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Biomedical subjects

G Wang

Publications and source records attributed to G Wang.

At least 127 records · Page 7Linked to original sources

AKT1/PKBalpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells.

Extensive studies have demonstrated that the Akt/AKT1 pathway is essential for cell survival and inhibition of apoptosis; however, alterations of Akt/AKT1 in human primary tumors have not been well documented. In this report, significantly increased AKT1 kinase activity was detected in primary carcinomas of prostate (16 of 30), breast (19 of 50), and ovary (11 of 28). The results were confirmed by Western blot and immunohistochemical staining analyses with phospho-Ser473 Akt antibody. The majority of AKT1-activated tumors are high grade and stage III/lV (13 of 16 prostate, 15 of 19 breast, and 8 of 11 ovarian carcinomas). Previous studies showed that wild-type AKT1 was unable to transform NIH3T3 cells. To demonstrate the biological significance of AKT1 activation in human cancer, constitutively activated AKT1 (Myr-Akt) was introduced into NIH3T3 cells. Overexpression of Myr-Akt in the stably transfected cells resulted in malignant phenotype, as determined by growth in soft agar and tumor formation in nude mice. These data indicate that AKT1 kinase, which is frequently activated in human cancer, is a determinant in oncogenesis and a potential target for cancer intervention.

3T3 Cells↗

Dynamic and static control of the human knee joint in abduction-adduction.

It is unclear whether humans can voluntarily control dynamic and static properties in knee abduction-adduction, which may be important in performing functional tasks and preventing injuries, whether the main load is about the abduction axis or not. A joint-driving device was used to perturb the knee in abduction-adduction at full knee extension under both passive (muscle relaxed) and active (muscle contracted in abduction or adduction) conditions. Dynamic control properties in knee abduction-adduction were characterized by joint stiffness, viscosity, and limb inertia, and quasi-static knee torque-angle relationship was characterized by knee abduction-adduction laxity and quasi-static stiffness (at a 20Nm moment). It was found that the subjects were capable of generating net abduction and adduction moment through differential co-contraction of muscles crossing the medial and lateral sides of the knee, which helped to reduce the abduction-adduction joint laxity (p< or =0.01) and increase stiffness (p<0.027) and viscous damping. Knee abduction laxity was significantly lower than adduction laxity (p=0.043) and the quasi-static abduction stiffness was significantly higher than adduction stiffness (p<0.001). The knee joint showed significantly higher stiffness and viscosity in abduction-adduction than their counterparts in knee flexion-extension at comparable levels of joint torque (p<0.05). Similar to dynamic flexion-extension properties, the system damping ratio remained constant over different levels of contraction, indicating simplified control tasks for the central nervous system; while the natural undamped frequency increased considerably with abduction-adduction muscle contraction, presumably making the knee a quicker system during strenuous tasks involving strong muscle contraction.

Adult↗

Surface water phosphorus dynamics in rice fields receiving fertiliser and manure phosphorus.

A long-term randomised block field experiment was established in 1997 to study the dynamics of total P and dissolved P in the surface waters of rice fields receiving two application rates of fertiliser P and one rate of combined fertiliser and manure P. Preliminary results from the first two crops show that concentrations of both total P and dissolved P in the surface waters increased significantly following P application, especially during the first 2 weeks after application. P concentrations subsequently declined sharply within about 10 days, then declined steadily and remained almost constant from about 1 month after application. The initial increase in P concentration of surface waters was higher with increasing rate of fertiliser P, and the P concentration at the highest fertiliser rate peaked within about 1 week of application. The elevated P concentrations following fertiliser P application declined more rapidly than those following the combined application of fertiliser and manure P. When fertiliser and manure P were applied together, about 7 days later the surface water P concentrations were significantly higher than when the same rate of P (or double) was applied as fertiliser only. Disturbance of the surface soil by hand harrowing further increased the P concentrations in surface waters, with a subsequent decline to a steady value after about 1 week. Application of P fertiliser to the high P status soil in this experiment gave no crop yield response and may have increased the risk of pollution of adjacent surface waters through drainage from heavy rainfall events during the rice growing season. Therefore, fertiliser P should not be applied to such soils. If, however, fertiliser or manure P is applied, the application should be made during the dry winter to reduce P losses. Manure should be applied with particular care because of the higher risk of P losses to surface water arising from the relatively long period of high P concentrations in surface waters and the potential for greater release of P to field surface waters from the soil. Hand harrowing should also be avoided during wet weather to protect water quality.

Animals↗

The importance of catchment and lake processes in the phosphorus budget of a large lake.

Total phosphorus (P) river inputs and lake concentrations for the Neagh system in Northern Ireland are compared from the period 1974-1997. The main routes of P transfer between the lake water and the sediment are settlement of abiotic particles and planktonic diatoms, summer sediment release and re-sedimentation in the last months of the year. The annual river loading to the lake varied between 0.7 and 1.8 g P m(-2), and sediment release can be as much as 1.4 g P m(-2). A simple model evaluated the effect of sediment-water exchanges on the phosphorus available for spring phytoplankton growth. It showed that re-sedimentation of released P and washout over the winter greatly mitigated its effect. Correlation analysis demonstrated that the very large summer releases of sediment P were not related directly to the spring inputs from diatom settlement. No long-term trends in P release were seen.

Fresh Water↗

Synthesis and cytotoxicity of 4'-C- and 5'-C-substituted toyocamycins.

Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcome the weakness of these nucleoside analogues, substitution of a variety of modified sugars for the ribofuranose was explored in our laboratories with expectation that certain sugar-modified toyocamycin analogues may be selectively cytotoxic to cancer cells. In this article, we report synthesis and cytotoxicity of 4'-C- and 5'-C-substituted toyocamycins, which were prepared via the condensations of 4-C- and 5-C-substituted ribofuranose derivatives 11, 12, 13, 20, 21, and 26 with the silylated form of 4-amino-6-bromo-5-cyanopyrrolo[2,3-]pyrimidine (27) and subsequent debromination and debenzoylation. When compared to the parent toyocamycin, all these analogues showed much lower cytotoxicity to human prostate cancer cells (HTB-81), mouse melanoma cancer cells (B16) as well as normal human fibroblasts. Compound 1e showed a significant cytotoxicity to the prostate cancer cells and a moderate selectivity. The results suggested that sugar modifications, especially those that may affect phosphorylation of nucleosides, could alter cytotoxicity profile significantly.

Animals↗

Effects of pH and acetylation on Hg(2+)-induced purple to blue transition in bacteriorhodopsin.

Effects of Hg(2+) ions on the absorption spectrum of bacteriorhodopsin have been measured at different pH values and after acetylation. UV-difference spectroscopy and CD spectra show that Hg(2+)-induced color change is essentially similar to that caused by removal of cations or acidification. The ability of Hg(2+)-induced purple-to-blue transition is pH-dependent and exhibits a maximum at pH 5.5. Acetylation influences the absorption in the same way as Hg(2+) ions and accelerates Hg(2+)-induced purple to blue transition. All these results strongly suggest that the Hg(2+) effect is not a specific binding but just a replacement of intrinsic cations on the membrane surface, where they form a double layer. The composition of the double layer determines the surface pH on the membrane, which affects the color of the bacteriorhodopsin.

Acetylation↗

A point of view: quantitative and qualitative imbalance in disease pathogenesis; pulmonary surfactant protein A genetic variants as a model.

The high degree of similarity at the molecular level, between humans and other species, has provided the rationale for the use of a variety of species as model systems in research, resulting in enormous advances in biological sciences and medicine. In contrast, the individual variability observed among humans, for example, in external physique, organ functionality and others, is accounted for, by only a fraction of 1% of differences at the DNA level. These small differences, which are essential for understanding disease pathogenesis, have posed enormous challenges in medicine, as we try to understand why patients may respond differently to drugs or why one patient has complications and another does not. Differences in outcome are most likely the result of interactions among genetic components themselves and/or the environment at the molecular, cellular, organ, or organismal level, or the macroenvironment. In this paper: (1) we consider some issues for multifactorial disease pathogenesis; (2) we provide a review of human SP-A and how the knowledge gained and the characteristics of the hSP-A system may serve as a model in the study of disease with multifactorial etiology; and (3) we describe examples where hSP-A has been used in the study of disease.

Alleles↗

Localization error analysis for stereo X-ray image guidance with probability method.

The mean value and standard deviation of localization error for the stereo imaging systems are derived based on probability theory. Compared with the maximum error analysis method used in our previous study, the new approach yields more informative and precise results as the guidance for X-ray imaging system design and protocol optimization. The prototype for our current study is a CCD based monoplane digital stereo X-ray imaging system. The imaging model consists of two X-ray sources and one detector plane. With perspective geometry, the least-square solution is derived to reconstruct 3-dimensional object points, such as a biopsy needle tip, from a pair of 2-dimensional digital radiographs. Under the conditions of our specific prototype, the measurement errors of interested points in the radiographs are modeled as random variables with Gaussian distribution. Such variables account for finite image system noise and positioning errors. Then, the 3D localization error, in terms of mean value and standard deviation, is formulated using measurement error, feature point location, and separation between the two X-ray sources and distance from source to detector. Both theoretical analysis and numerical simulation are performed. The mean value and standard deviation of the localization error are first evaluated using numerical simulation under practical imaging conditions. Then, the error estimates are given in simply analytic forms. Simulation and theoretical results are in excellent agreement. The results show that our prototype X-ray stereological imaging system is accurate and reliable to locate feature points in 3D for medical intervention. Imaging protocols can be effectively optimized through the 3D localization error analysis using the approximate formulas proposed in this study.

Algorithms↗

Homocysteine stimulates the expression of monocyte chemoattractant protein-1 in endothelial cells leading to enhanced monocyte chemotaxis.

Hyperhomocysteinemia has been identified as an independent risk factor for atherosclerosis. The infiltration of monocytes into the arterial wall is one of the key events during atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates the migration of monocytes into the intima of the arterial wall. The mechanism by which increased monocyte infiltration occurs in atherosclerotic lesions in patients with hyperhomocysteinemia has not been delineated. The objective of the present study was to investigate the effect of homocysteine on MCP-1 production in endothelial cells. Cells were incubated with homocysteine. The secretion of MCP-1 protein was significantly increased (195% as compared to the control) in cells treated with pathological concentrations of homocysteine. Such effect was accompanied by an increased expression of MCP-1 mRNA (176% as compared to the control) in endothelial cells which resulted in enhanced monocyte chemotaxis. The p38 MAP kinase as well as other members of the p38 MAP kinase pathway, including MKK3, MKK6, ATF-2 and Elk-1, were activated in homocysteine-treated cells. Homocysteine-induced MCP-1 expression and subsequent monocyte chemotaxis were blocked by a p38 MAP kinase inhibitor (SB203580) suggesting that the p38 MAP kinase pathway might be involved in homocysteine-induced MCP-1 expression in endothelial cells. In contrast, staurosporine, a protein kinase C inhibitor, had no effect on homocysteine-induced MCP-1 expression. In conclusion, our results indicate that homocysteine stimulates MCP-1 expression in endothelial cells leading to enhanced monocyte chemotaxis.

Activating Transcription Factor 2↗

Purification of natural antikeratin autoantibodies from normal human serum and their effect on human keratinocytes cultured in vitro.

BACKGROUND: Antikeratin (AK) autoantibodies, circulating antibodies against epidermal keratins, have been detected in all normal human sera. However, direct evidence on the biological significance of AK autoantibodies is still lacking. OBJECTIVES: To purify AK autoantibodies from human serum and to make a preliminary study of their biological effects on human keratinocytes. METHODS: We first extracted keratin polypeptides from human stratum corneum and analysed their purity using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Next, a keratin affinity column was prepared with the extracted keratins, and AK autoantibodies were purified from pooled normal human serum. Antibodies obtained were identified with SDS-PAGE, enzyme-linked immunosorbent assay, immunoperoxidase staining, immunoelectron microscopy and Western blotting. The biological effect of AK autoantibodies on cultured human keratinocytes was studied using a DNA synthesis assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric determination and cell cycle analysis. RESULTS: On average, 1.83 +/- 0.24 mg of antibodies could be purified from 10 mL of pooled human serum. High-titre IgG (about 1 : 70) and low-titre IgM (about 1 : 30) AK autoantibodies were obtained. The DNA synthesis assay and MTT colorimetric determination demonstrated that AK autoantibodies have a significant dose-dependent inhibitory effect on cultured keratinocytes. Correlation coefficients in the two experiments were - 0.583 and - 0.797, respectively. Cell cycle analysis indicated that a small dose of AK autoantibodies leads to inhibition of proliferation of cultured keratinocytes, whereas a large dose of AK autoantibodies causes a visible hypodiploid peak, suggesting apoptosis of keratinocytes. CONCLUSIONS: The present research lays a solid foundation for further investigation into the biological significance of natural AK autoantibodies.

Adult↗

Personal dose monitoring of employees at the institute of modern physics, China.

The radiation field at the accelerator facility consists of radiation produced immediately and of secondary radiation induced by activation etc. As the accelerator building and the experimental hall are closed and inaccessible during accelerator operation, the exposure received by the employees at the IMP (Institute of Modern Physics) comes almost totally from the induced radiation. The methods and the results of personal dose monitoring from 1986 to 1999 at the IMP are presented. During the period, the total number of monitored individuals was 1960, and the average annual effective dose was 0.10 mSv. The number recording less than 0.1 mSv of effective dose was 1471 individuals. amounting to 77% of the total. Only six individuals had received effective doses between 5.0 mSv and 10 mSv. The maximum effective dose of 10 mSv was received by workers repairing the accelerator.

Calibration↗

Muscle strength in knee varus and valgus.

PURPOSE: The purpose of this study was to investigate the lower-limb muscle strength in knee varus-valgus and its dependence on knee varus-valgus position. The hypothesis was that humans could differentially contract the medial and lateral muscles crossing the knee and generate significant moments in knee valgus-varus. METHODS: The subjects sat with the knee at full extension and secured from the medial, lateral, anterior, and posterior sides. Both hips were clamped from the lateral sides. The subjects adducted (abducted) the ipsilateral hip during the knee valgus (varus) maximal voluntary contraction with EMG signals recorded from muscles crossing the knee and knee joint moments measured using a six-axis force sensor. Frontal plane tibiofemoral movement was evaluated using a fluoroscope. RESULTS AND CONCLUSIONS: The subjects differentially contracted the medial and lateral muscles, and fluoroscope images showed the corresponding tibiofemoral movement. The subjects showed considerable strength in knee varus and valgus. The active knee varus strength increased significantly with increasing knee valgus angle, and the valgus strength was significantly higher when the knee was in varus position (P < 0.039). Active valgus muscle strength at 5 degrees knee varus was significantly higher than the active varus strength at 5 degrees valgus (P = 0.002). The passive resistance moment increased linearly with increasing knee valgus and varus angles, and it accounted for 28% and 35% of the total (active plus passive) moment at the 5 degrees varus and 5 degrees valgus, respectively. The significant varus-valgus muscle strength demonstrated in this study may play important roles in performing various functional tasks, maintaining joint stability, and preventing potential injuries, whether the major load and motion at the knee is in the frontal plane or not.

Adult↗

Beneficial effects of growth hormone on bacterial translocation during the course of acute necrotizing pancreatitis in rats.

Because bacterial translocation from the gut is one of the important sources of bacterial infection in acute necrotizing pancreatitis (ANP) and growth hormone (GH) has the ability to promote the intestinal epithelial proliferation, we investigated the effects of GH on bacterial translocation in a rat ANP model. ANP was induced in rats by injection of 5% sodium taurocholate into the biliopancreatic duct. The rats with ANP were treated with either human recombinant GH or placebo. Laparotomized animals without induction of ANP (sham operation [SO]) served as controls. At 24 hours after operation, blood was drawn for bacterial culture and determination of amylase, lipase, and endotoxin. Peritoneal fluid and specimens of mesenteric lymph nodes (MLN), liver, pancreas, and spleen were taken for bacterial culture by standard techniques. Intestinal mucosal permeability was assessed by measuring the movement of 125I-labeled albumin from blood to intestinal lumen. Insulin-like growth factor-1 (IGF-1) mRNA was detected in the liver and ileum by reverse transcriptase-polymerase chain reaction (RT-PCR). Morphologic changes of pancreas and ileum were also analyzed. Administration of GH significantly decreased the serum amylase, lipase activities, plasma endotoxin level, and incidence of bacterial translocation. Moreover, the survival rate of ANP rats was improved. The severity of inflammation in pancreas and ileum was alleviated by GH treatment. Ileal mucosal thickness, villus height, and crypt depth in GH treatment rats were obviously increased compared with those of ANP rats. The intestinal permeability was markedly improved in the GH group versus the ANP group. GH treatment resulted in up-regulation of IGF-1 mRNA expression in ileum, but not in liver. These results suggested that exogenous GH had beneficial effects in maintaining the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation in rats with ANP. One of the mechanisms might be the up-regulation of IGF-1 mRNA in intestine by GH treatment.

Amylases↗

A case of Kaposi's sarcoma associated with pemphigoid nodularis.

Pemphigoid nodularis is a rare variant of bullous pemphigoid. Bullous pemphigoid complicated by internal malignancy has been well documented. There have been only a few reported cases of bullous pemphigoid associated with Kaposi's sarcoma. We described a case of pemphigoid nodularis who later developed Kaposi's sarcoma that might be related to immunosupressive therapy, a situation that has not been reported previously.

Aged↗

Half-scan cone-beam CT fluoroscopy with multiple x-ray sources.

To develop volumetric micro-CT fluoroscopy for small animal imaging, we have proposed a cone-beam system with multiple x-ray sources. In this paper, we extend Parker's single-source half-scan weighting scheme to the case of an odd number of x-ray sources that are equiangularly distributed, and apply it for half-scan Feldkamp-type reconstruction in this unique geometry. In the numerical simulation with the Shepp-Logan phantom, representative images indicate that the proposed half-scan Feldkamp-type algorithm produces temporal resolution significantly superior to that with a single x-ray source cone-beam system.

Algorithms↗

Spontaneous mutations that confer antibiotic resistance in Helicobacter pylori.

In this study, we systematically examined in vitro frequencies and spectra of the spontaneous mutations in Helicobacter pylori that confer resistance to clarithromycin (Cla(r)), metronidazole (Mtz(r)), amoxicillin (Amx(r)), ciprofloxacin (Cip(r)), and rifampin (Rif(r)). The mutation rate of Rif(r) or Cip(r) determined in a fluctuation assay is 1 x 10(-8) to 2 x 10(-8) per cell per division. In contrast, the mutation rates of Cla(r), Mtz(r), and Amx(r) are much lower (<10(-9)). However, Mtz(r) mutants could be readily selected in vitro by using the serial passage method, suggesting that the mutagenic effect and selective effect of a sublethal dose of metronidazole contribute to the rapid development of Mtz(r). Analysis of spontaneous Rif(r), Cla(r), and Cip(r) mutants confirmed previous results indicating that mutations within the rpoB gene, the 23S rRNA gene, and the gyrA gene, respectively, are responsible; also, several new mutant alleles were identified. Mtz(r) mutants resulted most frequently, but not always, from mutations in the rdxA gene. DNA fragments containing each mutant allele could readily transform susceptible H. pylori strains to resistance, confirming that each mutant allele is responsible for the resistance phenotype.

Anti-Bacterial Agents↗

Impact of genotypic variation of Borrelia burgdorferi sensu stricto on kinetics of dissemination and severity of disease in C3H/HeJ mice.

Various genotypes of Borrelia burgdorferi sensu stricto have been previously identified among a large collection of isolates cultured from patients with Lyme disease in the United States. Furthermore, association of specific genotypes with hematogenous dissemination early in the disease course has been observed. The present study assessed kinetics of spirochete dissemination and disease severity in C3H/HeJ mice infected with two different genotypes of B. burgdorferi. Spirochete load in plasma and ear and other tissue samples of infected mice was measured by quantitative PCR, and these data were compared to those obtained by culture and histopathologic analysis. In mice infected with isolate BL206 (a type 1 strain), the peak number of spirochetes was observed in plasma between day 4 and 7, in heart and ear tissue on day 14, and in joints on day 28 postinoculation. There was a correlation between the peak number of spirochetes in plasma on day 4 or 7 and that in ear biopsy and joint specimens on day 14. By contrast, spirochete burdens in plasma of mice infected with isolate B356 (a type 3 strain) were 16- and 5-fold lower than those of BL206-infected mice on days 7 and 14 of infection, respectively. Similarly, approximately 6- and 13-fold fewer spirochetes were detected in the heart tissues of B356-infected mice compared to BL206-infected mice. Histopathologically, severe arthritis and aortitis were noted only in mice infected with isolate BL206. Spirochete dissemination and disease severity vary significantly in mice infected with distinct genotypes of B. burgdorferi, suggesting that genotypic differences in the infecting spirochetes play a key role in the pathogenesis and development of clinical disease.

Animals↗