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Biomedical subjects

M Stewart

Publications and source records attributed to M Stewart.

At least 127 records · Page 7Linked to original sources
PubMed1999

Using the patient-centered method to achieve excellence in care for women with breast cancer.

The diagnosis of breast cancer remains one of the most threatening and emotionally debilitating diagnoses given to patients. Breast cancer elicits fears of loss of ability, control, hope, and at worst--loss of life. Patients and their families, devastated by the diagnosis of cancer, often feel unsupported or dismissed by their health care providers. Using the example of breast cancer, this paper describes how the application of the patient-centred clinical method can assist physicians in caring for patients diagnosed with breast cancer. Composite cases and quotes drawn from qualitative research studies with breast cancer patients are used to illustrate the application of the patient-centred clinical method.

Attitude to Health↗
PubMed1999

Pictures in cell biology. Structures of nuclear-transport components.

The past three years have seen the solution of several nuclear transport component structures and recently of the structure of a regulator bound to part of a nuclear pore complex (NPC) protein. These structures have provided a wealth of valuable information about the proteins involved and suggested strategies for further investigation of their properties. We do not have space here to go into detail about this information, so instead we are illustrating the structures and providing primary references enabling interested readers to find further information. On this page, we are concentrating on the GTPase Ran and proteins that modulate its activity, and on the facing page are the other transport factors, some of which also interact directly with Ran. Notably absent at the moment are the nuclear pore complex component s, apart from one domain of RanBP2. Only when theses are characterized fully will we really be able to understand how transport substrates move across the nuclear envelope.

Animals↗
PubMed1999

Structural basis for dimerization of the Dictyostelium gelation factor (ABP120) rod.

Gelation factor (ABP120) is one of the principal actin-cross-linking proteins of Dictyostelium discoideum. The extended molecule has an N-terminal 250-residue actin-binding domain and a rod constructed from six 100-residue repeats that have an Ig fold. The ability to dimerize is crucial to the actin cross-linking function of gelation factor and is mediated by the rod in which the two chains are arranged in an antiparallel fashion. We report the 2.2 A resolution crystal structure of rod domains 5 and 6, which shows that dimerization is mediated primarily by rod domain 6 and is the result of a double edge-to-edge extension of beta-sheets. Thus, contrary to earlier proposals, the chains of the dimeric gelation factor molecule overlap only within domain 6, and domains 1-5 do not pair with domains from the other chain. This information allows construction of a model of the gelation factor molecule and suggests how the chains in the related molecule filamin (ABP280) may interact.

Amino Acid Sequence↗
PubMed1999

Locally advanced breast cancer: the outcome of primary polychemotherapy based on infusional 5 fluorouracil.

Over a 5-year period, 75 patients with locally advanced breast cancer presenting to the Edinburgh Breast Unit were managed with a policy of infusional primary chemotherapy. For 65 patients, the regimens comprised infusional 5 fluorouracil with anthracycline and/or either cyclophosphamide or cisplatinum (AcF, CAF or ECF) whilst 10 older patients had CMF-inf. The overall activity and tolerability for the regimens was good with a 76% objective response rate including 15% clinical complete responses. Surgery was possible in 64% and pathological complete responses confirmed in 7 (9.3%). Median disease free survival (DFS) is 5.23 years. Factors predicting for DFS or Overall Survival (OS) were assessed in this small group and ER positive patients did better than ER negative although there was surprisingly no negative DFS or OS association with inflammatory disease or advancing age. We found a paradoxical interaction with use of post-chemotherapy tamoxifen which was significantly associated with poorer DFS and OS overall and in the ER negative subgroups.

Journal Article↗
PubMed1999

Correlates between hematopoiesis and neuropoiesis: neural stem cells.

There are many parallels between the neuropoietic and lymphohematopoietic systems. The lymphohematopoietic stem/progenitor cell system has been extensively characterized, but there are still major questions relating to the definitive stem cell assay, the structure of the system (i.e., hierarchical versus cell cycle-based), and the nature of differentiation (i.e., stochastic versus deterministic). Recent data have established the existence of an epidermal growth factor (EGF)-responsive neural stem cell in adult mice. We have studied these neural progenitor/stem cells in fetal (day 15) and 2-day postnatal mice and established a single-cell progenitor assay and a variety of putative uni-, bi-, and tripotential stem cells that form in response to EGF. Neurospheres are the EGF-responsive neural units that grow in liquid culture, and we have found that cells derived from these neurospheres express a wide array of cytokines and their receptors. This will provide a window on the hemopoietic progenitor system analogous to that created by the description of in vitro growth of clonal hematopoietic progenitors.

Animals↗
PubMed1999

Helping students to understand that outward currents depolarize cells.

The physiology of excitable membranes is a fundamental topic in neuroscience and physiology courses at graduate and undergraduate levels. From the building blocks of ionic gradients and membrane channels whose permeability is selective and variable, we build the concepts of resting potential, action potential, and propagation in neurons and muscle fibers. Many students have an intuitive understanding of the movements of ions and the associated changes in membrane potential. For example, potassium ions leaving a cell through potassium-selective channels become unbalanced positive charges on the outside of the cell (and leave unbalanced negative charges on the inside), thus producing a potential across the membrane with the inside negative with respect to the outside. Later, when we discuss the local circuit currents that underlie propagation or the basis for extracellular stimulation, we make the general statement that "outward currents depolarize cells." Students respond with utter disbelief. Two simple additions to a discussion of membranes are suggested that permit the formulation of a consistent set of rules that apply to everything from the resting and action potentials of nerve and muscle through synaptic potentials and stimulation techniques.

Cell Physiological Phenomena↗
PubMed1999

Breast cancer survivors' perceptions of complementary/alternative medicine (CAM): making the decision to use or not to use.

The study described in this article explored breast cancer survivors' perceptions and experiences as they decided whether to use a variety of complementary/alternative therapies. Six focus groups were conducted composed of women who had been diagnosed with breast cancer. Each 2-hour session was audiotaped and transcribed verbatim. In this article, the process by which the participants made the decision to use or not to use complementary/alternative therapies, including their discovery and investigation of complementary/alternative medicine (CAM) and their experiences using or not using CAM, are described. Barriers to using CAM included cost, access, and time. Family and friends generally supported the decision to use CAM; however, the participants described health care practitioners' reactions as mixed.

Adult↗
PubMed1999

Evidence on patient-doctor communication.

This chapter covers important and well-studied aspects of patient-doctor communication. First the paper describes the lessons learned from studies about patients' satisfactions or dissatisfactions related to patient-doctor communication, making the point that complaints about doctors are usually due to communication problems and not technical competency issues. The next section of the chapter deals with time. It is often assumed that effective communication is inefficient. While this is not necessarily the case, the research results are complex and very interesting. The third part of the chapter covers communication in relation to patient adherence with the management plan recommended by the doctor. There is strong evidence that communication affects patient adherence and that there are four key aspects of communication that can enhance the patients' co-operation with the management plan. The final topic is patients' health. Twenty-two studies indicate the generally positive effect of key dimensions of communication on actual patient health outcomes such as pain, recovery from symptom, anxiety, functional status, and physiologic measures of blood pressure and blood glucose.

Attitude to Health↗
PubMed1999

The diagnostic value, parental and patient acceptability of micturating cysto-urethrography in children.

OBJECTIVES: To evaluate the medical indications and outcome including psychological and physical consequences of micturating cysto urethrography. METHODS: A prospective study of 165 consecutive children undergoing MCUG during a 3 month period. Medical data, including outcome was recorded. The distress of the child was recorded by the radiographer at the time of the examinations. Postal questionnaires were sent to parents one week after the test to obtain information on their own and their child's perception of the test, and any physical and/or behavioural changes. RESULTS: Age distribution for first and subsequent MCUG. [table: see text] 73% of first MCUG's were requested because of urinary tract infection. 52% of first MCUG's in infants were abnormal compared with 13% in older children aged 1 to 4 years. 29 children aged 4 and over underwent a second or subsequent MCUG (53% abnormal). These children would be suitable for indirect cystography. One quarter of children experienced difficulty in passing urine following the test, haematuria was experienced by four. Radiographers recorded severe distress in 27% of children and 27% of parents also recorded distress. CONCLUSIONS: A high incidence of distress was detected for both parent and child. Units should establish special guidelines for the use of this invasive procedure. A clear explanation of the investigation to parents and children should be standard practice. Routine employment of sedation for patients may be advisable. Alternative methods of imaging should be considered and evaluated, and indirect isotope cystography employed where appropriate.

Anxiety↗
PubMed1998

The structure of the Q69L mutant of GDP-Ran shows a major conformational change in the switch II loop that accounts for its failure to bind nuclear transport factor 2 (NTF2).

We report the 2.3 A resolution X-ray crystal structure of the GDP-bound form of the RanQ69L mutant that is used extensively in studies of nucleocytoplasmic transport and cell-cycle progression. When the structure of GDP-RanQ69L from monoclinic crystals with P21 symmetry was compared with the structure of wild-type Ran obtained from monoclinic crystals, the Q69L mutant showed a large conformational change in residues 68-74, which are in the switch II region of the molecule which changes conformation in response to nucleotide state and which forms the major interaction interface with nuclear transport factor 2 (NTF2, sometimes called p10). This conformational change alters the positions of key residues such as Lys71, Phe72 and Arg76 that are crucial for the interaction of GDP-Ran with NTF2 and indeed, solution binding studies were unable to detect any interaction between NTF2 and GDP-RanQ69L under conditions where GDP-Ran bound effectively. This interaction between NTF2 and GDP-Ran is required for efficient nuclear protein import and may function between the docking and translocation steps of the pathway.

Animals↗
PubMed1998

Solution structure of the motile major sperm protein (MSP) of Ascaris suum - evidence for two manganese binding sites and the possible role of divalent cations in filament formation.

The major sperm protein (MSP) of Ascaris suum mediates amoeboid motility by forming an extensive intermeshed system of cytoskeletal filaments analogous to that formed by actin in many other amoeboid cells. MSP is a dimeric molecule that polymerizes to form non-polar filaments constructed from two helical subfilaments that wind round one another. Moreover, MSP filaments can interact with one another to form higher-order assemblies without requiring the range of accessory proteins usually employed in actin-based systems. A knowledge of how MSP polymerizes and forms the hierarchical series of helical MSP macromolecular assemblies is fundamental to understanding locomotion in these cells. Here we describe the solution structure of MSP dimers determined by NMR spectroscopy under conditions where MSP does not polymerize to form filaments. The solution structure is indistinguishable from that observed in putative MSP subfilament helices by X-ray crystallography, indicating that MSP polymerization is not accompanied by a major conformational change. We also show that the rate of MSP polymerization associated with movement of vesicles in an in vitro motility assay is enhanced by the presence of magnesium and manganese ions and use NMR to show that the primary residues that bind these ions are 24-25 and 83-86. These residues are distant from the interface formed between MSP dimers in subfilament helices, and so are probably not involved in this level of polymerization. Instead the manganese and magnesium ion binding appears to be associated with the assembly of subfilaments into filaments and their subsequent aggregation into bundles.

Animals↗
PubMed1998

Location of the binding site of the mannose-specific lectin comitin on F-actin.

We have used electron microscopy and computer image processing to produce a three-dimensional reconstruction of F-actin filaments decorated with the putative lectin and actin-binding protein comitin. These reconstructions show that comitin binds to F-actin at high radius primarily to actin subdomain 1. This location is distinctly different from the binding site on F-actin for other actin bundling proteins, such as members of the alpha-actinin family, and may result from the positively charged comitin interacting with negatively charged sites near the actin N terminus in subdomain 1. The location of the comitin binding site and its restriction to subdomain 1 on a single actin monomer is consistent with comitin's having a function distinct from other actin-binding proteins and, for example, would enable comitin to link bundled actin filaments to the Golgi.

Actins↗