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Biomedical subjects

E Little

Publications and source records attributed to E Little.

15 recordsLinked to original sources
PubMed2006

Thermoelastic analysis of high-pressure angioplasty balloons.

Failures in angioplasty balloons are investigated using typical destructive techniques. The material properties of moulded balloons are derived from tensile tests and used to establish the reasons for failure of the balloons. Thermoelastic stress analysis is used to determine the stress distribution in the balloons, and a means of interpreting the data to derive actual stresses is described. The departure from linear elastic behaviour in the angioplasty balloons is identified using thermoelastic analysis. The results from the thermoelastic analysis are discussed and compared with those from the destructive tests, and the thermoelastic technique is shown to be a potential new means for non-destructive analysis of angioplasty balloons.

Angioplasty, Balloon, Coronary↗
PubMed1996

Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ] propenamide and related compounds.

The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.

Acrylamides↗
PubMed1996

Determining divergence times of the major kingdoms of living organisms with a protein clock.

Amino acid sequence data from 57 different enzymes were used to determine the divergence times of the major biological groupings. Deuterostomes and protostomes split about 670 million years ago and plants, animals, and fungi last shared a common ancestor about a billion years ago. With regard to these protein sequences, plants are slightly more similar to animals than are the fungi. In contrast, phylogenetic analysis of the same sequences indicates that fungi and animals shared a common ancestor more recently than either did with plants, the greater difference resulting from the fungal lineage changing faster than the animal and plant lines over the last 965 million years. The major protist lineages have been changing at a somewhat faster rate than other eukaryotes and split off about 1230 million years ago. If the rate of change has been approximately constant, then prokaryotes and eukaryotes last shared a common ancestor about 2 billion years ago, archaebacterial sequences being measurably more similar to eukaryotic ones than are eubacterial ones.

Amino Acid Sequence↗
PubMed1996

Induction of glucose-regulated protein (glucose-regulated protein 78/BiP and glucose-regulated protein 94) and heat shock protein 70 transcripts in the immature rat brain following status epilepticus.

Prior to 21 days of age, the immature rat brain is relatively resistant to excitotoxicity caused by the glutamate analogue, kainate. As stress-inducible proteins (GRP78, GRP94 and HSP70) have been proposed to possess molecular chaperone activity and protect cells from the deleterious effects of damaged proteins, we examined the pattern of expression of their respective messenger RNAs following systemic kainate at different postnatal ages. In untreated rats between seven and 21 days old, there was a higher basal level of grp78 and grp94 expression compared to hsp70. Unlike hsp70, which was inducible only in 21-day-old rats, kainate-mediated grp94 induction occurred in several regions of the brain as early as postnatal day 7. Grp78 messenger RNA expression was also increased by kainate treatment in 14-day-old rats, and the induction was most pronounced in the kainate-resistant dentate gyrus. With increasing age, longer lasting expression of both grp78 and grp94 messenger RNAs was observed in kainate-vulnerable regions, similar to observations in the adult rat brain. These results demonstrate non-overlapping expression patterns of glucose-regulated proteins and HSP70 in the immature central nervous system, suggesting that they serve different functions. While hsp70 induction could be a marker for potential cell injury and death, increased expression of grp78 and grp94 could play a neuroprotective role in the developing rat brain.

Animals↗
PubMed1995

Generation of a mammalian cell line deficient in glucose-regulated protein stress induction through targeted ribozyme driven by a stress-inducible promoter.

GRP94 is an endoplasmic reticulum (ER) localized glycoprotein with Ca2+ binding and protein chaperoning properties. Using a ribozyme driven by a stress-inducible promoter and targeted against grp94 mRNA, we have generated a cell line deficient in its ability to induce GRP94. The effect of the ribozyme is mediated by the cleavage of the grp94 message just downstream of the initiation codon, and not by an antisense effect, as determined by the level of intact grp94 mRNA. Unexpectedly, this cell line's ability to induce GRP78 is also impaired. Transient overexpression of recombinant human lysosomal hydrolase alpha-L-iduronidase in the ribozyme expressing cells indicates that the secretion ratio of this enzyme is reduced by about 6-fold. Additionally, the ribozyme expressing cells showed increased sensitivity to Ca2+ depletion from ER caused by either A23187 or thapsigargin, an ER-Ca(2+)-ATPase inhibitor, but not to tunicamycin. These combined results show that the induction of GRP94 may play important roles in ER to nuclear signaling, protein sorting and secretion, and specific protection against Ca2+ depletion stress.

Animals↗
PubMed1994

Tracing the spread of fibronectin type III domains in bacterial glycohydrolases.

The evolutionary spread of 22 fibronectin type III (Fn3) sequences among a dozen bacterial enzymes has been traced by searching databases with the non-Fn3 parts of the enzyme sequences. Numerous homologues were found that lacked the Fn3 domains. In each case the related sequences were aligned, phylogenetic trees were constructed, and the occurrences of Fn3 units on the trees were noted. Comparison with phylogenetic trees prepared from the Fn3 segments themselves allowed inferences to be made about when the Fn3 units were shuffled into their present positions.

Amino Acid Sequence↗
PubMed1994

The glucose-regulated proteins (GRP78 and GRP94): functions, gene regulation, and applications.

The knowledge of GRPs as molecular chaperones is rapidly evolving. It is anticipated that the GRPs will make special contributions in the areas of basic cell biology, biotechnology, and cancer biology. In particular, they may play a role as the prototype of a class of genes that are regulated by signal transduction pathways originating in the ER and traveling to the nucleus. GRP78 and GRP94 function as molecular chaperones and can bind to malfolded proteins and unassembled complexes. They are induced in response to stress, but once the stress is removed the GRPs are posttranscriptionally modified into biologically inactive forms. The promoters of the grp genes are highly conserved, with several CCAAT-like motifs and GC-rich regions. The high level of redundancy that exists in the mammalian grp promoters may act to ensure that the expression of the genes, both of which are single copy, is unlikely to be significantly lowered in the event of mutation. These genes are thought to be controlled by several transcription factors whose complex interactions with the grp promoters allow variable patterns of grp induction. The promoters of the grp genes constitutively express their gene products, and their promoter activities can be further enhanced in cellular environments of low glucose or oxygen. The grp78 promoter is known to retain its strong activity in differentiated and undifferentiated tissues. These features make it an attractive alternative to viral promoters for use in gene therapy. Gene therapy may also be useful in treating cancer in some cases, especially solid tumors. In these instances, GRP levels are already likely to be quite high. These high levels of GRPs may inhibit the efficacy of several anti-cancer treatments. Suppression of GRP induction, perhaps by anti-sense or ribozyme technology, may prove to be useful in conjunction with anti-cancer drugs to treat tumors.

Animals↗
PubMed1993

Rapid prenatal diagnosis of Patau's syndrome in a fetus with an abdominal wall defect by 72 hour culture of cells from amniotic fluid.

A woman in the 32nd week of pregnancy was referred for investigation because of fetal abnormalities, including an abdominal wall defect, detected by ultrasonography. In view of the increased risk of chromosome abnormality, amniocentesis was performed to enable informed decisions about the management of the pregnancy and delivery to be taken. Cells from the liquor were inoculated into standard lymphocyte culture medium and incubated for 72 h. Slides with a high mitotic index and good quality metaphases, comparable to those from a blood culture, were obtained after harvesting. Cytogenetic analysis showed the karyotype to be 46,XY, - 14,+t(13q14q), which is consistent with Patau's syndrome. This technique appears to be an option for rapid karyotyping in cases of abdominal wall defect, where a chromosomal abnormality is suspected.

Abdominal Muscles↗
PubMed1992

Breast cancer in Canada: to screen or not to screen?

Lomas (1988) and Sabatier (1987) have suggested models by which to examine the roles that values, scientific knowledge, institutions, and the learning process play in the formulation of both national and clinical health-care policies. Utilizing their frameworks, this article offers an explanation for the development of high-volume screening mammography policies in Canada, despite the suggested inefficacy of screening technologies for 'unavoidable' illnesses such as carcinoma in the breast. The preliminary results of Canada's National Breast Screening Study further complicate this tissue. Inappropriate framing of the 'problem' in the policy-making process, by actors highly influenced by societal values and scientific evidence, is identified as the reason for present and planned policies and practices contradicting the first principles of health-policy analysis.

Adult↗
PubMed1987

Lack of sampling site variation in chorion villus biopsy as assessed by DNA, enzymatic, morphological and cytogenetical analyses.

A study of villus samples from eight random sites on five electively aborted chorion sacs was performed to determine any significant differences in yield, quality and composition of DNA, iduronate sulphate sulphatase activity and karyotype status. The villi were also examined for their histological characteristics (e.g. stem, intermediate or terminal villi) and for HCG and BGP immuno-reactivities. The overall findings indicated no significant site to site variations in any of the parameters studied. It is therefore proposed that any villus should be equally suitable for prenatal diagnosis.

Chorion↗