Biomedical subjects

A R Marks

Publications and source records attributed to A R Marks.

76 records · Page 5Linked to original sources

PubMed1989

Identification of high-risk and low-risk subgroups of patients with mitral-valve prolapse.

Mitral-valve prolapse is a common cardiac valvular disorder with a wide range of severity and diverse clinical outcomes. The lack of a standard definition of mitral-valve prolapse may explain the variation in reported complication rates. To identify high-risk and low-risk subgroups, we retrospectively analyzed clinical and two-dimensional echocardiographic data from 456 patients with mitral-valve prolapse. Mitral-valve prolapse was defined on the basis of echocardiographic findings as systolic displacement into the left atrium of one or both leaflets beyond the plane of the mitral annulus in the parasternal long-axis view. Two groups of patients were compared: those with thickening of the mitral-valve leaflets and redundancy (designated the classic form; n = 319) and those without leaflet thickening (designated the nonclassic form; n = 137). The two groups were similar in age and sex ratio. Complications or a history of complications was more prevalent in the classic than the nonclassic form: infective endocarditis, 3.5 percent and 0 percent, respectively (P less than 0.02); moderate-to-severe mitral regurgitation, 12 percent and 0 percent (P less than 0.001); and the need for mitral-valve replacement, 6.6 percent and 0.7 percent (P less than 0.02). However, the frequency of stroke was similar in the two groups: 7.5 percent and 5.8 percent (P not significant). We conclude that in a selected population of patients with mitral-valve prolapse, those with the classic form (leaflet thickening and redundancy) are at higher risk than those without these features for the infectious and hemodynamic complications of mitral-valve prolapse, but not for stroke.

Cerebrovascular Disorders↗

PubMed1989

Molecular cloning and characterization of the ryanodine receptor/junctional channel complex cDNA from skeletal muscle sarcoplasmic reticulum.

Major progress has been made in elucidating the calcium release mechanism involved in excitation-contraction coupling. The ryanodine receptor of sarcoplasmic reticulum has been isolated and found to be morphologically identical to the foot structure, which is involved in the junctional association of terminal cisternae with the transverse tubule. The foot structure also contains the calcium release channel itself. For this reason, we refer to the foot structure as the junctional channel complex (JCC). The JCC consists of an oligomer of a single high molecular weight protein. Although progress has been made in characterizing important aspects of the structure and function of the JCC, further understanding of the JCC protein subunit awaits the molecular cloning of the JCC. We report on the isolation of cDNA clones encoding portions of the JCC from rabbit fast-twitch skeletal muscle and its tissue distribution and expression. The large size and lack of solubility of the JCC protein posed particular challenges to cloning this molecule. Among these was the necessity to develop techniques for partially digesting the JCC protein subunit with endoproteases in the presence of detergent. With this approach we obtained partial amino acid sequences from regions of the JCC and designed oligonucleotide primers and probes to synthesize and screen cDNA libraries. The rabbit skeletal muscle JCC mRNA encodes an approximately 16-kilobase mRNA present in skeletal, heart, and aortic smooth muscle, as determined by RNA blot analysis with a 700-base-pair cDNA probe. Whereas the JCC mRNA appears to be relatively abundant in adult rabbit fast-twitch skeletal muscle, it is much less abundant in heart and smooth muscle. The JCC mRNA in BC3H1 (a myoblast cell line) is reversibly regulated by growth factors in a manner similar to muscle-specific contractile protein genes.

Amino Acid Sequence↗

PubMed1986

Conservation of the DNA binding domain and other properties between porcine and rat glucocorticoid receptors.

Activated glucocorticoid receptor protein (GCR) was partially purified from porcine liver cytosol by sequential chromatography on phosphocellulose and DNA-cellulose using a modification of a protocol developed for purification of rat GCR. This partially purified preparation, when separated by SDS-polyacrylamide gel electrophoresis and immunoblotted, indicated that a Mr = 94,000 protein band cross-reacts with a monoclonal antibody against rat GCR. A nitrocellulose filter binding assay showed that both the partially purified porcine and rat GCRs interact specifically with a cloned synthetic 24 base pair deoxyoligonucleotide containing the GCR binding sequence in the first intron of the human growth hormone (hGH) gene. This specific protein-DNA interaction is blocked by a single base pair change in the binding site. All three putative domains of the GCR molecule: the steroid binding, immunoreactive, and DNA binding have been conserved between two divergent species.

Animals↗

PubMed1985

The first intron of the human growth hormone gene contains a binding site for glucocorticoid receptor.

Glucocorticoid receptor (GCR) protein stimulates transcription from a variety of cellular genes. We show here that GCR partially purified from rat liver binds specifically to a site within the first intron of the human growth hormone (hGH) gene, approximately 100 base pairs downstream from the start of hGH transcription. GCR binding is selectively inhibited by methylation of two short, symmetrically arranged clusters of guanine residues within this site. A cloned synthetic 24-base-pair deoxyoligonucleotide containing the predicted GCR binding sequence interacts specifically with GCR. The hGH binding site shares sequence homology with a GCR binding site upstream from the human metallothionein II gene and a subset of GCR binding sites from mouse mammary tumor virus. All of these binding sites for this eukaryotic transcriptional regulatory protein show remarkable similarity in overall geometry to the binding sites for several prokaryotic transcriptional regulatory proteins.

Animals↗