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Biomedical subjects

G Richards

Publications and source records attributed to G Richards.

At least 73 records · Page 4Linked to original sources

Analysis of a DNase I-hypersensitive site in transgenic Drosophila reveals a key regulatory element of Sgs3.

We have undertaken chromatin studies on transformed Drosophila strains carrying DNA sequences modified in the region of the DNase I (EC 3.1.4.5)-hypersensitive sites -750 and -600 base pairs upstream from the Sgs3 start site. Although both sites are developmentally specific, modifications in the -750 site have little or no effect on Sgs3-encoded transcript levels, whereas either deletion or replacement of sequences at the -600 site causes an important reduction in transcript levels. The element associated with the -600 site enhances Sgs3 transcription when displaced with respect to the start site. This combined approach has defined sequence elements necessary both for normal transcript levels as well as the chromatin structure characteristic of Sgs3 activity in vivo.

Animals↗

The Drosophila sgs3 gene: an in-vivo test of intron function.

An intronless Drosophila melanogaster sgs3 "glue" gene from the Formosa strain was constructed and inserted by P element transformation into a strain carrying an sgs3 variant that produces a larger mRNA and protein. By comparing both the RNAs and proteins produced by the two alleles we show that the intron has no detectable effect on sgs3 expression.

Animals↗

Sps-3 transcript levels are determined by multiple remote sequence elements.

The region from 1.4 to 2.7 kb upstream of Drosophila melanogaster gene Sgs-3 is responsible for a 10-fold increase in Sgs-3 transcript levels in the third instar larval salivary gland. This region includes the related Sgs-7 gene from the 68C glue gene cluster as well as 400 bp of its 5' sequences. We show that two elements are involved, each contributing a modest 3-fold effect. One of these includes Sgs-7 transcribed sequences some 2.3 kb upstream of Sgs-3, although Sgs-7 transcription is not involved. Although important for the overall levels of Sgs-3 expression, they are clearly not strong, viral-like enhancer elements. We propose that many position effects observed in P element transformation studies are the consequence of insertion in the vicinity of similar elements dispersed throughout the genome and having modest effects on transcript levels.

Animals↗

Low-density lipoprotein metabolism in cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare disorder characterized by a defect in conversion of cholesterol into bile acids, increased plasma levels of cholestanol, and accumulations of sterols in tendons, brain, and coronary arteries. Despite the presence of tendon xanthomas, patients with CTX frequently have low levels of plasma cholesterol and low density lipoproteins (LDL). The mechanisms for a low LDL are not understood. The present study, therefore, was carried out to examine the metabolism of LDL in a 58-year-old black man with CTX. This particular patient had an LDL-cholesterol in the mid-normal range (149 +/- 6 mg/dL). Nonetheless, his fractional catabolic rate (FCR) for LDL-apolipoprotein (apo-LDL) was 0.45 pools/d, which was increased compared to 15 aged-matched men (FCR, 0.30 +/- 0.01 pools/d). His production rate for apo-LDL (18.5 mg/kg-d) also was increased compared to those of middle-aged men (13.5 +/- 2.5 mg/kg-d). Since the underlying defect in CTX can be reversed by administration of chenodeoxycholic acid (chenodiol), the patient was treated with chenodiol (250 mg 4X daily), and measurements of LDL kinetics were repeated. During chenodiol therapy, his LDL-cholesterol concentration rose significantly to 165 +/- 12 mg/dL; his FCR for apo-LDL fell to 0.29 pools/d; and his production rate of apo-LDL declined to 14.4 mg/kg-d. We postulate that chenodiol suppressed the excessive synthesis of cholesterol and bile acids, which had two effects. It curtailed both the overproduction of LDL and the excessive synthesis of LDL receptors, the latter being responsible for the high FCR of apo-LDL in the untreated state.

Apolipoproteins↗

Explosive anaesthetic agents. A regional survey on the use of ether and cyclopropane.

A total of 156 consultant anaesthetists in the North East Thames Regional Health Authority were circulated with a questionnaire on their personal use of ether and cyclopropane and their attitudes towards restriction or withdrawal of these agents: 144 completed questionnaires were received (92% response). Four anaesthetists (3%) claimed to use ether regularly at least once a month and 27 anaesthetists (19%) felt that their anaesthetic practice would suffer if ether were withdrawn. Cyclopropane had 62 regular users (43%) and 65 anaesthetists (45%) felt that their practice would suffer if it were withdrawn. Ninety-two anaesthetists (64%) were prepared to confine their use of explosive agents to either the anaesthetic room or the operating room; of these, three-quarters favoured the anaesthetic room. There were few notable differences in the pattern of use of explosive agents between anaesthetists with more than 21 years in the specialty and those with less than 21 years.

Anesthesia, Inhalation↗

Curtains.

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Attitude to Death↗

Changes in the chromatin structure of Drosophila glue genes accompany developmental cessation of transcription in wild type and transformed strains.

Three Drosophila salivary gland glue genes show a dramatic transition in their DNAse I hypersensitive sites during the short period between the late third instar and the white prepupa, which correlates with the cessation of their transcription. In culture cells, where the genes are inactive, there is a chromatin configuration similar to that of prepupal salivary glands. In two transformed fly strains where the sgs3 gene is active at new chromosomal sites, including one in which 2.6 kb of sgs3 upstream sequences have been inverted, the same DNAase I hypersensitive sites and developmental transitions are seen over the same DNA regions. These results, together with the analysis of transformants carrying rearranged sgs3 genes, suggest that there is at least one distal DNAase I hypersensitive site associated with an element of regulation which may be exchanged between sgs genes.

Animals↗

Insulin resistance with acanthosis nigricans: the roles of obesity and androgen excess.

The roles of hyperandrogenemia and obesity in the syndrome of severe insulin resistance with acanthosis nigricans were evaluated in studies of 11 females with this condition. Our results in these subjects were compared to evaluations of control subjects matched for degree of androgen excess or obesity. Fasting insulin levels were 3-, 5-, and 15-fold higher in the obese (OB), hyperandrogenemic (HO), and acanthosis nigricans (AN) groups, respectively, when compared to normal females. Responsiveness to a standard bolus of exogenous insulin was 78% of normal in the OB group, 40% of normal in the HO group, and 30% of normal in the AN group. Insulin binding to monocytes from both the OB group, and the HO group was modestly diminished primarily due to decreased receptor number. As a group, AN subjects when compared to either normal or weight-matched controls, demonstrated a significant decrease in monocyte insulin binding predominantly due to a decrease in receptor number. However, two patients in the AN group had normal insulin binding suggesting a postreceptor mechanism for the insulin resistance in at least some of these subjects. In vivo glucose utilization insulin dose response curves were determined in 3 acanthotic subjects using the euglycemic clamp technique. All 3 of these subjects had a right shift of the curve and diminished maximal utilization, consistent with combined receptor and postreceptor defects in insulin action. In evaluating the relationship between hyperandrogenemia, insulin resistance, and acanthosis nigricans, significant correlations among basal levels of plasma insulin, and both testosterone and androstenedione were demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthosis Nigricans↗