late stages of viral replication.

We have examined the role of the human immunodeficiency virus type 1 (HIV-1) Tat protein in the regulation of reverse transcription. We show that a two-exon but not a one-exon form of Tat markedly suppressed cell-free reverse transcriptase (RT) activity. Conversely, viruses expressing two-exon Tat (pNL43 and pNL101) showed rapid replication kinetics and more efficient endogenous RT activity compared with viruses expressing one-exon Tat (pM1ex). The pM1ex virions, as well as pM1ex-infected cells, also contained higher levels of viral DNA than did either the pNL43 or pNL101 viruses, indicating that reverse transcription might have continued during later stages of viral replication in the absence of the second Tat exon. Moreover, degradation of viral genomic RNA was more apparent in the pM1ex virions. Accordingly, we propose that the two-exon Tat may help augment viral infectivity by suppressing the reverse transcription reaction during late stages of viral synthesis and by preventing the synthesis of potentially deleterious viral DNA products.

Cell Line↗