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Biomedical subjects

M Andrews

Publications and source records attributed to M Andrews.

At least 19 recordsLinked to original sources
PubMed2006

Observation of muon neutrino disappearance with the MINOS detectors in the NuMI neutrino beam.

This Letter reports results from the MINOS experiment based on its initial exposure to neutrinos from the Fermilab NuMI beam. The rates and energy spectra of charged current nu(mu) interactions are compared in two detectors located along the beam axis at distances of 1 and 735 km. With 1.27 x 10(20) 120 GeV protons incident on the NuMI target, 215 events with energies below 30 GeV are observed at the Far Detector, compared to an expectation of 336+/-14 events. The data are consistent with nu(mu) disappearance via oscillations with |Delta(m)2/32|=2.74 +0.44/-0.26 x10(-3)eV(2) and sin(2)(2theta(23))>0.87 (68% C.L.).

Journal Article↗
PubMed2005

A role for shoot protein in shoot-root dry matter allocation in higher plants.

BACKGROUND AND AIMS: It is stated in many recent publications that nitrate (NO3-) acts as a signal to regulate dry matter partitioning between the shoot and root of higher plants. Here we challenge this hypothesis and present evidence for the viewpoint that NO3- and other environmental effects on the shoot:root dry weight ratio (S:R) of higher plants are often related mechanistically to changes in shoot protein concentration. METHODS: The literature on environmental effects on S:R is reviewed, focusing on relationships between S:R, growth and leaf NO3- and protein concentrations. A series of experiments carried out to test the proposal that S:R is dependent on shoot protein concentration is highlighted and new data are presented for tobacco (Nicotiana tabacum). KEY RESULTS/EVIDENCE: Results from the literature and new data for tobacco show that S:R and leaf NO3- concentration are not significantly correlated over a range of environmental conditions. A mechanism involving the relative availability of C and N substrates for growth in shoots can explain how shoot protein concentration can influence shoot growth and hence root growth and S:R. Generally, results in the literature are compatible with the hypothesis that macronutrients, water, irradiance and CO2 affect S:R through changes in shoot protein concentration. In detailed studies on several species, including tobacco, a linear regression model incorporating leaf soluble protein concentration and plant dry weight could explain the greater proportion of the variation in S:R within and between treatments over a wide range of conditions. CONCLUSIONS: It is concluded that if NO3- can influence the S:R of higher plants, it does so only over a narrow range of conditions. Evidence is strong that environmental effects on S:R are often related mechanistically to their effects on shoot protein concentration.

Nitrates↗
PubMed2005

Extension growth of Impatiens glandulifera at low irradiance: importance of nitrate and potassium accumulation.

BACKGROUND AND AIMS: The summer annual Impatiens glandulifera can reach 3 m in height within deciduous woodland. The primary objective was to determine if NO(3)(-) accumulation, and hence its osmotic effect, is an important physiological mechanism allowing Impatiens to achieve substantial height under low irradiance. METHODS: Stem extension, concentrations of K(+) and NO(3)(-) in leaves and concentrations of K(+), NO(3)(-) and other inorganic anions, malate, sugars, total N and total osmoticum in stem were measured in I. glandulifera sampled at different irradiance levels in deciduous woodland and in a glasshouse. Also, the energetic costs, as absorbed photons, of generating osmolarity in stem cell vacuoles with KNO(3), K(2)malate or hexose sugar were determined. KEY RESULTS: Results were similar in the woodland and glasshouse. At 50-100 % relative irradiance (Ir; open ground PAR = 100 % Ir) and 2-10 % Ir, plant height increased from 7-14 cm to 130-154 cm in 64-67 d. Leaf and stem NO(3)(-) concentrations were negligible at 50-100 % Ir while K(+), malate(2-) and sugars, respectively, accounted for 33.2-50.1 %, 19.3-20.8 % and 2.0-2.6 % of total osmoticum in stems. At 2-10 % Ir, NO(3)(-) concentrations were four to eight times greater in stems than leaves. Here, NO(3)(-) constituted 26.7-34.3 % of the total osmotic concentration in the stem and NO(3)(-)-N constituted 69-81 % of total N in stem tissue. Also at 2-10 % Ir, K(+) comprised 44.9-45.9 % and malate plus sugars 2.2-3.1 % of total osmotic concentration. The energy cost of osmoticum as KNO(3) was calculated as less than half that of malate and less than one-seventh that for hexose. Further calculations suggest that use of KNO(3), K(2)malate or glucose as osmoticum at low irradiance would, respectively, cost approx. 7 %, 16 % and 50 % of the total construction cost of the stem. CONCLUSIONS: It is concluded that accumulation of NO(3)(-) in place of organic molecules in stems is an important mechanism allowing I. glandulifera to achieve substantial height at low irradiance.

Acclimatization↗
PubMed2003

Tissue chamber model of acute inflammation in farm animal species.

A tissue chamber model of acute inflammation for use in comparative studies in calves, sheep, goats and pigs has been established and validated. Tissue chambers were prepared from silicon rubber tubing, of inner diameter 12.7 mm, length 115 mm and volume 15 ml, with 10 holes, each of 6mm diameter, at each end. In each animal two or four chambers were inserted at subcutaneous sites. Six weeks after implantation an acute inflammatory reaction in a single cage was generated by the intracaveal injection of 0.5 ml of 1% carrageenan solution. Serial samples of exudate (injected chamber), transudate (non-injected chamber) and blood were collected for measurement of exudate and transudate leucocyte count, prostaglandin (PG)E(2) concentration in exudate and serum thromboxane (Tx)B(2) concentration. In addition, skin temperature changes over exudate and transudate chambers were recorded. In all four species, carrageenan induced an acute inflammatory response, indicated by increases to peak values followed by return towards baseline in skin temperature, leucocyte count and PGE(2) concentration. For each of these variables in calves, sheep and goats the increases were significantly greater for exudate than for transudate. The degree of intra-species variation in each variable was acceptable. Marked inter-species differences were recorded: skin temperature rise was greatest in calves and least in sheep and goats; exudate PGE(2) concentration was increased in the order sheep>goat>pig>calf; serum TxB(2) concentration was increased in the order calf>goat>sheep>pig and exudate leucocyte count was increased to a greater extent in the pig than in the three ruminant species. The model has advantages over some previously described tissue chamber models of inflammation and will be suitable for use in comparative studies of inflammatory mechanisms and the pharmacokinetics and pharmacodynamics of anti-inflammatory drugs.

Acute Disease↗
PubMed2001

Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor.

Until recently, very little was known about the molecular mechanisms responsible for the development of glaucoma, a leading cause of blindness worldwide. Mutations in the glaucoma gene myocilin (MYOC, GLC1A) are associated with elevated intraocular pressure and the development of autosomal dominant juvenile glaucoma and a subset of adult-onset glaucoma. MYOC is expressed in the trabecular meshwork (TM), a tissue responsible for drainage of aqueous humor from the eye, and the tissue involved in elevated intraocular pressure associated with glaucoma. To better understand the role of MYOC in glaucoma pathogenesis, we examined the expression of normal and mutant myocilin in cultured ocular (TM) and non-ocular cells as well as in the aqueous humor of patients with and without MYOC glaucoma. Normal myocilin was secreted from cultured cells, but very little to no myocilin was secreted from cells expressing five different mutant forms of MYOC. In addition, no mutant myocilin was detected in the aqueous humor of patients harboring a nonsense MYOC mutation (Q368X). Co-transfection of cultured cells with normal and mutant myocilin led to suppression of normal myocilin secretion. These studies suggest that MYOC glaucoma is due either to insufficient levels of secreted myocilin or to compromised TM cell function caused by congestion of the TM secretory pathway.

Animals↗
PubMed2001

A retrieval study of capital hip prostheses with titanium alloy femoral stems.

We have examined 26 retrieved, failed titanium-alloy femoral stems. The clinical details, radiological appearances and the histology of the surrounding soft tissues in each patient were also investigated. The stems were predominantly of the flanged design and had a characteristic pattern of wear. A review of the radiographs showed a series of changes, progressive with time. The first was lateral debonding with subsidence of the stem. This was followed by calcar resorption and fragmentation or fracture of the cement. Finally, osteolysis was seen, starting with a radiolucency at the cement-bone interface and progressing to endosteal cavitation. Three histological appearances were noted: granulomatous, necrobiotic and necrotic. We suggest that an unknown factor, possibly related to the design of the stem, caused it to move early. After this, micromovement at the cement-stem interface led to the generation of particulate debris and fracture of the cement. A soft-tissue reaction to the debris resulted in osteolysis and failure of fixation of the prostheses.

Aged↗
PubMed2000

A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo.

The strongest susceptibility genes for the development of systemic lupus erythematosus (SLE) in humans are null mutants of classical pathway complement proteins. There is a hierarchy of disease susceptibility and severity according to the position of the missing protein in the activation pathway, with the severest disease associated with C1q deficiency. Here we demonstrate, using novel in vivo models of apoptotic cell clearance during sterile peritonitis, a similar hierarchical role for classical pathway complement proteins in vivo in the clearance of apoptotic cells by macrophages. Our results constitute the first demonstration of an impairment in the phagocytosis of apoptotic cells by macrophages in vivo in a mammalian system. Apoptotic cells are thought to be a major source of the autoantigens of SLE, and impairment of their removal by complement may explain the link between hereditary complement deficiency and the development of SLE.

Animals↗
PubMed2000

Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4).

The PDS gene encodes a transmembrane protein, known as pendrin, which functions as a transporter of iodide and chloride. Mutations in this gene are responsible for Pendred syndrome and autosomal recessive non-syndromic hearing loss at the DFNB4 locus on chromosome 7q31. A screen of 20 individuals from the midwestern USA with non-syndromic hearing loss and dilated vestibular aqueducts identified three people (15%) with PDS mutations. To determine whether PDS mutations in individuals with Pendred syndrome differ functionally from PDS mutations in individuals with non-syndromic hearing loss, we compared three common Pendred syndrome allele variants (L236P, T416P and E384G), with three PDS mutations reported only in individuals with non-syndromic hearing loss (V480D, V653A and I490L/G497S). The mutations associated with Pendred syndrome have complete loss of pendrin-induced chloride and iodide transport, while alleles unique to people with DFNB4 are able to transport both iodide and chloride, albeit at a much lower level than wild-type pendrin. We hypothesize that this residual level of anion transport is sufficient to eliminate or postpone the onset of goiter in individuals with DFNB4. We propose a model for pendrin function in the thyroid in which pendrin transports iodide across the apical membrane of the thyrocyte into the colloid space.

Alleles↗
PubMed2000

The role of cognitive cueing in eliciting vocal variability.

Variation in duration and frequency during three readings of each of eight sentences by 9 normal and 4 voice-disordered subjects are compared. Instructions to the subjects varied with respect to the amount and type of cognitive cueing presented in the trials, and the sentences were read in random order. Variability in fundamental frequency (F0) was greater when pitch variation was specifically cued. Also, the portion of the sentence that was cued had greater variability in F0 than other parts of the sentence. Variation in fundamental frequency was significantly greater in the cued versus uncued sentence trials for the voice-disordered subjects but not for the normal subjects. However, all subjects exhibited significantly greater duration for cued versus uncued readings of the same sentences. Implications for theory and practice are discussed.

Adult↗
PubMed2000

Effects of stimulation techniques on vocal responses: implications for assessment and treatment.

During voice evaluation and treatment it is customary for clinicians to elicit samples of the vowel /a/ from clients using various elicitation techniques. The purpose of this study was to compare the effects of four commonly used stimulation tasks on the laryngeal mechanism. Eleven female singing students, studying at a university music school, served as subjects for the study. The subjects phonated the vowel /a/ using 4 vocal stimulation techniques: yawn-sigh, gentle onset, focus, and the use of the voiceless fricative. Videoendoscopic and acoustic evaluations of their productions were done. Results show that, in the first 100 ms following the end of the formant transition, these techniques affected voice differently. The fundamental frequency was found to be highest in the yawn-sigh condition, whereas the maximum frequency perturbation was obtained for the voiceless fricative condition. Planned comparisons were made by comparing the data across 2 dimensions: (1) vowels elicited with voiced contexts versus those elicited with voiceless consonantal contexts and (2) vowels elicited with obstruent versus vowels elicited with nonobstruent consonantal contexts. Some changes in acoustic parameters brought about by these stimulation techniques may be explained on the basis of coarticulatory effects of the consonantal context.

Adolescent↗
PubMed2000

The nature and purpose of the role of the nurse lecturer in practice settings.

This paper examines the role of lecturers in nursing in pre-registration education. It focuses on the nature and purpose of the nurse lecturer's contribution in the practice setting, with particular emphasis on the issues surrounding clinical credibility. This is particularly pertinent in the light of current recommendations, which emphasise the importance of clinical learning in pre-registration education programmes. The purpose of the lecturer's role in clinical practice settings is ill defined. This lack of clear consensus regarding the expected outcomes for lecturers (in practice), leads to difficulty outlining what they should do in practice settings. Although lecturers accept that they have an important part to play in maximizing the learning opportunities for students in both university and practice settings, they are less clear about how this should be achieved in the latter. This paper argues that: It is opportune to examine and realign the lecturers contribution in practice settings given that there has been a shift in the responsibility for clinical learning; nurse education is now embedded in the higher education sector and there is a need for a greater emphasis on practice development. Clinical credibility for lecturers is about the development of nursing practice through education which is not always achieved by 'hands on' care. For example, assisting nurses in a ward area to develop expertise in evidence based practice may not involve 'hands on' care giving but does involve being conversant with current research and practice issues. The lecturer's expertise in practice settings is in teaching and facilitating learning, rather than direct care giving. No one common model for practice may be either feasible or desirable. However, it is important that nurse lecturers do not follow a particular approach because the debate about the nurse lecturer's role in practice settings fails to acknowledge the strengths and weaknesses of each model. It is important that the approach is based on sound rationale.

Clinical Competence↗
PubMed2000

Student and mentor perceptions of mentoring effectiveness.

The following is an account of a small pilot study conducted over a 3-month period which ascertained the views of staff nurses and students about the mentoring process. In particular, whether the possession of a teaching qualification influences the effectiveness of mentors. The research was conducted in a district general hospital in North Wales. The findings demonstrate that staff nurses with a teaching and assessing qualification consistently rate themselves as more effective and supportive than those without. Other findings show that students consistently rate their mentors positively irrespective of whether they held a teaching and assessing qualification and that students rate their mentors more positively than the mentors themselves. Although these findings are not generalizable in the accepted sense they may be applicable to other practice settings. The findings and discussion indicate several implications for future practice including the need for: More consistency in practice regarding the nature and purpose of mentorship Clear criteria and selection processes for potential mentors, including more extensive use of the Measuring Mentor Potential (MMP) scale as a predictive tool A review of current mentor preparation programmes to align them with the needs of diploma and degree students and to ensure comparability of standards throughout the UK More discussion regarding the nature and purpose of mentorship including further examination of a range of mentorship models.

Adult↗
PubMed2000

The role of the personal tutor in the academic context.

This paper is the second of a series on the role of the nurse teacher and is based on a review of the literature and the personal experience of the authors. Identifying the most appropriate way to support students in both the academic and clinical setting has been a major concern for nurse teachers. The move of nurse education into the higher education arena has increased the diverse nature of the nurse teachers role and raised questions about the nature and function of the personal tutor in relation to students undertaking nursing courses. This paper discusses the concept of the personal tutor, with particular focus on the academic aspects of the role. The time implication of adopting an all encompassing personal tutor role, within the current climate of higher education, is considered. The paper also highlights that the roles tutors adopt in practice are diverse and usually as a result of convenience rather than identified outcomes.

Counseling↗
PubMed2000

Artificial nutrition and hydration at the end of life.

Patients who are terminally ill do not respond to administration of artificial nutrition and hydration in the same way as patients who have potential for recovery. Knowledge of end-stage disease and ethical and legal parameters are necessary for health care team members to make clinically and morally sound therapeutic decisions in conjunction with the patient and family.

Decision Making↗
PubMed1999

EPR spin trapping and 2-deoxyribose degradation studies of the effect of pyridoxal isonicotinoyl hydrazone (PIH) on *OH formation by the Fenton reaction.

The search for effective iron chelating agents was primarily driven by the need to treat iron-loading refractory anemias such as beta-thalassemia major. However, there is a potential for therapeutic use of iron chelators in non-iron overload conditions. Iron can, under appropriate conditions, catalyze the production of toxic oxygen radicals which have been implicated in numerous pathologies and, hence, iron chelators may be useful as inhibitors of free radical-mediated tissue damage. We have developed the orally effective iron chelator pyridoxal isonicotinoyl hydrazone (PIH) and demonstrated that it inhibits iron-mediated oxyradical formation and their effects (e.g. 2-deoxyribose oxidative degradation, lipid peroxidation and plasmid DNA breaks). In this study we further characterized the mechanism of the antioxidant action of PIH and some of its analogs against *OH formation from the Fenton reaction. Using electron paramagnetic resonance (EPR) with 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap for *OH we showed that PIH and salicylaldehyde isonicotinoyl hydrazone (SIH) inhibited Fe(II)-dependent production of *OH from H2O2. Moreover, PIH protected 2-deoxyribose against oxidative degradation induced by Fe(II) and H2O2. The protective effect of PIH against both DMPO hydroxylation and 2-deoxyribose degradation was inversely proportional to Fe(II) concentration. However, PIH did not change the primary products of the Fenton reaction as indicated by EPR experiments on *OH-mediated ethanol radical formation. Furthermore, PIH dramatically enhanced the rate of Fe(II) oxidation to Fe(III) in the presence of oxygen, suggesting that PIH decreases the concentration of Fe(II) available for the Fenton reaction. These results suggest that PIH and SIH deserve further investigation as inhibitors of free-radical mediated tissue damage.

Cyclic N-Oxides↗