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Biomedical subjects

K Smith

Publications and source records attributed to K Smith.

At least 199 records · Page 11Linked to original sources
PubMed1998

Direct measurement of recognition forces between proteins and membrane receptors.

The interactions between the protein, cholera toxin B subunit attached to an atomic force microscope, AFM, cantilever, CTB and its receptor the ganglioside, GM1 have been measured in a dilute electrolyte solution, pH 5.5. Although there is variation in the force separation data obtained, particularly on approach of the AFM tip to the GM1 surface where usually, but not always an attraction is noted, an adhesion is always noted on separation of the surfaces. The strength of this adhesion varies from experiment to experiment, but appears to be quantised at a value of around 90 pN. Addition of cholera toxin to the aqueous electrolyte solution completely removes the attractive interaction and adhesion. This gives us confidence that in the earlier experiments, a specific interaction between the CTB and GM1 was measured.

Cell Membrane↗
PubMed1998

Decision making: the context of nurse prescribing.

From October 1994 qualified district nurses and health visitors from eight demonstration sites in England have been able to prescribe from a limited list of formulary items. Data collected from nurses formed only one part of the evaluation of nurse prescribing. These data highlighted a number of areas where prescribing nurses were faced with difficult decisions. A number of authors have considered how both doctors and nurses make decisions, and the factors which may influence the decision making process. With reference to the literature this paper focuses on the findings related to decision making in the context of nurse prescribing.

Community Health Nursing↗
PubMed1998

Collecting patients' views and perceptions of continence services: the development of research instruments.

This paper describes one part of a feasibility study carried out in England which examined the costs, quality and effectiveness of continence services in areas with different approaches to provision. It involved the design of instruments to collect the views and perceptions of patients and an investigation of ways to develop a methodology to implement comparative studies. It is the design and piloting of the questionnaires and the way patients responded that forms the focus of this paper. The main sample group recruited for the study were women who had recently sought formal help with urinary incontinence and were likely to receive conservative treatment or management in the community. They were interviewed and asked to complete four questionnaires at two points in time. A smaller sub-group of disabled women, interviewed only once, were included to compare cost profiles for different client groups. The questionnaires which were developed address the impact of urinary incontinence (using a standard scale), the effectiveness of service provision in terms of patients' clinical history, expectations and hoped-for outcomes, service receipt and its cost, and patients' satisfaction with several aspects of service provision. In total 118 women were interviewed, including 28 disabled women. The study generated a set of survey instruments which might be used for a variety of purposes including audit and future research and which could inform purchaser and provider decisions by using patients' perspectives of quality of life outcomes to enhance service development.

Attitude to Health↗
PubMed1998

The distribution of community psychiatric nurses in England: are they where they should be?

Given the substantial increase in the numbers of community psychiatric nurses (CPNs) in England in the last 15 years this paper asks the question: is CPN activity where it should be? In-other words is activity distributed around the country according to need? Various indicators of need are suggested including population age structure, deprivation indices and suicide rates. We find no evidence -- based on information from scatterplots, Spearman correlations and more innovative measures of inequality -- that CPNs are distributed according to need. If this is confirmed by further research it is cause for alarm -- CPNs should be where they are most needed.

Adolescent↗
PubMed1998

Nurse-patient relationships: the context of nurse prescribing.

Nurse prescribing was initiated in the United Kingdom in October 1994 in eight demonstration sites. The evaluation of this extension to the community nurses' role explored both economic and qualitative benefits to patients, carers, nurses and other health care professionals. In this paper the impact of nurse prescribing on patients is explored. Benefits experienced by patients are described along with the difficulties encountered. The patients' views regarding nurses as prescribers are also explored. Data were collected by means of interviews with patients/carers, the focus of which was to evaluate changes associated with nurse prescribing. Patients raised a number of issues associated with their relationship with nurses. Patients valued nurses for both their accessibility and approachability, which led them to discuss health issues which would not otherwise have been brought to the attention of the general practitioner. The arguments which support the incorporation of these qualities into an expanded nursing role are presented.

Attitude to Health↗
PubMed1998

Tissue distribution of hantavirus antigen in naturally infected humans and deer mice.

The Sin Nombre virus (SNV) is the etiologic agent of hantavirus pulmonary syndrome in humans but does not cause disease in chronically infected deer mice (Peromyscus maniculatus), the natural host. In this study, murine antiserum raised against recombinant SNV nucleocapsid protein was utilized to localize viral antigen immunohistochemically in tissues from both humans (n = 20; 11 positive, 9 negative) and deer mice (n = 6; 4 positive, 2 negative). Viral infection status was confirmed by Western blot or reverse transcriptase-polymerase chain reaction. SNV antigen was detected in pulmonary and cardiac endothelium in both species, but positive cells in deer mice were rare. Other deer mouse tissues, including kidney, were negative; in contrast, vascular elements of several tissues from infected humans were positive, with strong staining of renal endothelium. The paucity of positive cells in chronically infected mice suggests a low virus burden compared with that of acutely infected humans.

Animals↗
PubMed1998

The Ottawa telehealth project.

OBJECTIVE: To examine the telehealth system as a means of improving access to cardiac consultations and specialized health services in remote areas of Ontario. METHODS: The University of Ottawa Heart Institute has set up a telehealth test program, Healthcare and Education Access for Remote Residents by Telecommunications (HEARRT), in collaboration with industry and the provincial and federal government, as well as several remote clinical test sites. The program makes off-site cardiology consultations possible. History taking and physical examinations are conducted by video and electronic stethoscope. Laboratory results and echocardiograms are transmitted by document camera and VCR. The technology is being tested in both stable outpatient and emergency situations. Various telecommunications bandwidths and encoding systems are being evaluated, including satellite and terrestrial-based asynchronous transfer-mode circuits. Patient satisfaction and cost-effectiveness are also being assessed. RESULTS: Bandwidths from as low as 384 kbps using H.320 encoders to 40 Mbps using digital transport of NTSC video signals have been evaluated. Although lower bandwidths are sufficient for sending echocardiographic and electrocardiogram data, bandwidths with transport speeds of 4 to 6 Mbps appear necessary to capture the nuances of the cardiac physical examination. A preliminary satisfaction survey of 19 patients noted that all felt that they could communicate effectively with the cardiologist by video, and each had confidence in the advice offered. None reported that he or she would rather have traveled to the doctor in person. Initial and projected examination of the costs suggested that telehealth will effectively reduce overall health care spending while decreasing travel expenses for rural patients. CONCLUSION: Telehealth technology is sufficiently sophisticated to allow off-site cardiology assessments. Preliminary results suggest there is a sound business case for the implementation of telehealth technology to meet the needs of remote residents in northern Ontario. Working closely with government and industry, we will develop a marketing and commercialization plan to support the use of this technology throughout Ontario and expand application to patient education and continuing medical education.

Cardiology↗
PubMed1998

Ribozymes targeted to stearoyl-ACP delta9 desaturase mRNA produce heritable increases of stearic acid in transgenic maize leaves.

Ribozymes are RNAs that can be designed to catalyze the specific cleavage or ligation of target RNAs. We have explored the possibility of using ribozymes in maize to downregulate the expression of the stearoyl-acyl carrier protein (Delta9) desaturase gene. Based on site accessibility and catalytic activity, several ribozyme constructs were designed and transformed into regenerable maize lines. One of these constructs, a multimer hammerhead ribozyme linked to a selectable marker gene, was shown to increase leaf stearate in two of 13 maize lines. There were concomitant decreases in Delta9 desaturase mRNA and protein. The plants with the altered stearate phenotype were shown to express ribozyme RNA. The ribozyme-mediated trait was heritable, as evidenced by stearate increases in the leaves of the R1 plants derived from a high-stearate line. The increase in stearate correlated with the presence of the ribozyme gene. A catalytically inactive version of this ribozyme did not produce any significant effect in transgenic maize. This is evidence that ribozymes can be used to modulate the expression of endogenous genes in maize.

Amino Acid Sequence↗
PubMed1998

Cutaneous epithelioid schwannomas: a rare variant of a benign peripheral nerve sheath tumor.

Although benign epithelioid peripheral nerve sheath tumors have been described, they are rare, and benign epithelioid schwannomas have not yet been established as a specific histologic variant. We present four cases of tumors which we believe would meet criteria to be classified as benign epithelioid schwannomas. Biopsy specimens obtained from four different patients were examined with routine and immunohistochemical staining. All the tumors were well-circumscribed lesions that were surrounded by a capsule containing EMA-positive cells. The cellular component was composed of epithelioid cells, in which there was a lack of mitotic activity. Immunohistochemical studies showed the tumor cells were S-100 protein and Leu 7 positive and HMB-45 negative. In addition, type IV collagen encircled individual cells within the tumor, indicating a continuous basal lamina. We report a group of cutaneous epithelioid schwannomas. Although the presence of such tumors is not unexpected, this diagnosis may not be initially considered because of this rare cytologic feature.

Adult↗
PubMed1998

Cutaneous fibrous perineurioma.

Tumors of perineurial origin are rare. Three variants of perineuriomas have been described, a storiform perineurial fibroma, an intraneural perineurioma, and a recently described sclerosing perineurioma. We present two patients with cutaneous fibrous perineurioma located in acral areas. Both tumors had a deep circumscribed margin with a prominent vascular component. They contained small round cells and spindle cells that express EMA and show membrane staining for type IV collagen. Cutaneous fibrous perineuriomas fit within the spectrum of neurocristicly derived cellular proliferations.

Adult↗
PubMed1998

The role of mouse adenovirus type 1 early region 1A in acute and persistent infections in mice.

Mouse adenovirus type 1 (MAV-1) early region 1A (E1A) viral mutants were used to determine the importance of this region in pathogenesis and establishment of a persistent infection in the natural host. Lethal dose analysis with adult male Swiss outbred mice revealed a significant reduction in virulence for all of the E1A mutants. During acute infections with 10(5) PFU of virus, an E1A null mutant, pmE109, was found in the same organs (brain, spleen, and spinal cord) and the same cell types (endothelial cells and mononuclear cells in lymphoid tissue) as wild-type virus. Another null mutant, pmE112, was detected in the same organs but in lower numbers. However, when mice were given a lower dose, 1 PFU, pmE109 and pmE112 reached none of the target organs analyzed by 14 days postinfection (p.i.). The absence of E1A did not hinder the ability of MAV-1 to establish a persistent infection. Viral nucleic acid was detected by PCR amplification or in situ hybridization in the kidneys, brains, spleens, and prefemoral lymph nodes of mice infected with wild-type or mutant virus up to 55 weeks p.i. The brain, spleen, and lymph node are recognized sites of acute viral infection but are previously unrecognized sites for MAV-1 persistence. Evidence for the potential reactivation of persistent MAV-1 infections is also presented.

Adenoviridae↗
PubMed1998

Mouse adenovirus type 1 early region 1A is dispensable for growth in cultured fibroblasts.

Mouse adenovirus type 1 (MAV-1) mutants with deletions of conserved regions of early region 1A (E1A) or with point mutations that eliminate translation of E1A were used to determine the role of E1A in MAV-1 replication. MAV-1 E1A mutants expressing no E1A protein grew to titers comparable to wild-type MAV-1 titers on mouse fibroblasts (3T6 fibroblasts and fibroblasts derived from Rb+/+, Rb+/-, and Rb-/- transgenic embryos). To test the hypothesis that E1A could induce a quiescent cell to reenter the cell cycle, fibroblasts were serum starved to stop DNA replication and cellular replication and then infected with the E1A mutant and wild-type viruses. All grew to equivalent titers. Steady-state levels of MAV-1 early mRNAs (E1A, E1B, E2, E3, and E4) from 3T6 cells infected with wild-type or E1A mutant virus were examined by Northern analysis. Steady-state levels of mRNAs from the mutant-infected cells were comparable to or greater than the levels found in wild-type virus infections for most of the early regions and for two late genes. The E2 mRNA levels were slightly reduced in all mutant infections relative to wild-type infections. E1A mRNA was not detected from infections with the MAV-1 E1A null mutant, pmE109, or from infections with similar MAV-1 E1A null mutants, pmE112 and pmE113. The implications for the lack of a requirement of E1A in cell culture are discussed.

Adenovirus E1A Proteins↗
PubMed1998

Effects of flooding amino acids on incorporation of labeled amino acids into human muscle protein.

We investigated the effects of the nature of the flooding amino acid on the rate of incorporation of tracer leucine into human skeletal muscle sampled by biopsy. Twenty-three healthy young men (24.5 +/- 5. 0 yr, 76.2 +/- 8.3 kg) were studied in groups of four or five. First, the effects of flooding with phenylalanine, threonine, or arginine (all at 0.05 g/kg body wt) on the incorporation of tracer [13C]leucine were studied. Then the effects of flooding with labeled [13C]glycine [0.1 g/kg body wt, 20 atoms percent excess (APE)] and [13C]serine (0.05 g/kg body wt, 15 APE) on the incorporation of simultaneously infused [13C]leucine were investigated. When a large dose of phenylalanine or threonine was administered, incorporation of the tracer leucine was significantly increased (from 0.036 to 0. 067 %/h and 0.037 to 0.070 %/h, respectively; each P < 0.01). However, when arginine, glycine, or serine was administered as a flooding dose, no stimulation of tracer leucine incorporation could be observed. These results, together with those previously obtained, suggest that large doses of individual essential, but not nonessential, amino acids are able to stimulate incorporation of constantly infused tracer amino acids into human muscle protein.

Adult↗
PubMed1998

Modulation of whole body protein metabolism, during and after exercise, by variation of dietary protein.

The aim of this study was to investigate dietary protein-induced changes in whole body leucine turnover and oxidation and in skeletal muscle branched chain 2-oxo acid dehydrogenase (BCOADH) activity, at rest and during exercise. Postabsorptive subjects received a primed constant infusion of L-[1-13C,15N]leucine for 6 h, after previous consumption of a high- (HP; 1.8 g . kg-1 . day-1, n = 8) or a low-protein diet (LP; 0.7 g . kg-1 . day-1, n = 8) for 7 days. The subjects were studied at rest for 2 h, during 2-h exercise at 60% maximum oxygen consumption, then again for 2 h at rest. Exercise induced a doubling of both leucine oxidation from 20 micromol . kg-1 . h-1 and BCOADH percent activation from 7% in all subjects. Leucine oxidation was greater before (+46%) and during (+40%, P < 0.05) the first hour of exercise in subjects consuming the HP rather than the LP diet, but there was no additional change in muscle BCOADH activity. The results suggest that leucine oxidation was increased by previous ingestion of an HP diet, attributable to an increase in leucine availability rather than to a stimulation of the skeletal muscle BCOADH activity.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1998

Balance retraining in a hemiparetic patient using center of gravity biofeedback: a single-case study.

A single-subject experimental design was used to evaluate the effects of center of gravity biofeedback on retraining balance control in a 72-yr.-old male hemiparetic patient. For both assessment and training the subject stood on dual force-plates enclosed on three sides by a visual surround. A 4-wk. training period consisted of subject-initiated shifts in body weight to control movement of a real-time computer display of the subject's center of gravity. A Sensory Organization Test and evaluation of weight distribution indicated that biofeedback retraining positively affected balance control during dynamic conditions and when the ground support moved forward.

Aged↗
PubMed1998

Anomalies in Nef expression within the central nervous system of HIV-1 positive individuals/AIDS patients with or without AIDS dementia complex.

In determining levels of expression of HIV-1 Nef protein within the central nervous system (CNS) we assessed antibody responses to the protein both peripherally and in CNS. Antibodies to Nef were not detected within the CNS despite detection of antibodies to both gp41 and Nef in peripheral blood and representative virus isolates derived from CNS and peripheral blood (PB) samples containing full length nef sequence and virus-infected cells expressing Nef protein. We conclude from this that expression of Nef within the CNS is such that little or no antibody production occurs and that these differences indicate that Nef protein may not be directly contributing to the AIDS dementia complex. Expression of Nef protein in PHA-activated peripheral blood mononuclear cells from CNS derived isolates was different to that of coincidental PB derived isolates in that partial surface expression was observed for the latter. The results suggest that antigenic presentation of Nef within the CNS is anomalous and that Nef protein expression, at least for the limited number of in vitro derived isolates tested, has a different localization pattern.

AIDS Dementia Complex↗
PubMed1998

Development of a non-high pressure liquid chromatography assay to determine testosterone hydroxylase (CYP3A) activity in human liver microsomes.

The major pathway of testosterone oxidation by human liver microsomes is the formation of 6beta-hydroxytestosterone, which is catalyzed by CYP3A4/5 and which accounts for 75-80% of all metabolites formed. In the present study, we describe a non-high pressure liquid chromatography assay (HPLC) of CYP3A4/5 activity based on the release of tritium (with formation of tritiated water) upon incubation of [1,2,6,7-3H]testosterone with human liver microsomes and NADPH. Unreacted testosterone and its metabolites were quantitatively extracted from the incubation mixture with activated charcoal under conditions that resulted in no extraction of tritiated water. The amount of tritiated water formed was quantified by liquid scintillation spectrometry and compared with the amount of hydroxylated testosterone metabolites formed, as determined by HPLC. Rates of tritium release from [1,2,6, 7-3H]testosterone paralleled rates of testosterone 6beta-hydroxylation as a function of incubation time, the amount of microsomal protein, and the concentration of substrate (which yielded identical apparent Km and Vmax values). The sample-to-sample variation in tritium release from [1,2,6,7-3H]testosterone with a panel of human liver microsomes was highly correlated with rates of testosterone 6beta-hydroxylation and terfenadine metabolism, two commonly used markers of CYP3A activity. Several recombinant human P450 enzymes were incubated with [1,2,6,7-3H]testosterone, and only cDNA-expressed CYP3A4 catalyzed a high rate of tritium release. The close agreement between the tritium-release assay and HPLC procedure for measuring testosterone oxidation indicates that tritium release from [1,2,6,7-3H]testosterone provides a simple and rapid alternative to the HPLC procedure for measuring CYP3A4/5 activity in human liver microsomes. However, the tritium-release assay may have limited value in measuring CYP3A activity in liver microsomes from other species due to the presence of other P450 enzymes that can catalyze tritium release from [1,2,6,7-3H]testosterone.

Aryl Hydrocarbon Hydroxylases↗