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Biomedical subjects

C Richmond

Publications and source records attributed to C Richmond.

At least 19 recordsLinked to original sources
PubMed1997

Production, characterization and functional activities of v-Ski in cultured cells.

The v-ski oncogene was introduced into mammalian cells in order to study its biochemical and biological properties. v-Ski, produced at relatively high levels by mouse L cells stably transfected with this DNA, was localized to the cell nucleus, was of correct apparent molecular mass, and was capable of complexing with DNA. Transient transfection of reporter plasmids into control or Ski producing mouse L cells revealed that Ski acts as a transcriptional activator of various transcriptional regulatory elements, including CMVie, RSV LTR and SV40. These results indicate that mouse L cells contain the nuclear cofactor(s) required for the ability of v-Ski to bind to DNA and also suggest that the v-Ski present within the cells is functional.

Animals↗
PubMed1997

DNA binding and transcriptional activation by the Ski oncoprotein mediated by interaction with NFI.

The Ski oncoprotein has been found to bind non-specifically to DNA in association with unindentified nuclear factors. In addition, Ski has been shown to activate transcription of muscle-specific and viral promoters/enhancers. The present study was undertaken to identify Ski's DNA binding and transcriptional activation partners by identifying specific DNA binding sites. We used nuclear extracts from a v-Ski-transduced mouse L-cell line and selected Ski-bound sequences from a pool of degenerate oligonucleotides with anti-Ski monoclonal antibodies. Two sequences were identified by this technique. The first (TGGC/ANNNNNT/GCCAA) is the previously identified binding site of the nuclear factor I (NFI) family of transcription factors. The second (TCCCNNGGGA) is the binding site of Olf-1/EBF. By electophoretic mobility shift assays we find that Ski is a component of one or more NFI complexes but we fail to detect Ski in Olf-1/EBF complexes. We show that Ski binds NFI proteins and activates transcription of NFI reporters, but only in the presence of NFI. We also find that homodimerization of Ski is essential for co-activation with NFI. However, the C-terminal dimerization domain of c-Ski, which is missing in v-Ski, can be substituted by the leucine zipper domain of GCN4.

Animals↗
PubMed1997

Cost of malpractice protection on rise in UK, too.

As in Canada, medical malpractice premiums in the United Kingdom are on the rise. In recent years there has been a 15%-20% annual rise in the cost of claims, and litigation costs for the National Health Service are soaring. Now, reports Caroline Richmond, another surge of litigation may be on the horizon because a 1996 change makes it possible for lawyers to take cases on a contingency basis.

Canada↗
PubMed1997

Identification of a core functional and structural domain of the v-Ski oncoprotein responsible for both transformation and myogenesis.

The v-ski oncogene promotes cellular transformation and myogenic differentiation. In quail embryo fibroblasts the two properties are displayed simultaneously and terminal muscle differentiation occurs only among cells already transformed by v-ski. To understand how the two phenotypes are derived from a single gene, we have undertaken to identify functionally important regions in v-ski and to test whether these regions can promote one phenotype without the other. We have generated both random and targeted mutations in v-ski and evaluated the effects of these mutations on expression, intracellular location, transformation, and myogenesis. Among a total of 26 mutants analysed, we have not found complete separation of the myogenic and transforming properties. Mutations in the region of v-Ski encoded by exon 1 of c-ski frequently abolish both its transformation and muscle differentiation activities, whereas mutations outside of this region are always tolerated. When expressed in cells from a minigene containing only the exon 1 sequence, the protein displays the transforming and myogenic activities similar to v-Ski. These results argue that the amino acid sequence encoded by exon 1 contains the core functional domain of the oncoprotein. To determine whether this functional domain has a structural counterpart, we have fragmented the v-Ski protein by limited proteolysis and found a single proteolytically stable domain spanning the entire exon 1-encoded region. Physical studies of the polypeptide encoded by exon 1 confirms that it folds into a compact, globular protein. The finding that both the transforming and myogenic properties of v-Ski are inseparable by mutation and are contained in a single domain suggests that they are derived from the same function.

Cell Transformation, Neoplastic↗
PubMed1997

Specific interactions between ATPase subunits of the 26 S protease.

The regulatory complex of the 26 S protease contains at least 15 distinct subunits. Six of these subunits (S4, S6, S6', S7, S8, and S10b) belong to a novel subfamily of presumptive nucleotidases that we call subunit 4 (S4)-like ATPases. Each of these putative ATPases was synthesized in reticulocyte lysate containing [35S]methionine, and the radiolabeled proteins were used in binding studies. S4, S6, S10b, and S6' displayed specific binding to components of the regulatory complex separated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) or two-dimensional PAGE. S4 bound to S7, and S6 bound two proteins: S8 and centractin, a component of the dynactin complex. S10b bound to S6' and bound much more weakly to S1 and p50, another component of the dynactin complex. S6' bound to S10b. Two subunits, S7 and S8, did not bind any components present on nitrocellulose membranes, presumably because S7 and S8 are already oligomeric following synthesis. Co-translation and sucrose gradient sedimentation of 35S-labeled ATPases demonstrated the formation of S6'-S10b dimers in solution but revealed more complex associations, namely the formation of trimers and tetramers, among S4, S6, S7, and S8. Progressive COOH-terminal deletions that removed as much as 300 amino acids from S4 had no effect on the binding of S4 to S7. In striking contrast, truncation of 85 NH2-terminal amino acids from S4 abrogated binding, clearly implicating the NH2 terminus of S4 in its specific interaction with S7. Since S4-like ATPases contain putative coiled-coils within the first 150 NH2-terminal amino acids, we propose that coiled-coil interactions are responsible for the specificity of the observed subunit associations and that these associations are important for self-assembly of the regulatory complex.

Adenosine Triphosphatases↗
PubMed1997

Mad cows and Englishmen: the aftermath of a BSE scare.

The consumption of prime beef cuts is down, animals have been slaughtered by the thousand and 3 farmers have committed suicide as the mad-cow issue continues to cause concern in the United Kingdom. In this report from London, Caroline Richmond also notes that the royal colleges have published a report stating that chronic fatigue syndrome is a real illness and patients need help.

Animals↗
PubMed1996

Debate about multiple pregnancies moves to new heights in Britain.

The controversy about multiple pregnancy and abortion has taken on a new dimension in Britain as a result of two widely publicized cases. A mother who was carrying twins wanted to give birth to only one child, so one fetus was aborted. Public outrage turned to dismay when it was revealed another mother who had been taking fertility drugs refused selective termination, a standard procedure to ensure the growth of healthy fetuses, in an ill-fated attempt to give birth to eight babies.

Adult↗
PubMed1996

Fighting the odds in the UK.

Caroline Richmond reports on miscellaneous winners and losers from the health care scene in the United Kingdom. The winners include a young patient who is holding her own against formidable medical odds after receiving heroic treatment for leukemia, and the country's osteopaths, who have won the right to compile a statutory register. The losers are the venerable St. Bartholomew's Hospital, which appears to have lost its battle to stay open, and a 32-year-old man who almost made it to medical school by posing as a teenager.

Female↗
PubMed1996

NHS waiting list have been a boon for private medicine in the UK.

Health care: public, private or both? In Great Britain, about 13% of the population is covered by private health insurance, and everyone else is served by the public health care system known as the National Health Service, or NHS. Caroline Richmond, who examined the impact of private medical practice in Britain, says people become private patients for one compelling reason: to avoid the NHS's notoriously long waiting lists for surgery. According to Professor Alan Maynard, a health care researcher, the mainstays of the private sector are the "three h's" --hips, hernias and hemorrhoids-- along with some elective surgery, particularly in gynecology and opthalmology. Another small sector focuses on fertility regulation and cosmetic surgery. Although the levels are not monitored closely, physician consultants are not permitted to earn more than 10% of their income from private practice.

Canada↗
PubMed1996

Triviality and frequency of night calls irk British GPs.

British general practitioners, who are tired of their 24-hour responsibility, recently had a showdown with government about providing medical care outside normal hours. Physicians will be paid more for after-hours calls, but many would prefer not to do the work at all. They say such calls are often a waste of their time.

Attitude of Health Personnel↗
PubMed1995

The strange case of the misplaced suppository.

In a controversial decision, the General Medical Council has found a consultant anesthetist guilty of serious professional misconduct for giving a painkilling suppository without forewarning the patient and obtaining consent. Even though the suppository was misplaced in the patient's vagina, this was accepted as a mistake, at issue was whether a specific separate consent was required for insertion of the suppository.

Anesthesiology↗
PubMed1995

Is the issue the price of a child's life, or the futility of heroic measures?

Britain's High Court has been asked to rule whether a $160,000 experimental treatment with a 1% chance of saving the life of a 10-year-old girl should be paid for by the National Health Service. Child B, who has had one bone-marrow transplant, has had acute myeloblastic leukemia for a year and is near death. However, after her Cambridge doctors advised that further treatment would not be beneficial, her family found a hematologist willing to try an experimental treatment and a second transplant. The media debate in Britain has focused on financial aspects of the situation, not on the usually futile use of heroic measures.

Child↗
PubMed1995

Different fates await authors after two journal reports declared invalid in UK.

Two London gynecologists have left their positions in disgrace amid accusations of fraud connected with two research papers published in a British obstetrics journal. The merger of four medical schools, the first stage of the closure of the eminent St. Bartholomew's Hospital and hospital trust appointments also caught the attention of our London correspondent.

Female↗