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Biomedical subjects

S Huang

Publications and source records attributed to S Huang.

At least 91 records · Page 5Linked to original sources
PubMed2001

Mechanisms of resistance to rapamycins.

Rapamycins represent a novel family of anticancer agents, currently including rapamycin and its derivatives, CCI-779 and RAD001. Rapamycins inhibit the function of the mammalian target of rapamycin (mTOR), and potently suppress tumor cell growth by arresting cells in G1 phase or potentially inducing apoptosis of cells, in culture or in xenograft tumor models. However, recent data indicate that genetic mutations or compensatory changes in tumor cells influence the sensitivity of rapamycins. First, mutations of mTOR or FKBP12 prevent rapamycin from binding to mTOR, conferring rapamycin resistance. Second, mutations or defects of mTOR-regulated proteins, including S6K1, 4E-BP1, PP2A-related phosphatases, and p27(Kip1) also render rapamycin insensitivity. In addition, the status of ATM, p53, PTEN/Akt and 14-3-3 are also associated with rapamycin sensitivity. To better explore the role of rapamycins against tumors, this review will summarize the current knowledge of the mechanism of action of rapamycins, and progress in understanding mechanisms of acquired or intrinsic resistance.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Nucleocytoplasmic shuttling of polypyrimidine tract-binding protein is uncoupled from RNA export.

Polypyrimidine tract binding protein, PTB/hnRNP I, is involved in pre-mRNA processing in the nucleus and RNA localization and translation in the cytoplasm. In this report, we demonstrate that PTB shuttles between the nucleus and cytoplasm in an energy-dependent manner. Deletion mutagenesis demonstrated that a minimum of the N terminus and RNA recognition motifs (RRMs) 1 and 2 are necessary for nucleocytoplasmic shuttling. Deletion of RRM3 and 4, domains that are primarily responsible for RNA binding, accelerated the nucleocytoplasmic shuttling of PTB. Inhibition of transcription directed by either RNA polymerase II alone or all RNA polymerases yielded similar results. In contrast, selective inhibition of RNA polymerase I did not influence the shuttling kinetics of PTB. Furthermore, the intranuclear mobility of GFP-PTB, as measured by fluorescence recovery after photobleaching analyses, increased significantly in transcriptionally inactive cells compared with transcriptionally active cells. These observations demonstrate that nuclear RNA transcription and export are not necessary for the shuttling of PTB. In addition, binding to nascent RNAs transcribed by RNA polymerase II and/or III retards both the nuclear export and nucleoplasmic movement of PTB. The uncoupling of PTB shuttling and RNA export suggests that the nucleocytoplasmic shuttling of PTB may also play a regulatory role for its functions in the nucleus and cytoplasm.

3T3 Cells↗
PubMed2001

Evidence for down-regulation of ethanolic fermentation and K+ effluxes in the coleoptile of rice seedlings during prolonged anoxia.

Ethanolic fermentation, the predominant catabolic pathway in anoxia-tolerant rice coleoptiles, was manipulated in excised and 'aged' tissues via glucose feeding. Coleoptiles with exogenous glucose survived 60 h of anoxia, as evidenced by vigorous rates of K+ and phosphate net uptake and growth of roots and shoots when re-aerated. In contrast, coleoptiles without exogenous glucose showed net losses of K+ and phosphates starting 12 h after anoxia was imposed and these did not recover fully when re-aerated after 60 h of anoxia. Ethanol production (micromol x g(-1) FW x h(-1)) declined from about 7.5 during the first 12 h of anoxia to 5 or 2.2 after 48-60 h, in coleoptiles with or without exogenous glucose, respectively. Carbohydrate concentrations changed only slightly in anoxic coleoptiles with exogenous glucose due to net glucose uptake at 2.6 micromol x g(-1) FW x h(-1). Ethanolic fermentation, and therefore ATP production, may have been down-regulated after an initial period of acclimation to anoxia in coleoptiles with exogenous glucose. Maintenance requirements for energy were assessed to be 3.4-7.6-fold lower in these anoxic coleoptiles than published estimates for non-growing aerated leaf tissues. A modest part of the required economy in energy consumption would have been derived from diminished ion transport; anoxia reduced K+ and phosphate net uptake by 70-90% in these coleoptiles. K+ efflux was 10-fold lower in anoxic than in aerated coleoptiles with exogenous glucose. Using the unidirectional efflux equation, the membrane permeability to K+ was estimated to be 17-fold lower in anoxic than in aerated coleoptiles, presumably due to predominantly closed K+ channels.

Adenosine Triphosphate↗
PubMed2001

Induction of dental pulp fibroblast matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expression by interleukin-1alpha and tumor necrosis factor-alpha through a prostaglandin-dependent pathway.

Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) are involved in the degradation of extracellular matrix in many inflammatory diseases. Little is known regarding the expression of these mediators in dental pulp fibroblasts. The effects of proinflammatory cytokines (interleukin (IL)-1alpha and tumor necrosis factor-alpha (TNF-alpha)) and prostaglandin E2 (PGE2) on pulp fibroblast MMP-1 and TIMP-1 gene expression were investigated. Northern hybridization showed that IL-1alpha and TNF-alpha induced significant MMP-1 gene expression, with only little effect on TIMP-1 gene. Exogenous PGE2, however, upregulated TIMP-1 mRNA synthesis but not MMP-1. Concomitant addition of IL-1alpha and PGE2 or TNF-alpha and PGE2 suppressed MMP-1 mRNA production, compared with the groups treated with IL-1alpha or TNF-alpha alone. In contrast, PGE2 enhanced the upregulatory effects of TIMP-1 mRNA by IL-1alpha or TNF-alpha. Furthermore, cytokine stimulation of MMP-1 and TIMP-1 gene expressions can be enhanced or blocked by indomethacin, respectively, and reversed by exogenous PGE2. These results suggested that cytokine-stimulated MMP-1 and TIMP-1 gene expression in dental pulp fibroblasts was mediated, at least in part, by a prostaglandin-dependent pathway. The differential regulation of IL-1alpha or TNF-alpha-induced MMP-1 and TIMP-1 mRNA synthesis, as well as the direct upregulation of TIMP-1 gene expression by PGE2, also implied that prostaglandin may serve as a protective mechanism from excessive tissue breakdown during pulpitis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Cloning of an Arabidopsis patatin-like gene, STURDY, by activation T-DNA tagging.

Activation T-DNA tagging can generate dominant gain-of-function mutants by overexpression of a particular endogenous gene. We identified an activation-tagged mutant, sturdy, exhibiting a stiff inflorescence stem, thicker leaves, shorter siliques, larger seeds, round-shaped flowers, and delayed growth. It is most important that unlike its wild-type counterpart, this mutant is less prone to lodging. Cloning of STURDY revealed that in sturdy, there is an open reading frame containing a single intron encoding a patatin-like homolog. The T-DNA is inserted into the 3' region of the second exon. The mutant phenotype was shown to be the result of overexpression of STURDY by mRNA analysis and transgenic studies. Preliminary histological studies have revealed an increase in cell number in the inflorescence stem of mutant plants; however, additional studies are needed to better understand the overexpression phenotype.

3' Untranslated Regions↗
PubMed2001

The biocompatibility, integrity, and positional stability of an injectable microstimulator for reanimation of the paralyzed larynx.

The biocompatibility, integrity, positional stability, and potential use of hermetically sealed injectable wireless micromachined microstimulators were investigated for reanimation of the paralyzed larynx. The device, consisting of silicon and glass, has been tested and proven to be biocompatible with no evidence of pathological tissue reaction or rejection up to one-year implantation in the rat dorsum and canine larynx. By one month, each unit was encapsulated by a thin membrane, which thickened to form a fibrous layer of less than 500 microm at 6-12 months. The microstimulators demonstrated long-term in vivo durability: the hermetic seal of only one in ten devices was breached. Once implanted, migration of the device varied from 0 to 3 cm, depending upon the extent of surgical dissection. No discernable migration was noted when the tissue dissection was minimal. Studies utilizing a modified device equipped with electrodes indicated that migration was nominal with sufficient positional stability to ensure activation of target muscles for glottis opening. This study supported the feasibility of using a microstimulator for reanimation of paralyzed laryngeal muscles that open the airway during breathing. This innovative approach to treatment would alleviate the need for a tracheotomy or surgical resection of the vocal fold.

Animals↗
PubMed2001

Functional analysis of the cyclin-dependent kinase inhibitor Pho81 identifies a novel inhibitory domain.

In response to phosphate limitation, Saccharomyces cerevisiae induces transcription of a set of genes important for survival. A phosphate-responsive signal transduction pathway mediates this response by controlling the activity of the transcription factor Pho4. Three components of this signal transduction pathway resemble those used to regulate the eukaryotic cell cycle: a cyclin-dependent kinase (CDK), Pho85; a cyclin, Pho80; and a CDK inhibitor (CKI), Pho81. Pho81 forms a stable complex with Pho80-Pho85 under both high- and low-phosphate conditions, but it only inhibits the kinase when cells are starved for phosphate. Pho81 contains six tandem repeats of the ankyrin consensus domain homologous to the INK4 family of mammalian CKIs. INK4 proteins inhibit kinase activity through an interaction of the ankyrin repeats and the CDK subunits. Surprisingly, we find that a region of Pho81 containing 80 amino acids C terminal to the ankyrin repeats is necessary and sufficient for Pho81's CKI function. The ankyrin repeats of Pho81 appear to have no significant role in Pho81 inhibition. Our results suggest that Pho81 inhibits Pho80-Pho85 with a novel motif.

Amino Acid Sequence↗
PubMed2001

Radio-frequency ablation of liver tumors: assessment of therapeutic response and complications.

An alternative to surgical resection of liver tumors, radio-frequency ablation induces in situ thermal coagulation necrosis through the delivery of high-frequency alternating current to the tissues. Imaging helps to detect treatable lesions, guide the placement of the probe, and assess the effect of therapy. Computed tomography (CT) is used most frequently to determine whether the ablation is complete and to screen for early recurrences that may benefit from reablation. Complete ablation creates an area of necrosis that, at CT, is of low attenuation compared with the surrounding liver tissue, is often homogeneous, and has smooth margins. The most important features are the size of the necrotic defect, which, immediately after treatment, should be larger than that of the pretreatment tumor, and the sharpness of the margins, which indicates an abrupt change in attenuation between the necrotic tissue and surrounding liver tissue. Enhancement, when present, is due to perfusion abnormality or granulation tissue and forms a regular rim or a homogeneous zone at the margin of the defect. It is seen immediately after ablation but may be prolonged. Enhancement is affected by the scanning technique. Over time, the size of the defect remains stable or decreases. Any variation from this general pattern is suggestive of incomplete ablation or recurrence.

Adult↗
PubMed2001

Prevention of anterior glottic restenosis in a canine model with topical mitomycin-C.

To develop a model for recurrent anterior glottic stenosis and to test the efficacy of topical mitomycin-C in preventing restenosis, we induced anterior glottic stenosis with a CO2 laser in 5 dogs. In 3 dogs, recurrence was established after surgical lysis. Subsequently, the 3 dogs received a single topical 3-minute treatment with a 1% solution of mitomycin-C after a second surgical lysis. In a parallel experiment, the other 2 dogs received a single topical 3-minute treatment with a 1% solution of mitomycin-C after the initial surgical lysis. An anterior glottic web was induced in all 5 dogs with the CO2 laser. The 3 dogs experienced restenosis at the anterior glottis after surgical lysis alone. Mitomycin-C prevented anterior glottic restenosis in 2 of the 3 dogs treated twice and in both of the dogs treated once (p = .02). We conclude that a recurrent stenosis of the anterior glottis may be induced reproducibly in the canine model with the CO2 laser. Application of topical mitomycin-C after lysis of an anterior glottic stenosis produces a statistically significant reduction in the rate of restenosis as compared to surgical lysis alone.

Administration, Topical↗
PubMed2001

Genomics, complexity and drug discovery: insights from Boolean network models of cellular regulation.

The completion of the first draft of the human genome sequence has revived the old notion that there is no one-to-one mapping between genotype and phenotype. It is now becoming clear that to elucidate the fundamental principles that govern how genomic information translates into organismal complexity, we must overcome the current habit of ad hoc explanations and instead embrace novel, formal concepts that will involve computer modelling. Most modelling approaches aim at recreating a living system via computer simulation, by including as much details as possible. In contrast, the Boolean network model reviewed here represents an abstraction and a coarse-graining, such that it can serve as a simple, efficient tool for the extraction of the very basic design principles of molecular regulatory networks, without having to deal with all the biochemical details. We demonstrate here that such a discrete network model can help to examine how genome-wide molecular interactions generate the coherent, rule-like behaviour of a cell - the first level of integration in the multi-scale complexity of the living organism. Hereby the various cell fates, such as differentiation, proliferation and apoptosis, are treated as attractor states of the network. This modelling language allows us to integrate qualitative gene and protein interaction data to explain a series of hitherto non-intuitive cell behaviours. As the human genome project starts to reveal the limits of the current simplistic 'one gene - one function - one target' paradigm, the development of conceptual tools to increase our understanding of how the intricate interplay of genes gives rise to a global 'biological observable' will open a new perspective for post-genomic drug target discovery.

Animals↗
PubMed2001

A simple analysis of gene expression and variability in gene arrays based on repeated observations.

BACKGROUND AND AIM: At the present time there is an explosion of research in the area of gene arrays, and their application for detection of genes related to disease as well as its therapeutic manipulation. However, as individual arrays are expensive, comparisons of gene expression are often not repeated. In the current study, gene array experiments were repeated multiple times in order to understand the variability associated with measurements of gene expression. By focusing upon the pharmacologically important target of prostate cancer cell detachment, the current study employed multiple repeats of gene array experiments. This was used as a model system to demonstrate the utility of the experimental approach and statistical methods used. METHODS: To identify genes involved in detachment of prostate cancer cells (a prerequisite for metastases), we analyzed gene expression changes in metastatic variant PC3-M cells undergoing spontaneous detachment in culture. The data were interpreted using an elementary statistical approach. The between-experiment and within-repeated-observations variability in expression of 3582 genes possibly related to prostate cancer was also evaluated. RESULTS: One important gene related to prostate cell detachment was identified, based on the magnitude of its change in expression, as measured by a ratio of the expression after cell detachment and expression before detachment. On average, the variation between experiments was greater by about 30 to 40% than the variation between repeated observations. CONCLUSION: These findings have implications relating to the use of gene arrays to detect variance of gene expression, and should be taken into consideration in the prospective design of array experiments.

Cell Adhesion↗
PubMed2001

Mycoplasma infections and different human carcinomas.

AIM: To explore relationships between human carcinomas and mycoplasma infection. METHODS: Monoclonal antibody PD4, which specifically recognizes a distinct protein from mycoplasma hyorhinis, was used to detect mycoplasma infection in different paraffin embedded carcinoma tissues with immunohistochemistry. PCR was applied to amplify the mycoplasma DNA from the positive samples for confirming immunohistochemistry. RESULTS: Fifty of 90 cases (56%) of gastric carcinoma were positive for mycoplasma hyorhinis. In other gastric diseases, the mycoplasma infection ratio was 28% (18/49) in chronic superficial gastritis, 30% (14/46) in gastric ulcer and 37% (18/49) in intestinal metaplasia. The difference is significant with gastric cancer (chi(2) = 12.06, P < 0.05). In colon carcinoma, the mycoplasma infection ratio was 55.1% (32/58),but it was 20.9% (10/49)in adenomarous polyp (chi(2)=13.46, P < 0.005). Gastric and colon cancers with high differentiation had a higher mycoplasma infection ratio than those with low differentiation (P < 0.05). Mycoplasma infection in esophageal cancer, lung cancer, breast cancer and glioma was 50.9% (27/53), 52.6% (31/59), 39.7% (25/63) and 41% (38/91), respectively. The mycoplasma DNA was successfully amplified with the DNA extracted from the cancer tissues that were positive for mycoplasma infection (detected with antibody PD4). CONCLUSION: There was high correlation between mycoplasma infection and different cancers, which suggests the possibility of an association between the two. The mechanism involved in oncogenesis by mycoplasma remains unknown.

Antibodies, Monoclonal↗
PubMed2001

RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum.

The retinoblastoma protein interacting zinc finger (RIZ) gene is a candidate tumor suppressor gene on 1p36, a region frequently rearranged in a wide variety of human tumors. As the RIZ gene harbors several microsatellites within its coding region, it is a candidate for an inactivating mutation in microsatellite instability (MSI) mediated carcinogenesis. In this study, we examined mutations of two poly adenine tracts, A(8) and A(9), within the coding region of the RIZ gene, in MSI-high (MSI-H) primary cancers occurring in the pancreas, stomach, and colorectum. Frameshift mutations were found in one (10%) of 10 pancreatic, four (36%) of 11 gastric, and two (25%) of eight colorectal cancers. These results indicate that mutations of the RIZ gene play an important role in the pathogenesis of some MSI-H cancers.

Colorectal Neoplasms↗
PubMed2001

[Gene mapping on Blepharophimosis Epicanthus Inversus and Ptosis syndrome type I in Chinese family].

OBJECTIVE: To map the gene responsible for Blepharophimosis Epicanthus Inversus and Ptosis syndrome(BPES) type I in a Chinese family. METHODS: Polymorphisms of 4 satellite markers of 3q were analyzed and linkage analysis was performed using linkage software (MLINK, Version 5.2). RESULTS: No deletion was detected for the four markers. The maximum lod scores were: 0.77 (theta = 0.00) at D3S3045; 3.61 (theta = 0.00) at D3S1764; 0.11 (theta = 0.3) at D3S3053 and -0.03 (theta = 0.4) at D3S2436. CONCLUSION: The gene responsible for BPES in the Chinese family was tightly linked to D3S1764.

Abnormalities, Multiple↗
PubMed2001

[The absorbed rate and distribution rule of rare earth elements in wheat by 141Ce as tracer].

The study on absorption, distribution rules and transportation rates of cerium in the interface of water-wheat by 141Ce in culture solution were carried out. The results showed that the concentrations of cerium in wheat seedling were gradually increased during the experiment, and so did the same after increasing the concentration of cerium adding in the culture solution. The concentrations of cerium in roots of winter wheat were significantly high than that in tops (steam & leave). The absorption rates of cerium in wheat with different treatments of cerium were distinct. The quantitative formulas, which describe the rule of absorption rate and culture time, was given resulting from the fit of the experimental data.

Adsorption↗
PubMed2001

[Effects of tumor necrosis factor alpha on the expression of connective tissue growth factor in hepatic stellate cells].

OBJECTIVE: To investigate the effect of tumor necrosis factor alpha (TNF-alpha) on the expression of connective tissue growth factor (CTGF) in rat hepatic stellate cells (HSC) in vitro. METHODS: HSCs were prepared from SD rats by in situ perfusion and single-step Nycodenz gradient, and were treated with TNF-alpha and TGF-beta 1. The expression of CTGF in HSC was assessed using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Both TNF-alpha and TGF-beta 1 could stimulate the expression of CTGF mRNA in HSC. The expression of CTGF was not found in HSC after treatment with TNF-alpha(10microgram/L) for 6 hours, but was observed after TNF-alpha treatment for 24 and 48 hours. TGF-beta1 could induce the mRNA expression for CTGF just after 6 hours of treatment at 1microgram/L concentration. CONCLUSIONS: TNF-alpha is able to induce the expression of CTGF in HSC, and this may be one of the mechanisms for TNF-alpha involving in the liver fibrosis.

Animals↗