Publications
Department of Medicine faculty members published more than 3,000 peer-reviewed articles in 2022.
1991
1991
The Rex protein of the type I human T-cell leukemia virus (HTLV-I) is essential for the replication of this pathogenic retrovirus and, surprisingly, can also replace the function of the structurally distinct Rev protein of the type 1 human immunodeficiency virus (HIV-1). Rex action requires a 255-nucleotide viral RNA stem-loop structure termed the Rex RNA response element (RexRE) located in the 3' retroviral long terminal repeat. Rex function leads to the induced cytoplasmic expression of the incompletely spliced family of viral mRNAs that uniquely encode the HTLV-I structural and enzymatic proteins (Gag, Pol, and Env). Our studies now demonstrate that Rex acts by binding directly to the RexRE in a sequence-specific manner. These effects of Rex require the presence of a 10-nucleotide subregion of the RexRE that is essential for Rex function in vivo. Dominant-negative mutants of Rex also bind to the RexRE with high affinity, while a recessive-negative Rex mutant altered within its arginine-rich, positively charged domain fails to engage the RexRE. Analogously, both the wild-type and dominant-negative Rex proteins specifically bind to the structurally distinct HIV-1 Rev response element, a finding that likely underlies the respective stimulatory and inhibitory effects of these HTLV-I proteins in the heterologous HIV-1 system. However, consistent with their lack of amino acid homology, the binding sites for Rex and Rev within the HIV-1 Rev response element are distinct.
View on PubMed1991
Previous studies using Doppler echocardiography to evaluate left ventricular diastolic filling have shown that myocardial ischemia induced by coronary balloon angioplasty or atrial pacing results in a decrease in the left ventricular inflow peak early (E) to peak atrial (A) velocity ratio. To investigate the effects of exercise-induced ischemia on Doppler-derived filling variables, 20 patients with coronary artery disease and exercise-induced electrocardiographic changes and regional wall motion abnormalities determined by two-dimensional echocardiography were evaluated and compared with 20 patients without evidence of exercise-induced ischemia. Doppler echocardiography was performed at rest and immediately after exercise before the resolution of exercise-induced wall motion abnormalities. Peak E and A velocities increased from rest to postexercise in both the ischemic and nonischemic groups, although the ischemic group demonstrated a greater increase in peak E velocity (from 68 +/- 15 cm/s at rest to 88 +/- 22 cm/s after exercise) than the nonischemic group (70 +/- 13 to 77 +/- 18 cm/s) (p less than 0.05 for the difference in response between groups). Accompanying these changes was a slight increase in the peak E/A velocity ratio in the ischemic group (1.04 +/- 0.28 at rest to 1.13 +/- 0.42 after exercise) versus a decrease in the nonischemic group (1.07 +/- 0.30 to 0.90 +/- 0.28) (p less than 0.05 intergroup difference).(ABSTRACT TRUNCATED AT 250 WORDS)
View on PubMed1991
1991
1991
1991
1991
The integrins are a large family of heterodimeric cell-surface glycoproteins that play key roles in the adherence of cells to other cells and to extracellular matrix proteins. We have previously reported the identification of a novel integrin beta subunit partial cDNA from leukocytes. We have now determined the complete sequence of this subunit, designated as beta 7, from overlapping clones obtained from a PEER T leukemia cell library and a peripheral T cell library. The beta 7 cDNA contains a single large open reading frame predicted to encode a 798-amino acid protein precursor (signal peptide plus mature protein). The beta 7 protein, like the other beta subunit proteins, is predicted to contain a large extracellular portion, a transmembrane domain, and a cytoplasmic tail. The deduced beta 7 amino acid sequence is 32-46% identical to the six previously sequenced human integrin beta subunits. beta 7 is most similar to the leukocyte integrin common beta subunit (beta 2, CD18). Analysis of variant beta 7 cDNA clones and reverse transcription-polymerase chain reaction products suggest that alternatively spliced beta 7 mRNAs can be generated by the removal of exons that encode most of the cysteine-rich region of the extracellular portion of beta 7. By Northern blot analysis, beta 7 mRNA was detected in T and B cell lines and in macrophage-like cell lines, but not in any of the nonleukocyte cell lines tested. Peripheral T cells and some lymphoma lines express little beta 7 mRNA before stimulation; but after stimulation with phorbol ester, beta 7 mRNA levels increased markedly. Integrin beta 7 is expected to play a role in adhesive interactions of leukocytes.
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