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Biomedical subjects

W A Scott

Publications and source records attributed to W A Scott.

At least 73 records · Page 4Linked to original sources
PubMed1988

Cis-acting elements involved in the regulated expression of a human HSP70 gene.

Expression of reporter genes under the control of upstream sequences of a human hsp70 gene was examined in microinjected Xenopus oocytes, transfected monkey COS and human HeLa cells. The genes were strictly heat-regulated in all three cell systems. A 69 nucleotide long segment of hsp70 5' non-transcribed sequence that included at least one functional heat shock regulation sequence was sufficient for heat-controlled expression in Xenopus and monkey cells but not in human HeLa cells. An additional segment of about 200 nucleotides in length was required for optimal activity. This segment contains two heat shock regulation elements, each of which appears to contribute to the overall activity in heat-treated human cells. Upstream non-transcribed sequences of the human hsp70 gene are capable of conferring heat regulation on a heterologous promoter. The potential roles in transcription regulation of a bending center in the TATA box region, a CCAAT-like sequence and some of many potential Sp1 binding sites in the hsp70 5' non-transcribed region were investigated.

Animals↗
PubMed1988

Determinants for the DNase I-hypersensitive chromatin structure 5' to a human HSP70 gene.

A DNase I hypersensitive site was detected in chromatin formed over a human hsp70 gene segment after amplification in COS7 cells. Deletion mutant analysis was used to evaluate the sequence requirements for this chromatin structure. Determinants sufficient to form the hypersensitive site are contained in a 280 base-pair sequence corresponding approximately to the region that is hypersensitive. Deletion of sequences from either end of this region resulted in reduced hypersensitivity, suggesting that multiple genetic elements contribute to the formation of this chromatin structure. As has been reported for other heat shock genes, the hypersensitive chromatin structure is present prior to heat treatment and does not change in intensity or position after heat shock, in spite of the fact that hsp70 gene expression is completely dependent on heat induction. Sequence requirements for hypersensitivity were generally similar to those for heat-induced gene expression when mutant plasmids were tested at low copy number (e.g. in HeLa cells or in COS cells without amplification); however, deletion of sequences between -223 and -162 with respect to the start of transcription abolished the hypersensitive site but had no effect on gene expression. A barrier to exonuclease III digestion was detected within this region (near an imperfect inverted repeat sequence centered at position -202), suggesting that proteins are tightly bound to the DNA at this location.

Animals↗
PubMed1988

Surgical management of children and young adults with the Wolff-Parkinson-White syndrome.

The Wolff-Parkinson-White syndrome, as originally described, includes palpitations, tachycardia, and an abnormal electrocardiogram (short PR interval and wide QRS complex). The clinical manifestations are dependent upon a reentrant tachycardia supported by an accessory connection bridging the atrioventricular junction and frequently appear during the first two decades of life. Palpitations are the usual symptoms; less frequently, severe symptoms, such as syncope and sudden death, may result from very rapid atrioventricular conduction across the accessory connection during atrial fibrillation. We report the surgical management of 30 young patients with this syndrome, including 6 with life-threatening tachycardia. Surgical interruption of the accessory connection(s) was curative in 90% (27/30) of the patients; life-threatening symptoms were eliminated in the other three. Based on the limited knowledge of the natural history of the Wolff-Parkinson-White syndrome, the individual patient symptoms, and the electrophysiologic properties of each patient's accessory pathway(s), an algorithm is presented outlining the treatment options. This experience strongly suggests that surgical treatment of the Wolff-Parkinson-White syndrome is safe, effective, and possibly the preferred treatment for this disorder in selected young symptomatic patients.

Adult↗
PubMed1988

Repair of interrupted aortic arch in infancy.

Twenty-one patients undergoing repair of interrupted aortic arch between December of 1979 and January of 1987 were reviewed to determine the cause(s) of late morbidity and mortality. Ten underwent staged repair, and 11 had complete repair including all coexisting defects at the initial operation. Sixty-two percent are alive and clinically well 6 months to 6 years after the initial operation. Among the five patients who died late postoperatively, four had severe left ventricular outflow tract obstruction. Two other patients have had surgical relief of severe subaortic stenosis. In addition, significant recurrent or residual coarctation was found in four patients; it was relieved by balloon angioplasty in two patients, and two had surgical repair. None of the most recent seven patients, however, have had a residual ascending-descending aortic gradient. Careful follow-up for the detection of previously masked or newly developed left ventricular outflow tract obstruction is imperative and may be lifesaving.

Aorta, Thoracic↗
PubMed1986

Evidence for sequential signals in the induction of the arachidonic acid cascade in macrophages.

We have examined the requirement for Na+, Ca2+, and protein synthesis in the induction of the arachidonic acid (20:4) cascade in cultured murine peritoneal macrophages. Replacement of extracellular Na+ with choline or with K+ inhibited receptor-mediated 20:4 release by 60-90%, but did not inhibit release stimulated by the soluble triggers PMA and A23187. Cells that had preingested zymosan particles in a K+ medium could be induced to secrete 20:4 metabolites merely by changing the medium to one containing Na+. The Ca2+ ionophore A23187 caused cells in Na+-free medium to release and metabolize 20:4 to prostacyclin, PGE2, leukotriene C, and hydroxyeicosatetraenoic acids, suggesting that the phospholipase(s), cyclooxygenase, and lipoxygenase enzymes do not have a requirement for extracellular Na+. These data suggest that receptor-mediated 20:4 secretion has a requirement for extracellular Na+, while 20:4 release triggered by soluble stimuli do not. Immune complex- and A23187-induced 20:4 release was absolutely dependent on extracellular Ca2+. PMA-triggered 20:4 secretion was inhibited 50% in Ca2+-free medium, but could be inhibited completely by preloading the cells with the Ca2+ antagonist quinine. Protein and RNA synthesis was required for 20:4 release induced by zymosan, immune complex, and PMA, but not by A23187. Cycloheximide and emetine were effective within 15 min of addition, while actinomycin D was an effective inhibitor within 45 min. We suggest that receptor-mediated signal response coupling in the 20:4 cascade in macrophages comprises a sequential series of signals that includes an Na+ influx, synthesis of a rapid turnover-protein, and finally an increase in intracellular Ca2+.

Animals↗
PubMed1986

Growth and proportionality in early childhood. II. Some population differences.

The postnatal growth patterns of children in four different populations are compared with a sample born and brought up in Oxford. Three indices of proportionality were investigated. Among the three caucasian groups Swedish children had the smallest heads and tallest stature, resulting in particularly low head-chest and head-stature ratios. Denver children had unusually small chest from 2 years onwards; their head-chest ratios were significantly higher than those in Oxford, but head-stature and chest-stature ratios were lower. Japanese children were smaller than Oxford children in all dimensions; but apart from some minor fluctuations they were similar in shape by all three indices used. Guatemalan children of both sexes had extremely high chest-stature ratios from 3 years onwards. Head-stature ratios were also raised, but to a lesser extent. Compared with children in more highly-favoured communities their stature and head circumference were reduced more than weight and chest circumference.

Birth Weight↗