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D Cox

Publications and source records attributed to D Cox.

At least 163 records · Page 9Linked to original sources
PubMed1986

Construction and analysis of an EMBL-3 phage library containing partially digested human chromosome 21-specific DNA inserts (15-20 kb).

In the mouse-human hybrid cell line SCC 16-5, chromosome 21 is the only human chromosome present. Fractions highly enriched for this chromosome were obtained by applying the chromosome velocity sedimentation technique to this cell line. DNA prepared from these chromosomal fractions was partially digested with Mbo I, size fractionated on an NaCl gradient, and cloned in the EMBL-3 phage vector. The phage library thus prepared was highly enriched for human chromosome 21-specific recombinant DNA sequences 15-20 kb long. Of the approximately 21,000 phage clones obtained, at least 99% were recombinant. Following phage plaque filter hybridization and Southern blotting, it was found that half of the recombinants were positive for human repetitive DNA. Almost all phages harbored highly or middle repetitive human or mouse DNA sequences owing to the large size of the recombinant inserts. In this library, the human chromosome 21 is represented approximately four times. All human recombinants studied thus far contained DNA inserts originating from chromosome 21 only. The employed cloning strategy is discussed with regard to utility, purity, quality, and completeness of chromosome-specific recombinant DNA libraries.

Animals↗
PubMed1986

Isolation of the eclosion gene cluster and the developmental expression of the Gld gene in Drosophila melanogaster.

During the development of Drosophila melanogaster the expression of glucose dehydrogenase (GLD) changes from non sex-limited to male limited. We have isolated the Gld gene and three other functionally related genes in the eclosion gene cluster by the method of chromosome walking. The Gld gene has been identified by two deletions and a translocation which genetically define the gene. A 2.8-kb RNA has been identified as the putative GLD mRNA. The temporal and spatial expression of this RNA is correlated with the expression of the GLD enzyme and levels of the steroid hormone ecdysterone. Using single-strand antisense probes we have detected three RNA species. However these three transcripts are not derived from the Gld locus. One of these RNAs is weakly detected by the multiple cloning site of the pSP65 vector. The level of detection of this latter RNA is greatly increased by the insertion of a specific Gld gene fragment in the pSP65 vector.

Animals↗
PubMed1986

Maintenance chemotherapy for anaplastic small cell carcinoma of the bronchus: a randomised, controlled trial.

Since March 1980, 309 patients with anaplastic small cell carcinoma of the bronchus (ASCB) have received remission induction therapy prior to randomisation to maintenance (M) or no maintenance (NM) chemotherapy. Induction therapy consisted of six courses of vincristine, doxorubicin and cyclophosphamide (VAC) given IV every 3 weeks. Those with limited disease also received mediastinal irradiation. Consenting patients with no unequivocal residual disease were randomised to have no further treatment until relapse or a further eight courses of VAC, at a lower dosage, every 4 weeks. Patients failing to achieve randomisation status received palliative treatment only. The median survival for all patients with limited disease (LD) is 363 days and that for patients with extensive disease (ED) is 272 days (P less than 0.00001). Sixty-one patients with ED were randomised. Those having maintenance chemotherapy lived significantly longer (median 372 days) than those who did not continue therapy (median 259 days) (P = 0.006). An imbalance in the proportion of 'complete remitters' randomised to maintenance therapy does not account for this difference. There is no significant difference between the M and NM groups in the 32 randomised LD patients. Continuing treatment during remission with agents used to induce the remission can prolong survival in patients with extensive stage ASCB.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

ADR1-mediated regulation of ADH2 requires an inverted repeat sequence.

DNA sequence analysis of wild-type and mutant ADH2 loci suggested that two unusual features 5' of the promoter, a 22-base-pair perfect dyad sequence and a (dA)20 tract, were important for regulation of this gene (D. W. Russell, M. Smith, D. Cox, V. M. Williamson, and E. T. Young, Nature [London] 304:652-654, 1983). Oligonucleotide-directed mutagenesis was used to construct ADH2 genes lacking the 22-base-pair dyad or the (dA)20 tract (V.-L. Chan and M. Smith, Nucleic Acids Res. 12:2407-2419, 1984). These mutant genes and other ADH2 deletions constructed by BAL 31 endonuclease digestion were studied after replacing the wild-type chromosomal locus with the altered alleles by the technique of gene transplacement (T. L. Orr-Weaver, J. W. Szostak, and R. S. Rothstein, Proc. Natl. Acad. Sci. USA 78:6354-6358, 1981), using canavanine resistance as the selectable marker. Deletions lacking the dyad failed to derepress normally and did not respond to mutations at the ADR1 locus, which encodes a protein necessary to activate ADH2. Deletions of the (dA)20 tract did not have a detectable phenotype. A small deletion located just 3' to the (dA)20 tract (between positions -164 and -146) had a low amount of ADR1-dependent transcription during repressed growth conditions, indicating that the regulatory protein encoded by ADR1 is present in a potentially active form during repression and that alterations of a DNA sequence in the promoter region can unmask its latent activity.

Alcohol Dehydrogenase↗
PubMed1985

New antiallergic pyrano [3,2-g]quinoline-2,8-dicarboxylic acids with potential for the topical treatment of asthma.

A number of antiallergic pyranquinolinedicarboxylic acid derivatives with potential for the topical treatment of asthma have been synthesized. All the compounds have been evaluated against rat passive cutaneous anaphylaxis and in a dog hypotension screen. This is the first detailed description of the application of the latter screen for the identification of antiallergic agents. Two compounds, disodium 9-ethyl-6, 9-dihydro-4,6-dioxo-10-propyl-4H-pyrano [3,2-g]quinoline-2,8-dicarboxylate (86) and disodium 6-(methylamino)-4-oxo-10-propyl-4H-pyrano[3,2-g]-quinoline-2, 8-dicarboxylate (72), were selected and further evaluated for their ability to induce phosphorylation of a 78000 molecular weight protein associated with the rat peritoneal mast cell. Their ability to inhibit histamine release from these cells and from a mucosal mast cell preparation has also been evaluated. These compounds, nedocromil sodium (TILADE 86) and minocromil (the free acid of 72), are at present undergoing therapeutic evaluation. The rationale for the screening procedure and the relevance of the second carboxylic acid function of these dibasic acids to receptor binding are discussed.

Administration, Topical↗
PubMed1984

Studies on continuous positive airway pressure breathing systems.

A study was undertaken to compare CPAP/IMV systems shown to be in common use in the U.K. The most frequently used system (Servo 900B) has characteristics which are likely to increase the work of breathing. Recommendations are made regarding the theoretically most acceptable systems.

Adult↗
PubMed1984

Development of an enzyme-linked immunosorbent assay for determination of lysozyme in human parotid and submandibular-sublingual salivas.

The specificity of lysozyme determinations in human parotid and submandibular-sublingual salivas of two subjects was assessed by comparison of lysozyme concentrations in native acidified salivas with purified enzyme obtained by immunoadsorbent fractionation of the salivas. Lysozyme concentrations were measured by the turbidimetric catalytic method and by a newly developed enzyme-linked immunosorbent assay (ELISA). The validity of the assays was established by comparing assay results with enzyme concentration values determined from optical density-extinction coefficient calculations of the purified lysozyme peak. Values for purified enzyme were found to be similar, irrespective of the assay used to determine lysozyme concentrations, and were in agreement with extinction coefficient calculations. Based on the ELISA technique, recoveries of lysozyme from both parotid and submandibular-sublingual salivas were greater than 75 and 90%, respectively. Similar recoveries were noted for parotid saliva when determinations were based on the turbidimetric assay. However, the ELISA and turbidimetric assays differed with respect to lysozyme levels in submandibular-sublingual saliva because of the apparent presence of an enhancement factor which gave rise to higher lysozyme values in the catalytic assay and therefore resulted in low recoveries of purified enzyme. This catalytic enhancement factor was present in the nonadsorbed fraction of both subjects, as higher lysozyme activities were noted when nonadsorbed fractions were added to affinity-purified lysozymes. Lysozyme levels were also determined in the parotid and submandibular-sublingual salivas of caries-resistant and -susceptible adults. In general, levels of lysozyme in parotid saliva were lower in comparison to submandibular -sublingual saliva; however, significant differences in enzyme concentration were not evident between the caries-resistant and caries-susceptible subjects.

Dental Caries↗
PubMed1983

An experimental analysis of fearlessness and courage.

In an attempt to assess the performance under stress of people who had received awards for gallantry, the subjective, behavioural and psychophysiological reactions of a group of seven decorated bomb-disposal operators were measured during a conflict test. Compared to a group of seven equally experienced and successful, but non-decorated, bomb-disposal operators, the decorated subjects maintained a lower cardiac rate when making difficult discriminations under threat of shock. There were no differences between the groups on subjective reactivity or on their performance under stress. Both groups of bomb-disposal operators reported having experienced fewer fearful reactions than did a small number of comparison subjects. The implications of the results for theories of fear and of courage are considered.

Adult↗
PubMed1983

Characterization of transposable element-associated mutations that alter yeast alcohol dehydrogenase II expression.

Seven cis-dominant, constitutively expressed mutations of the normally glucose-repressible isozyme of alcohol dehydrogenase (ADHII) from the yeast Saccharomyces cerevisiae are caused by insertion of transposable elements from the Ty1 family in front of the ADHII structural gene (ADR2) (V. M. Williamson, E. T. Young, and M. Ciriacy, Cell 23:605-614, 1981). We cloned ADR2 with its associated Ty1 element from five S. cerevisiae strains carrying these mutations. Comparison of the Ty1 elements by heteroduplex studies and restriction enzyme analyses indicated that four were very similar; the fifth, although the same size as the others (about 5.6 kilobases), differed by the presence of two large substitutions of approximately 1 and 2 kilobases. The DNA sequences of the terminal direct repeats (deltas) were very homologous but not identical and were similar to previously reported Ty1 element direct repeats. We determined the 5'-flanking sequences of the ADR2 gene isolated from a wild-type strain and from five Ty1-associated mutations. The 5-base pair target sequence at the site of Ty1 insertion was present at both ends of each Ty1 element. The sites of insertion of the elements were all different and occurred from 125 to 210 base pairs in front of the coding region of ADR2. The 5' end of the major transcript as determined by S1 mapping was the same in wild-type cells and in Ty1-associated constitutive mutants and was approximately 54 base pairs upstream from the coding region. ADR2 transcripts were not detected when a solo delta sequence was present in the 5'-flanking region of this gene.

Alcohol Dehydrogenase↗
PubMed1983

Salvage of myocardial function by coronary artery reperfusion 1, 2, and 3 hours after occlusion in conscious dogs.

The effects of coronary artery occlusion and reperfusion at 1 hour (1-hr group), 2 hours (2-hr group), and 3 hours (3-hr group) were compared with a permanently occluded group (P group) on measurements of overall left ventricular and regional endocardial function over a 4-week period. The studies were conducted in conscious dogs 1-2 weeks after recovery from instrumentation with solid state left ventricular pressure gauges, aortic, and left atrial catheters, hydraulic occluders, and Doppler flow transducers on the left anterior descending or left circumflex coronary arteries, and multiple pairs of ultrasonic transducers implanted in the endocardial third of the left ventricular free wall to measure endocardial segment shortening. During coronary artery occlusion, similar effects were observed in the four groups. At 1 hour after coronary artery occlusion, three classes of ischemia-induced dysfunction were observed; dyskinetic (systolic shortening completely lost and replaced by paradoxical bulging), severely hypokinetic (systolic shortening depressed by 65-95%), and moderately hypokinetic (systolic shortening depressed by 40-65%). Compared with the P group, significant (P less than 0.05) return of systolic shortening and velocity of shortening gradually occurred over the 4-week period following reperfusion in all classes of segments in the 1-hour group. In the 2-hour group, systolic shortening returned in the moderately and severely hypokinetic segments, but was slight and not significant in the dyskinetic segments. In the 3-hour group, significant systolic shortening returned only in the moderately hypokinetic segments. The effects of isoproterenol, 0.04 micrograms/kg per min, and exercise were compared on "salvaged" dyskinetic segments prior to and at 1, 2, 3, and 4 weeks after coronary artery occlusion and reperfusion. The responses to isoproterenol were significantly depressed at 1 week after reperfusion and gradually recovered over the 4-week period. At 3-4 weeks after reperfusion, severe exercise also increased shortening and velocity of shortening in "salvaged" segments. Thus, in the conscious dog, coronary artery reperfusion at 1 hour after coronary artery occlusion results in substantial return of endocardial function even in the most severely ischemic myocardium. The "salvaged" myocardium responds adequately to myocardial stress with increases in the extent and velocity of systolic shortening, as long as 3-4 weeks after reperfusion are allowed for recovery. However, after 3 hours of coronary artery occlusion, little salvage of regional myocardial function can be induced by acute reperfusion in this model.

Animals↗
PubMed1981

Murine embryonal carcinoma hybrids: decreased ability to spontaneously differentiate as a dominant trait.

The F9 murine embryonal carcinoma (ec) cell line does not differentiate spontaneously at high frequency either in vitro or in vivo. A derivative of this variant ec cell line resistant to ouabain and thioguanine was fused with the PSA1 ec cell line, which retains the ability to differentiate to a variety of cell types, either in vitro or in vivo. Hybrids were selected in media containing ouabain, hypoxanthine, aminopterin, and thymidine at a frequency of approximately 10(-3). Authentic hybrids were chosen by screening for the expected hybrid DNA content by flow microfluorometry and the lack of parental cell contamination in appropriate selective media. After injection into strain 129 mice, five or eight independently isolated hybrids formed tumors composed exclusively of embryonal carcinoma cells. The remaining three hybrids of this cross caused tumors composed of greater than 95% embryonal carcinoma cells but with small foci of differentiated tissues as well. Like the F9-derived parental line, less than 10 percent of the clones, formed by the hybrids after six days of growth, contained cells that secreted plasminogen activator. Since control hybrids derived from the fusion of either two F9 derivatives or two pluripotent cell lines resembled their parental cell lines with regard to the types of tumors formed and their differentiation in vitro, it appears that the F9 phenotype is dominant to the pluripotent phenotype in early passage embryonal carcinoma hybrids.

Animals↗