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S Covington

Publications and source records attributed to S Covington.

9 recordsLinked to original sources

Rat arylalkylamine N-acetyltransferase gene: upstream and intronic components of a bipartite promoter.

The daily rhythm in the activity of arylalkylamine N-acetyltransferase (AA-NAT) controls the rhythm in melatonin synthesis in the pineal gland. In the rat, transcriptional regulatory mechanisms play a major role in determining the observed pattern of AA-NAT gene expression. Remarkably, high levels of AA-NAT transcripts can only be detected in the night pineal; significant levels can also be found in the retina. To characterize the regulatory events that impinge upon the activity of the AA-NAT gene we embarked on the systematic analysis of the AA-NAT promoter. To this end we transfected several AA-NAT promoter derivative constructs to monitor reporter gene activity in both pineal and non-pineal primary cell cultures. Our studies revealed a cooperative arrangement between upstream promoter and downstream intronic regions which appear to contain most of the key elements necessary to ensure the proper spatio-temporal pattern of AA-NAT gene expression.

Animals↗

The rat arylalkylamine N-acetyltransferase gene promoter. cAMP activation via a cAMP-responsive element-CCAAT complex.

A 10-100-fold rhythm in the activity of arylalkylamine N-acetyltransferase (AA-NAT; EC 2.3.1.87) controls the rhythm in melatonin synthesis in the pineal gland. In some mammals, including the rat, the high nocturnal level of AA-NAT activity is preceded by an approximately 100-fold increase in AA-NAT mRNA. The increase in AA-NAT mRNA is generated by norepinephrine acting through a cAMP mechanism. Indirect evidence has suggested that cAMP enhances AA-NAT gene expression by stimulating phosphorylation of a DNA-binding protein (cAMP-responsive element (CRE)-binding protein) bound to a CRE. The nature of the sites involved in cAMP activation was investigated in this report by analyzing the AA-NAT promoter. An approximately 3700-base pair fragment of the 5'-flanking region of the rat AA-NAT gene was isolated, and the major transcription start points were mapped. The results of deletion analysis and site-directed mutagenesis indicate that cAMP activation requires a CRE.CCAAT complex consisting of a near-perfect CRE and an inverted CCAAT box located within two helical turns.

Animals↗

Cochlear blood flow. The effect of six hours of noise exposure.

The effect of six hours of high-frequency, high-intensity noise exposure on cochlear blood flow (CoBF) was investigated in adult gerbils. The CoBF was measured by microsphere-surface preparation methods. Intracardiac injection of the microspheres (diameter, 11.1 microns; Dupont/New England Nuclear Research Products, Boston) was performed in the last few minutes of the sixth hour of continuous noise exposure, and reference blood was withdrawn from the iliac artery at a rate of 0.165 mL/min. The number of microspheres in the investigated tissue was assessed by direct counting under a microscope. The number of microspheres in the reference blood was counted by a Coulter counter. These experiments have shown that CoBF at the end of six hours of continuous noise exposure does not significantly differ from the CoBF in control animals.

Acoustic Stimulation↗

Virulence of wild-type E. coli uroisolates in experimental pyelonephritis.

This study was designed to analyze the colonizing and invasive properties of wild-type bacteriuric E. coli possessing a variety of phenotypic characteristics in experimental nonobstructive pyelonephritis (P and Type 1 [T] fimbriae, hemolysin [Hly], presence of K capsules, flagella [H], serotype, biotype, human and mouse serumcidal resistance). Special emphasis was on the role of Gal-Gal adhesin (P fimbriae) of non-genetically engineered uroisolates. It was shown that organisms that are P+ or T+ or Hly+ are more likely to colonize bladders than strains negative for those parameters (P less than 0.001). Additionally, P+ strains were more often associated with kidney histopathology than P- E. coli (P less than 0.05). However, the data also indicated that fimbriae (P and Type 1) were not sole determinants of virulence since two strains devoid of fimbriae, hemolysin, K capsules and sensitive to human serumcidal activity caused incipient and acute pyelonephritis. Even among identical serotypes and biotypes, the presence/absence of fimbriae did not appear to be the critical factor in urovirulence, nor did the presence of several positive characteristics (hemolysin, K capsule, flagella, serum resistance) in a given strain enhance uropathogenicity. Therefore, these properties do not need to work together to render an E. coli urovirulent. These phenotypic characters may simply represent associated or serologic markers with the host serving as the dominant determinant of susceptibility to urinary infection. The findings emphasize the inherent limitations in relating and extrapolating colonizing and invasive properties of genetically engineered strains to those of naturally occurring, wild-type E. coli human uroisolates causing pyelonephritis.

Adhesins, Escherichia coli↗

Alterations in cholinergic muscarinic and somatostatin binding sites in a patient with idiopathic intestinal pseudo-obstruction.

We present a comparative study of cholinergic muscarinic and somatostatin binding sites on isolated membranes from mucosa and tunica muscularis of normal and dilated parts of the proximal jejunum obtained at surgery from a patient with idiopathic intestinal pseudo-obstruction (IIP) syndrome. We found a statistically significant diminution of cholinergic muscarinic and somatostatin binding sites in mucosa taken from the dilated part of the jejunum, compared with those taken from the normal part. Tunica muscularis of the dilated part of the jejunum contained a significantly higher concentration of peripheral cholinergic muscarinic binding sites (M2) than the normal part did, whereas concentration of M1 cholinergic muscarinic and somatostatin binding sites was similar in both examined parts. These results indicate that IIP-syndrome may be related to alterations in cholinergic muscarinic binding sites in the tunica muscularis of the intestine.

Adult↗

Adult T-cell leukemia-lymphoma. Unusual features of two patients from a low-incidence area.

The occurrence of adult T-cell leukemia-lymphoma in two New Orleans patients, one native-born, the other originally from Honduras, is reported. Both exhibited an unusual feature. One patient was diagnosed following an atypical episode of sinusitis and demonstrated lymphomatous infiltration of the nasopharynx. A second patient had a fulminant course complicated by severe diarrhea and was found to have both tumor involvement and cytomegalovirus inclusions in the colon. Both had high titers of antibodies to HTLV-I. A cell line with T-lymphocyte characteristics was established from the peripheral blood of the first patient. Such studies may help better establish the clinical course, detection, and epidemiologic features of this difficult disease.

Antibodies, Viral↗

A legacy of violence in nonorganic failure to thrive.

It is often postulated that a mother's past experiences influence her ability to function as a parent. If those past experiences involve her as a victim of abuse, what lies ahead for her offspring? We studied 59 mothers of children referred for nonorganic failure to thrive (NOFTT) to the University of Colorado Health Sciences Center and compared their abuse history with a group of 131 mothers of children with normal growth. The mothers of NOFTT children were younger but of the same socioeconomic groups as the comparison mothers. Mothers of NOFTT children had a significantly higher history of abuse when compared to the comparison group p < 0.001. A surprising 80% of mothers of NOFTT children reported they were victims of abuse. We alert clinicians to the likelihood that mothers of children with NOFTT may be victims of abuse and that successful treatment of the child depends upon treatment of the mother-child dyad.

Adult↗