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PubMed1980

Spontaneous fluctuations of potassium channels in the apical membrane of frog skin.

1. The previously demonstrated K+-dependent short-circuit current through the skin of frog species Rana temporaria (Zeiske & Van Driessche, 1979), bathed with mucosal K+- and serosal Na+-Ringer solution, was investigated with current-fluctuation analysis. 2. The current-noise spectra were recorded in the frequency range from 1 to 800 Hz and showed a Lorentzian component with a mean plateau value S0 = (1.50 +/- 0.05).10(-20) A2.s.cm-2 and a corner frequency of fc=(81.0 +/- 3.4)Hz(n=14). 3. S0 increased with mucosal K+ concentration, [K]o, while fc remained almost unchanged. A decrease in S0 was observed when serosal Na+ was replaced by K+. 4. Mucosal Cs+ (10 mM) depressed, reversibly, the K+-dependent current noise to the level of the background noise. Moreover, a linear decrease in fc with increasing Cs+ concentration was observed. 5. Among the other tested alkali cations, Rb+ was the only blocker though less potent than Cs+. Tetraethylammonium, 4-aminopyridine, 2.4.6-triaminopyrimidine and amiloride had no effect. 6. Alterations in the transcellular transport of Na+ contained in a mucosal solution with high [K]o resulted in significant changes in K+ current noise. 7. The current-fluctuation intensities decreased with increasing contact time to high [K]o; these changes were concomitant with the previously reported time dependence of the short-circuit current (Zeiske & Van Driessche, 1979). 8. The K+-dependent fluctuations are thought to originate from K+-selective pathways in the apical cell membranes. The description of the K+-current noise by a single Lorentzian suggests that the "K+ channels" switch randomly between an open and closed state. 9. Assuming a two state model for the channel-kinetics, the single channel current i and the channel density M were calculated as i=(0.37 +/- 0.05)pA and M=(0.53 +/- 0.08) mu-2 (n=13).

Animals↗
PubMedDate not supplied

Measurement of fibrous cap thickness in atherosclerotic plaques by spatiotemporal analysis of laser speckle images.

Necrotic-core fibroatheromas (NCFA) with thin, mechanically weak fibrous caps overlying lipid cores comprise the majority of plaques that rupture and cause acute myocardial infarction. Laser speckle imaging (LSI) has been recently demonstrated to enable atherosclerotic plaque characterization with high accuracy. We investigate spatio-temporal analysis of LSI data, in conjunction with diffusion theory and Monte Carlo modeling of light transport, to estimate fibrous cap thickness in NCFAs. Time-varying laser speckle images of 20 NCFAs are selected for analysis. Spatio-temporal intensity fluctuations are analyzed by exponential fitting of the windowed normalized cross-correlation of sequential laser speckle patterns to obtain the speckle decorrelation time constant, tau(rho), as a function of distance rho from the source entry location. The distance, rho', at which tau(rho) dropped to 65% of its maximum value is recorded. Diffusion theory and Monte Carlo models are utilized to estimate the maximum photon penetration depth, zmax(rho'), for a distance equal to rho', measured from LSI. Measurements of zmax(rho') correlate well with histological measurements of fibrous cap thickness (R=0.78, p<0.0001), and paired t-tests show no significant difference between the groups (p=0.4). These results demonstrate that spatio-temporal LSI may allow the estimation of fibrous cap thickness in NCFAs, which is an important predictor of plaque stability.

Algorithms↗
PubMed1989

Differential roles of splanchnic and peripheral tissues in determining diurnal fluctuation of glucose tolerance.

To identify the mechanisms and the sites of the diurnal fluctuation in glucose tolerance in humans, we selectively quantitated the components of net splanchnic glucose balance, i.e., splanchnic glucose uptake and hepatic glucose output, as well as peripheral glucose uptake, by combining tritiated glucose infusion with hepatic and femoral venous catheterization. The studies were carried out in 11 healthy volunteers at 8:00 A.M. and at 6:00 P.M. on different days after 12 h of fasting. After intravenous glucose infusion (6.5 mg.kg-1.min-1 for 120 min) blood glucose rose twofold at 8:00 A.M. and threefold at 6:00 P.M. (P less than 0.01). Insulin levels did not differ significantly between the two series of tests. Splanchnic glucose balance switched from the net output of the basal state to a net uptake in both morning and afternoon studies. However, this effect was more marked at 6:00 P.M. than at 8:00 A.M. (at 60-120 min, P less than 0.05). The different pattern of splanchnic glucose balance was entirely accounted for by a greater rise in splanchnic glucose uptake in the afternoon, as the suppression of endogenous glucose output by the glucose load was practically complete in both series of studies. In contrast, glucose uptake by leg tissues increased less at 6:00 P.M. than at 8:00 A.M. (at 30-60 min, P less than 0.05; at 75 and 90 min, P less than 0.01; at 105 and 120 min, P less than 0.005). These data indicate that the mechanism responsible for the reduced glucose tolerance later in the day resides in the peripheral tissues whose ability to dispose of a glucose load is drastically decreased.

Adult↗
PubMed1997

Contribution of humoral systems to the short-term variability of blood pressure after severe hemorrhage.

The aim of this study was to generate hemorrhage-triggered fluctuations in blood pressure (BP) at low frequency (LF, < 0.2 Hz) in conscious rats and investigate with spectral analysis the relative roles of hemorrhage-activated catecholamines, the renin-angiotensin system (RAS), and arginine vasopressin (AVP) on the generation of these fluctuations. The individual contribution of these factors was assessed using a combination of the selective antagonists, prazosin, losartan, and Manning compound (AVPX). At rest, systolic BP (SBP) LF fluctuations were slightly increased by losartan. The mid-frequency (MF; 0.2-0.6 Hz) oscillations of SBP and diastolic BP (DBP) were decreased by prazosin alone or associated with AVPX or losartan. The high-frequency (HF; respiratory) oscillations of SBP were increased by prazosin, prazosin plus losartan, and prazosin plus AVPX. After severe hemorrhage (20 ml/kg), the spontaneous BP recovery was characterized by the occurrence of slow fluctuations of SBP and DBP, centered approximately 0.065 Hz, and by increases of MF (89%) oscillations of SBP. The HF component of SBP variability tended to be increased by blood loss. The occurrence of the SBP LF fluctuations was prevented when alpha 1-adrenergic activity was blocked by prazosin. These oscillations were always present, despite inhibition of angiotensin II, and were increased after inhibition of the AVP activity. Pretreatment with the specific inhibitors used in these studies favored the amplifying effect of hemorrhage on HF fluctuations while they prevented the postbleeding increase in MF oscillations. In conclusion, the present results show an association between the dependence of the postbleeding blood pressure level on catecholamines and the occurrence of slow fluctuations of BP. The buffering role of AVP suggests the establishment of a hierarchy between humoral systems in the genesis of the LF oscillations of BP, with the slow oscillations being generated by the main pressor system and being dampened by the other systems. The postbleeding rise in the MF component of SBP variability could be considered a reflection of the activations of both the sympathetic vasomotor drive and the RAS. The postbleeding increase in the HF component of BP variability was dampened by the activation of the humoral systems. These effects may reflect the low preload state due to hypovolemia.

Animals↗
PubMed2004

Reduction of coherent artifacts in dynamic holographic three-dimensional displays by diffraction-specific pseudorandom diffusion.

An electroholographic display based on diffraction-specific computation can reduce speckle by electronic diffusion through selective addition of a pseudorandom sequence. Intensity fluctuation as a result of the introduction of pseudorandom noise does not affect three-dimensional (3-D) images significantly since spatial windows formed by diffused basis fringes do not widen noticeably at low pseudorandom spread, whereas the features of the fluctuation are much smaller than human visual resolution. Experimental results obtained on the Massachusetts Institute of Technology holographic video system confirmed that the diffusion smooths 3-D images and improves the intensity nonuniformity among horizontal holographic lines.

Journal Article↗
PubMed2003

Diagnosis, therapy, and prevention of the cracked tooth syndrome.

Many morphologic, physical, and iatrogenic factors, such as deep grooves, pronounced intraoral temperature fluctuation, poor cavity preparation design, and wrong selection of restorative materials, may predispose posterior teeth to an incomplete fracture. The resulting cracked tooth syndrome is frequently associated with bizarre symptoms that may complicate diagnosis and can persist for many years. Epidemiologic data reveal that splits or fractures are the third most common cause of tooth loss in industrialized countries, primarily affecting maxillary molars and premolars and mandibular molars. This finding indicates that the cracked tooth syndrome is of high clinical importance. Thus, at-risk teeth should be reinforced early, for instance by castings with cusp coverage or by internal splinting with adhesive ceramic restorations.

Bicuspid↗
PubMed1990

Casodex: preclinical studies.

Antiandrogens are effective drugs in the treatment of advanced prostatic cancer. The main problems associated with their use are their short half-lives, leading to fluctuating serum levels, and their non-selectivity, which leads to increases in serum LH and testosterone through centrally-mediated actions. Casodex is a pure, potent antiandrogen which, in pre-clinical studies, has been shown to have a long half-life and a high degree of peripheral selectivity. Casodex is as effective as surgical castration or medical castration with Zoladex in inhibiting the growth of a transplantable Dunning prostate tumor in rats. These properties suggest that Casodex, given once daily, would be an effective and well-tolerated monotherapy for advanced prostatic cancer.

Anilides↗
PubMed1994

[The circadian rhythms of the level of ACTH, cortisol and 17-hydroxycorticosteroids in bronchial asthma patients].

The circadian rhythm of hydrocortisone and ACTH in plasma and 17-OCS in the urine were registered in 10 patients with bronchial asthma and 5 healthy subjects. It was found that maximal concentrations of hydrocortisone occurred in the day time whereas those of ACTH at nights in moderate asthma. In its severe forms neither hydrocortisone nor ACTH followed circadian rhythms. It is recommended to treat patients with severe bronchial asthma on the individual basis selecting glucocorticosteroid doses with reference to plasma fluctuations of hydrocortisone.

17-Hydroxycorticosteroids↗
PubMed1997

Problems complicating the genetic epidemiology of rheumatoid arthritis.

I review problems inherent in considering the genetic epidemiology of rheumatoid arthritis (RA). The major area of concern is in case definition, both in assigning criteria and in establishing time of onset of disease, since presentation fluctuates throughout life. Other problem areas include selection of case and controls and the appropriate approach to analysis. Awareness of the problems in study design and conduct is fundamental to undertaking valid studies in this area.

Arthritis, Rheumatoid↗
PubMed1998

[Varicocele and its repercussion on infertility. Indications and limitations of surgical intervention].

According to different Authors, varicocele incidence in unselected population fluctuates from 8 to 22% but in selected population affected by sterility incidence ranges from 21 to 39%. However other Authors have demonstrated that about 50% of patients suffering from varicocele have semen alterations. Various mechanisms have been suggested for testicular dysfunction associated with varicocele: intrascrotal hyperthermia, reflux of renal and adrenal metabolites from the renal vein and hypoxia. The most important semen alterations are observed in patients suffering from grade 2 and 3 varicocele and especially these patients must undergo surgical operation. According to recent findings, better results about the improvement of semen quality are obtained by operating children in puberal age. This clinical approach allows a prevention of testicular hypotrophy or, when this is already present, its reversibility. Varicocele surgical treatment makes use of traditional techniques microsurgical or not and mininvasive techniques. After renouncing of intrascrotal varicocelectomy, traditional techniques provide ligature and section of ectasic spermatic veins, after a surgical high (at level of the internal inguinal ring) or low (over inguinal canal) skin incision. Microsurgery allows recognition and protection of lymphatic and arterial vessels and execution of microsurgical anastomosis between venous spermatic and ileo-femoral circle vessels, when this is necessary. Internal spermatic vessels and vas deferens can be visualized through the laparoscope and so laparoscopic varicocele treatment was suggested. These new techniques and traditional operation are burdened with the same percentage of relapses but in laparoscopic procedure complications are more important. Recently radiographic occlusion techniques are also utilized (internal spermatic vein retrograde scleroembolization); the percentage of relapses is between 4 and 11%, with no risk of postvaricocelectomy hydrocele but with risk of loss of kidney (migration of the ballon or coil into the renal vein). Surgical treatment of varicocele produces a significant improvement in semen analysis in 60 to 80 per cent of patients affected by testicular dysfunction. Pregnancy rates after varicocelectomy are including from 20 to 60 per cent with most series averaging about 35 per cent.

Adolescent↗
PubMed1994

Human leukocyte antigens and natural selection by malaria.

The extraordinary polymorphism of human leukocyte antigens (HLA) poses a question as to how this remarkable diversity arose and is maintained. The explanation that infectious pathogens are largely responsible is theoretically attractive but clear and consistent associations between HLA alleles and major infectious diseases have rarely been identified. Large case-control studies of HLA types in African children with severe malaria indicate that HLA associations with this parasitic infection do exist and it is becoming possible to investigate the underlying mechanisms by identification of peptide epitopes in parasite antigens. Such analysis reveals how the magnitude and detectability of HLA associations may be influenced by numerous genetic and environmental factors. These complex interactions will give rise to variation over time and space in the selective pressures exerted by infectious diseases and this fluctuation may, in itself, contribute to the maintenance of HLA polymorphism.

Biological Evolution↗
PubMed2005

Protein evolution in viral quasispecies under selective pressure: a thermodynamic and phylogenetic analysis.

The evolution of RNA viruses under antiviral pressure is characterized by high mutation rates and strong selective forces that induce extremely rapid changes of protein sequences. This makes the course of molecular evolution directly observable on time scales of months. Here we study the interplay between selection for drug resistance and selection for thermodynamic stability in the protease (PR) and the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) clones extracted from two patients with complex treatment histories. This analysis shows that folding thermodynamic properties may fluctuate very strongly in the course of quasispecies evolution under selective pressure. For the first case, our data suggest that folding efficiency of the RT is sacrificed at the advantage of drug resistance, while the corresponding PR seems to undergo selection for thermodynamic stability in the absence of substitutions associated to resistance. The PR of the second case is not submitted to antiviral pressure during the period analyzed and seems to initiate random fluctuations that lead to the accidental increase of its folding efficiency. In summary, joint consideration of sequence evolution and thermodynamic parameters can represent a more comprehensive approach for the study of the evolution of RNA viruses.

Anti-HIV Agents↗
PubMed2002

Fluctuating sensorineural hearing loss in children.

Childhood sensorineural hearing loss (SNHL) that fluctuates or is progressive enhances parental concern and complicates medical management, hearing aid selection, and individualized educational planning for the affected child. Despite intensive multidisciplinary evaluation and intervention, continued threshold fluctuation or a gradual decline in auditory acuity may proceed unabated in a significant percentage of these youngsters. With the adoption of universal newborn hearing screening mandates by an increasing number of states, any challenges to the accurate determination of auditory thresholds must be addressed within the first few months of life.

Auditory Threshold↗
PubMed1998

Selection of macronutrients by goldfish operating self-feeders.

In the wild, both food availability and an animal's requirements may fluctuate. Given the choice to feed on different diets, animals may exhibit preferences in their selection. Although macronutrient selection has been investigated in mammals and birds, few attempts have been made to investigate dietary selection in fish. In the present study we investigate the feeding of goldfish on three "pure" macronutrient diets. Twelve single goldfish and one group of four goldfish, initially weighing 163.1 +/- 7.4 and 70.2 +/- 8.0 g, respectively, were maintained in 54-liter tanks at 20 degrees C under a 12 h:12 h light-dark (LD) cycle. Three pelleted diets were made containing 50% of each macronutrient: protein (casein + gelatin), fat (fish oil + soy oil), or carbohydrate (dextrin). All the diets included mixtures of vitamins and minerals, a binder (sodium alginate), and cellulose as a filler. During trials, three self-feeding devices delivering the protein, fat, or carbohydrate diet were installed in each aquarium. Goldfish soon learned to select from among the three diets. Overall daily food and digestible energy demands differed significantly between macronutrients. The demand for protein was lower than that for carbohydrate (16.6 and 33.7 g/kg BW/day, respectively), and the digestible energy demand for protein was lower than for fat (108.6 and 308.5 kJ/kg BW/day, respectively). Goldfish made their dietary selections on the basis of energy content, so that food demand increased to compensate for changes in the digestible energy density of the diets. Correlation analysis revealed a significant positive relationship between carbohydrate and fat demand (n = 8), whereas there were significant negative (n = 3) and positive (n = 1) relationships between protein and fat. Different daily patterns for the selection of each macronutrient were detected in some fish (i.e., carbohydrate during daytime, protein at the beginning of the night, and fat during the transition phase). In short, our results demonstrated the ability of goldfish to compose their own diet from three basic macronutrients, highlighting the complex pattern of behavior in their selection. Therefore, these new findings should be considered when studying feeding rhythms and the design of diets for fish.

Animal Feed↗
PubMed1993

Preclamol and parkinsonian fluctuations.

Preclamol, the (-)enantiomer of 3-PPP (= 3(3-hydroxyphenyl)-N-n-propyl piperidine), has a selective dopamine autoreceptor- and postsynaptic mixed agonist-antagonist profile. Its action on patients with disabling on-off parkinsonian fluctuations has been studied and compared with those of placebo and subcutaneous apomorphine. Preclamol had a mild but unequivocal antiakinetic effect, less than that caused by subcutaneous apomorphine, but it provoked less dyskinesia. Further studies to explore the therapeutic potential of preclamol seem justified.

Antiparkinson Agents↗
PubMed1985

Long-term fluctuations versus actual field loss in glaucoma patients.

In following glaucomatous visual fields with automated perimetry, one becomes aware of the difficulty in differentiating between long-term fluctuations and actual changes. We have analyzed visual fields of one randomly selected eye of each of 34 patients (mean age = 61.8 +/- 12.3 years) with proven glaucoma chronicum simplex and at least 4 (mean = 5.6 +/- 1.9) visual field examinations with programs 31 and/or 33 of the Octopus 201 within at least 21 months (mean = 32.6 +/- 6 months). When a group of earlier visual fields is compared with a group of later ones utilizing the statistical program delta-change, the results of regression analysis, based on data from program delta-series, are juxtaposed to the results of the t test with very good correlation. This investigation confirms that glaucomatous visual fields exhibit considerable long-term fluctuations; as long as field loss and gain observed over a longer time period are evenly distributed, the symmetrical portions of the distribution curve may serve as the outer limits of long-term fluctuation. In this regard, definite visual field deterioration was discerned in none of our medically treated patients over an average observation period of 32 months. If more selective criteria for differentiating between long-term fluctuations and actual field change are used (such as measurement of long-term fluctuations performed in earlier investigations, the t test of program delta-change, regression analysis of the data produced by program delta-series, as well as the correspondence between the t test and the correlation coefficient of the regression analysis), 3 eyes have changed for the worse regarding loss per test location, and 3 have changed for the worse regarding sensitivity.

Computers↗
PubMed2005

Identification of dynamical correlations within the myosin motor domain by the normal mode analysis of an elastic network model.

In order to systematically analyze functionally relevant dynamical correlations within macromolecular complexes, we have developed computational methods based on the normal mode analysis of an elastic network model. First, we define two types of dynamical correlations (fluctuation-based and density-based), which are computed by summing up contributions from all low-frequency normal modes up to a given cutoff. Then we use them to select dynamically important "hinge residues" whose elastic distortion affects the fluctuations of a large number of residues. Second, in order to clarify long-range dynamical correlations, we decompose the dynamical correlations to individual normal modes to identify the most relevant modes. We have applied these methods to the analysis of the motor domain of Dictyostelium myosin and have obtained the following three interesting results that shed light on its mechanism of force generation: first, we find the hinge residues are distributed over several key inter-subdomain joints (including the nucleotide-binding pocket, the relay helix, the SH1 helix, the strut between the upper 50 kDa and the lower 50 kDa subdomains), which is consistent with their hypothesized roles in modulating functionally relevant inter-subdomain conformational changes; second, a single mode 7 (for structure 1VOM) is found to dominate the fluctuation-based correlations between the converter/strut and the nucleotide-binding pocket, revealing a surprising simplicity for their intriguing roles in the force generation mechanism; finally, we find a negative density-based correlation between the strut and the nucleotide-binding pocket, which is consistent with the hypothesized signaling pathway that links the actin-binding site's opening/closing with the nucleotide-binding pocket's closing/opening.

Animals↗
PubMed1992

Are paw preference differences in HI and LO mice the result of specific genes or of heterosis and fluctuating asymmetry?

Collins (1985) has described two separate mouse strains, obtained by selective breeding, which differ in having high (HI) or low (LO) degrees of paw preference on a standard test. In this paper I argue that the differences between these strains may not be due to a specific gene (or genes) but, instead, probably reflect differences in the total heterozygosity of the strains, such that the HI strain is more heterotic than the LO strain. Greater degrees of heterozygosity are argued to buffer against fluctuating asymmetry and hence result in a greater degree of paw preference.

Animals↗