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Biomedical subjects

C M Fan

Publications and source records attributed to C M Fan.

48 records · Page 3Linked to original sources

Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog.

An early step in the development of vertebrae, ribs, muscle, and dermis is the differentiation of the somitic mesoderm into dermomyotome dorsally and sclerotome ventrally. To analyze this process, we have developed an in vitro assay for somitic mesoderm differentiation. We show that sclerotomal markers can be induced by a diffusible factor secreted by notochord and floor plate and that heterologous cells expressing Sonic hedgehog (shh/vhh-1) mimic this effect. In contrast, expression of dermomyotomal markers can be caused by a contact-dependent signal from surface ectoderm and a diffusible signal from dorsal neural tube. Our results extend previous studies by suggesting that dorsoventral patterning of somites involves the coordinate action of multiple dorsalizing and ventralizing signals and that a diffusible form of Shh/Vhh-1 mediates sclerotome induction.

Animals↗

[Doppler echocardiographic assessment of prosthetic heart valve function].

The normal hemodynamic parameters of 90 patients with St. Jude bileaflet valve, Medtronic-Hall, Sorin and GK tilting disc valves were investigated and compared to those of 30 control subjects by transthoracic Doppler echocardiographic technique. The results showed that although the mitral prosthetic valve area increased significantly and the peak velocity and the peak pressure gradient decreased significantly after mitral valve replacement, the effective orifice area (EOA), peak velocity (Vmax), and peak gradient (PG) in 4 different prosthetic valve groups still had significant differences from those of the normal native valve group. Among the 4 types of prosthetic valves St. Jude bileaflet valve had the largest EOA (3.12 +/- 0.47 cm2) and the lowest peak pressure gradients (9.3 +/- 1.1 mmHg). The EOA of the other 3 types of tilting disc valves showed no significant difference. The possibility of determining the indication of mitral valve replacement by Doppler echocardiography was also discussed.

Adolescent↗

Hemodynamic evaluation of bovine pericardial xenograft valves in the mitral position by stress Doppler echocardiography.

The function of a bovine pericardial xenograft valve in the mitral position was studied in 18 patients by using stress Doppler echocardiography after submaximal supine exercise. In 10 patients with normally functioning tissue valve, peak and mean gradients increased from 9.3 +/- 1.3 and 2.7 +/- 0.7 mmHg, respectively at rest, to 14.7 +/- 0.9 and 4.1 +/- 1.0 mmHg at peak exercise. The tissue valve area assessed by the Doppler pressure half-time method increased from 2.69 +/- 0.38 cm2 at rest, to 3.15 +/- 0.38 cm2 at peak exercise (P < 0.05). In 6 patients with mitral regurgitation, peak and mean gradients increased from 17.3 +/- 5.3 and 7.0 +/- 1.8 mmHg, respectively at rest, to 24.3 +/- 5.0 and 9.0 +/- 2.6 mmHg at peak exercise, but there was no significant change in valve area at peak exercise. Patients with severe isolated mitral regurgitation had a Vmax of more than 2 m/s and elevated pressure gradients at peak exercise. But the pressure half-time was relatively unaffected, allowing their differentiation from patients with tissue valvular stenosis. Stress Doppler echocardiography is a simple, noninvasive and reliable method for the evaluation of the mitral tissue valve function which is recommendable for patients with suspected mitral tissue valve dysfunction.

Adult↗

[Hemodynamic evaluation of GK and Medtronic-Hall prosthetic mitral valves by exercise Doppler echocardiography].

Hemodynamic alterations were studied in 42 patients with GK and Medtronic-Hall (M-H) prosthetic valves by stress Doppler echocardiography after submaximal supine exercise. In the GK group, peak and mean gradients increased from 10.1 +/- 1.7 and 3.4 +/- 1.3 mmHg respectively, at rest to 15.3 +/- 3.1 and 5.4 +/- 1.5 mmHg at peak exercise (mean +/- s), mitral valve area increased from 2.61 +/- 0.34 cm2 at rest to 2.86 +/- 0.45 cm2 at peak exercise (P < 0.05). In the M-H group, peak and mean gradients increased from 11.3 +/- 1.8 and 4.3 +/- 1.0 mmHg respectively, at rest to 15.0 +/- 1.9 and 5.8 +/- 1.5 mmHg at peak exercise. Mitral valve area increased from 2.66 +/- 0.43 cm2 at rest to 2.94 +/- 0.38 cm2 at peak exercise (P < 0.05). The results showed that peak and mean gradients at rest in patients with GK prosthetic valve were lower than those of M-H group. But after exercise, the two prosthetic valves showed similar characteristics in hemodynamics. Exercise Doppler echocardiography is a simple, noninvasive and reliable method for the evaluation of the function of mechanical mitral prostheses.

Adult↗

Generation of p50 subunit of NF-kappa B by processing of p105 through an ATP-dependent pathway.

The transcription factor NF-kappa B is a heterodimer consisting of two proteins encoded by different members of the rel gene family (p50 and p65). The p50 subunit is unusual among DNA-binding proteins in that its functional form is encoded in an open reading frame of relative molecular mass 105,000 (p105; ref. 4). The N-terminal region of this open reading frame encodes p50, whereas the remaining C terminus contains ankyrin repeats. Although p50 binds to DNA, full-length p105 translated in vitro does not. The mechanism by which p50 is generated in vivo, and the fate of the C-terminal region of p105 have not been established. Here we show that functional p50 is produced by ATP-dependent proteolysis of p105. Moreover, we find that the C-terminal half of p105 is not required for processing in vivo, and is rapidly degraded on processing. We propose that the C-terminal region of p105 is involved in the cytoplasmic assembly of the complex between the p50/p65 heterodimer and the inhibitor I kappa B.

Adenosine Triphosphate↗

A DNA-binding protein containing two widely separated zinc finger motifs that recognize the same DNA sequence.

We have isolated a full-length cDNA clone encoding a protein (PRDII-BF1) that binds specifically to a positive regulatory domain (PRDII) of the human IFN-beta gene promoter, and to a similar sequence present in a number of other promoters and enhancers. The sequence of this protein reveals two novel structural features. First, it is the largest sequence-specific DNA-binding protein reported to date (298 kD). Second, it contains two widely separated sets of C2-H2-type zinc fingers. Remarkably, each set of zinc fingers binds to the same DNA sequence motif with similar affinities and methylation interference patterns. Thus, this protein may act by binding simultaneously to reiterated copies of the same recognition sequence. Although the function of PRDII-BF1 is not known, the level of its mRNA is inducible by serum and virus, albeit with different kinetics.

Amino Acid Sequence↗

The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction.

The DNA binding protein NF-kappa B has been implicated in gene regulation in B and T lymphocytes. We have found that NF-kappa B also has a central role in virus induction of human beta-interferon (beta-IFN) gene expression. A critical virus-inducible element of this gene, PRDII, behaves interchangeably with the NF-kappa B binding site from the Ig kappa enhancer in both B lymphocytes and virus-infected fibroblasts. Single base substitutions that impair inducibility of the beta-IFN gene in vivo also reduce the binding of NF-kappa B to PRDII in vitro. Virus infection potently activates the binding and nuclear localization of NF-kappa B and, in pre-B lymphocytes, results in the expression of both the beta-IFN gene and the Ig kappa gene. The wide variety of cell types in which beta-interferon can be induced and the divergent set of gene induction processes involving NF-kappa B suggest that this transcription factor plays a broad role in gene regulation as a mediator of inducible signal transduction.

Binding Sites↗

Two different virus-inducible elements are required for human beta-interferon gene regulation.

We show that the human beta-interferon gene promoter contains two different virus-inducible regulatory elements, PRDI and PRDII (positive regulatory domains I and II). A single copy of either element alone has no discernible transcriptional activity in mouse fibroblasts. However, multiple copies of either element function as a constitutive or virus-inducible transcription element depending on the cell line in which the sequence was tested. These results in conjunction with previous studies suggest that virus induction of the human beta-interferon gene is achieved through cooperative interactions between two entirely distinct virus-inducible elements. Comparison of the properties of these elements reveals that multiple copies of PRDI, but not PRDII, can be activated by three different inducers, beta-IFN, gamma-IFN and virus. These results suggest that the pathways of virus and interferon induction may share at least one common regulatory component.

Animals↗

Transcription mapping of the varicella-zoster virus genome.

RNA was isolated from varicella-zoster virus-infected Flow 5000 cells (diploid fibroblasts) at late times after infection. With the use of overlapping DNA probes representing all regions of the varicella-zoster genome, an extensive Northern blot analysis of the RNA was carried out. The analysis revealed at least 58 discrete transcripts ranging in size from approximately 0.8 to 6.5 kilobases. RNAs were found to be homologous to all probes used except for those mapping at approximately map unit 0.3, where no RNA transcripts could be detected. Comparison of the sizes and locations of RNA transcripts mapping in the right-hand ends of the varicella-zoster virus and the herpes simplex virus DNAs shows a number of striking analogies, suggesting their similar genomic organization.

Chromosome Mapping↗