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Biomedical subjects

M Wong

Publications and source records attributed to M Wong.

At least 397 records · Page 22Linked to original sources

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Botany↗

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China↗

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China↗

Sonochemically produced fluorocarbon microspheres: a new class of magnetic resonance imaging agent.

With the intent of increasing the signal-to-noise ratio (SNR) of fluorine magnetic resonance imaging and enabling new applications, we have developed a novel class of agents based on protein encapsulation of fluorocarbons. Microspheres formed by high-intensity ultrasound have a gaussian size distribution with an average diameter of 2.5 microns. As with conventional emulsions, these microspheres target the reticuloendothelial system. However, our sonochemically produced microspheres, because of a high encapsulation efficiency, show increases in the SNR of up to 300% compared to commercially available emulsions. We also demonstrate an increase in the circulation lifetime of the microspheres with the bloodstream by more than 30-fold with a chemical modification of the outer surface of the microsphere. Finally, by encapsulating mixtures of fluorocarbons that undergo solid/liquid phase transitions, we can map temperature in the reticuloendothelial system, with signal changes of approximately 20-fold over a 5 degrees C range.

Animals↗

Surface and subsurface morphology of bovine humeral articular cartilage as assessed by atomic force and transmission electron microscopy.

Maintenance of superficial structural integrity is essential for the load-bearing function of articular cartilage. In this study, we used atomic force microscopy (AFM) to image the 3-D surface and subsurface morphology of fresh bovine humeral head articular cartilage maintained in physiological solution. Complementary ultrastructural data were obtained by transmission electron microscopy (TEM) of cryo-processed samples. The surface irregularities observed in previous scanning electron microscopic studies were not apparent with AFM. The most superficial layer, typically 200-500 nm thick, consisted of acellular and nonfibrous tissue. Occasionally, it exhibited local discontinuities through which the underlying network of collagen fibrils, oriented parallel to the surface and displaying the characteristic periodic banding, could been seen. Local variations in force-curve measurements indicate the existence of differences in micromechanical properties along the articular surface. AFM thus furnishes a new method for characterizing the surface structure and properties of freshly excised articular cartilage in physiologically relevant conditions. It confirms the existence of an amorphous, nonfibrous articular surface which may be vital for its normal lubrication and wearing properties in vivo.

Animals↗

Web-based telemicroscopy.

By taking advantage of network-based computing and the recent developments in Web interfaces, centralized research facilities housing specialized and unique imaging instruments along with associated high-performance computing can be made available to researchers for use from their own laboratories. In addition to increasing access and utilization of these facilities, operation over the Internet is expected to enhance research by facilitating collaboration between researchers. We describe the implementation of a platform-independent Web-based system written in Java that supplements automated functions with video-guided interactive, collaborative remote control and data acquisition from an intermediate-high-voltage electron microscope.

Academies and Institutes↗

Effects of a biologically active LHRH fragment on CA1 hippocampal neurons.

The actions of a behaviorally active luteinizing hormone-releasing hormone fragment, Ac-LHRH(5-10), on CA1 pyramidal cells were studied utilizing conventional intracellular recordings from the in vitro rat hippocampal slice preparation. The behaviorally active fragment (10(-7) M) and the natural decapeptide [LHRH(1-10), 10(-8) M] had similar actions on CA1 neurons: a long-duration depolarization associated with increased input resistance, a reduction in the slow afterhyperpolarization (AHP), and a decrease in accommodation. In contrast, a biologically inactive LHRH fragment [LHRH(1-6) at 10(-7) M] had no effect on electrical properties of CA1 neurons. These data suggest that Ac-LHRH(5-10), like LHRH(1-10), may have a modulatory action on hippocampal neurons.

Animals↗

Left and right ventricular flows by Doppler echocardiography: serial measurements in patients with aortic regurgitation during exercise, cold pressor stimulation, and vasodilation.

To test the practicality of Doppler echocardiography to measure serial change, biventricular outputs were measured in 15 patients with aortic regurgitation during control periods and during interventions of bicycle exercise, cold pressor stimulation, and vasodilation. Biventricular stroke volumes were measured in 10 normal subjects for validation of methods and differed by 2.8%. Reading errors were 3.7%. Signal quality improved between the first and last observation (p less than 0.05). Velocity signals were corrected for intercept angles, which averaged 12 and 19 degrees for right heart flows and 31 and 32 degrees for the left side of the heart in all subjects. Negative correlations occurred between intercept angles and the chronologic order in which the patients were studied for left (p = 0.02) and right (p = 0.05) flows. Mean flow areas varied 9% in the left ventricle and 20% in the right ventricle. Total variability for measuring flow determined from control values was 11% to 13%. When twice the variability was used as the detectable level of change, only exercise provoked real increases in biventricular flows in the majority of patients. We conclude that serial measurements of flow by Doppler echocardiographic methods had to exceed 20% to 25% to achieve significant change. Measuring intercept angle, resolving flow area, and learning are variables that need greater emphasis.

Aortic Valve Insufficiency↗

Steroidogenic factor 1 (SF-1) is essential for endocrine development and function.

Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, initially was isolated as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Thereafter, analyses of sites of SF-1 expression during mouse embryological development hinted at considerably expanded roles for SF-1, roles that were strikingly confirmed through the analyses of SF-1 knockout mice. These SF-1 knockout mice exhibited adrenal and gonadal agenesis, associated with male-to-female sex reversal of their internal and external genitalia and death from adrenocortical insufficiency. These findings showed unequivocally that SF-1 is essential for the embryonic survival of the primary steroidogenic organs. SF-1 knockout mice also had impaired pituitary expression of gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), establishing that SF-1 regulates reproductive function at all three levels of the hypothalamic-pituitary gonadal axis. This article reviews the experiments that have defined these essential roles of SF-1 in endocrine development and highlights important areas for future studies.

Animals↗

Analysis of the mutation to forskolin-resistance in Y1 adrenocortical tumor cells.

Forskolin reduced the plating efficiency of Y1 adrenocortical tumor cells in a concentration-dependent manner--more than 5-orders of magnitude at 10 uM forskolin and at least 6-orders of magnitude at 50 uM forskolin. This effect was related to the diterpene's ability to increase adenylate cyclase activity and adenosine 3',5'-monophosphate (cAMP) levels in Y1 cells. Stable, forskolin-resistant mutants were isolated following growth of Y1 cells for 3 to 4 weeks in the presence of 10 uM forskolin. These mutants were stable, were present in the population at a ratio of approximately 15 mutants per million cells and appeared to result from a defect in cAMP accumulation rather than cAMP action. The forskolin-resistant phenotype was associated with a reduced ability of forskolin to stimulate adenylate cyclase activity in intact cells and in cell homogenates. The adenylate cyclase system of forskolin-resistant mutants was responsive to NaF, but was virtually insensitive to corticotropin (ACTH). As determined by a modified fluctuation analysis, the forskolin-resistant phenotype arose by spontaneous mutation at a frequency consistent with a mutational event at a single genetic locus (2 mutants per million cells per generation). These results indicate that the mutation which rendered Y1 cells insensitive to ACTH likely was the same as that which led to forskolin-resistance. Furthermore, the mutation seemed to behave dominantly. Although the gene product altered by the mutation is unknown, it does not appear to be the catalytic subunit of the enzyme.

Adenylyl Cyclases↗

Immune response against 3LL Lewis lung carcinoma potentiates the therapeutic efficacy of endostatin.

The ability of the antitumor immune response to potentiate the therapeutic efficacy of the antiangiogenic agent endostatin was investigated. The antitumor effects of endostatin were tested against weakly immunogenic 3LL Lewis lung carcinoma and its highly immunogenic variant 3LL-C75. Using in vivo Matrigel assay, it was found that the recombinant endostatin produced in the authors' laboratory has a potent antiangiogenic effect. Endostatin manifested a more potent antitumor effect against highly immunogenic 3LL-C75 than weakly immunogenic 3LL tumor. Endostatin induced regression of immunogenic 3LL-C75 tumor in 40% of C57BL/6 mice, whereas partial inhibition and no regression were found in mice bearing weakly immunogenic 3LL tumor. 3LL and 3LL-C75 cells produced similar amounts of Vascular Endothelial Growth Factor, and immunohistochemical analysis revealed that endostatin treatment reduced microvessel density in both 3LL and 3LL-C75 tumors. However, infiltration of T lymphocytes was observed in 3LL-C75 but not in 3LL tumors. These results suggest that the host's immune response may potentiate the antitumor effects of antiangiogenic agents. This possibility was further supported by findings that the antitumor activity of endostatin against 3LL-C75 tumor was lower in immunodeficient than in immunocompetent mice. Stimulation of immune response against 3LL tumor by vaccination with highly immunogenic 3LL-C75 cells substantially increased the antitumor effect of endostatain, resulting in a complete and permanent regression of 3LL tumor in 50% of mice. Tumor vaccination or endostatin treatment applied separately inhibited but did not induce regression of 3LL tumor. These results suggest that the combined attack against tumor cells and the tumor vascular system using antitumor immune mechanisms and antiangiogenic drugs can be a promising strategy for cancer treatment.

Angiogenesis Inhibitors↗

Outcomes for infants weighing less than 1000 grams cared for with a nasal continuous positive airway pressure-based strategy.

OBJECTIVE: To compare outcomes for infants weighing less than 1000 g treated with a predominantly nasal continuous positive airways pressure (CPAP) approach (modelled on that of Columbia University, New York) with outcomes audited by the Australian and New Zealand Neonatal Network (ANZNN). METHODS: Data on all infants weighing less than 1000 g admitted for intensive care were collected prospectively for the 29 neonatal units contributing to the ANZNN database. Outcomes for infants treated at Middlemore Hospital over a 3-year period (1998-2001) were compared with the ANZNN data for 1999. RESULTS: Sixty-four infants were admitted to Middlemore Hospital and 954 to the other 28 neonatal units. The two groups were similar with respect to birthweight, Apgar scores, sex and delivery method. Gestational age was lower in the Middlemore infants and outcome variables were adjusted for this difference. Fewer babies at Middlemore were born to mothers who had completed antenatal corticosteroids. The Middlemore Hospital group spent longer on CPAP (P < 0.001) but had less time in oxygen (median 4 days compared to 54 days; P < 0.001). Fewer of the Middlemore cohort were in oxygen at both 28 days (odds ratio 0.17 with 95% CI 0.09-0.30) and 36 weeks corrected gestation (odds ratio 0.15 95% CI 0.07-0.32) and fewer infants were discharged home on oxygen (odds ratio risk 0.38 95% CI 0.16-0.90). Other outcomes were a reduction in the number of infants with culture proven sepsis at Middlemore Hospital but a higher rate of necrotizing enterocolitis. Length of hospital stay and survival rates were not significantly different. CONCLUSIONS: Improved respiratory outcomes for infants weighing less than 1000 g were evident at Middlemore Hospital. This was attributed to the use of a nasal CPAP-based respiratory support system.

Continuous Positive Airway Pressure↗