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Biomedical subjects

E F Wheeler

Publications and source records attributed to E F Wheeler.

At least 37 records · Page 2Linked to original sources

The amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences.

The nucleotide sequence of a 5' segment of the human genomic c-fms proto-oncogene suggested that recombination between feline leukemia virus and feline c-fms sequences might have occurred in a region encoding the 5' untranslated portion of c-fms mRNA. The polyprotein precursor gP180gag-fms encoded by the McDonough strain of feline sarcoma virus was therefore predicted to contain 34 v-fms-coded amino acids derived from sequences of the c-fms gene that are not ordinarily translated from the proto-oncogene mRNA. The (gP180gag-fms) polyprotein was cotranslationally cleaved near the gag-fms junction to remove its gag gene-coded portion. Determination of the amino-terminal sequence of the resulting v-fms-coded glycoprotein, gp120v-fms, showed that the site of proteolysis corresponded to a predicted signal peptidase cleavage site within the c-fms gene product. Together, these analyses suggested that the linked gag sequences may not be necessary for expression of a biologically active v-fms gene product. The gag-fms sequences of feline sarcoma virus strain McDonough and the v-fms sequences alone were inserted into a murine retroviral vector containing a neomycin resistance gene. Both constructs were biologically active when transfected into NIH 3T3 cells and produced morphologically transformed foci at equivalent efficiencies. When transfected into a cell line (psi 2) expressing complementary viral gene functions, G418-resistant (Neor) cells containing either of these vector DNAs produced high titers of transforming viruses. Analysis of proteins produced in cells containing the vector lacking gag gene sequences showed that gP180gag-fms was not synthesized, whereas normal levels of both immature gp120v-fms and mature gp140v-fms were detected. The glycoprotein was efficiently transported to the cell surface, and it retained wild-type tyrosine kinase activity. We conclude that a cryptic hydrophobic signal peptide sequence in v-fms was unmasked by gag deletion, thereby allowing the correct orientation and transport of the v-fms gene product within membranous organelles. It seems likely that the proteolytic cleavage of gP180gag-fms is mediated by signal peptidase and that the amino termini of gp140v-fms and the c-fms gene product are identical.

Amino Acid Sequence↗

Requirements for transformation by the fms oncogene product (CSF-1 receptor).

The c-fms proto-oncogene product is a transmembrane glycoprotein that is probably identical to the cell surface receptor for the mononuclear phagocyte colony stimulating factor, CSF-1. An analogous glycoprotein encoded by the viral oncogene v-fms includes the extracellular ligand-binding domain, membrane spanning segment, and cytoplasmic tyrosine kinase domain of the CSF-1 receptor. The v-fms and c-fms gene products differ significantly at their distal carboxylterminal ends where the truncated viral transforming protein has lost a single tyrosine residue (tyr969) that may negatively regulate the receptor kinase activity. Introduction of v-fms into a CSF-1 dependent murine macrophage cell line induced factor independence and tumorigenicity by a nonautocrine mechanism. Thus, although the v-fms gene product can bind CSF-1, its constitutive tyrosine-specific protein kinase provides growth stimulatory signals in the absence of ligand. Transfection of human c-fms cDNA into mouse NIH-3T3 cells conferred a CSF-1 responsive phenotype. Although neither the wild-type c-fms (tyr969) gene nor a mutant c-fms (phe969) allele induced transformation of NIH-3T3 cells, cotransfection with human CSF-1 cDNA gave rise to transformed foci. In cells cotransfected with the CSF-1 gene, the efficiency of focus formation induced by the mutant c-fms (phe969) gene was greater than that of the wild-type gene and equivalent to that of v-fms alone. A chimeric v-fms/c-fms molecule in which the carboxylterminus of the v-fms gene product was replaced by the corresponding region of the wild type c-fms (tyr969) was weakly transforming, whereas chimeric molecules containing phe969 transformed NIH-3T3 cells efficiently. Thus, complete oncogenic activation of the c-fms gene appears to require two events: one which alters a putative negative regulatory site of tyrosine phosphorylation, and a second which phenocopies a ligand-induced conformational change.

Animals↗

A study of different dietary survey methods among 30 civil servants.

A sample of 30 volunteers from a population of 100 Ministry of Agriculture, Fisheries and Food (MAFF) civil servants took part in a series of dietary assessments. Food frequency interview, 24-hour dietary recalls, 7-day weighed food record, duplicate diet analysis and 28-day household food purchase records were all used to estimate intakes of energy and a range of nutrients. When results for energy, fat and iron, using the five different methods, were compared there appeared to be systematic differences between methods. The highest results came from food purchase records for the women and from food frequency interviews for the men. Lowest results came from the duplicate diet analysis for fat and energy but from the 24-hour recall for iron, for men and women alike. The implications of these findings, together with possible explanations for them, are discussed.

Adult↗

Seasonal variations, and the intra-household distribution of food in a Bangladeshi village.

Individual food intakes and body weights were measured in 53 rural Bangladeshi households at four seasons. Energy and protein intakes (kcal/kg/d) showed significant seasonal differences for adults and young children (1-4 yr). Energy intakes of women and children were expressed as a proportion of the male household heads', to give an indicator of food allocation. Women's and older children's proportional energy intakes remained constant through the year, and in line with expected values. Young children's proportional intakes were low, girls' being lower than boys'. The only seasonal variation was an increase in young girls' proportional energy intake when household food supplies were lowest. It is concluded that women's proportional intakes are not depressed when family food intake decreases. There is evidence that young girls receive particularly low intakes.

Adolescent↗

Food choice and the US dietary goals.

Nobody has a completely free choice of food, but we may be so used to the limits of our choice that we are not aware of them. The purpose of this paper is to review proposals which have been put to the US Government and which, if followed through, would change the boundaries of food choice. To begin with, therefore, the framework of food choice is briefly considered. The paper falls into three parts: a general discussion on food choice, a review of the US proposals, and a discussion of their implications.

Aged↗

High energy feeding in protein-energy malnutrition.

The use of a high-fat diet in malnourished children produced accelerated growth of lean tissues as well as adipose tissue, and resulted in rapid nutirtional rehabilitation in 25 seriously malnourished babies. Such diets are easy to prepare and relatively cheap, and they offer important advantages over conventional feeding in the hospital treatment of malnourished children.

Body Weight↗

Variations in the apparent nutrient content of foods: a study of sampling error.

1. Successive portions of boiled and mashed potatoes, roast pork, cooked, freeze-dried peas and ice-cream were taken in order to determine the total (sampling and experimental) error involved in the 'duplicate analysis' method of dietary survey. 2. These samples were analysed for water, nitrogen, fat, iron and energy. 3. The experimental error of the methods was also studied separately. 4. The sampling and experimental errors ranged from 0-3% for water in potatoes, to 23% for Fe in ice-cream. Sampling error was significantly greater than experimental error for all nutrients studied. 5. It is concluded that in reporting the results from dietary surveys, it is necessary to take account of the erros inherent even in the most precise methods.

Analysis of Variance↗

Water balance and body weight: studies in a tropical climate.

Total body weight, water balance and energy balance were estimated in young adult men in a hot climate, over three 6-day periods. The aim was to determine the relative contributions to body weight changes of fluctuations in water and energy stores. In these subjects, the small observed body weight changes were due almost entirely to water balance changes. Water balance was regulated to within +/- 1% of body weight from day-to-day.

Adult↗