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PubMed1983

Electrical properties of sheep Purkinje strands. Electrical and chemical potentials in the clefts.

The impedence of sheep Purkinje strands, measured to 3-5 kHz, is interpreted with circuit models based on morphology. The strand is described as a one-dimensional electrical cable. Clefts between myocytes of the strand allow radial current to flow in parallel with current across the outer membrane. A lumped model of the clefts, in which all the cleft membrane is in series with 100 omega-cm2, fits only below 20 Hz. Two distributed models, pie and disk, fit at all frequencies with somewhat different (31%) luminal resistivities, but with similar membrane parameters. Series resistance representing the endothelial sheath is small. Simulations of voltage clamp experiments include measured linear parameters and nonlinear membrane channels, as well as radial variation of cleft concentration, membrane flux, voltage, and current. Cleft potential is drastically nonuniform when sodium current flows. Cleft potential is reasonably uniform when calcium and potassium currents flow, but the calcium and potassium concentrations change markedly, enough to turn off the calcium current, even if the calcium channel did not inactivate. We conclude that physiological current flows produce significant nonuniformities in electrochemical potentials in the clefts of this cardiac preparation.

Animals↗

PubMed1992

Cooperativity of thiol-modified myosin filaments. ATPase and motility assays of myosin function.

The effects of chemical modifications of myosin's reactive cysteines on actomyosin adenosine triphosphatase (ATPase) activities and sliding velocities in the in vitro motility assays were examined in this work. The three types of modifications studied were 4-[N-[(iodoacetoxy)ethyl]-N-methylamino]-7-nitrobenz-2-oxa-1,3- diazole labeling of SH2 (based on Ajtai and Burghart. 1989. Biochemistry. 28:2204-2210.), phenylmaleimide labeling of SH1, and phenylmaleimide labeling of myosin in myofibrils under rigor conditions. Each type of modified myosin inhibited the sliding of actin in motility assays. The sliding velocities of actin over copolymers of modified and unmodified myosins in the motility assay were slowest with rigor-modified myosin and most rapid with SH2-labeled myosin. The actin-activated ATPase activities of similarly copolymerized myosins were lowest with SH2-labeled myosin and highest with rigor-modified myosin. The actin-activated ATPase activities of myosin subfragment-1 obtained from these modified myosins decreased in the same linear manner with the fraction of modified heads. These results are interpreted using a model in which the sliding of actin filaments over myosin filaments decreases the probability of myosin activation by actin. The sliding velocity of actin over monomeric rigor-modified myosin exceeded that over the filamentous form, which suggests for this myosin that filament structure is important for the inhibition of actin sliding in motility assays. The fact that all cysteine modifications examined inhibited the actomyosin ATPase activities and sliding velocities of actin over myosin poses questions concerning the information about the activated crossbridge obtained from probes attached to SH1 or SH2 on myosin.

Actins↗

PubMed1992

Spectral hole burning study of protoporphyrin IX substituted myoglobin.

Protoporphyrin IX substituted myoglobin reveals excellent hole burning properties. We investigated the frequency shift of persistent spectral holes under isotropic pressure conditions in a range from 0 to 2.4 MPa. In this range, the protein behaves like an elastic solid. The shift of the holes under pressure shows a remarkable frequency dependence from which the compressibility of the protein can be determined. The compressibility, in turn, allows for an estimation of the equilibrium volume fluctuations. Within the frame of the model used to interpret the pressure data, it is possible to determine the absorption frequency of the isolated chromophore and the associated solvent shift in the protein environment.

Animals↗

PubMed1997

Small-angle neutron scattering by a strongly denatured protein: analysis using random polymer theory.

Small-angle neutron scattering profiles are presented from phosphoglycerate kinase, in the native form and strongly denatured in 4 M guanidinium chloride (GdnHCl) solution. The data are interpreted using a model in which the excess scattering density associated with the protein is represented as a finite freely jointed chain of spheres. The similarity of the model-derived scattering function to experiment increases asymptotically with the number of spheres. The improvement of the fit obtained with more than approximately 200 spheres (i.e., two residues per sphere) is insignificant. The effects of finite size of the scattering units and of scattering length variation along the polypeptide chain are examined. Improved agreement with experiment is obtained when these effects are taken into account. A method for rapid calculation of the scattering profile of a full, all-atom configuration is examined. It is found that a representation of the chain containing two scattering units per residue, placed at the backbone and side-chain scattering length centroids, reproduces the full, all-atom profile to within 2%.

Fourier Analysis↗

PubMed2001

Delya's story: from expert to novice, a critique of Benner's concept of context in the development of expert nursing practice.

The concepts identified within Benner's Nineteen Eighty Four research 'From Novice to Expert' have been widely adopted within UK nursing education and development. This paper combines a narrative from a post-registration student with analysis of the literature as a case study for gaining greater understanding of Benner's work in practice. Delya's story both validates aspects of the concept of skill acquisition and challenges some of the interpretations of the model within professional education. The focus of the critique of Benner's work within the literature to date has been on a deconstruction of the concepts and semantics of her work. In presenting verbatim extracts from a case study this paper seeks to move the focus to nursing practice.

Decision Making↗

PubMed2003

The effects of endogenous diuretic and antidiuretic peptides and their second messengers in the Malpighian tubules of Tenebrio molitor: an electrophysiological study.

The Malpighian tubules of Tenebrio molitor provide a model system for interpreting the actions of endogenous diuretic and antidiuretic peptides. The effects of diuretic (Tenmo-DH(37)) and antidiuretic (Tenmo-ADFa) peptides and their respective second messengers (cyclic AMP and cyclic GMP) on basolateral (V(bl)) and transepithelial (V(te)) potentials of Tenebrio Malpighian tubules were determined using conventional microelectrodes. In the presence of 6 mmol l(-1) Ba(2+), Tenmo-DH(37) (100 nmol l(-1)) reversibly hyperpolarized V(bl) and depolarized V(te). A similar response was seen with the addition of 1 mmol l(-1) cyclic AMP; however, the apical membrane potential (V(ap)) then showed a hyperpolarization, whereas a depolarization of V(ap) was observed with Tenmo-DH(37). Bafilomycin A(1) (5 micromol l(-1)) inhibited fluid secretion of stimulated tubules and reversed the hyperpolarization of V(bl) in response to Tenmo-DH(37). In response to 100 nmol l(-1) Tenmo-ADFa or 1 mmol l(-1) cyclic GMP, V(bl) and V(te) depolarized, although cyclic GMP affected membrane potentials somewhat differently by causing an initial hyperpolarization of V(bl) and V(te). In high [K(+)]-low [Na(+)] Ringer, 1 mmol l(-1) amiloride decreased fluid secretion rates, and depolarized both V(bl) and V(te). Amiloride significantly decreased luminal pH in paired experiments, indicating the presence of a K(+)/nH(+) exchanger in tubule cells of Tenebrio. The results suggest that the endogenous factors and their second messengers stimulate/inhibit fluid secretion by acting on the apical V-ATPase, basolateral K(+) transport, and possibly Cl(-) transport.

Amiloride↗

PubMed1985

Species differences in the sensitivity to GnRH analogs.

The effects of several GnRH agonists and antagonists with high biological activity, have been investigated in rats, mice, rabbits and monkeys. Striking differences exist in the response of different species to the antigonadal and antipituitary effects of these peptides. Of all the animals studied, the rat is the most sensitive. The magnitude of the response to GnRH agonists seems to depend on the sensitivity of the pituitary and the presence of GnRH receptors in the target organs. Findings from animal models require careful interpretation before predictions can be made regarding their possible effects in the human.

Animals↗

PubMedDate not supplied

A review of randomized trials of psychiatric consultation-liaison studies in primary care.

The field of consultation-liaison (C-L) psychiatry has developed a variety of research interventions to try to improve the recognition and treatment of mental disorders in primary care. The authors review the results of three generations of randomized trials of mental health interventions developed by C-L psychiatrists. In general, these trials have been more successful in improving detection of mental illness and increasing the application of mental health treatments by primary care physicians than in changing patient outcomes. The results of these randomized trials are interpreted by using models developed in the health services field.

Clinical Trials as Topic↗

PubMed1996

The rate of annealing of actin tropomyosin filaments depends strongly on the length of the filaments.

Actin tropomyosin filaments were sheared to produce short filaments. Following incubation for 0 to 10000 s annealing of the filaments was assayed by determination of the rate of polymerization of monomeric actin onto the filament ends. The rate of decrease of the concentration of filament ends was found to be proportional to its fourth power. In contrast, the rate of end-to-end association of actin filaments in the absence of tropomyosin was proportional to the square of the concentration of filament ends. The strong dependence on the filament length of the rate of annealing of actin tropomyosin filaments was interpreted by the model of Hill (Biophys. J., 44, 285-288 (1983)) who pointed out that the rate constant of end-to-end association of long rod-like filaments is expected to depend on the length of the filaments for sterical conditions.

Actins↗

PubMed1995

David Byar's approach to the analysis of survival data with covariates.

The analysis of censored survival data with covariates was central to most of David Byar's research in cancer epidemiology and clinical trials. His general approach is outlined briefly, with particular reference to the construction of risk groups. Other topics include the choice between fully and semiparametric models, and the interpretation of interactions.

Biometry↗

PubMed1997

Determination of the seven apparent equilibrium constants for the binding of oxygen by hemoglobin from measured fractional saturations.

Subunit dissociation has to be taken into account in the determination of the oxygen binding constants of hemoglobin, as described by Ackers and Halvorson in 1974. The seven apparent equilibrium constants for a particular set of conditions can be determined by using extrapolations to determine the fractional saturations YT of tetramer and YD of dimer from measured values of the fractional saturation Y of partially dissociated hemoglobin. Analytical methods are used to show that YT as a function of [O2] for tetramers can be calculated from Y of hemoglobin by linear extrapolation of measured Y values at high [heme] versus [heme]-1/2 to [heme]-1/2 = 0. YD for dimers can be calculated from measured Y values by linear extrapolation of Y versus [heme] to [heme] = 0 if sufficiently low [heme] can be used. These extrapolations have been tested with numerical calculations of Y for a particular hemoglobin as a function of [heme] and [O2] by using the seven apparent equilibrium constants determined by Mills, Johnson, and Ackers in 1976. The proposed procedure also yields the apparent association constant K" for 2TotD = TotT, where TotD is the sum of the dimers and TotT is the sum of the tetramers. This thermodynamic analysis of experimental data to determine the seven apparent equilibrium constants is independent of the model used to interpret the values of the thermodynamic parameters.

Chemical Phenomena↗

PubMed2000

Functional imaging of vocal fold vibration: digital multislice high-speed kymography.

For the diagnosis of voice disorders, and especially for the classification of hoarseness, direct observation of vocal fold vibration is essential. Furthermore, a quantitative description of the movement of the vocal fold becomes increasingly necessary to document and compare findings as well as the progression of speech therapy. On the base of digital high-speed sequences of vocal fold vibration, multiple "functional images"-also called digital kymograms-are obtained using image- and signal-processing algorithms. Digital kymograms can serve as a powerful aid for visualization, description, and classification of vocal fold vibration and as an intermediate step for image interpretation by biomechanical modeling. This visualization technique will be discussed and compared to other techniques currently available: videokymography and videostroboscopy. The technique is applied to several clinical examples: aperiodic processes (phonation onset), irregular vocal fold vibration (paralysis of the recurrent nerve), particular vibration modes (anterior-posterior modes), and running speech.

Humans↗

PubMed2001

Adjustment for selection bias in cohort studies: an application of a probit model with selectivity to life course epidemiology.

Sample attrition is potentially a source of bias in cohort studies. The outcome may not be observed in a considerable proportion of the subjects. This article proposes the application of a probit model with sample selection to handle the problem. Two equations are simultaneously estimated and their error terms allowed to correlate: one regressing an observed outcome on a set of baseline variables, another regressing the probability of the outcome being observed upon a set of (perhaps the same) baseline variables. The method was applied to a study of a birth cohort, half of whose members were interviewed again at age 26. Baseline variables were observed for all the subjects included. The focus was on the association between birth weight and mental health in adults. The probit model with sample selection revealed a stronger and more significant (P = 0.037) relation between birth weight and mental health than an ordinary probit regression model (P = 0.170). Interpretation and practical considerations are discussed.

Adult↗

PubMed2002

Microbiological degradation of phenol using mixed liquors of Pseudomonas putida and activated sludge.

This work investigated the biodegradation potential of phenol using mixed liquors of Pseudomonas putida (ATCC 31800) and activated sludge. Experiments were made as a function of solution pH (6-10), temperature (30-36 degrees C), nitrogen source (NH4)2SO4 (0.5-0.8 g/l), and carbon source glucose (0.5-0.8 g/l). Response surface methodology by the Box-Behnken model was used to examine the role of four process factors on phenol degradation. It was shown that a second-order polynomial regression model could properly interpret the experimental data with an R2-value of 0.9997 and an F-value of 3605.45, based on which the maximum degradation of phenol was estimated up to 80.1% within the range examined. Interactions between process parameters and each significance effect on phenol degradation were also discussed.

Biodegradation, Environmental↗

PubMed1999

Mapping the X(+1) binding site of the Grb2-SH2 domain with alpha,alpha-disubstituted cyclic alpha-amino acids.

A series of phosphopeptides containing alpha,alpha-disubstituted cyclic alpha-amino acids (Ac(n)c, 3 < or = n < or = 7; n refers to the number of carbons in the ring) at the X(+1) position of Ac-Tyr(PO3H2)-X(+1)-Asn-NH2 has been synthesised and their inhibitory activity as antagonists of the Grb2-SH2 domain has been determined in competitive binding assays. The SAR data obtained have been interpreted by using models constructed from the X-ray structure of the ligand-bound Grb2-SH2 domain. The used of alpha,alpha-disubstituted cyclic alpha-amino acids to map the binding pockets of proteins expands the classical alanine scan concept and takes advantage of the known conformational preferences of these amino acids.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Health care provider's attitudes and beliefs towards chronic low back pain: the development of a questionnaire.

Attitudes and beliefs, or the treatment orientation, of health care providers appear to be important in the management of non-specific chronic low back pain (CLBP). The aims of the current study were two-fold: First of all, the physiotherapists' opinion towards various aspects of the management of CLBP was surveyed. Secondly, in a principal factor analysis, it was investigated whether underlying dimensions could be identified in order to develop the Pain Attitudes and Beliefs Scale for Physiotherapists (PABS_PT). In total, 421 physiotherapists (response rate 62.3%) participated in this study. The results suggested that the majority of physiotherapists hold the opinion that CLBP is not a dangerous condition, that sport should not be discouraged and that patients should not refrain from all physical activity. Moreover physiotherapists seem to hold the opinion that the way patients view their pain influences the progress of symptoms. Finally, physiotherapists seem to hold the opinion that therapy can completely alleviate the functional symptoms and that therapy may have been successful even if pain remains. The principal factor analysis (PAF) yielded an interpretable 2-factor model. Based on highest loading items, factor 1 was labelled 'biomedical orientation', whereas factor 2 was labelled 'behavioural orientation'. The internal consistency (Cronbach's Alpha) of factor 1 was 0.84 and for factor 2, 0.54 explaining 25.2% and 8.2%, respectively, of the total variance. Assessment of the effect of the physiotherapists' characteristics on scores on the different scales was encouraging as results pointed in the directions one would expect. Physiotherapists who attended biopsychosocial education courses had statistically significantly higher scores on the 'behavioural orientation' factor and vice versa. Biomedical specialists scored statistically significantly higher on the 'biomedical orientation' factor. Furthermore, the findings suggested that the PABS_PT discriminates between physiotherapists with a 'behavioural orientation' vs those with a 'biomedical orientation'. To examine the influence of these different treatment orientations with regard to CLBP on patient outcome is a challenge for the near future.

Adult↗

PubMed2003

The Madrid card sorting test (MCST): a task switching paradigm to study executive attention with event-related potentials.

Event-related potentials (ERPs) provide valuable information about the fast brain dynamics subserving cognitive functions such as attention and working memory. Most ERP studies employ cognitive paradigms with a fixed task-set (i.e., press a button to coloured targets), but few have measured ERPs time-locked to shifts in set using a task-switching paradigm. The Madrid card sorting test (MCST) is a dual task protocol in which feedback cues signal unpredictable shifts in set (i.e., from 'sort cards by colour' to 'sort cards by shape'). This protocol allows for an integrated analysis of ERPs to both feedback cues and target card events, providing separate ERP features for the shifting, updating, and rehearsal of attention sets in working memory. Two of these ERP indices are the frontal and posterior aspects of the P300 response. Feedback cues that direct a shift in set also elicit a frontally distributed P3a potential (300-400 ms). Instead, target card events evoke increasingly larger posterior P3b (350-600 ms) activity as the new task set becomes gradually rehearsed. The observed modulations in the frontal and posterior aspects of the P300 response system are interpreted from current models of prefrontal cortex function in the executive control of attention.

Adolescent↗

PubMed2000

Development of ideomotor praxis representation.

To create a short screening instrument to investigate the development of ideomotor praxis representation (IPR), 357 normally developing children between the ages of 2 1/2 and 9 1/2 years were investigated. The IPR screening consisted of six mimed actions which had to be performed on verbal request. The greatest change in the representational style is the transition from performing the action using the body as the object to performing with an imaginary object (i.e. symbolic representation). This transition suggests a development from a concrete and egocentric level of performance to an abstract and allocentric level. Before the age of 6 years differences are evident between self-directed and externally directed gestures. The level of symbolic representation has to be dissociated from the degree of motor precision, which shows hardly any improvement after 6 years of age. With the proposed model one may interpret the level of IPR in clinical practice. IPR screening is clinically relevant from the age of 4 1/2 years onwards.

Activities of Daily Living↗

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