Echocardiography for the assessment of myocardial viability.

The identification of viable myocardium in the setting of acute myocardial infarction or chronic coronary artery disease with reduced left ventricular function has important prognostic and therapeutic implications. Many noninvasive methods have been used to assess viability, and recently, dobutamine stress echocardiography has been studied for this purpose. Dobutamine stress echocardiography is a safe, accessible, and relatively inexpensive technique. Moreover, its accuracy for detecting viability approaches that of positron emission tomography and thallium scintigraphy. In addition to dobutamine stress echocardiography, other echocardiographic techniques, such as myocardial contrast echocardiography and dipyridamole stress echocardiography, are being developed to delineate viability. In the future, echocardiographic methods may identify viability with enough accuracy to allow us to better select patients for revascularization procedures when the indications are otherwise unclear.

Right ventricular dysfunction after acute pulmonary embolism: pathophysiologic factors, detection, and therapeutic implications.

Acute PE may lead to right ventricular dilatation and failure. Through ventricular interdependence and decreased left ventricular filling, cardiac output and systemic circulation also may be compromised. The associated decrease in coronary perfusion pressure to the acutely overloaded right ventricle may produce ischemia and worsening right heart failure. This downward cycle of right ventricular failure and ischemia may ultimately progress to right ventricular infarction, circulatory arrest, and death. Certain clinical findings, hemodynamic values, and, particularly, echocardiographic signs can identify right ventricular dysfunction after PE. Detection of right ventricular hypokinesis helps to stratify patients' risk, because right ventricular dysfunction confers a worse prognosis than does normal right ventricular function after PE. The concept of "hemodynamic instability" after PE should be expanded to include right ventricular dilatation and wall motion abnormalities, even among normotensive patients. Aggressive intervention with thrombolytic therapy, vasoactive agents, or mechanical embolectomy may improve right ventricular function and clinical outcome.

In vitro cDNA amplification from individual intestinal crypts: a novel approach to the study of differential gene expression along the crypt-villus axis.

The mouse small intestine is lined with a monolayer of continuously renewing epithelial cells. Cells of four distinct epithelial lineages are derived clonally from the stem cell zone, located near the crypt base, from which cells differentiate and migrate to the villus tip. The kinetics of the multilineage process are well understood. However, the molecular mechanisms underlying gene expression during lineage commitment and cell proliferation and differentiation remain obscure. A novel approach to the problem is presented here. Single intact epithelial crypts were isolated by incubation in ethylenediaminetetraacetic acid and mechanical vibration of everted mouse intestinal or colonic segments. Crypts isolated in this manner were suitable for mRNA-directed polymerase chain reaction, thus generating crypt epithelium-specific cDNA. The fidelity of transcript amplification was confirmed by Southern blot hybridization with cloned intestinal transcripts. To demonstrate the potential utility of crypt-specific cDNA, the amplified transcripts from a single jejunal crypt were used to construct a cDNA library, characterization of which revealed a high representation of cryptdin-1-related transcripts. This study presents a technique which will facilitate comprehensive analyses of gene expression in the differentiating mammalian intestine.

A novel mouse gene family coding for cationic, cysteine-rich peptides. Regulation in small intestine and cells of myeloid origin.

Cryptdin is a Paneth cell corticostatin/defensin in the mouse small bowel. To help define the intestinal role of cryptdin, cryptdin-related sequence (CRS) mRNAs have been characterized with respect to developmental regulation, sequence homology, putative coding function, and occurrence in myeloid cells. Cryptdin, CRS1C, and CRS4C mRNAs are transcribed from separate genes, occur at equivalent abundance in small intestine, and appear in the small bowel in concert during the 2nd and 3rd weeks postpartum. Cryptdin and CRS1C mRNAs are not detectable in adult mouse bone marrow, but probes specific for the 5'- or the 3'-untranslated regions of CRS4C mRNA hybridize to a moderately abundant 1.05-kilobase bone marrow mRNA in contrast to a highly abundant 0.75-kilobase mRNA in small intestine. Nucleotide sequences corresponding to the deduced prepro-coding regions of cryptdin, CRS1C, and CRS4C mRNAs contain a highly conserved 200-base pair region of 92% sequence similarity (CSE.2), but the mRNAs are not homologous otherwise. The deduced CRS1C and CRS4C polypeptides are apparent precursors of secreted, cationic, proline- and cysteine-rich peptides that contain Cys-Pro-X repeats. Unlike cryptdin, however, the proposed CRS1C and CRS4C mature peptide regions lack the structural motif characteristic of defensins. Attempts to find homologies between the putative CRS peptides and existing protein sequences have been unsuccessful, leading us to speculate that CRS1C and CRS4C represent a new family of nondefensin antimicrobial peptides in the mouse small bowel.