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Biomedical subjects

G Wang

Publications and source records attributed to G Wang.

At least 109 records · Page 6Linked to original sources

Helicobacter pylori seropositivity and subsite-specific gastric cancer risks in Linxian, China.

BACKGROUND: Helicobacter pylori carriage (i.e., persistent exposure to the organism without gastric epithelial cell invasion) is an established risk factor for noncardia gastric cancer. However, its association with the risk of cancer of the gastric cardia is controversial. Consequently, we designed this prospective, nested case-control study to further explore the subsite-specific gastric cancer risks associated with H. pylori seropositivity (a surrogate marker for persistent exposure). METHODS: A total of 99 patients with gastric cardia cancer, 82 patients with noncardia gastric cancer, and 192 cancer-free subjects were selected from among the participants (n = 29 584) of a nutrition intervention trial previously conducted in Linxian, China. H. pylori seropositivity was determined by assaying for the presence of H. pylori whole cell and CagA antibodies in baseline serum samples from all subjects. Seropositivity was defined as one or both serum assays being positive. Odds ratios (ORs) for subsite-specific gastric cancer were estimated by multivariate logistic regression analyses. All statistical comparisons were two-sided (alpha =.05). RESULTS: H. pylori seropositivity rates for subjects with gastric cardia cancer, noncardia gastric cancer, and gastric cardia and noncardia cancers combined were 70% (P =.02), 72% (P: =.01), and 71% (P =.003) compared with 56% for cancer-free control subjects. OR estimates for H. pylori seropositivity were 1.87 (95% confidence interval [CI] = 1.10 to 3.17) for gastric cardia cancer, 2.29 (95% CI = 1.26 to 4.14) for noncardia gastric cancer, and 2.04 (95% CI = 1.31 to 3.18) for gastric cardia and noncardia cancers combined. CONCLUSIONS: H. pylori seropositivity was associated with increased risks for both gastric cardia cancer and noncardia gastric cancer in this well-characterized cohort. Thus, H. pylori carriage may increase the risk of cancer throughout the stomach.

Adenocarcinoma↗

Synthesis of 7,8-disubstituted benzolactam-V8 and its binding to protein kinase C.

7-Methoxy-8-decynyl-benzolactam-V8 4 is synthesized using a catalytic asymmetric alkylation reaction as a key step. This compound shows potent activity to three PKC isozymes tested (Ki =45.6, 91.1, and 121.3 nM to PKCalpha, delta, and epsilon, respectively), indicating that introduction of a suitable substituent at the 7-position of 8-decynyl-benzolactam-V8 only slightly reduces the PKC binding affinity.

Binding, Competitive↗

Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain.

Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug in children for the treatment of attention deficit hyperactivity disorder (ADHD), yet the mechanisms responsible for its therapeutic effects are poorly understood. Whereas methylphenidate blocks the dopamine transporter (main mechanism for removal of extracellular dopamine), it is unclear whether at doses used therapeutically it significantly changes extracellular dopamine (DA) concentration. Here we used positron emission tomography and [(11)C]raclopride (D2 receptor radioligand that competes with endogenous DA for binding to the receptor) to evaluate whether oral methylphenidate changes extracellular DA in the human brain in 11 healthy controls. We showed that oral methylphenidate (average dose 0.8 +/- 0.11 mg/kg) significantly increased extracellular DA in brain, as evidenced by a significant reduction in B(max)/K(d) (measure of D2 receptor availability) in striatum (20 +/- 12%; p < 0.0005). These results provide direct evidence that oral methylphenidate at doses within the therapeutic range significantly increases extracellular DA in human brain. This result coupled with recent findings of increased dopamine transporters in ADHD patients (which is expected to result in reductions in extracellular DA) provides a mechanistic framework for the therapeutic efficacy of methylphenidate. The increase in DA caused by the blockade of dopamine transporters by methylphenidate predominantly reflects an amplification of spontaneously released DA, which in turn is responsive to environmental stimulation. Because DA decreases background firing rates and increases signal-to-noise in target neurons, we postulate that the amplification of weak DA signals in subjects with ADHD by methylphenidate would enhance task-specific signaling, improving attention and decreasing distractibility. Alternatively methylphenidate-induced increases in DA, a neurotransmitter involved with motivation and reward, could enhance the salience of the task facilitating the "interest that it elicits" and thus improving performance.

Administration, Oral↗

Fold recognition and accurate query-template alignment by a combination of PSI-BLAST and threading.

A homology-based structure prediction method ideally gives both a correct fold assignment and an accurate query-template alignment. In this article we show that the combination of two existing methods, PSI-BLAST and threading, leads to significant enhancement in the success rate of fold recognition. The combined approach, termed COBLATH, also yields much higher alignment accuracy than found in previous studies. It consists of two-way searches both by PSI-BLAST and by threading. In the PSI-BLAST portion, a query is used to search for hits in a library of potential templates and, conversely, each potential template is used to search for hits in a library of queries. In the threading portion, the scoring function is the sum of a sequence profile and a 6x6 substitution matrix between predicted query and known template secondary structure and solvent exposure. "Two-way" in threading means that the query's sequence profile is used to match the sequences of all potential templates and the sequence profiles of all potential templates are used to match the query's sequence. When tested on a set of 533 nonhomologous proteins, COBLATH was able to assign folds for 390 (73%). Among these 390 queries, 265 (68%) had root-mean-square deviations (RMSDs) of less than 8 A between predicted and actual structures. Such high success rate and accuracy make COBLATH an ideal tool for structural genomics.

Algorithms↗

Molecular mechanics and calorimetric studies of phosphatidylethanols.

Phosphatidylethanols (PEths) are negatively charged diacyl phospholipids that are ubiquitously present in humans under the condition of alcohol intoxication. These lipids, derived in vivo from other naturally occurring phospholipids such as phosphatidylcholines (PC) via transphosphatidylation reaction as catalyzed by phospholipase D in the presence of ethanol, are well known to affect many biochemical properties of the cell membranes in humans. In this communication, we applied the combined approach of molecular mechanics (MM) simulations and high-sensitivity differential scanning calorimetry (DSC) to investigate the structure and phase transition behavior of PEth. We first determined the energy-minimized structures of tetrameric C(15):C(15)PEth arranged in two types of packing motif by the MM approach. An inwardly bent orientation of the lipid headgroup was observed; specifically, the methyl terminus of PEth's headgroup was juxtaposed intramolecularly to the C(2) atom of the sn-2 acyl chain. Clearly, this headgroup conformation was rather unique among all naturally occurring phospholipids. Subsequently, the phase transition behavior of the fully hydrated lipid bilayers prepared individually from 11 species of saturated C(X):C(Y)PEth with the same MW was studied by DSC, and the resulting Tm values were codified in terms of the normalized acyl chain asymmetry (deltaC/CL). A V-shaped Tm profile was observed in the plot of Tm versus deltaC/CL for each subclass of these lipids, suggesting two types of packing motif for C(X):C(Y)PEth at T < Tm. Moreover, it was observed that within each packing motif these Tm values were, on average, 2.0 +/- 0.9 degrees C smaller than the Tm values of the corresponding saturated PC. However, based on the unique headgroup conformation of PEth, we were able to predict that monounsaturated PEth with a cis double bond near the H2O/hydrocarbon interface would exhibit a higher Tm than the corresponding PC. Most interestingly, this prediction was indeed borne out by DSC results obtained with C(18):C(20:1delta5)PC and C(18):C(20:1delta5)PEth.

Brassica↗

Inactivity-Associated medical costs among US adults with arthritis.

OBJECTIVE: To analyze direct medical costs among US adults with arthritis and estimate the proportion associated with inactivity. METHODS: In the 1987 National Medical Expenditure Survey, arthritis was defined using questions on self-reported, doctor-diagnosed arthritis or rheumatism. Physical activity was defined using a self-report question on level of activity. Inactivity-associated medical costs were derived by subtracting costs for active adults from costs for inactive adults after controlling for functional limitation. RESULTS: Among 5,486 adults with arthritis, inactive persons had higher medical costs than did active persons in all demographic groups examined. In multivariate models adjusting for key covariates, the proportion of costs associated with inactivity averaged 12.4% ($1,250 in 2000 dollars) and ranged from 7.8% to 14.3% among various demographic groups. CONCLUSION: Inactivity-associated medical costs among persons with arthritis are considerable. Physical activity interventions may be a cost-effective strategy for reducing the burden of arthritis.

Activities of Daily Living↗

Allelic loss and gain, but not genomic instability, as the major somatic mutation in primary hepatocellular carcinoma.

To identify genetic abnormalities in primary hepatocellular carcinoma (HCC), we performed microsatellite analysis (MSA) on 60 Chinese HCC specimens. Utilizing a semi-quantitative MSA and 292 highly polymorphic markers spanning all 22 autosomes, we found that somatic allelic imbalance (AI) occurred frequently in HCC. To evaluate the nature of the AI, comparative genomic hybridization was performed on 20 HCC specimens. The combined use of these two methods revealed frequent allelic loss on 17p, 9p21-p23, 4q, 16q21-q23.3, 13q, 8p21-p23, and 6q24-q27, whereas there was frequent allelic gain on 1q, 17q, and 8q24. The region with the highest incidence of genomic imbalance was 17p13 (65%), followed by 9p21-p23 (55%), 4q (35-51%), 16q21-q23.3 (52%), 17p12 (49%), 13q (39-46%), 8p21-p23 (41-45%), 8q24 (41%), and 1q32 (40%). In addition, aberrations of 19p13.3, 16p13.3, 13q33-q34, 9q13-31, and 7q were reported for the first time. The presence of a close correlation of 17p13 deletion with abnormalities of some other loci implies that 17p13 could play a crucial role in oncogenesis. Interestingly, microsatellite instability was rarely seen in our patients, in contrast to that observed in European HCC samples.

Adult↗

Reactions of first-row transition metal ions with propargyl alcohol in the gas phase.

The gas-phase reactions with propargyl alcohol (PPA) of all the singly charged ions of the first-row transition metals, generated by laser ablation in an external ion source, were studied by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICRMS.). The reactivities of the metal ions change irregularly across the periodic table, and the reactivity of each ion is a function of its electronic configuration and corresponding metal-oxygen (M-O) bond energies. The 10 metal ions were classified into three categories according to their reactivities: Sc(+), Ti(+) and V(+) are the most reactive ions which react with PPA to give many kinds of oxygen-rich products due to stronger M-O bonds; Fe(+), Co(+) and Ni(+) are less reactive; Cr(+), Mn(+), Cu(+) and Zn(+) are the most unreactive ions, due to the half and completely occupied valence electronic configurations. The order of reactivity is Ti(+) > V(+) > Sc(+) >> Co(+) > Fe(+) approximately Ni(+) > Zn(+) > Cr(+) approximately Mn(+) approximately Cu(+).

Journal Article↗

Characterization of tetrathiofulvalene compounds using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Tetrathiofulvalene compounds are important components of charge-transfer complexes, which may be applied in various fields of scientific research and practical applications. Some of these compounds cannot be characterized by mass spectrometry. Here, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was used for the characterization of tetrathiofulvalenes. The samples could be easily desorbed and ionized to form singly charged ions, and mass spectra with isotopic resolution readily obtained. The mass spectrometric results for 26 compounds have shown that MALDI-TOF is more effective and convenient than other mass spectrometry methods, and resolves the problem of mass spectrometric characterization of tetrathiofulvalene compounds.

Journal Article↗

Localization of agmatine in vasopressin and oxytocin neurons of the rat hypothalamic paraventricular and supraoptic nuclei.

Agmatine (decarboxylated l-arginine), an endogenous ligand of imidazoline and alpha(2) adrenoreceptors, is particularly enriched in the rat hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. The present study utilized light and electron microscopic immunocytochemical methods to determine the distribution and extent of colocalization of agmatine relative to subpopulations of vasopressin- (VP) and oxytocin- (OT) producing neurons in PVN and SON nuclei. By light microscopy, agmatine-immunoreactive perikarya were found in both the magnocellular and the parvocellular neuronal subdivisions of PVN and SON. Confocal and electron microscopy revealed that agmatine-immunoreactivity (I) within neuronal perikarya was associated with the nuclear membrane as well as mitochondria, Golgi complexes, endoplasmic reticula, and plasmalemma. Additionally, agmatine-I was identified in both axons and axonal terminals, which were enriched in large dense-core vesicles. Dual and triple immunocytochemical labeling experiments also demonstrated that agmatine coexists with VP or OT in most PVN and SON magnocellular neurons. Combinations of iontophoretic injections of Fluorogold into the dorsomedullary complex with immunocytochemical labeling revealed that many retrogradely labeled neurons in the parvocellular region of the PVN contained agmatine-I and either VP or OT. These findings provide evidence that agmatine may function as a modulator of both hypothalamically mediated neuroendocrine and autonomic responses.

Agmatine↗

Infection of human airway epithelia with H1N1, H2N2, and H3N2 influenza A virus strains.

Three subtypes of influenza A virus cause human disease: H1N1, H2N2, and H3N2. Although all result in respiratory illness, little is known about how these subtypes infect differentiated airway epithelia. Therefore, we assayed A/PR/8/34 (H1N1), A/Japan/305/57 (H2N2), and X31 (H3N2) influenza virus strains for binding and infection on fully differentiated primary cultures of airway epithelia isolated from human bronchus, grown on semiporous filters at an air-liquid interface. In this model system, viral infectivity was highest when virus was applied to the apical versus the basolateral surface; Japan was most infectious, followed by PR8. The X31 strain showed very low levels of infectivity. Confocal microscopy and fluorescence-resonance energy transfer studies indicated that Japan virus could enter and fuse with cellular membranes, while infection with X31 virions was greatly inhibited. Japan virus could also productively infect human trachea explant tissues. These data show that influenza viruses with SAalpha2,3Gal binding specificity, like Japan, productively infect differentiated human airway epithelia from the apical surface. These data are important to consider in the development of pseudotyped recombinant viral vectors for gene transfer to human airway epithelia for gene therapy.

Antibodies, Viral↗

Expression of angiopoietin-2 gene and its receptor Tie2 in hepatocellular carcinoma.

To explore the relationship of angiogenesis-related angiopoietin-2 gene and its receptor Tie2 with angiogenesis and the biology of hepatocellular carcinoma (HCC), angiopoietin-2 gene, Tie2 and CD34 protein expression in 22 resected HCC, 8 cirrhotic and 8 control liver specimens were investigated by in situ hybridization and immunohistochemistry respectively, and the level of angiopoietin-2 and Tie2 expression in HCC were compared in terms of tumor biological parameters. It was found that CD34 was not expressed in control liver, expressed scarcely in cirrhotic liver (17.8 +/- 13.5/HP), but intensively expressed in HCC (86.3 +/- 34.8/HP, P < 0.01). Tie2 receptor was not expressed in controls, expressed at low level in cirrhotic liver (11.3 +/- 8.7/HP), while strongly positive in the microvascular endothelia of HCC (52.4 +/- 16.7/HP, P < 0.01). The level of Tie2 receptor expression in HCC was closely related with tumor diameter, angiogenesis and portal invasion. Angiopoietin-2 gene was not expressed in control liver, expressed mildly in cirrhotic liver (11.2 +/- 9.7/HP), but extensively in tumor zone (36.4 +/- 17.5/HP), the level of angiopoietin-2 expression was closely related with angiogenesis, portal invasion and histological grading of HCC. It is concluded that angiogenesis is increased in HCC; angiopoietin-2/Tie2 expression in human hepatic carcinoma is closely related with angiogenesis, which are probably involved in the HCC angiogenesis regulation, promoting the development and metastasis of human hepatic cancer.

Angiopoietin-2↗

The influence of phorbol ester on the effect of tamoxifen in breast cancer cells.

To investigate the correlation between the activity of kinases in the growth factor signal transduction pathway and the development of resistance of breast cancer to tamoxifen, reporter gene regulated by the regulating fragment of CCD1 was transfected into the MCF-7 cells, and the influence of tamoxifen on the reporter gene expression was examined under different conditions of TPA treatment. Our results showed that the reporter gene expression was inhibited by tamoxifen and promoted by TPA. Furthermore, tamoxifen exerts an agonist effect on the reporter gene expression when the cells was treated by TPA previously for 12 h. It is concluded that TPA could induce estrogen-like effect of tamoxifen on estrogen receptor positive breast cancer cells and it may be one of the mechanisms responsible for the development of tamoxifen resistance.

Antineoplastic Agents, Hormonal↗

Concurrent quantification of tremor and depression of locomotor activity induced in rats by harmaline and physostigmine.

RATIONALE: Both harmaline and physostigmine are known to produce whole-body tremors in rodents, yet there is little quantitative information on the differential frequency characteristics of these tremors or on other possible motor effects of these drugs. In addition, the degree to which tolerance develops to their tremorogenic effects is uncertain. OBJECTIVES: The purpose of this work was to use a new kind of instrument (the force-plate actometer) to describe quantitatively the frequency characteristics of tremor induced by the two drugs and simultaneously to measure locomotor activity effects. Another aim was to detect any tolerance effects on the tremor or locomotor measurements. METHODS: Sprague-Dawley rats in four separate groups received harmaline (0, 4.0, 8.0, and 16.0 mg/kg) while another four groups received physostigmine (0, 0.10, 0.25, and 0.50 mg/kg). Dosing continued for 4 consecutive days. Each day, every rat's whole-body tremor and locomotor activity were recorded for 30 min. Fourier analysis of the force-plate recordings was used to quantify tremor and characterize its frequency components. RESULTS: Harmaline induced a dose-related tremor that peaked in the 10 Hz region of the spectrum, while the dose related-tremor of physostigmine was demonstrably of a broader-band frequency composition. While harmaline tremor exhibited pronounced tolerance, physostigmine tremor remained substantial across the 4 days of dosing. Both drugs suppressed locomotor activity, and there was no tolerance on this measure for either drug. CONCLUSIONS: In regard to tremor, harmaline and physostigmine induced quantitatively different kinds of tremor, and these differences probably reflect the drugs' different sites of action in the brain (harmaline: inferior olive; physostigmine: basal ganglia). For harmaline, tolerance to the tremorogenic effect was concurrent with a lack of tolerance to locomotor suppression, and this finding suggested the presence of a strong motor effect of harmaline that continued to be expressed despite the absence of tremor.

Animals↗

Measurement of the bioactivity of interleukin and tumour necrosis factor in synovial fluid of Kashin-Beck disease.

We studied the bioactivity of interleukin (IL-1) and tumour necrosis factor (TNF) in the synovial fluid of 12 patients with Kashin-Beck disease (KBD), 8 patients with osteoarthritis (OA) and 8 normal controls. C57 female mouse T cell proliferation method was used to test the bioactivity of IL-1, and lethality method with L929 cells to test the bioactivity of TNF. The bioactivities of IL-1 and TNF in the synovial fluid from patients with KBD were higher than those in the synovial fluid of osteoarthritis and normal controls, indicating the participation of IL-1 and TNF in the pathogenesis of KBD.

Adult↗

A study of protein-protein interactions in living cells using luminescence resonance energy transfer (LRET) from Renilla luciferase to Aequorea GFP.

We have previously reported that Escherichia coli and mammalian cells containing a fusion protein consisting of the Renilla luciferase linked to Aequorea GFP exhibited luminescence resonance energy transfer (LRET) from luciferase to GFP in the presence of coelenterazine. In this paper, we describe the construction of two gene fusions in which the cDNA for insulin-like growth factor II (IGF-II) is connected to the cDNA for a "humanized" GFP, and the cDNA for insulin-like growth factor binding protein 6 (IGFBP-6) is linked to a cDNA encoding the Renilla luciferase (RUC). The expression of the fusion gene constructs in CHO cells resulted in single polypeptides with the molecular weights expected for IGF-II-GFP and IGFBP-6-RUC, respectively, based on the use of antibodies against GFP and Renilla luciferase. The secretion of IGF-II-GFP from CHO cells was verified by fluorescence microscopy and the presence of IGFBP-6-RUC in the culture medium was confirmed by luminometry. The interaction between the two known binding partners, IGF-II and IGFBP-6, was monitored by measuring LRET from the IGFBP-6-RUC protein to IGF-II-GFP in the presence of coelenterazine, using a low-light imaging system and spectrofluorometry. Based on these data, luciferase-to-GFP LRET holds great promise for the study of protein-protein interactions in eukaryotic cells in real time.

Animals↗

Semiautomatic segmentation of the cochlea using real-time volume rendering and regional adaptive snake modeling.

The human cochlea in the inner ear is the organ of hearing. Segmentation is a prerequisite step for 3-dimensional modeling and analysis of the cochlea. It may have uses in the clinical practice of otolaryngology and neuroradiology, as well as for cochlear implant research. In this report, an interactive, semiautomatic, coarse-to-fine segmentation approach is developed on a personal computer with a real-time volume rendering board. In the coarse segmentation, parameters, including the intensity range and the volume of interest, are defined to roughly segment the cochlea through user interaction. In the fine segmentation, a regional adaptive snake model designed as a refining operator separates the cochlea from other anatomic structures. The combination of the image information and expert knowledge enables the deformation of the regional adaptive snake effectively to the cochlear boundary, whereas the real-time volume rendering provides users with direct 3-dimensional visual feedback to modify intermediate parameters and finalize the segmentation. The performance is tested using spiral computed tomography (CT) images of the temporal bone and compared with the seed point region growing with manual modification of the commercial Analyze software. Our method represents an optimal balance between the efficiency of automatic algorithm and the accuracy of manual work.

Cochlea↗