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At least 199 records · Page 11Linked to original sources

PubMed1994

Regulation of transducin GTPase activity in bovine rod outer segments.

The photoreceptor G-protein, transducin, belongs to the class of heterotrimeric GTP-binding proteins that transfer information from activated seven-span membrane receptors to effector enzymes or ion channels. Like other G-proteins, transducin acts as a molecular clock. It is activated by photoexcited rhodopsin which catalyzes the exchange of transducin-bound GDP for GTP and then stays active until bound GTP is hydrolyzed by an intrinsic GTPase activity. Our previous study on the components of the amphibian phototransduction cascade (Arshavsky, V. Y., and Bownds, M. D. (1992) Nature 357, 416-417) has shown that transducin GTPase can be significantly accelerated by the target enzyme, cGMP phosphodiesterase (PDE), and more specifically its gamma-subunit (PDE gamma). Here we report that an analogous mechanism is present in bovine photoreceptors. Addition of recombinant PDE gamma to the test photoreceptor membranes which retain transducin but are depleted of endogenous PDE causes a significant acceleration of transducin GTPase activity. A similar effect was observed with the PDE holoenzyme, but not with the complex of PDE alpha- and beta-subunits prepared by a limited proteolysis of PDE with trypsin. The activating effect of PDE gamma is increased as test membrane concentration increases, exceeding 20-fold at rhodopsin concentrations over 80 microM and approaching the rate of the photoresponse turnoff. This suggests either that photoreceptor membranes contain a further factor which is essential for PDE-dependent regulation of transducin-bound GTP hydrolysis or that components of the phototransduction cascade interact in a cooperative manner. We also report that the GTPase-activating epitope is located within the C-terminal third of PDE gamma: the peptide corresponding to the 25 C-terminal amino acid residues of PDE gamma can accelerate transducin GTPase almost as well as the full-length PDE gamma. A part of the GTPase activating epitope is located within the 3 C-terminal amino acid residues: the truncation PDE gamma mutant lacking these residues accelerates transducin GTPase considerably less than the whole length PDE gamma.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2002

A re-examination of proximodistal patterning during vertebrate limb development.

The 'progress zone' model provides a framework for understanding progressive development of the vertebrate limb. This model holds that undifferentiated cells in a zone of fixed size at the distal tip of the limb bud (the progress zone) undergo a progressive change in positional information such that their specification is altered from more proximal to more distal fates. This positional change is thought to be driven by an internal clock that is kept active as long as the cells remain in the progress zone. However, owing to cell division, the most proximal of these cells are continually pushed outside the confines of the zone. As they exit, clock function ceases and cells become fixed with the positional value last attained while within the zone. In contrast to this model, our data suggest that the various limb segments are 'specified' early in limb development as distinct domains, with subsequent development involving expansion of these progenitor populations before differentiation. We also find, however, that the distal limb mesenchyme becomes progressively 'determined', that is, irreversibly fixed, to a progressively limited range of potential proximodistal fates.

Animals↗

PubMed1992

New short period mutations of the Drosophila clock gene per.

Earlier work has indicated that the period length of Drosophila circadian behavioral rhythms is dependent on the abundance of the period (per) gene product. Increased expression of this gene has been associated with period shortening for both the circadian eclosion (pupal hatching) rhythm and circadian locomotor activity rhythms of adult Drosophila. In this study it is shown that a wide variety of missense mutations, affecting a region of the per protein consisting of approximately 20 aa, predominantly generate short period phenotypes. The prevalence of such mutations suggests that short period phenotypes may result from loss or depression of function in this domain of the per protein. Possibly mutations in the region eliminate a regulatory function provided by this segment, or substantially increase stability of the mutant protein.

Amino Acid Sequence↗

PubMed2007

Diurnal rhythm of the chromatin protein Hmgb1 in rat photoreceptors is under circadian regulation.

Hmgb1 belongs to a family of structure-specific DNA binding proteins with DNA chaperone-like properties that mediate chromatin remodeling in a wide range of nuclear processes including regulation of transcription, DNA repair, genome stability, and stress response. A diurnal oscillation of Hmgb1 at the protein level occurs in rat retinal photoreceptor cells and to a lesser extent in bipolar neurons. Expression of Hmgb1 was least at night at Zeitgeber time (ZT) 18 and maximal in the middle of the lights-on period (ZT6). Since rhythmic expression of Hmgb1 protein in photoreceptors continued in complete darkness, it is likely under control of a circadian clock. Within photoreceptor nuclei, Hmgb1 colocalized with acetylated histone H3, a marker of euchromatin. Outside the nucleus a distinct smaller-sized isoform of Hmgb1 was present in photoreceptor inner segments and bound to a membrane fraction with characteristics of endoplasmic reticulum membranes. The rhythmic expression of Hmgb1 protein may underlie the circadian change in chromatin remodeling in addition to histone acetylation.

Aged↗

PubMedDate not supplied

An introduction to the Mumford-Shah segmentation model.

Some papers of this special issue concern recent results on mathematical models of segmentation. As they are rather technical we propose here a pedagogical introduction for the non-mathematical reader. We briefly present the variational model of image segmentation proposed by David Mumford and we summarize some fundamental results of De Giorgi's school.

Animals↗

PubMed2002

Scleral buckling technique without retinopexy for treatment of rhegmatogeneous: a pilot study.

PURPOSE: To evaluate the role of retinopexy in the surgical management of primary rhegmatogenous retinal detachment (RD) without proliferative vitreoretinopathy. The primary outcome was retinal attachment, and secondary outcomes were visual acuity results and complications. METHODS: A randomized controlled trial including 60 patients with RD caused by a break or a group of breaks no larger than one clock hour. Thirty eyes received no retinopexy (group 1), and 30 eyes received transscleral cryotherapy (group 2). An encircling buckle was placed in all eyes. In eyes with posterior breaks, segmental buckles were also added. In some eyes, subretinal fluid drainage or anterior chamber paracentesis and/or intravitreal air bubble injection was performed. RESULTS: No differences were found between the groups in terms of the preoperative clinical variables evaluated: age; sex; axial length; lens status; type, number, and location of breaks; extension of detachment; and macula status. There were no differences in the surgical procedures performed. The reattachment rate in group 1 was 90%, and in group 2, it was 87% (a difference that was not significant [P = 1.00]). Final visual acuity improved by two lines or more in 22 patients in group 1 and in 20 patients in group 2 (P = 0.317). CONCLUSIONS: Our results indicate that primary rhegmatogenous RD can be successfully treated with scleral buckling without retinopexy.

Adult↗

PubMedDate not supplied

Subjective time scaling: influence of age, gender, and Type A and Type B behavior.

Forty-eight subjects, divided into 4 equal groups (young and older female, young and older male), reproduced 19 time intervals varying in logarithmic steps between 1.3 and 20 s. The durations were indicated by noise of 50 dB SL. To assess Type A and Type B behavior, the subjects were administered a Swedish version of Jenkins Activity Survey with 21 items. It was found that 1. reproductions of durations by older subjects are longer than those by younger subjects, and 2. reproductions by male subjects are shorter than those by female, although an interaction was also detected between gender and the standard durations. Type A and Type B behavior did not show any main effect. The data were treated in accordance with the "parallel-clock model", whereby the parameters of the psychophysical power function are determined from duration reproduction data. As in previous experiments, the data showed a break in the function, entailing two segments. The effect of both age and gender could be explained by the weight coefficient of the upper relative to the lower segment of the psychophysical function, the coefficient being lower for male and higher for older subjects.

Acoustic Stimulation↗

PubMed1994

Block in nuclear localization of period protein by a second clock mutation, timeless.

In wild-type Drosophila, the period protein (PER) is found in nuclei of the eyes and brain, and PER immunoreactivity oscillates with a circadian rhythm. The studies described here indicate that the nuclear localization of PER is blocked by timeless (tim), a second chromosome mutation that, like per null mutations, abolishes circadian rhythms. PER fusion proteins without a conserved domain (PAS) and some flanking sequences are nuclear in tim mutants. This suggests that a segment of PER inhibits nuclear localization in tim mutants. The tim gene may have a role in establishing rhythms of PER abundance and nuclear localization in wild-type flies.

Animals↗

PubMed1995

Autonomic, ischaemic, circadian and rhythmic factors as causes of the spontaneous variability of ventricular arrhythmias.

Ventricular arrhythmias present with strongly varying intensity. This spontaneous variability makes it difficult to use one of the existing arrhythmia grading systems for risk or therapy efficacy studies. We attempted to explain the variability by the changing autonomic, ischaemic, circadian, and rhythmic factors. Four (two learning, two test) 24-h Holter tapes were made within one month in 31 patients with chronic frequent ventricular ectopic beats of miscellaneous aetiology and under constant drug regimen. The data were segmented into 5-min episodes, in which ectopy (dependent variable) was measured, together with heart rate, amount of heart rate variability, fraction low-frequency heart rate variability, ST depression, and clock time (independent variables). Forty-three percent of the fluctuations in arrhythmia incidence could be explained with a multiple regression procedure, and more than 50% of the variance in arrhythmia incidence could be explained in 36% of the cases. Our study demonstrates that much of the spontaneous variability of ventricular arrhythmias can be attributed to the varying conditions. This method of dealing with arrhythmia variability might lead to an alternative to the current arrhythmia grading systems used in risk and drug efficacy studies.

Adult↗

PubMedDate not supplied

Comparing the incomparable: hemodialysis versus peritoneal dialysis in observational studies.

A randomized trial comparing survival in hemodialysis and peritoneal dialysis remains a utopian aspiration. Dialysis is still relatively rare on a population basis, and a natural tension exists between desirability and feasibility in terms of quality of evidence. In practice, it is very difficult to perform prospective comparisons with large groups of contemporary representative subjects, and much of the literature comes from retrospective national registries. This article considers several questions to address when trying to compare the outcomes of peritoneal dialysis and hemodialysis. Prognostic similarity at baseline is a fundamental issue. Traditionally, adjustment for known prognostic factors has been used in an attempt to minimize the bias caused by nonrandom treatment assignment. Propensity scores have been suggested to be superior, and matched-case analysis may also be a useful method for comparison. Other questions include, when, in relation to starting dialysis, to start the observation clock; the definition and handling of switches of dialysis therapy; and the decision to censor at transplantation. Finally, comparisons are complicated by hazards ratios that vary over time, and time-segmented analysis is obligatory. Many types of analytical approaches are needed to begin to appreciate outcome disparities between dialysis therapies.

Humans↗

PubMed1998

Color Doppler ultrasound assessment of urethral artery location: potential implication for technique of visual internal urethrotomy.

PURPOSE: We assessed the location of urethral arteries in patients with urethral stricture using color Doppler ultrasound. MATERIALS AND METHODS: We performed 41 color ultrasound studies of the urethra in 33 patients 17 to 76 years old. The linear array transducer was placed on the ventral surface of the penis and perineum to image the urethra and periurethral structures. In addition to evaluating the extent of stricture disease, color Doppler ultrasound determined the location of the urethral arteries at the segment with stricture. RESULTS: The number and site of the urethral arteries vary among individuals. Contrary to the common belief that these arteries are located at the 3 and 9 o'clock positions, we have found that in the bulbous urethra the arteries are at the 1 to 2 o'clock positions in 14% of cases, 3 to 4 in 22%, 5 to 6 in 17%, 7 to 8 in 18%, 9 to 10 in 18% and 11 to 12 in 11%. The arteries may be close to the surface of the urethral lumen, especially in patients who have undergone previous urethral procedures. Preoperative evaluation of urethral artery location may be helpful for preventing arterial bleeding at visual internal urethrotomy. CONCLUSIONS: Color Doppler ultrasound can effectively assess the extent of stricture disease and urethral artery sites. Because the location of the urethral arteries varies among patients, individual preoperative assessment is advisable. Color Doppler ultrasound is currently our imaging method of choice for evaluating strictures of the pendulous and bulbous urethra.

Adolescent↗

PubMed2002

Kinematic control of walking.

The planar law of inter-segmental co-ordination we described may emerge from the coupling of neural oscillators between each other and with limb mechanical oscillators. Muscle contraction intervenes at variable times to re-excite the intrinsic oscillations of the system when energy is lost. The hypothesis that a law of coordinative control results from a minimal active tuning of the passive inertial and viscoelastic coupling among limb segments is congruent with the idea that movement has evolved according to minimum energy criteria (1, 8). It is known that multi-segment motion of mammals locomotion is controlled by a network of coupled oscillators (CPGs, see 18, 33, 37). Flexible combination of unit oscillators gives rise to different forms of locomotion. Inter-oscillator coupling can be modified by changing the synaptic strength (or polarity) of the relative spinal connections. As a result, unit oscillators can be coupled in phase, out of phase, or with a variable phase, giving rise to different behaviors, such as speed increments or reversal of gait direction (from forward to backward). Supra-spinal centers may drive or modulate functional sets of coordinating interneurons to generate different walking modes (or gaits). Although it is often assumed that CPGs control patterns of muscle activity, an equally plausible hypothesis is that they control patterns of limb segment motion instead (22). According to this kinematic view, each unit oscillator would directly control a limb segment, alternately generating forward and backward oscillations of the segment. Inter-segmental coordination would be achieved by coupling unit oscillators with a variable phase. Inter-segmental kinematic phase plays the role of global control variable previously postulated for the network of central oscillators. In fact, inter-segmental phase shifts systematically with increasing speed both in man (4) and cat (38). Because this phase-shift is correlated with the net mechanical power output over a gait cycle (3, 4), phase control could be used for limiting the overall energy expenditure with increasing speed (22). Adaptation to different walking conditions, such as changes in body posture, body weight unloading and backward walk, also involves inter-segmental phase tuning, as does the maturation of limb kinematics in toddlers.

Animals↗

PubMed1988

Fifty years of migraine research.

The prevalence of ice-pick pains and ice-cream headache in migrainous patients and their localisation to the habitual site of migraine headache, suggest that segments of the central pain pathways remain hyperexcitable between spontaneous attacks. Excessive afferent stimulation (flashing lights, noise, strong perfumes) or hypothalamic changes resulting from emotion, stress or the operation of some internal clock may set in motion brainstem mechanisms, including spontaneous unilateral or bilateral discharge of pain pathways. Studies in the experimental animal have shown that certain monoaminergic brainstem nuclei can influence the cerebral circulation unilaterally and that they and the trigeminal system can induce a reflex dilatation of the external carotid circulation. Descending pathways from the same brainstem nuclei cause the adrenal gland to secrete noradrenaline, which in turn can release serotonin from blood platelets. Free serotonin may become adsorbed to the arterial wall, thus increasing sensitivity to pain, augmenting afferent input and adding a pulsating quality to migrainous pain. Both neural and vascular components of migraine implicate monoamines, specifically noradrenaline and serotonin, as neurotransmitters and humoral agents. The recent pharmacological classification of serotonin (5HT) receptors indicates that agonists of a subset of the 5HT1 receptor and antagonists of 5HT2 receptors are most likely to be helpful in the treatment of migraine.

Animals↗

PubMed1980

The changes in pattern of myocardial shortening by reduction of regional coronary blood flow.

The relationship between the grade of a decrease in the regional coronary blood flow and the movement of ventricular myocardium of that region was investigated in open chest dog. Blood flow in left anterior descending artery (FLAD) was reduced by stepwise constriction of LAD with ligature. Ventricular segment length was measured in a circumferential plane on the endocardial surface by ultrasonic dimension system. For the elimination of the noise caused by ultrasonic dimension system, the synchronizer was inserted between sample clock of the dimension system and the trigger circuit of the electromagnetic flowmeter. A 20% reduction of FLAD affected the pattern of ischemic myocardial shortening very little. Discontinuance of shortening to the end of systole was occurred by a 20 to 60% reduction in FLAD. Early and/or late systolic bulging was induced by a 60% reduction of FLAD. Systolic bulging with early diastolic shortening was seen in the cases with a 60 to 80% reduction in FLAD. Frank systolic bulging which was always seen by complete occlusion of LAD was produced by a 60 to 90% reduction of FLAD in few cases.

Animals↗

PubMed1992

Time perception: effects of sex and sound intensity on scales of subjective duration.

Six women and six men reproduced ten time intervals varying in logarithmic steps between 1.3 and 20 s. The durations were indicated by white noise of 10, 25, 40 and 55 dB SL, different sound intensities in different sessions. It was found that (i) greater sound intensity entails shorter reproductions, and (ii) reproductions by male observers are shorter than those by female, although for both (i) and (ii) there is an interaction with the standard durations. The data were treated in accordance with the "parallel-clock model" (Eisler, 1975), whereby the parameters of the psychophysical power function are determined from duration reproduction data. As in previous experiments (Eisler, 1975), the data showed a break in the function entailing two segments. The effect of sound intensity could be attributed to the exponent, which was lower for stronger noise, and the effect of sex to the weight coefficient of the upper relative to the lower segment of the psychophysical function, the coefficient being lower for men.

Adult↗

PubMed2000

Quantitative analysis of intestinal motor patterns: spatiotemporal organization of nonneural pacemaker sites in the rat ileum.

BACKGROUND & AIMS: Intestinal contractions are triggered by electric activity of pacemaker cells within the smooth muscle. However, the precise spatial organization of the pacemaker system is unknown. We directly assessed the spatiotemporal organization of pacemakers by video image analysis combined with manometry and electromyography. METHODS: Isolated segments of rat ileum were perfused arterially with oxygenated fluorocarbon solution and luminally with saline. Luminal end pressures, extracellular electric activity, and images of the intestine were recorded simultaneously. Tetrodotoxin, N(G)-nitro-L-arginine methyl ester (L-NAME), L-arginine, and eserine were administered arterially. RESULTS: Myogenic contractions originated in discrete areas (dominant pacemakers) and propagated faster in aboral than in oral direction. Dominant pacemakers were distributed along the intestine at regular intervals. The preparations were mostly driven by 1 pacemaker at the time, but 2 or 3 pacemakers with different frequencies could be active simultaneously. Tetrodotoxin decreased aboral propagation velocity and revealed multiple regularly spaced pacemaker areas. Eserine increased, whereas L-arginine decreased, their frequency. After L-NAME, pacemaker activity increased and isolated pacemakers with higher frequency appeared. CONCLUSIONS: Nonneural pacemakers in rat ileum are functionally organized not as a continuous system but show a segmental arrangement, spatially and temporally modulated by neural activity.

Animals↗

PubMed2005

Quantifying errors in spectral estimates of HRV due to beat replacement and resampling.

Spectral estimates of heart rate variability (HRV) often involve the use of techniques such as the fast Fourier transform (FFT), which require an evenly sampled time series. HRV is calculated from the variations in the beat-to-beat (RR) interval timing of the cardiac cycle which are inherently irregularly spaced in time. In order to produce an evenly sampled time series prior to FFT-based spectral estimation, linear or cubic spline resampling is usually employed. In this paper, by using a realistic artificial RR interval generator, interpolation and resampling is shown to result in consistent over-estimations of the power spectral density (PSD) compared with the theoretical solution. The Lomb-Scargle (LS) periodogram, a more appropriate spectral estimation technique for unevenly sampled time series that uses only the original data, is shown to provide a superior PSD estimate. Ectopy removal or replacement is shown to be essential regardless of the spectral estimation technique. Resampling and phantom beat replacement is shown to decrease the accuracy of PSD estimation, even at low levels of ectopy or artefact. A linear relationship between the frequency of ectopy/artefact and the error (mean and variance) of the PSD estimate is demonstrated. Comparisons of PSD estimation techniques performed on real RR interval data during minimally active segments (sleep) demonstrate that the LS periodogram provides a less noisy spectral estimate of HRV.

Adult↗

PubMed2002

The motor efficacy of the artificial colonic pacemaker in colonic inertia patients.

We have recently demonstrated that the colon possesses at least 4 pacemakers which presumably generate electric waves and that colonic pacing evokes electric activity in colonic inertia. We tested the hypothesis that electric waves produced by artificial colonic pacing in colonic inertia patients may initiate colonic motilitiy and effect evacuation. 17 patients with constipation due to total colonic inertia were divided into 2 groups: 10 (age 45.6 ( 6.3 years, 7 women) in the study group and 7 (age 43.7 ( 5.8 years, 5 women) as controls. 7 healthy volunteers were included in the study. Colonic pacing was tested at 2 sites of pacemakers: mid-transverse colon and colosigmoid junction. A stimulating electrode was hooked to the colonic mucosa at the pacemaker site and 2-3 recording electrodes distally to it. Healthy volunteers showed resting electric waves in the form of pacesetter and action potentials which increased significantly on colonic pacing. Inertia patients exhibited no basal electric activity. Colonic pacing in the study group evoked electric waves and caused expulsion of small volume balloon. Balloon distension at pacemaker site produced mass movement of balloon, while away from pacemaker site step-wise movement. In conclusion, colonic pacing evoked electric waves in colonic inertia patients and effected balloon expulsion. We postulate that the pacemaker generates electric waves which spread along pacemaker branches that are composed of interstitial cells of Cajal and nerve fibers of the enteric nervous plexus and effect colonic mass contraction. Ex-pacemaker stimulation presumably leads to local activation of interstitial cells of Cajal and segmental step-wise contraction.

Action Potentials↗