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D Leonard

Publications and source records attributed to D Leonard.

At least 37 records · Page 2Linked to original sources
PubMed1996

Inhibitors of farnesyl:protein transferase--a possible cancer chemotherapeutic.

The recent interest in inhibitors of farnesyl:protein transferase (FPTase) has resulted in a better understanding of the enzymology of this protein. Rationally designed inhibitors of prenyl transfer have emerged as potential new drug candidates because of the insight gained over how a prenyl group is enzymatically transferred onto a peptide thiol. This paper will explore how advances in our understanding of FPTase mediated catalysis has affected the design of FPTase inhibitors as possible cancer therapeutic agents. Without structural information of the enzyme, substrate analogues comprise the first area of drug design: these include peptidomimetics of the four C-terminal amino acids of rasP21 as well as farnesyl diphosphate analogs. In addition, phosphate anion was found to enhance the inhibitory potency of certain compounds known to be competitive with respect to farnesyl diphosphate and therefore incorporation of the phosphate anion may also provide a basis for improved inhibitor design.

Alkyl and Aryl Transferases↗
PubMed1995

Which way kaikai blo umi? Food and nutrition in the Torres Strait.

The people of the Torres Strait suffer a disproportionate level of diet-related disease, especially diabetes. The Torres Strait Health Strategy identified the difficulty in obtaining healthy food, particularly fruit and vegetables, as a major problem for people living in the Torres Strait. This study examined traditional plant food supply systems and current local production of fruit and vegetables. The supply system of fruit and vegetables from mainland Australia was also examined. Traditional garden food production was seen to continue (mainly to provide food for ceremonial occasions), but had declined because of easy access to store foods, changes in the physical, social and economic environment, limited access to land and water, and quarantine restrictions on movement of garden produce. Supplies of fruit and vegetables from the Australian mainland were infrequent and the prolonged transit time meant that produce was often in poor condition on arrival and prone to continued rapid deterioration due to limited store-level storage facilities. Demand for fresh produce exceeded supply.

Agriculture↗
PubMed1995

The study of the relationship between lifestyle characteristic self-reported drinking patterns and trauma.

A total of 161 usable interviews were obtained with 297 consecutive admissions to a Level I trauma center for purposes of evaluating patient socioeconomic patterns related to trauma. The median age of the purposeful sample was 31. There were 67.1% males, 29.2% females, and 3.7% unidentified; 43.5% were MVAs, 8.1% motorcycles, 2.5% pedestrians, 10.6% falls, and 3.7% penetrating trauma. Of those patients found ETOH positive, 40.8% admitted to drinking and driving regularly, 12.5% admitted to being previously arrested for DUI, 45% admitted that alcohol caused their current trauma, 28.6% had been previously arrested for traffic violation. Three-fourths did not routinely wear seat belts. The average education level of trauma victims was 12.2 years; 94% are blue collar workers. In summary the average trauma victim was a young adult male who had completed high school, somewhat below average earnings, and had a strong history of regular alcohol use as part of his lifestyle.

Accidents, Traffic↗
PubMed1994

Overexpression of the short form of the growth hormone receptor in 3T3-L1 mouse preadipocytes.

In rodents, the gene for the growth hormone receptor (GHR) gives rise to two mRNA transcripts encoding two proteins: a larger membrane spanning receptor (GHRL) and a smaller isoform, GHRs that consists of the extracellular domain and a unique hydrophilic carboxyl terminus. We examined the hypothesis that GHRs may contribute to cellular binding of GH and play a role in growth hormone (GH) signaling. Rat cDNA encoding GHRs was ligated into the mammalian expression vector pcDNA-I/neo and stably transfected into mouse 3T3-L1 preadipocytes which have endogenous GH receptors and, when differentiated into adipocytes, have the biochemical machinery to express the various GH effects. Sixteen of 24 neomycin resistant clones secreted at least twice as much GHRs in the growth medium as cells transfected with the vector alone, and in nine of these, GH binding was increased 2- to 4-fold. The amount of GHRL in extracts of these cells was unchanged, indicating that increased binding could not be accounted for by effects on formation or degradation of GHRL. The transfected cDNA for GHRs directs the synthesis of a 50 kDa protein. Cross-linking of [125I]hGH to transfected 3T3-L1 cells indicated a 3.5-fold increase in a 72 kDa GHRs[125I]hGH complex. In the presence of 10% newborn calf serum, incorporation of [35S]methionine into cellular proteins was similar in transfected clones and control cells. Deprivation of serum for 2 hr decreased protein synthesis by approximately 70% in control cells, but in the transfected cells, protein synthesis was reduced only by approximately 50% or 30% in cells exhibiting 2x or 3x increases in GH binding. In all cells, 1 nM IGF-1 restored protein synthesis to the serum replete level. Similarly, although 3H-2-deoxy-D-glucose (2DG) uptake was comparable in all cells after 2 hr of serum deprivation, 18 hr of serum deprivation decreased uptake by approximately 70% in control cells, but only by approximately 30% in cells with increased GH binding. One nanomolar IGF-1 restored 2DG uptake to levels seen after 2 hr or serum deprivation. IGF-1 had no effect after only 2 hr of serum deprivation. Measurement of IGF-1 secreted into the medium, revealed that clones which overexpress GHRs produce greater amounts of IGF-1 than control cells or transfected clones that failed to overexpress GHRs. We conclude that GHRs contributes to GH binding and may therefore be a functional receptor. In addition, overexpression of GHRs in 3T3-L1 cells altered cell function in the absence of GH.

3T3 Cells↗
PubMed1994

Diane Leonard, RN.

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Hospital Units↗