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D Krane

Publications and source records attributed to D Krane.

4 recordsLinked to original sources

A ceramic system for delivering interleukin-2.

Interleukin-2 (IL-2) is a potentially effective cytokine to be used for cancer treatment. Since keeping IL-2 doses at a low, continuous level is important to avoid side effects which accompany high IL-2 doses, a ceramic which release IL-2 could prove to be a beneficial method of drug delivery for cancer patients [1]. In vitro studies were performed to determine the optimal hydroxyapatite (HA) to IL-2 ratio for continuous release of IL-2 from HA using both a matrix and insert ceramic pellet. In the matrix pellet experiment, HA to IL-2 ratios of 25:1, 50:1 and 100:1 were tested by compressing a homogenous mixture of each variable in triplicate and placing each ceramic in 2.5 mL simulated body fluid (SBF) at 37 degrees C. The fluid was collected and replaced for each ceramic every two hours for 12 hours and at 24 hours. The collected fluid was then assayed for IL-2 content. Pellets consisting of 25:1 ceramic to drug ratio delivered almost the entire amount of IL-2 at the fastest rate. Composites of 100:1 IL-2 to HA delivered the least amount of IL-2 at the slowest rate. Release of IL-2 from the 50:1 ratio pellets was intermediate with respect to speed and amount of delivery. In the insert pellet experiment, similar laboratory procedures were used to show that 100:1 ratio insert pellets delivered IL-2 at a slower rate and in lesser amounts than 50:1 ratio insert pellets. Results of this study show that HA can deliver IL-2 at different rates by varying the ratio of HA to IL-2 in both matrix and insert ceramic pellets.

Biocompatible Materials↗

Sequence and comparative analysis of the rabbit alpha-like globin gene cluster reveals a rapid mode of evolution in a G + C-rich region of mammalian genomes.

A sequence of 10,621 base-pairs from the alpha-like globin gene cluster of rabbit has been determined. It includes the sequence of gene zeta 1 (a pseudogene for the rabbit embryonic zeta-globin), the functional rabbit alpha-globin gene, and the theta 1 pseudogene, along with the sequences of eight C repeats (short interspersed repeats in rabbit) and a J sequence implicated in recombination. The region is quite G + C-rich (62%) and contains two CpG islands. As expected for a very G + C-rich region, it has an abundance of open reading frames, but few of the long open reading frames are associated with the coding regions of genes. Alignments between the sequences of the rabbit and human alpha-like globin gene clusters reveal matches primarily in the immediate vicinity of genes and CpG islands, while the intergenic regions of these gene clusters have many fewer matches than are seen between the beta-like globin gene clusters of these two species. Furthermore, the non-coding sequences in this portion of the rabbit alpha-like globin gene cluster are shorter than in human, indicating a strong tendency either for sequence contraction in the rabbit gene cluster or for expansion in the human gene cluster. Thus, the intergenic regions of the alpha-like globin gene clusters have evolved in a relatively fast mode since the mammalian radiation, but not exclusively by nucleotide substitution. Despite this rapid mode of evolution, some strong matches are found 5' to the start sites of the human and rabbit alpha genes, perhaps indicating conservation of a regulatory element. The rabbit J sequence is over 1000 base-pairs long; it contains a C repeat at its 5' end and an internal region of homology to the 3'-untranslated region of the alpha-globin gene. Part of the rabbit J sequence matches with sequences within the X homology block in human. Both of these regions have been implicated as hot-spots for recombination, hence the matching sequences are good candidates for such a function. All the interspersed repeats within both gene clusters are retroposon SINEs that appear to have inserted independently in the rabbit and human lineages.

Animals↗

Pediatricians' attitudes affecting decision-making in defective newborns.

A questionnaire designed to identify the factors that influence the resolution of ethical dilemmas was returned by 230 (57% of the total) Massachusetts pediatricians. The decision to recommend surgery for an infant with Down's syndrome with duodenal atresia when the parents had refused surgery was influenced by religious affiliation (P less than .01), religious activity (P less than .04), and sex (P=.05). Of those favoring surgery, 40.2% would pursue a court order. The decision to recommend surgery for an infant with severe meningomyelocele when the parents' position was not stated was influenced by age (P less than .01), religious activity (P less than .02), and specialization (P less than .008). When the parents' wishes were expressed, the majority of the pediatricians modified their decision in accord with these wishes. In response to general ethical questions, 79.6% of all pediatricians thought that parents should have the right to withold consent for surgery. Equal numbers thought that psychosocial reasons justified witholding lifesaving procedures. Among a variety of factors, they thought that willingness of the parents to care for the child would influence the decision to take heroic measures. There were 90.4% who thought that ethics should be part of medical education; 55.7% indicated this need throughout their careers.

Adult↗