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Antigenic variation of gonococcal pilus involves assembly of separated silent gene segments.

The pilus is a major outer-membrane protein of Neisseria gonorrhoeae that undergoes phase and antigenic variation. In strain MS11 pilus expression is regulated at two expression loci on the chromosome, pilE1 and pilE2, although many other regions contain silent pilin information. A comparison of variant pilin sequences has revealed that the gene can be divided into a constant, a semivariable, and a hypervariable region. We report here that complete pilin genes are found only at the expression loci. Silent constant and variable region pilin gene segments are located on separate and distinct restriction fragments, and the generation of a complete pilin gene within the expression loci is the result of multiple recombination events. Conserved sequences within and flanking the pilin gene are proposed to act as recombination sites during the gene conversion events needed to produce a functional pilin gene.

Antigens, Bacterial↗

DNA and cholesterol biosynthesis in synchronized embryonic rat fibroblasts. I. Temporal relationships between HMG-CoA reductase activity, sterol biosynthesis and thymidine incorporation into DNA.

Temporal relationships between hydroxymethylglutaryl-CoA reductase activity, biosynthesis of C27 sterols, and [3H]thymidine incorporation into DNA were studied in a rat embryo fibroblast cell line synchronized by double thymidine block and cultured in cholesterol-containing medium. Cyclic variations of HMG-CoA reductase activity and C27 sterols occurred, with two maxima in S and G2M phases; the relative shortness of the G1 phase (3 h) in these cells could be responsible for the shift of sterol synthesis in the S phase. No noticeable variation of the individual C27 sterols was observed during the entire cell cycle. In each experiment, there was a good linear correlation between HMG-CoA reductase activity and C27 sterol synthesis, but from one experiment to another, a given level of enzymatic activity led to varying levels of [2-14C]acetate incorporation into sterols. In our experimental conditions, total HMG-CoA reductase activity is measured, and the preceding observation could be explained by a varying degree of phosphorylation of the enzyme depending on the metabolic state of the cells at the start of the experiment. The cyclic variations of the enzyme activity seem to be due more to increased synthesis at given times of the cycle than to periodic dephosphorylation. We question the existence of a relationship between cell division and cyclic sterol synthesis occurring in cells cultured in cholesterol-containing medium.

Acetates↗

Visual cerebral lateralization over phases of the menstrual cycle: a preliminary investigation.

This study investigated whether visual cerebral asymmetries would change in phase with hormonal variations during the menstrual cycle. Lexical decision and line orientation tasks were administered during follicular, luteal, and menstrual phases of each woman's cycle. These tasks were also administered to a reference group of male subjects. Signal detection analyses indicated an unvarying RVF advantage in word/nonword discriminability (d') throughout the menstrual cycle, but a phase-dependent shift in left hemisphere response criterion (log beta). Gender differences were present for discriminability of line orientation, and female performance on this task varied over the cycle. The results imply that the neural systems subserving some cognitive functions are sensitive to fluctuations in gonadal steroids and suggest a hormonal basis for gender differences in some visual-spatial functions.

Adolescent↗

Outer membrane protein profiles of Yersinia ruckeri.

The outer membrane protein (OMP) profiles of 135 isolates of Yersinia ruckeri, obtained from nine European countries (100 isolates), North America (23 isolates), Australia (six isolates) and South Africa (two isolates), and including four reference strains, were examined by SDS-PAGE. Outer membranes were isolated by selective solubilisation of the cytoplasmic membrane with 0.5% (w/v) sodium N-lauroyl sarcosinate (Sarkosyl). Outer membrane proteins were stable after in vitro passage and there was no variation in OMP profiles due to colony selection. With the exception of a 39.5 kDa peptidoglycan-associated protein there was also no variation at different stages of the growth cycle. The 39.5 kDa protein was not produced during logarithmic growth phase but increased in abundance as the stationary phase progressed. Interstrain variation occurred in the possession of a 36.5 or 38 kDa heat-modifiable protein and in the possession of peptidoglycan-associated proteins in the molecular weight range 36.5 to 40.5 kDa. Based on variation of these proteins five OMP-types, designated OMP-types 1-5, were identified among the 135 isolates examined. Outer membrane protein analysis was demonstrated to be useful in epidemiological studies of Y. ruckeri.

Animals↗

An Australian casemix classification for palliative care: technical development and results.

OBJECTIVES: To develop a palliative care casemix classification for use in all settings including hospital, hospice and home-based care. SAMPLE: 3866 palliative care patients who, in a three-month period, had 4596 episodes of care provided by 58 palliative care services in Australia and New Zealand. METHOD: A detailed clinical and service utilization profile was collected on each patient with staff time and other resources measured on a daily basis. Each day of care was costed using actual cost data from each study site. Regression tree analysis was used to group episodes of care with similar costs and clinical characteristics. RESULTS: In the resulting classification, the Australian National Sub-acute and Non-acute Patient (AN-SNAP) Classification Version 1, the branch for classifying inpatient palliative care episodes (including hospice care) has 11 classes and explains 20.98% of the variance in inpatient palliative care phase costs using trimmed data. There are 22 classes in the ambulatory palliative care branch that explains 17.14% variation in ambulatory phase cost using trimmed data. DISCUSSION: The term 'subacute' is used in Australia to describe health care in which the goal--a change in functional status or improvement in quality of life--is a better predictor of the need for, and the cost of, care than the patient's underlying diagnosis. The results suggest that phase of care (stage of illness) is the best predictor of the cost of Australian palliative care. Other predictors of cost are functional status and age. In the ambulatory setting, symptom severity and the model of palliative care are also predictive of cost. These variables are used in the AN-SNAP Version 1 classification to create 33 palliative care classes. The classification has clinical meaning but the overall statistical performance is only moderate. The structure of the classification allows for it to be improved over time as models of palliative care service delivery develop.

Ambulatory Care↗

Circadian variation of blood pressure and neurohumoral factors during the acute phase of stroke.

This study was to investigate the relationship between circadian blood pressure (BP) variation and circadian variation of neurohumoral factors during the acute phase of stroke. We studied 17 patients with cerebral infarction in 16 and cerebral hemorrhage in one. We performed 24-hour ambulatory BP monitoring and examined plasma renin activity (PRA), catecholamine, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endothelin 1 (ET1) and prothrombin fragment 1+2 (PT F1+2) and urinary catecholamine. Our result showed that the circadian variation of BP, neurohumoral and coagulation factors were diminished. There were significant relationships between BP levels and plasma BNP levels, nocturnal urinary adrenalines and ET1s. There were also significant relationships between night/day ratio of BP and plasma ET1 level. In conclusion the abnormal patterns of circadian BP rhythm were frequently observed during the acute phase of stroke. The cause of this abnormality may result from the diminished circadian rhythms of neurohumoral factors.

Aged↗

Acute normovolaemic haemodilution does not reduce the inflammatory process induced by facial surgery.

The place of preoperative acute normovolaemic haemodilution (haematocrit = 28%-32%) in reducing postoperative inflammation was evaluated after facial surgery. Thirty-two patients scheduled for mandibular osteotomy were randomized to a nonhaemodiluted group or to a haemodiluted group. The degree of postoperative inflammation was evaluated: first by an x-ray technique (radiotelemetry) providing measurements of the tissue thickness (quantitation of facial oedema), and second by the measurement of four acute phase protein plasma concentrations during the first postoperative week. Throughout the study, no changes in facial oedema or in variation of acute phase proteins were detected after haemodilution. It is concluded that acute normovolaemic haemodilution has no effect on the intensity of facial oedema and the biological inflammation process after facial surgery.

Acute-Phase Proteins↗

Human sleep: its duration and organization depend on its circadian phase.

Two- to threefold variations in sleep length were observed in 12 subjects living on self-selected schedules in an environment free of time cues. The duration of polygraphically recorded sleep episodes was highly correlated with the circadian phase of the body temperature rhythm at bedtime and not with the length of prior wakefulness. Furthermore, the rate of REM (rapid eye movement) sleep accumulation , REM latency, bedtime selection, and self-rated alertness assessments were also correlated with the body temperature rhythm.

Adult↗

Exploring phase space localization of chaotic eigenstates via parametric variation.

In a previous paper [Phys. Rev. Lett. 77, 4158 (1996)], a new correlation measure was introduced that sensitively probes phase space localization properties of eigenstates. It is based on a system's response to varying an external parameter. The measure correlates level velocities with overlap intensities between the eigenstates and some localized state of interest. Random matrix theory predicts the absence of such correlations in chaotic systems whereas in the stadium billiard, a paradigm of chaos, strong correlations were observed. Here, we develop further the theoretical basis of that work, extend the stadium results to the full phase space, study the Planck's over 2pi dependence, and demonstrate the agreement between this measure and a semiclassical theory based on homoclinic orbits.

Journal Article↗

Field analysis of a tape helix with embedded bio-media for microwave hyperthermia.

A general field theory has been developed for the EM wave propagation on a tape helix with embedded bone, muscle, fat and skin co-axial biological layers in a multilayered dielectric environment. The electric and magnetic fields in every biological/dielectric layer is formulated in terms of complex modified Bessel functions and complex exponentials, i.e. in terms of complex radial and axial propagation constants for the azimuthally symmetric and higher order spatial harmonics. A complete dispersion relation is derived by substituting the field expressions into as many boundary conditions as there are unknown constants. The dispersion relation is numerically solved for the complex axial propagation constant and hence for the phase velocity and depth of penetration for n = 0 and 1 modes propagating along three dielectric loaded tape helices of different dimensions at several spot frequencies within the range of 300 MHz to 3.00 GHz. The results for variations in normalized phase velocity and depth of penetration with frequency for these modes separately and for the combined mode are presented. The patterns of specific absorption rate (SAR) across the cross-section of the dielectric loaded helices are also computed and presented. The variations with frequency, and cross-sectional dimension of the helix of the normalized phase velocity, axial depth and SAR across the cross-section of each of the helices are discussed for the modes considered. The theoretical results for the propagation constant obtained by using a tape helix model for the azimuthally symmetric mode propagating along a wire helix loaded with a phantom muscle sample of known dielectric constant are compared with experimental results and with those obtained theoretically employing a sheath helix model at 2.45 and 2.55 GHz. The use of a helix for human limb hyperthermia is also discussed.

Absorption↗

Effects of cimetidine and ranitidine on interdigestive and postprandial lower esophageal sphincter pressures and plasma gastrin levels in normal subjects.

The purpose of this study was to investigate the effects of cimetidine and ranitidine on human lower esophageal sphincter pressure (LESP) and plasma levels of gastrin in all phases of the interdigestive motor complex and after a test meal. In a random, double-blind manner, placebo, cimetidine (1.0 mg/kg X h), and ranitidine (0.16 mg/kg X h) were administered by intravenous infusion to nine healthy volunteers. By using a sleeve catheter assembly, LESP was constantly monitored, as were esophageal, fundic, antral, and duodenal pressures. Considerable minute-to-minute and interdigestive motor phase-related LESP variations were observed. Cimetidine and ranitidine decreased the interdigestive LESP, but did not abolish the gradual increase in LESP from phase I to phase III. During the first 2 h after the meal, cimetidine and ranitidine had no significant effect on LESP. Plasma gastrin levels were increased by cimetidine and ranitidine, both in the interdigestive and in the postprandial state. The results indicate that the effect of H2-blockers on LESP is not gastrin-mediated. The results further indicate that, in studies on the effects of drugs on LESP, prolonged recording of LESP in all motor states is a prerequisite.

Adult↗

Re-sequencing of multiple single nucleotide polymorphisms by liquid chromatography-electrospray ionization mass spectrometry.

Allelic discrimination of single nucleotide polymorphisms (SNPs) and, particularly, determination of the phase of multiple variations are of utmost importance in genetics. The physicochemical separation of alleles by completely denaturing ion-pair reversed-phase high-performance liquid chromatography and their on-line sequence determination by electrospray ionization mass spectrometry is demonstrated. Simultaneous genotyping of two and three simple sequence polymorphisms contained within 73-114 bp was accomplished with low femtomolar amounts of unpurified amplicons from polymerase chain reaction. Determination of allelic composition is enabled by the high accuracy (better than 0.019%) of intact mass measurements or by comparative sequencing using gas-phase fragmentation and tandem mass spectrometry in combination with fully automated, computer-aided data interpretation.

Chromatography, Liquid↗

Structure of twist-grain-boundary-C phases.

We study properties of the Renn-Lubensky twist-grain-boundary-C (TGB(C)) phase, with layer normal rotating in a plane perpendicular to the pitch axis, and the Bordeaux TGB(C) phase, with the layer normal rotating on a cone parallel to the pitch axis near the upper critical twist k(c2) marking the transition to the cholesteric phase. We introduce a generalized model free energy for the smectic-C phase that allows either TGB(C) phase to be stable, and we calculate k(c2) and the order-parameter profile, which shows only modest spatial variation, for both phases.

Journal Article↗

Probabilistic characterization of simultaneous nerve impulse sequences controlling dipteran flight.

A probabilistic method of analysis of spike trains is presented which provides a complete statistical description of spike sequences and allows the elucidation of some of the properties of the neural interconnections producing the output patterns. The flight motor system of the blowfly, Calliphora terraenovae, is analyzed by this method. Individual motor units show large, non-serially correlated, cycle-to-cycle variations in frequency superimposed upon long term frequency trends. These trends are apparently not generated by averaging the cycle-to-cycle variations in input excitation over a long time period. The different motor units share the same short term input excitation and the excitation causing long term trends. Units in different muscles show no preferred phase or latency relationships; they maintain similar frequencies but their phases drift through all possible values. Frequency control without phase control may be accomplished by shared excitation with a total input frequency many times the output frequency. Units in the same muscle maintain strong phase relationships. Constant phase relationships during variations in frequency may, among other models, be due to reciprocal inhibition or a common linearly rising input. Sensory feedback cannot account for the degree of phase or frequency regulation shown. Thus central patterning of the output sequence is necessary, as in the locust, and the two flight systems can be considered as integradable evolutionary variations.

Animals↗

Reorganizational dynamics of multilamellar lipid bilayer assemblies using continuously scanning Fourier transform infrared spectroscopic imaging.

We employ an implementation of rapid-scan Fourier transform infrared (FT-IR) microspectroscopic imaging to acquire time-resolved images for assessing the non-repetitive reorganizational dynamics of aqueous dispersions of multilamellar lipid vesicles (MLVs) derived from distearoylphosphatidylcholine (DSPC). The spatially and temporally resolved images allow direct and simultaneous determinations of various physical and chemical properties of the MLVs, including the main thermal gel to liquid crystalline phase transition, comparisons of vesicle diffusion rates in both phases and the variation in lipid bilayer packing properties between the inner and outer lamellae defining the vesicle. Specifically, in the lipid liquid crystalline phase, the inner bilayers of the MLVs are more intermolecularly ordered than the outer regions, while the intramolecular acyl chain order/disorder parameters, reflecting the overall characteristics of the fluid phase, remain uniform across the vesicle diameter. In contrast, the lipid vesicle gel phase displays no intermolecular or intramolecular dependence as a function of distance from the MLV center.

Diffusion↗

How precise is neuronal synchronization?

Recent work suggests that synchronization of neuronal activity could serve to define functionally relevant relationships between spatially distributed cortical neurons. At present, it is not known to what extent this hypothesis is compatible with the widely supported notion of coarse coding, which assumes that features of a stimulus are represented by the graded responses of a population of optimally and suboptimally activated cells. To resolve this issue we investigated the temporal relationship between responses of optimally and suboptimally stimulated neurons in area 17 of cat visual cortex. We find that optimally and suboptimally activated cells can synchronize their responses with a precision of a few milliseconds. However, there are consistent and systematic deviations of the phase relations from zero phase lag. Systematic variation of the orientation of visual stimuli shows that optimally driven neurons tend to lead over suboptimally activated cells. The observed phase lag depends linearly on the stimulus orientation and is, in addition, proportional to the difference between the preferred orientations of the recorded cells. Similar effects occur when testing the influence of the movement direction and the spatial frequency of visual stimuli. These results suggest that binding by synchrony can be used to define assemblies of neurons representing a coarse-coded stimulus. Furthermore, they allow a quantitative test of neuronal network models designed to reproduce physiological results on stimulus-specific synchronization.

Anesthesia↗

Relationship between the secretion of the corpus luteum and the length of the follicular phase of the ovarian cycle.

The variation in the length of the follicular phase in many mammals may be related to the cellular origin of oestradiol secreted during the luteal phase. In all species the time taken for a small developing follicle (4-5 layers of granulosa cells) to mature to a preovulatory follicle may be the same as that which has been found experimentally in the mouse (10-17 days). In animals such as the sheep, in which there is no source of oestradiol other than the Graafian follicle, follicular development proceeds unimpaired throughout the luteal phase, and the 'follicular phse' which involves only the final stages of maturation of the Graafian follicle is relatively short. In primates, however, in which there is an extrafollicular source of oestrogen from the CL, the secretion of gonadotrophins is suppressed during each luteal phase to a level too low to initiate and maintain follicular development. At the end of each luteal phase and the beginning of the subsequent follicular phase, therefore, it is necessary to initiate the growth of a new crop of small follicles. The time taken for these follicles to develop inot preovulatory follicles determines the length of the follicular phase.

Animals↗

Assessing arterial blood flow and vessel area variations using real-time zonal phase-contrast MRI.

PURPOSE: To measure peripheral artery function using a real-time phase-contrast (PC)-MRI sequence with tailored image-processing algorithms for flow computation. MATERIALS AND METHODS: An approach to real-time flow measurements was developed based on two-dimensional spatially selective excitation pulses and consecutive tailored processing of the data to derive blood flow and vessel area variations. The data acquisition strategy allows for flow measurements at high spatial and temporal resolutions of 1 mm(2) and 50 msec, respectively. In postprocessing the vessel area is automatically extracted using correlation measures in conjunction with morphological image operators. By means of in vitro and in vivo validations, it is shown that the current methods provide accurate and reproducible measurements of flow and vessel area variations. RESULTS: In vitro the comparison between the lumen area measured with the presented method and the values obtained by caliper gauge measurement showed a difference of 3.4% +/- 3.4% (mean +/- 2 SD). Similarly, the comparison between the stroke volumes determined with the presented method and by stopwatch and bucket measurements yielded a difference of 6.1% +/- 2.1%. In vivo the results from the real-time measurements for lumen area and stroke volume were compared with those from a gated PC-MRI technique with differences of 4.8% +/- 14% and 3.0% +/- 24.7%, respectively. CONCLUSION: The presented method constitutes a reliable tool set for quantifying the variations of blood flow and lumen area in the superficial femoral artery during reactive hyperemia and for studying their correlation with cardiovascular risk factors.

Algorithms↗