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Biomedical subjects

I Gibson

Publications and source records attributed to I Gibson.

At least 37 records · Page 2Linked to original sources
PubMed1993

Analysis of ras point mutations and human papillomavirus 16 and 18 in cervical carcinomata and their metastases.

Paraffin-wax-embedded samples of normal cervical tissue and of primary cervical carcinomata and nodal metastases were obtained from each of 15 patients. They were analyzed for the presence of ras point mutations and human papillomavirus (HPV) types 16 and 18 using the polymerase chain reaction (PCR) and hybridization to oligomer probes. Only 1 patient was found to have a ras mutation: a codon 13 mutation of Ki-ras which was present in only two lymph node metastases, but not in the primary tumor or in a third metastasis. These results suggest that ras point mutation is not a common factor in the development of primary or metastatic cervical cancer. HPV 16 was detected in 7 of the 15 patients and was present in both primary and metastatic tumors in 6 of these 7 cases. HPV 18 was not detected in any of the 15 patients. These results do not suggest a role for HPVs 16 and 18 in producing metastatic behavior.

Adult↗
PubMed1992

Synthesis of diacylglycerol analogues as potential second-messenger antagonists and inhibitors of protein kinase C.

A series of analogues of diacylglycerol has been prepared and tested as inhibitors of protein kinase C (PKC). The diketone analogues, 10-hydroxymethyl-8,13-eicosanedione (24), 10-acetoxymethyl-8,13-eicosanedione (25), and 10-methoxymethyl-8,13-eicosanedione (26) each inhibited PKC activated by 2-O-acetyl-1-O-oleoylglycerol. Compound 24 was the most effective inhibitor of the growth of MR4 and HT29 cells in culture, and 26 was more effective than 24 against HL60 cells.

Animals↗
PubMed1992

The detection of oligodeoxynucleotide molecules following uptake into mammalian cells.

A mixed phosphodiester:phosphorothioate oligodeoxynucleotide was used in uptake studies with T15 mouse fibroblast cells. The presence of full-length unlabeled oligomers was identified in both cytoplasmic and nuclear extracts by a method involving gel electrophoresis and electroblotting followed by hybridization with a complementary radiolabeled probe. Detection did not depend on the presence of a label on the oligomer with the potential for its removal, often a problem in other studies. The fate of the oligonucleotides could then be followed with time for at least 3 days. This method of detection should be applicable to studies of nuclease resistance and uptake characteristics of newly developed oligonucleotide analogues.

3T3 Cells↗
PubMed1991

In vitro cleavage of an N-ras messenger-like RNA by a ribozyme.

A cDNA library was constructed in lambda gt10 from T-15 cells, a transformed mouse fibroblast line. The transforming N-ras sequence was recovered and subsequently used as a substrate for ribozyme cleavage. The design of the ribozyme was based on that of the hammerhead structure of the satellite tobacco ringspot autolytic processing sequence. Specificity to the N-ras substrate was conferred by 10 nucleotides homologous to the target site on the mRNA positioned on either side of the catalytic unit. The cleavage reaction was most efficient at higher temperatures but efficiency at lower temperatures was improved by the inclusion of urea in the reaction mixture. The ribozyme failed to cut an antisense ras sequence even at high temperature or in the presence of urea.

3T3 Cells↗
PubMed1989

ras p21 and other Gn proteins are detected in mammalian cell lines by [gamma-35S]GTP gamma S binding.

The presence of guanine nucleotide binding proteins in mouse and human cell lines was investigated using [gamma-35S]GTP gamma S and [gamma-32P]GTP. Cell lysate polypeptides were separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis and transferred to nitrocellulose. Incubation of the nitrocellulose blots with [gamma-35S]GTP gamma S identified 9 distinct GTP-binding polypeptides in all lysates. One of these is the ras oncogene product, p21, as demonstrated by subsequent immunochemical staining of the nitrocellulose blots. We have shown that this procedure provides a sensitive method for detection of p21 in culture cell lines.

Animals↗
PubMed1989

R-body-producing bacteria.

Until 10 years ago, R bodies were known only as diagnostic features by which endosymbionts of paramecia were identified as kappa particles. They were thought to be limited to the cytoplasm of two species in the Paramecium aurelia species complex. Now, R bodies have been found in free-living bacteria and other Paramecium species. The organisms now known to form R bodies include the cytoplasmic kappa endosymbionts of P. biaurelia and P. tetraurelia, the macronuclear kappa endosymbionts of P. caudatum, Pseudomonas avenae (a free-living plant pathogen), Pseudomonas taeniospiralis (a hydrogen-oxidizing soil microorganism), Rhodospirillum centenum (a photosynthetic bacterium), and a soil bacterium, EPS-5028, which is probably a pseudomonad. R bodies themselves fall into five distinct groups, distinguished by size, the morphology of the R-body ribbons, and the unrolling behavior of wound R bodies. In recent years, the inherent difficulties in studying the organization and assembly of R bodies by the obligate endosymbiont kappa, have been alleviated by cloning and expressing genetic determinants for these R bodies (type 51) in Escherichia coli. Type 51 R-body synthesis requires three low-molecular-mass polypeptides. One of these is modified posttranslationally, giving rise to 12 polypeptide species, which are the major structural subunits of the R body. R bodies are encoded in kappa species by extrachromosomal elements. Type 51 R bodies, produced in Caedibacter taeniospiralis, are encoded by a plasmid, whereas bacteriophage genomes probably control R-body synthesis in other kappa species. However, there is no evidence that either bacteriophages or plasmids are present in P. avenae or P. taeniospiralis. No sequence homology was detected between type 51 R-body-encoding DNA and DNA from any R-body-producing species, except C. varicaedens 1038. The evolutionary relatedness of different types of R bodies remains unknown.

Animals↗
PubMed1988

Evaluation of N-ras oncogene anti-sense, sense and nonsense sequence methylphosphonate oligonucleotide analogues.

We have investigated the potential for using anti-sense non-ionic methylphosphonate oligonucleotide analogues to study the relationship between oncogene expression and maintenance of the transformed phenotype in malignant cells. Our results confirmed that the methylphosphonates are resistant to biochemical degradation and are devoid of non-specific toxicity towards cultured human HT29 cells. At low temperature (less than 5 degrees C) both N-ras anti-sense and nonsense analogue 9-mers formed 1:1 complexes in solution with an N-ras sense phosphodiester oligodeoxynucleotide 20-mer, but these were largely dissociated at 25 degrees C. Only a fraction (10-20%) of the anti-sense molecules formed stable sequence specific hybrids (Tm 34 degrees C) with the 20-mer. The biological activity of the oligonucleotide analogues was tested in cell culture at 37 degrees C using T15 cells, a line of NIH 3T3 cells transfected with multiple copies of the human N-ras oncogene under control of the glucocorticoid inducible MMTV promoter. On balance the N-ras anti-sense methylphosphonate 9-mer (20-80 microM) had no effect on these cells. In only one of five experiments was an apparent reduction in dexamethasone-induced p21N-ras protein accumulation observed in the presence of the oligonucleotide analogue. Also without effect was an anti-sense 20-mer consisting of a phosphodiester sequence bounded by two methylphosphonate linkages at each end (25-50 microM in culture media; 4.8 microM by microinjection). We conclude from these experiments that, in order to achieve pronounced effects on oncogene expression, it may be necessary to use longer anti-sense methylphosphonate chains, affinity purified for their ability to hybridize with the target sequences.

Base Sequence↗
PubMed1985

The effects of 6-mercaptopurine nucleotide derivatives on the growth and survival of 6-mercaptopurine-sensitive and -resistant cell culture lines.

6-Mercaptopurine (MP)-sensitive and -resistant cell culture lines were used to further characterize the apparent ability of MP nucleotide derivatives to overcome resistance to the parent drug. 6-Mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [MPRP], bis(6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(MPR)P], bis(O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(dibut.MPR)P], and O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [dibut.MPRP] were tested for cytotoxic and/or growth inhibitory effects against MP-resistant sublines of V79 Chinese hamster lung fibroblasts (CH/TG) and L1210 mouse leukaemia cells (L1210/MPR) in which deficiencies of hypoxanthine-guanine phosphoribosyltransferase, and hence drug nucleotide forming capacity were the basis of resistance. L1210/MPR cells were totally resistant to 1 mM 6-mercaptopurine-9-beta-D-ribofuranoside [MPR] and 2 mM MPRP, but were inhibited by high concentrations (greater than 0.25 mM) of bis(MPR)P. These results suggested that bis(MPR)P was taken up by cells as the intact molecule since MPR and MPRP were its extracellular breakdown products. L1210/MPR cells were much more sensitive to the lipophilic bis(dibut.MPR)P derivative which had a predominantly cytotoxic action as judged by trypan blue staining and the ability of treated cells to produce macroscopic colonies in soft agar medium. However, cells killed by bis(dibut.MPR)P did not disintegrate appreciably over periods of up to 10 days. The effects of bis(dibut.MPR)P were probably the result of cellular uptake of the intact molecule. Dibut.MPRP showed minimal ability to inhibit L1210/MPR cells although this compound was a possible breakdown product of bis(dibut.MPR)P and a source of the same extracellular degradation products. The median cell size decreased in L1210/MPR cultures during exposure to both bis(MPR)P and bis(dibut.MPR)P. This effect was elicited more rapidly and at lower concentration by bis(dibut.MPR)P than by bis(MPR)P. In contrast, sodium butyrate, a breakdown product of bis(dibut.MPR)P induced increases in cell size at high concentration. Bis (dibut.MPR)P was also cytotoxic to MP-resistant CH/TG cells and was approximately 300 times more effective than bis(MRP)P and MPR which exhibited similar activity against this cell line. Bis(dibut.MPR)P and dibut.MPRP were equivalent and less active than MPR in their effects on MP-sensitive L1210/0 cells where their predominant mechanism of action was via degradation to release MPR.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1978

An investigation into the ability of elderly patients continuing to take prescribed drugs after discharge from hospital and recommendations concerning improving the situation.

An investigation was made by an Occupational Therapist into the problems encountered by 50 elderly patients in the self-administration of drugs prior to discharge home. The questions asked the patients are enumerated and recommendations are made concerning how improvements can take place so that many more of the elderly will take the prescribed drugs in the right doses at the right time on discharge home.

Aged↗