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Biomedical subjects

G Huang

Publications and source records attributed to G Huang.

At least 37 records · Page 2Linked to original sources

Nonlinear modulation of multidimensional lattice waves.

The equations governing weakly nonlinear modulations of N-dimensional lattices are considered using a quasidiscrete multiple-scale approach. It is found that the evolution of a short wave packet for a lattice system with cubic and quartic interatomic potentials is governed by the generalized Davey-Stewartson (GDS) equations, which include mean motion induced by the oscillatory wave packet through cubic interatomic interaction. The GDS equations derived here are more general than those known in the theory of water waves because of the anisotropy inherent in lattices. The generalized Kadomtsev-Petviashvili equations describing the evolution of long-wavelength acoustic modes in two- and three-dimensional lattices are also presented. Then the modulational instability of an N-dimensional Stokes lattice wave is discussed based on the N-dimensional GDS equations obtained. Finally, the one- and two-soliton solutions of two-dimensional GDS equations are provided by means of Hirota's bilinear transformation method.

Journal Article↗

Signaling through TNF receptor p55 in TNF-alpha-deficient mice alters the CXCL13/CCL19/CCL21 ratio in the spleen and induces maturation and migration of anergic B cells into the B cell follicle.

The organization of secondary lymphoid tissues into distinct T and B cell compartments supports proper regulation of an immune response to foreign Ags. In the splenic white pulp, this compartmentalization is also thought to be important in the maintenance of B cell tolerance. Using lymphotoxin-alpha-(LT-alpha)-, TNF-alpha-, or TNFRp55-deficient mice, all with disrupted splenic architecture, we tested whether normal T/B segregation and/or intact follicular structure are necessary for the maintenance of anti-dsDNA B cell anergy. This study demonstrates that anti-dsDNA B cells remain tolerant in LT-alpha(-/-), TNF-alpha(-/-), and TNFRp55(-/-) mice; however, TNF-alpha or a TNF-alpha-dependent factor is required for their characteristic positioning to the T/B interface. Providing a TNF-alpha signal in TNF-alpha(-/-) mice by systemic administration of an agonist anti-TNFRp55 mAb induces the maturation of the anti-dsDNA B cells and their movement away from the T cell area toward the B cell area. Additionally, the agonist Ab induces changes in the follicular environment, including FDC clustering, up-regulation of the CXC chemokine ligand CXCL13, and down-regulation of the CC chemokine ligands CCL19 and CCL21. Therefore, this study suggests that a balance between B and T cell tropic chemokine signals may be an important mechanism for positioning anergic B cells at the T/B interface of the splenic white pulp.

Animals↗

Phox homology domains specifically bind phosphatidylinositol phosphates.

The recruitment of specific cytosolic proteins to intracellular membranes through binding phosphorylated derivatives of phosphatidylinositol (PtdIns) controls such processes as endocytosis, regulated exocytosis, cytoskeletal organization, and cell signaling. Protein modules such as FVYE domains and PH domains that bind specifically to PtdIns 3-phosphate (PtdIns-3-P) and polyphosphoinositides, respectively, can direct such membrane targeting. Here we show that two representative Phox homology (PX) domains selectively bind to specific phosphatidylinositol phosphates. The PX domain of Vam7p selectively binds PtdIns-3-P, while the PX domain of the CPK PI-3 kinase selectively binds PtdIns-4,5-P(2). In contrast, the PX domain of Vps5p displays no binding to any PtdInsPs that were tested. In addition, the double mutant (Y42A/L48Q) of the PX domain of Vam7p, reported to cause vacuolar trafficking defects in yeast, has a dramatically decreased level of binding to PtdIns-3-P. These data reveal that the membrane targeting function of the Vam7p PX domain is based on its ability to associate with PtdIns-3-P, analogous to the function of FYVE domains.

Amino Acid Motifs↗

Synthesis and evaluation of hydroxylated polyamine analogues as antiproliferatives.

A new means of accessing N(1)-cyclopropylmethyl-N(11)-ethylnorspermine (CPMENSPM) and the first synthesis of (2R,10S)-N(1)-cyclopropylmethyl-2,10-dihydroxy-N(11)-ethylnorspermine [(2R,10S)-(HO)(2)CPMENSPM] are described. Both of these polyamine analogues are shown to be more active against L1210 murine leukemia cell growth than either N(1),N(11)-diethylnorspermine (DENSPM) or (2R,10R)-N(1),N(11)-diethyl-2,10-dihydroxynorspermine [(2R,10R)-(HO)(2)DENSPM] after 96 h of treatment; the activity was comparable to that of (2S,10S)-N(1),N(11)-diethyl-2,10-dihydroxynorspermine [(2S,10S)-(HO)(2)DENSPM] at 96 h. Both cyclopropyl compounds reduced putrescine and spermidine pools, but less effectively than did DENSPM and its derivatives. Only CPMENSPM, and not (2R,10S)-(HO)(2)CPMENSPM, lowered spermine pools. As with DENSPM and (2R,10R)-(HO)(2)DENSPM, both cyclopropyl analogues diminished ornithine decarboxylase and S-adenosylmethionine decarboxylase activity. Unlike the hydroxylated DENSPM compounds, both cyclopropyl norspermines substantially upregulated spermidine/spermine N(1)-acetyltransferase. The most interesting effect of hydroxylating CPMENSPM is the profound reduction in toxicity compared with that of the parent drug. The same phenomenon had been observed for the DENSPM/(2R,10R)-(HO)(2)DENSPM pair. Thus, hydroxylation of norspermine analogues appears to be a way to maintain the compounds' antiproliferative activity while reducing their toxicity.

Acetyltransferases↗

Effects of emulsifiers on the controlled release of paclitaxel (Taxol) from nanospheres of biodegradable polymers.

Paclitaxel (Taxol) is an antineoplastic drug effective for various cancers especially ovarian and breast cancer. Due to its high hydrophobicity, however, an adjuvant such as Cremophor EL has to be used in its clinical administration, which causes serious side-effects. Nanospheres of biodegradable polymers could be an ideal solution. This study investigates the effects of various emulsifiers on the physical/chemical properties and release kinetics of paclitaxel loaded nanospheres fabricated by the solvent extraction/evaporation technique. It is shown that phospholipids could be a novel type of emulsifiers. The nanospheres manufactured with various emulsifiers were characterized by laser light scattering for their size and size distribution; scanning electron microscopy (SEM) and atomic force microscopy (AFM) for their surface morphology; zeta potential analyser for their surface charge; and, most importantly, X-ray photoelectron spectroscopy (XPS) for their surface chemistry. The encapsulation efficiency and in vitro release profile were measured by high performance liquid chromatography (HPLC). It is found that dipalmitoyl-phosphatidylcholine (DPPC) can provide more complete coating on the surface of the products which thus results in a higher emulsifying efficiency compared with polyvinyl alcohol (PVA). Our result shows that the chain length and unsaturation of the lipids have a significant influence on the emulsifying efficiency. Phospholipids with short and saturated chains have excellent emulsifying effects.

Antineoplastic Agents, Phytogenic↗

Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation.

The RUNX family genes are the mammalian homologs of the Drosophila genes runt and lozenge, and members of this family function as master regulators of definitive hematopoiesis and osteogenesis. The RUNX genes encode the alpha subunit of the transcription factor PEBP2/CBF. The beta subunit consists of the non-RUNX protein PEBP2beta. We found that RUNX1/AML1, which is essential for hematopoiesis, is continuously subjected to proteolytic degradation mediated by the ubiquitin-proteasome pathway. When PEBP2beta is present, however, the ubiquitylation of RUNX1 is abrogated and this causes a dramatic inhibition of RUNX1 proteolysis. Heterodimerization between PEBP2beta and RUNX1 thus appears to be an essential step in the generation of transcriptionally competent RUNX1. Consistent with this notion, RUNX1 was barely detected in PEBP2beta(-/-) mouse. CBF(PEBP2)beta- SMMHC, the chimeric protein associated with inv(16) acute myeloid leukemia, was found to protect RUNX1 from proteolytic degradation more efficiently than PEBP2beta. These results reveal a hitherto unknown and major role of PEBP2beta, namely that it regulates RUNX1 by controlling its turnover. This has allowed us to gain new insights into the mechanism of leukemogenesis by CBFbeta-SMMHC.

Amino Acid Sequence↗

Color and duplex Doppler sonography of hemangiopericytoma.

We report the color Doppler sonographic features in a case of hemangiopericytoma of the thigh in a 52-year-old woman. Color Doppler sonography demonstrated the vascularity of the tumor, and spectral analysis showed waveform changes that suggested the presence of intratumoral arteriovenous shunting. The color Doppler findings correlated well with angiographic findings. Color Doppler sonography can demonstrate intratumoral arteriovenous shunting in hemangiopericytoma and may be used to help avoid profuse bleeding when performing a preoperative biopsy.

Angiography↗

Results of surgical resection of patients with primary lung cancer: a retrospective analysis of 1,905 cases.

BACKGROUND: Surgical resection, combined therapies, and lymphadenectomy are extensively utilized in the treatment of patients with lung cancer. In the present study, we summarized the clinical data of patients with primary lung cancer after surgical resection alone or combined with adjuvant therapy, and evaluate the main factors influencing long-term survival. METHODS: A retrospective review of 1,905 consecutive patients with primary lung cancer treated at the Cancer Institute of the Chinese Academy of Medical Sciences from March 1961 through December 1995 was performed. Statistical analysis was done using STATA software. The survival rate was estimated using the life-table method. Survival differences were performed using the log-rank test. The modified 1997 TNM staging system was used. RESULTS: There was a 12.28% morbidity rate and a 1.31% hospital mortality in our series. The 5-year survival rate for the complete resection was 49.5% and for the palliative resection 18.8% (p < 0.01). The 5-year survival rate was 72.0% in stage IA and 61.0% in stage IB (p < 0.05), 32.9% in stage IIA and 34.5% in stage IIB, 22.6% in stage IIIA and 15.9% in stage IIIB (p < 0.05), and 7.1% in stage IV. CONCLUSIONS: Multiple factors influence the long-term survival of patients with primary lung cancer after surgery. They include TNM staging, the extent of surgical resection (complete or palliative), resection margin (positive or negative), pathologic type of tumors, and type of resection.

Adult↗

Detection and differentiation of CAV-1 and CAV-2 by polymerase chain reaction.

Canine adenovirus type 1 (CAV-1) and type 2 (CAV-2) can be categorized in the laboratory by haemagglutination and neutralization tests, but they are difficult to differentiate from each other in specimens, especially when infection occurs in the digestive tract. The object of this study was to develop a simple method of detecting and differentiating them. One pair of common primers was designed and synthesized according to the sequences of the E3 and flanking regions and a polymerase chain reaction (PCR) assay was established using these two primers to amplify the virus-specific DNA fragment from clinical specimens as well as from cell cultures. After elecctrophoresis, under the same amplification conditions, 508 bp and 1030 bp PCR products were observed for CAV-1 and CAV-2, respectively. These were further shown to be adenovirus specific by dot hybridization and sequencing. As only one pair of primers was involved in the PCR procedure, it was faster and easier to perform than any of the other assays used for detecting canine adenovirus, making it applicable in the rapid confirmation of diagnosis and differentiation of the two types of canine adenoviruses.

Adenoviridae Infections↗

Association of ErbB2 Ser1113 phosphorylation with epidermal growth factor receptor co-expression and poor prognosis in human breast cancer.

The carboxyterminal domain of the epidermal growth factor receptor (EGFR)--a putative binding site for the ubiquitin ligase Cbl--is the site of serine phosphorylation events which are essential for ligand-dependent EGFR desensitization and degradation. Using a monoclonal antibody (aPS1113) which selectively recognizes the homologous phosphorylated domain in the ErbB2 oncoprotein, we show here that wild-type ErbB2 becomes Ser1113-phosphorylated following treatment of 3T3 cells with growth factors or tyrosine phosphatase inhibitors. In EGFR-overexpressing A431 cells, ligand-inducible aPS1113 immunoreactivity declines more rapidly than other detectable phosphorylation events and is followed by EGFR downregulation. Analysis of 65 ErbB2-expressing primary breast cancers reveals a highly significant relationship between Ser1113 phosphorylation and EGFR overexpression (p < 0.0001) as well as an association with poor prognosis (p = 0.005). We submit that ErbB2 Ser1113 phosphorylation status represents a novel and informative biomarker of cancer cell biology and tumor behavior.

Animals↗

Osteoclast clearance from periodontal tissues during orthodontic tooth movement.

The presence of osteoclasts at locations of alveolar bone remodeling is antecedent to orthodontic tooth movement. Cell recruitment and clearance are the mechanisms by which osteoclast populations are regulated. Research in other tissues has revealed that many cells die after their functional lives are past by a process called apoptosis, or programmed cell death. The purpose of this study was to examine the role of apoptosis in osteoclast clearance at orthodontically treated sites as a function of time and location. Orthodontic appliances were placed on 96 rats of the Sprague-Dawley strain. The rats were assigned to either treatment or sham (control) groups and killed 1, 3, 5, and 7 days after appliance placement. Tissue samples were prepared for histochemical evaluation and quantification of morphologic features. Tartrate-resistant acid phosphatase (TRAP) and ApopTag (TdT-mediated dUTP-biotin nick 3' end labeling) stains were used to identify osteoclasts and committed preosteoclasts and to discriminate between apoptotic and nonapoptotic nuclei. Pyknotic nuclei and apoptotic bodies were also counted as a morphologic assessment of apoptosis. The percentages of TRAP/ApopTag-positive nuclei were measured in 4 different periodontal regions. There was a highly significant difference in the overall percentage of TRAP/ApopTag-positive nuclei between the control and the treatment groups at 3, 5, and 7 days (P <.001). Morphologic criteria were also statistically different at days 5 and 7 (P <.05). These data strongly suggested that osteoclasts recruited for orthodontic tooth movement are, at least in part, cleared by apoptosis.

Acid Phosphatase↗

Column robustness case study for a liquid chromatographic method validated in compliance with ICH, VICH, and GMP guidelines.

This article presents a case study in dealing with robustness investigations and attempts by our analytical laboratory to address these issues without sacrificing valuable time in revamping the method validation prior to submission. A liquid chromatographic method is developed for the analysis of a novel triazinetrione anticoccidial product. The method effectively separates the active pharmaceutical ingredient (API), impurities, and preservatives in the API and product formulation. For much of the validation, the method holds up to the rigorous guidelines of the International Conference of Harmonization, the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products, and the Good Manufacturing Practices. However, in analyzing a base-degraded sample one of the impurity peaks yields inconsistent retention times (RTs) during a series of injections. When switching the system to another analytical column from the same supplier, this impurity peak elutes at a different retention window and the remaining peaks in the chromatographic profile remain essentially the same. This RT variation of a single peak in the chromatographic profile is observed with additional columns from the same supplier and from different manufacturing lots. This suitability problem is not encountered with the columns used in the method development stage. The method no longer meets the robustness criteria established for pharmaceutical methods. An investigation is commenced and it is discovered that with the addition of tetrabutylammonium hydroxide to the mobile phases, the impurity peak gives a consistent RT in relation to the active peak. The peak shows comparable RTs relative to that of the API peak with columns of different silica lots and bond lots. All peaks, including the aforementioned impurity peak, are well-resolved under the revised high-performance liquid chromatographic conditions. This temporary solution enables continued submission work for FDA, but the robustness of this method is still a concern. After further investigation, it is determined that inhomogeneity of the active sites on the column's stationary phase is the likely culprit. Fortunately, a new column is found to be more suitable for this method and a column qualification study is initiated.

Journal Article↗

Optimization of tylosin feeding rate profile in production of acetyl-isovaleryl tylosin (AIV) from tylosin by Streptomyces thermotolerans YN554.

An optimal feed rate profile of a substrate (tylosin) for a novel antibiotic, acetyl-isovaleryl tylosin (AIV) production process was investigated. In the first step of optimization, a kinetic model for production of AIV from tylosin by Streptomyces thermotolerans was established properly using the least square method, followed by the confirmation that the proposed model could be used to predict the production process of AIV from tylosin. An objective function, state equations and an inequality constraint with respect to the tylosin feeding rate profile were applied to maximize the amount of AIV produced from tylosin in a fed-batch culture. The optimized tylosin feeding rate profile was determined using a direct iterative search algorithm based on the modified complex method. The simulation of AIV production at the optimal tylosin feeding profile indicates that the final amount of AIV is expected to be about 30% higher than that at the conventional constant tylosin feeding rate, which was also confirmed experimentally using a 30-l jar fermentor.

Journal Article↗

Kojic acid production in an airlift bioreactor using partially hydrolyzed raw corn starch.

In a culture of Aspergillus oryzae MK-107-39 in a 3-l airlift bioreactor, kojic acid was not produced when glucose/wheat germ medium (GM1) was used. However, when a jar fermentor was used, the kojic acid yield was high. A suitable medium for culture in an airlift bioreactor consisting of partially hydrolyzed corn starch and a small amount of corn steep liquor (CSL) (SM1) was selected. In the cultivation in the airlift bioreactor using SM1, nearly 40 g/l of kojic acid was produced, which was the same as the amount produced in the jar fermentor containing GM1. The optimum aeration rate for the airlift bioreactor was 2.0 vvm (0.66 cm/s of superficial linear velocity (Vs)). The cost of SM1 using the airlift bioreactor was reduced to 40% that of GM1 using the jar fermentor. Furthermore, the energy cost of kojic acid production using SM1 in the airlift bioreactor was less than one-fourth of that for the jar fermentor using GM1.

Journal Article↗

[Influence of environmental factors on CH4 emission from Reed Wetland].

Determination of CH4 emission from reed wetland in Liaohe delta, China using closed chamber(enclosure area 0.64 m2) technique showed that average emission rate of CH4 was 520 micrograms.m-2.h-1 with significant seasonal patterns. When soil redox potential reached -110 mV, CH4 occured and increased with its decrease. CH4 emission was also influenced by water management and reduced with deep water cover. During the period of measurement, there was positive relation between temperature and CH4 flux(R2 = 0.196, n = 21, P < 0.05). In addition, the experimental result also showed that the methanogenic activites in 0-5 cm soil layer were higher and decreased obviously with soil deepening.

Methane↗

[Evidence for retinoic acid modulating expression of cyclin-dependent kinase inhibitors in rat hepatic stellate cells].

OBJECTIVE: To study the effects of retinoic acid on regulation of expressions of cyclin-dependent kinase inhibitors, i.e. p16, p21 and p27 in cultured rat hepatic stellate cells. METHODS: Stellate cells were isolated from healthy rat livers and cultured. After stimulated with 1 ng/ml transforming growth factor beta 1, subcultured hepatic stellate cells were treated with or without 1 nmol/ml retinoic acid. MTT assay, immunocytochemistry for p16, p21, p27 and alpha-smooth muscle actin protein, in situ hybridization for retinoic acid receptor beta 2 and p16, p21 and p27 mRNA and quantitative image analysis (partially) were performed. RESULTS: Retinoic acid markedly inhibited hepatic stellate cells proliferation (41.50%, P<0.05), decreased the protein level of alpha-smooth muscle actin (55.09%, P<0.05), and induced hepatic stellate cells to express retinoic acid receptor beta 2 mRNA. In addition, retinoic acid increased the protein level of p16 (218.75%, P <0.05) and induced p21 protein expression; meanwhile, p27 was undetectable by immunocytochemistry in both control and retinoic acid-treated hepatic stellate cells. However, retinoic acid had no influence on the mRNA level of p16, p21 or p27 as determined by in situ hybridization. CONCLUSIONS: Up-regulation of p16 and p21 on post-transcriptional level may contribute, in part, to retinoic acid inhibition of transforming growth factor beta 1-initiated rat hepatic stellate cells activation in vitro.

Animals↗

[The effect analysis of tuberculosis control project loaned by World Bank in Guangdong province].

OBJECTIVE: To evaluate the effect of tuberculosis control project loaned by World Bank in Guangdong province. METHODS: The registration and the treatment effect of pulmonary tuberculosis patients according to Guangdong tuberculosis report were analyzed. RESULTS: The above program had been conducted widespread since 1995. Over the past five years, 601,913 cases of suspicious tuberculosis patients have been received and diagnosed, in which 111,164 infectious patients (containing 91,612 newly-attacked infectious cases) were found. Just in 1999, the number of newly-attacked infectious patients was 1.2 times to that(19,858 newly-attacked infectious cases) of 1981-1990 prior to this program. And the average cure rate of infectious patients reached to 95.2%. The cure rate showed an uptrend amounting to 97.2% from 87.6%. CONCLUSION: Satisfactory effect have been achieved by the World-Bank loaned TB control project in Guangdong province.

China↗