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Biomedical subjects

L Hatfield

Publications and source records attributed to L Hatfield.

11 recordsLinked to original sources
PubMed1996

An essential component of the decapping enzyme required for normal rates of mRNA turnover.

A major pathway of messenger RNA degradation in eukaryotic cells is initiated by shortening of the poly(A) tail, which, at least in yeast, triggers a decapping reaction, thereby exposing the mRNA to 5' --> 3' degradation. Decapping is the key step in this decay pathway because the transcript body is rapidly degraded following decapping. Accordingly, decapping is the site of numerous controls, including inhibition of decapping by the poly(A) tail and modulation of mRNA decapping rate by specific sequences. Moreover, a specialized decay pathway that degrades aberrant transcripts triggers rapid mRNA decapping independently of poly(A)-tail shortening. We have identified a yeast gene, termed DCP1, that encodes the decapping enzyme, or an essential component of a decapping complex. The protein Dcp1 is required for the normal decay of many unstable and stable yeast mRNAs, as well as mRNAs that are decapped independently of deadenylation. These results indicate that mRNA-specific rates of decapping, and thus decay, will result from differences in the interaction of the DCP1 decapping enzyme with individual transcripts.

Amino Acid Sequence↗
PubMed1996

Mutations in trans-acting factors affecting mRNA decapping in Saccharomyces cerevisiae.

The decay of several yeast mRNAs occurs by a mechanism in which deadenylation precedes decapping and subsequent 5'-to-3' exonucleolytic decay. In order to identify gene products required for this process of mRNA turnover, we screened a library of temperature-sensitive strains for mutants with altered mRNA degradation. We identified seven mutations in four genes that inhibited mRNA turnover. Two mutations were alleles of the XRN1 5'-to-3' exoribonuclease known to degrade mRNAs following decapping. One mutation defined a new gene, termed DCP1, which in subsequent work was demonstrated to encode a decapping enzyme or a necessary component of a decapping complex. The other mutations defined two additional genes, termed MRT1 and MRT3 (for mRNA turnover). Mutations in the MRT1 and MRT3 genes slow the rate of deadenylation-dependent decapping, show transcript-specific effects on mRNA decay rates, and do not affect the rapid turnover of an mRNA containing an early nonsense codon, which is degraded by a deadenylation-independent decapping mechanism. Importantly, cell extracts from mrt1 and mrt3 strains contain normal levels of the decapping activity required for mRNA decay. These observations suggest that the products of the MRT1 and MRT3 genes function to modulate the rates of decapping that occur following deadenylation.

Alleles↗
PubMed1993

The NFIII/OCT-1 binding site stimulates adenovirus DNA replication in vivo and is functionally redundant with adjacent sequences.

The inverted terminal repeat (ITR) of adenovirus type 5 (Ad5) is 103 bp in length and contains the origin of DNA replication. Cellular transcription factors NFI/CTF and NFIII/OCT-1 bind to sites within the ITR and participate in the initiation of viral DNA replication in vitro. The ITR also contains multiple copies of two conserved sequence motifs that bind the cellular transcription factors SP1 and ATF. We have analyzed a series of viruses that carry deletions at the left terminus of Ad5. A virus carrying a deletion of the NFIII/OCT-1, SP1, and ATF sites within the ITR (mutant dl309-44/107) was wild type for virus growth. However, the deletion of these elements in addition to sequences immediately flanking the ITR (mutant dl309-44/195) resulted in a virus that grew poorly. The analysis of growth parameters of these and other mutants demonstrate that the NFIII/OCT-1 and adjacent SP1 sites augment the accumulation of viral DNA following infection. The function of these elements was most evident in coinfections with a wild-type virus, suggesting that these sites enhance the ability of a limiting trans-acting factor(s), that stimulates viral DNA replication, to interact with the ITR. The results of these analyses indicate functional redundancy between different transcription elements at the left terminus of the Ad5 genome and demonstrate that the NFIII/OCT-1 site and adjacent SP1 site, previously thought to be nonessential for adenovirus growth, play a role in viral DNA replication in vivo.

Adenoviruses, Human↗
PubMed1993

Supraventricular tachycardia: catheter ablation therapy in 72 patients.

Radiofrequency (RF) catheter ablation for recurrent supraventricular tachycardia (SVT) has been performed at the Charleston Area Medical Center since September 1991. Of the first 72 patients undergoing this procedure, a total of 76 tachycardias were treated and these included 41 accessory pathways, 21 junctionals, and 14 atrial tachycardias (atrial fibrillation, flutter, and intra-atrial reentry tachycardia). RF catheter ablation was successful in 67 of these patients (93%). This procedure is a highly effective treatment modality which should be considered in patients with recurrent symptomatic SVT.

Adult↗
PubMed1992

The use of head-up tilt table testing in the evaluation of unexplained syncope.

Head-up tilt table testing was performed in 50 patients for evaluation of syncope. A positive test occurred in 29 patients (58 percent). Of these 29 patients, 15 were categorized as vasovagal; 11 as orthostatic hypotension; and three as chronotropic incompetence. Isoproterenol facilitated the occurrence of a positive test in 13 patients. Medications were used to treat 15 of the 29 patients having a positive test result. Syncope recurred in two patients over a 9 +/- 5 month follow-up period. In patients having unexplained syncope, head-up tilt table testing may provide a diagnosis and can be used to assess therapy. Earlier use of this testing modality in selected patients may obviate more expensive testing.

Adolescent↗
PubMed1991

Redundant elements in the adenovirus type 5 inverted terminal repeat promote bidirectional transcription in vitro and are important for virus growth in vivo.

The adenovirus inverted terminal repeat (ITR) contains a number of cis-acting elements that are involved in the initiation of viral DNA replication, as well as multiple binding motifs for the cellular transcription factors SP1 and ATF. In this study, we utilized a Hela cell transcription extract to demonstrate that the adenovirus type 5 ITR promotes bidirectional transcription in vitro. Primer extension analyses demonstrated that the ITR directed transcription at initiation sites both within the terminal repeat and at fixed distances outside of the ITR. The ITR also strongly stimulated transcription at the early region 1A (E1A) initiation site when it was situated immediately upstream of the E1A TATA box region. Deletion and point mutational analyses demonstrated that two distinct cis-acting elements were involved in these ITR-dependent transcriptional activities in vitro. Cellular transcription factors SP1 and ATF were previously shown to bind to these two regions. Analysis of viral mutants in vivo demonstrated that the NFIII/OCT-1 binding site and a conserved ATF motif were important for efficient viral growth. Regulatory elements in the ITR flanking region were found to functionally substitute for these sites.

Adenoviruses, Human↗
PubMed1977

Statewide approach to emergency medical training.

In Kansas, an instructor/coordinator approach is used to train emergency medical technicians (EMTs) through two ten-day sessions at the University of Kansas. The students are trained in various aspects of the Department of Transportation (DOT) Dunlop course, in the use of audiovisual aids and in basic teaching and testing theory. Then, they return to their communities and offer EMT training programs as the need arises. There are 82 instructor/coordinators throughout the state. Law enforcement officers, frequently the first on the scene in rural Kansas, receive training in crash injury management through a 70-hour plus course developed through the Kansas Highway Patrol. Also, 110 advanced paramedics, or emergency mobile intensive care technicians, have been trained through 600 to 1500 hour courses at the Kansas University Medical Center.

Accidents, Traffic↗