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Biomedical subjects

G Farmer

Publications and source records attributed to G Farmer.

11 recordsLinked to original sources

Wild-type p53 activates transcription in vitro.

The p53 protein is an important determinant in human cancer and regulates the growth of cells in culture. It is known to be a sequence-specific DNA-binding protein with a powerful activation domain, but it has not been established whether it regulates transcription directly. Here we show that intact purified wild-type human and murine p53 proteins strongly activate transcription in vitro. This activation depends on the ability of p53 to bind to a template bearing a p53-binding sequence. By contrast, tumour-derived mutant p53 proteins cannot activate transcription from the template at all, and when complexed to wild-type p53, these mutants block transcriptional activation by the wild-type protein. Moreover, the simian virus 40 large T antigen inhibits wild-type p53 from activating transcription. Our results support a model in which p53 directly activates transcription but this activity can be inhibited by mutant p53 and SV40 large T antigen through interaction with wild-type p53.

Animals

The ranges of insulin response and glucose tolerance in lean, normal, and obese women during pregnancy.

OBJECTIVE: We characterized insulin secretion and glucose disposal in a large unselected group of women, encompassing the full spectrum of glucose tolerance in pregnancy, and related the findings to maternal obesity. STUDY DESIGN: Intravenous glucose tolerance and first-phase insulin response were measured at about 32 weeks' gestation in 690 unselected pregnancies. The women were designated as "lean," "normal," or "obese" on weight-for-height criteria. RESULTS: The distribution of insulin response was bimodal, but there was no corresponding dichotomy in maternal glucose disposal rate. Insulin response was greatest and glucose disposal rate slowest in obese women. In general, "poor" glucose tolerance was associated with relatively low insulin output. It was not possible to identify any cluster of women, obese or otherwise, in whom poor glucose tolerance was specifically associated with an unusually high insulin response. CONCLUSION: The data indicate that the distribution of glucose tolerance in pregnancy is a continuum. Glucose intolerance represents one end of that spectrum and is attributable to insufficient insulin secretion. This relative insufficiency is most frequent with maternal obesity.

Blood Glucose

Sturge-Weber and Klippel-Trenaunay syndromes with absence of inferior vena cava.

A baby girl born at 33 weeks' gestation weighing 2250 g presented with Sturge-Weber syndrome, features of the Klippel-Trenaunay syndrome, and absence of the inferior vena cava. We suggest that aplasia of the vena cava may be a feature of Klippel-Trenaunay syndrome when the capillary malformation affects the trunk.

Angiomatosis

The influence of maternal glucose metabolism on fetal growth, development and morbidity in 917 singleton pregnancies in nondiabetic women.

To study the effects on the fetus of variations in maternal glucose tolerance, a 25 g rapid intravenous glucose tolerance test was performed at or about 32 weeks gestation in 917 randomly selected nondiabetic women with singleton pregnancies. The results were withheld from the patients and their obstetricians and paediatricians, and no treatment or advice was offered. Fasting plasma glucose and indices of glucose disposal (including a new index which we have termed "summed glucose") were distributed unimodally, with no evidence of a separate pathological group towards the diabetic end of the distributions. Significant associations were found between maternal glucose metabolism and various measures of neonatal nutrition and morbidity, including the incidence of congenital malformations and morbidity related to asphyxia, suggesting that variations within the normal range in maternal glucose metabolism can influence growth and development in the fetus. These relationships were continuous throughout the range of maternal glucose tolerance and were not of predictive value in individual cases.

Birth Weight

Linkage analysis in von Recklinghausen neurofibromatosis (NF1) with DNA markers for chromosome 17.

The mutant gene causing von Recklinghausen neurofibromatosis (NF1) was recently shown to map to chromosome 17. We have used additional markers for chromosome 17 to narrow further the location of the gene defect. A preliminary multipoint linkage analysis suggests that the NF1 gene is located on the long arm of chroomsome 17, flanked by D17Z1 and NGFR. Linkage analysis with the human oncogene homolog erbA1, which maps to this region, suggests that this cancer-related gene is not the primary cause of NF1.

Chromosomes, Human, Pair 17

Perianal infection with group A streptococcus.

Anal fissure in childhood usually heals quickly after treatment with stool softeners and a local anaesthetic ointment; infection does not usually occur. Two cases are reported in which Lancefield group A beta haemolytic streptococci were isolated from cultures from the perianal skin, which was erythematous and excoriated.

Anus Diseases

Neonatal skinfold thickness. Measurement and interpretation at or near term.

Skinfold thickness was measured at five sites in 750 infants. The study population was unselected except that twin pregnancies and the infants of diabetic mothers were excluded, and very preterm infants were under represented. A pilot study had indicated that skinfold measurement was most reproducible at the thigh site. Thigh skinfold correlated better with the sum of other skinfolds than did skinfold measurement at any other site and closely resembled the summed skinfold in correlations with a number of maternal and fetal variables. Median skinfold increased with birthweight and was greater in girls than in boys. 'Corrected skinfold', a mathematical approach to comparing skinfolds in infants of differing sex and birthweight, is suggested as an alternative to absolute skinfold measurement.

Birth Weight