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PubMed2001

Protonation of platinated adenine nucleobases. Gas phase vs condensed phase picture.

Protonation of adenine carrying a Pt(II) moiety either at N7, N3, or N1 is possible in solution, but the site of protonation is influenced by the location of the Pt(II) electrophile and to some extent also by the overall charge of the metal entity (+2, +1, 0, -1), hence the other ligands (NH(3), Cl(-), OH(-)) bound to Pt(II). Quantum chemical calculations based on density functional theory (DFT) have been carried out for intrinsic protonation energies of adenine complexes carrying the following Pt(II) species at either of the three ring N atoms: [Pt(NH(3))(3)](2+) (1), trans- [Pt(NH(3))(2)Cl](+) (2a), cis-[Pt(NH(3))(2)Cl](+) (2b), trans-[Pt(NH(3))(2)Cl(2)] (3a), cis-[Pt(NH(3))Cl(2)] (3b), [PtCl(3)](-) (4), trans-[Pt(NH(3))(2)OH](+) (5a), cis-[Pt(NH(3))(2)(OH)](+) (5b), trans-[Pt(NH(3))(OH)(2)] (6a), cis-[Pt(NH(3))(OH)(2)] (6b), and [Pt(OH)(3)](-) (7). The data have been compared with results derived from solution studies (water) and X-ray crystallography, whenever available. The electrostatic effects associated with the charge of the metal entity have the major influence on the calculated intrinsic (gas phase) proton affinities, unlike the condensed phase data. Nevertheless, the relative gas phase trends correlate surprisingly well with condensed phase data; i.e., variation of the pK(a) values measured in solution is consistent with the calculated gas phase protonation energies. In addition to a systematic study of the ring proton affinities, proton transfer processes within the platinated adenine species were often observed when investigating Pt adducts with OH(-) ligands, and they are discussed in more detail. To the best of our knowledge, this is the first study attempting to find a systematic correlation between gas phase and condensed phase data on protonation of metalated nucleobases. The gas phase data provide a very useful complement to the condensed phase and X-ray experiments, showing that the gas phase studies are capable of valuable predictions and contribute to our understanding of the solvent and counterion effects on metal-assisted proton shift processes.

Adenine Nucleotides↗

PubMed1993

Would eliminating differences in physician practice style reduce geographic variations in cataract surgery rates?

This study uses Medicare physician-claims data to examine patient and physician contributions to variations in cataract surgery rates across U.S. metropolitan areas. Utilization is modelled as having two phases: the decision to seek an ophthalmologist's care, which is made by patients, and the decision to perform surgery on patients who seek care, which is partially controlled by ophthalmologists. Under this model, the effect of physician practice style on cataract surgery rates occurs through the influence of practice style on the second phase of utilization. Variation in patient care-seeking behavior contributed to the variation in the rate of cataract surgery. Moreover, multivariate regression analyses found that cataract surgery rates were influenced by economic and sociodemographic variables in predictable ways. Using the regression results, a "purged" cataract surgery rate that was free of any possible influence of physician practice style was calculated. Variation in the purged surgery rate was only slightly lower than variation in the observed surgery rate, suggesting that eliminating practice style as a factor in physician decision making (e.g., through practice guidelines) would reduce variations in cataract surgery rates by only a small amount.

Cataract Extraction↗

PubMed1992

Subclinical ischaemic episodes during the steady state of sickle cell anaemia.

AIMS: To determine the clinical, haematological, biochemical and rheological changes that occur in the asymptomatic steady state of sickle cell anaemia. METHODS: Patient self-assessment visual analogue scores (for wellbeing and tiredness), the blood concentration of acute phase proteins (C-reactive protein, orosomucoid, and fibrinogen), and blood rheology (percentage of dense cells and the number of sickled cells that occluded pores 5 microns in diameter) were studied longitudinally on 10 occasions in each of 20 outpatients with sickle cell anaemia. RESULTS: Patients in the steady state showed fluctuation in visual analogue scores, in concentration of acute phase proteins, and in rheological parameters consistent with minor episodes of tissue injury. Significantly more variation in acute phase proteins occurred in the steady state of 14 of the 20 patients who developed one or more vaso-occlusive crises during the 16 month study period. Rheological fluctuation in the steady state simulated rheological change during crisis, namely a transient rise and then fall in the number of dense and poorly filterable cells. CONCLUSIONS: The term "steady state" is a misnomer, being characterised by biochemical and rheological fluctuation consistent with minor episodes of microvascular occlusion that are insufficient to cause the overt tissue infarction of painful crisis.

Acute-Phase Proteins↗

PubMed2006

Use of dynamic electronic speckle pattern interferometry with the Hilbert transform method to investigate thermal expansion of a joint material.

A dynamic electronic speckle pattern interferometry method is applied to investigate thermal expansion of a joint material (ceramic-stainless steel) as a practical industrial object. The speckle interference signal is considered in the temporal domain and the phase is analyzed by the Hilbert transform method. Errors caused by the bias and modulation variations over the phase values are first examined by numerical simulation. Two experiments are performed with in-plane and out-of-plane sensitive systems to study the 3D deformation field thoroughly. The deformation field showed clearly the difference between the thermal expansions of the stainless steel and ceramic. It was also revealed that the boundary of materials and its vicinity suffer very large thermal strain due to the significantly large difference in the linear coefficient of thermal expansions.

Journal Article↗

PubMed2002

Intrinsic firing dynamics of vestibular nucleus neurons.

Individual brainstem neurons involved in vestibular reflexes respond to identical head movements with a wide range of firing responses. This diversity of firing dynamics has been commonly assumed to arise from differences in the types of vestibular nerve inputs to vestibular nucleus neurons. In this study we show that, independent of the nature of inputs, the intrinsic membrane properties of neurons in the medial vestibular nucleus substantially influence firing response dynamics. Hyperpolarizing and depolarizing inputs evoked a markedly heterogenous range of firing responses. Strong postinhibitory rebound firing (PRF) was associated with strong firing rate adaptation (FRA) and occurred preferentially in large multipolar neurons. In response to sinusoidally modulated input current, these neurons showed a pronounced phase lead with respect to neurons lacking strong PRF and FRA. A combination of the hyperpolarization-activated H current and slow potassium currents contributed to PRF, whereas FRA was predominantly mediated by slow potassium currents. An integrate-and-fire-type model, which simulated FRA and PRF, reproduced the phase lead observed in large neurons and showed that adaptation currents were primarily responsible for variations in response phase. We conclude that the heterogeneity of firing dynamics observed in response to head movements in intact animals reflects intrinsic as well as circuit properties.

Adaptation, Physiological↗

PubMed1988

High-performance liquid chromatographic separation of subcomponents of antimycin A.

Using a reversed-phase high-performance liquid chromatographic (HPLC) technique, a mixture of antimycins A was separated into eight hitherto unreported subcomponents, A1a, A1b, A2a, A2b, A3a, A3b, A4a, and A4b. Although a base-line resolution of the known four major antimycins A1, A2, A3, and A4 was readily achieved with mobile phases containing acetate buffers, the separation of the new antibiotic subcomponents was highly sensitive to variation in mobile phase conditions. The type and composition of organic modifers, the nature of buffer salts, and the concentration of added electrolytes had profound effects on capacity factors, separation factors, and peak resolution values. Of the numerous chromatographic systems examined, a mobile phase consisting of methanol-water (70:30) and 0.005 M tetrabutylammonium phosphate at pH 3.0 yielded the most satisfactory results for the separation of the subcomponents. Reversed-phase gradient HPLC separation of the dansylated or methylated antibiotic compounds produced superior chromatographic characteristics and the presence of added electrolytes was not a critical factor for achieving separation. Differences in the chromatographic outcome between homologous and structural isomers were interpreted based on a differential solvophobic interaction rationale. Preparative reversed-phase HPLC under optimal conditions enabled isolation of pure samples of the methylated antimycin subcomponents for use in structural studies.

Acetates↗

PubMed2003

An experimental investigation on intra-fractional organ motion effects in lung IMRT treatments.

Respiration-induced tumour motion can potentially compromise the use of intensity-modulated radiotherapy (IMRT) as a dose escalation tool for lung tumour treatment. We have experimentally investigated the intra-fractional organ motion effects in lung IMRT treatments delivered by multi-leaf collimator (MLC). An in-house made motor-driven platform, which moves sinusoidally with an amplitude of 1 cm and a period of 4 s, was used to mimic tumour motion. Tumour motion was simulated along cranial-caudal direction while MLC leaves moved across the patient from left to right, as in most clinical cases. The dose to a point near the centre of the tumour mass was measured according to geometric and dosimetric parameters from two five-field lung IMRT plans. For each field, measurement was done for two dose rates (300 and 500 MU min(-1)), three MLC delivery modes (sliding window, step-and-shoot with 10 and 20 intensity levels) and eight equally spaced starting phases of tumour motion. The dose to the measurement point delivered from all five fields was derived for both a single fraction and 30 fractions by randomly sampling from measured dose values of each field at different initial phases. It was found that the mean dose to a moving tumour differs slightly (<2-3%) from that to a static tumour. The variation in breathing phase at the start of dose delivery results in a maximum variation around the mean dose of greater than 30% for one field. The full width at half maximum for the probability distribution of the point dose is up to 8% for all five fields in a single fraction, but less than 1-2% after 30 fractions. In general, lower dose rate can reduce the motion-caused dose variation and therefore might be preferable for lung IMRT when no motion mitigation techniques are used. From the two IMRT cases we studied where tumour motion is perpendicular to MLC leaf motion, the dose variation was found to be insensitive to the MLC delivery mode.

Biophysical Phenomena↗

PubMed1995

Circadian variation in uterine artery blood flow indices during the follicular phase of the menstrual cycle.

We investigated for the presence of circadian variation in uterine artery blood flow indices during the late follicular phase of the menstrual cycle. Twenty women with regular menstrual cycles underwent transvaginal color Doppler assessment of blood flow in the uterine arteries on two occasions precisely 12 h apart on the same day in the follicular phase. Ultrasound examinations were performed between 06.00 and 10.00 and repeated between 18.00 and 22.00. Indices of uterine artery blood flow included the pulsatility index (PI) and the time-averaged maximum velocity (TAMX). The changes in PI and TAMX were related to variations in serum concentrations of estradiol and luteinizing hormone (LH). We noted a significantly higher PI and lower TAMX in the evening compared to the morning values, p < 0.001 and p = 0.01, respectively. There was no significant change in estradiol or LH concentrations between morning and evening (p > 0.05). There appears to be a circadian rhythm in uterine artery blood flow occurring independently of these hormonal parameters. The circadian changes in PI and TAMX may be larger than the previously described effects of hormones on these parameters. The accurate interpretation of uterine artery blood flow indices should take these time-related fluctuations into account.

Adult↗

PubMed2005

Locating counterions in guanosine quadruplexes: a contrast-variation neutron diffraction experiment in condensed hexagonal phase.

Guanosine, one of the primary components of nucleic acids, self-associates in water to form G-quadruplexes, four-stranded helicoidal aggregates, made by stacked planar tetramers, consisting of four planar guanine molecules. Essential for the stability of these supramolecular aggregates is the presence of monovalent cations. As G-quadruplexes show a lyotropic polymorphism, neutron diffraction, in combination with the H2O/D2O contrast variation technique, has been applied to study the cation structural features of quadruplexes in hexagonal phase at different hydrations and counterion concentrations. The guanosine 5'-monophosphate, dipotassium salt, was considered and G-quadruplexes in hexagonal phase were prepared in the different experimental conditions (contrast, hydration and KCl solution concentration) by using the osmotic stress technique. The calculated scattering length density distribution maps show that counterions fill the helix inner cavity and that atmospheric cations are bound to a second site, close to the external phosphate groups. The site occupancy turned out to be very high: we found on the inner site 0.87 K ions per tetramer in G-quadruplexes prepared in pure water and 0.97 K ions per tetramer in G-quadruplexes prepared in KCl 0.5 M, while in all cases 6 ions per unit cell were detected to occupy the outer sites, partially neutralizing the two formal negative charges per phosphate group. The very large K ions concentration difference between the binding sites and the bulk solution demonstrates that counterions are structurally involved in the formation and in the stabilization of the helices.

Cations↗

PubMed1988

The effect of interobserver variation in dating endometrial histology on the diagnosis of luteal phase defects.

Endometrial biopsy specimens (n = 62) were evaluated by five pathologists to assess the effect of interobserver variation on histologic dating of the endometrium. The potential effect of this variation on the diagnosis of luteal phase defects (LPDs) and resulting clinical management was also determined. Mean (+/- standard error) interobserver variation was 0.96 +/- 0.08 days, comparable to results reported by other investigators. The magnitude of the variation was not affected by whether the biopsy specimen was obtained in the mid or late luteal phase, the degree of lag between the dating and subsequent menses, or the presence of an LPD. Redating of a specimen by another pathologist would have resulted in a change in the determination of "in" or "out" of phase in 22% of cases. The subsequent probability of changing patient management altered ranged from 22% to 39% depending on the clinical setting.

Endometrium↗

PubMedDate not supplied

Circadian rhythms of testosterone and cortisol in saliva: effects of activity-phase shifts and continuous daylight.

The variations in concentrations of testosterone and cortisol in saliva samples collected by 4 healthy young men whilst on a scientific expedition from Britain to Spitzbergen are described. The rhythms observed in steroid concentrations in saliva were characterized mathematically by cosinor analysis of the levels of testosterone and cortisol determined in saliva samples collected before, during and after the expedition. Whilst in Spitzbergen, the subjects were maintained initially on the British sleep-wake schedule which was later subjected to an 8-h phase change. Variations in testosterone concentrations in saliva appeared to be largely related to subject activity rather than any photoperiodic effect with rapid resynchronization of the circadian acrophase in response to the phase shift of the sleep-wake schedule. In contrast, variation in salivary cortisol levels appeared to be less related to activity and more dependent on the slower resynchronization of an endogenous rhythm of cortisol secretion.

Adult↗

PubMed1997

Seasonal variations of rheological and hemostatic parameters and acute-phase reactants in young, healthy subjects.

The incidence of cardiovascular diseases is increased in winter months. Recent studies have shown seasonal changes in plasma viscosity, fibrinogen, and factor VII activity with elevated levels during winter. An increase in these factors generates a "hypercoagulable state," which may lead to a rise in cardiovascular morbidity and mortality. It has been suggested that an increase in upper respiratory infections might be the underlying cause for the raised acute-phase reactants, in particular fibrinogen, during the winter season. We investigated seasonal variations of 26 parameters, determining blood rheology and hemostasis in 16 healthy volunteers (8 men and 8 women) aged 20 to 41 years. They were seen at monthly intervals over a period of 1 year. Seasonal variation with peak fitted values in the winter months was found for plasma viscosity (P < .001 for the seasonal difference), red blood cell deformability (P < .001), whole blood viscosity (P < .001), hemoglobin (P < .001), hematocrit (P < .001), mean corpuscular volume (P = .001), platelet count (P = .01), alpha 1-glycoprotein (P < .001), fibrinogen (measured by immunonephelometry; P < .001), plasminogen activator inhibitor-1 (P = .002), LDL cholesterol (P = .003), and triglyceride levels (P < .001). HDL cholesterol (P < .001) and cortisol (P = .001) showed inverse seasonal patterns, with a maximum during summertime. No statistically significant seasonal variations were seen for red blood cell aggregation, complement factor C4, total cholesterol, ceruloplasmin, haptoglobin, white blood cell count, and plasminogen. These data do not support the hypothesis that increased morbidity and mortality from cardiovascular diseases during winter may be mainly attributable to increased synthesis of acute-phase proteins due to infections. The cause for the seasonal variations in rheological and hemostatic parameters remains unclear and should be studied in more detail.

Acute-Phase Proteins↗

PubMed2000

Steady-state visual evoked potentials and travelling waves.

OBJECTIVE: The amplitude and phase of the steady-state visual evoked potential (SSVEP) is sensitive to cognition and attention but the underlying mechanism is not well understood. This study examines stimulus evoked changes in the SSVEP phase topography and the putative role of travelling waves. METHODS: Eighteen subjects viewed a central-field checkerboard and full-field flicker stimulus temporally modulated at the peak alpha rhythm frequency. EEG was recorded from 10 midline scalp sites and the bipolar SSVEP obtained from differences between adjacent electrodes. RESULTS: The SSVEP phase comprised either progressive variations consistent with travelling waves or a phase reversal consistent with standing waves. The checkerboard pattern elicited travelling wave patterns in 14 subjects with estimated phase velocities ranging from 7 to 11 m/s after correcting for folded cortex. The flicker stimulus elicited phase reversals in 9 subjects, suggesting standing waves. Six subjects demonstrated a phase topography specific to the stimulus with travelling wave patterns associated with the checkerboard and standing wave patterns associated with the flicker. CONCLUSIONS: These differences suggest the emergence of travelling and standing waves under different spatial configurations of visual input to the cortex and that wave phenomena contribute to the spatiotemporal dynamics of the SSVEP.

Adult↗

PubMed1953

Respiration and intensity dependence of photosynthesis in Chlorella.

1. Respiration changes as a result of illumination. 2. In the absence of glucose or other supply of substrate, respiration decays in the dark showing at least two types-a fast decay in a few minutes and a slow decay lasting hours. 3. Respiratory response to illumination is delayed. 4. Intermittent illumination (in the absence of glucose, etc.) produces a periodic variation in respiration with a delay or phase lag. 5. Periodic variation of respiration may produce a higher average value in the dark than in the light due to the lag and depending upon the period of intermittent illumination. 6. Based upon average respiration values our data confirm the Kok effect. 7. Interpolated values of respiration, however, result in photosynthetic rates which are linearly dependent upon intensity of illumination. 8. Thus the quantum efficiency is found to be independent of intensity, over the wide range of intensities investigated.

Cell Respiration↗

PubMed2001

Radio-frequency Bloch-transistor electrometer.

A quantum electrometer is proposed which is based on charge modulation of the Josephson supercurrent in the Bloch transistor inserted in a superconducting ring. As this ring is inductively coupled to a high- Q resonance tank circuit, the variations of the charge on the transistor island are converted into variations of amplitude and phase of oscillations in the tank. These variations are amplified and then detected. At sufficiently low temperature of the tank the device sensitivity is determined by the energy resolution of the amplifier, that can be reduced down to the standard quantum limit of 1 / 2Planck's over 2pi. A "back-action-evading" scheme of subquantum limit measurements is proposed.

Journal Article↗

PubMed2005

Canine serum immunoreactivity to M. pachydermatis in vitro is influenced by the phase of yeast growth.

In western immunoblotting studies of canine sera using Malassezia pachydermatis extracts, the reported patterns of immunoreactivity vary between different laboratories. Because the duration of culture influences the antigenic composition of lipid-dependent Malassezia spp. when probed with human sera, we investigated whether the in vitro growth phase of M. pachydermatis influences immunoreactivity using canine sera. Extracts of M. pachydermatis CBS 1879 grown in Sabouraud's liquid medium at 37 degrees C for 2, 4, 6, 8 and 10 days were prepared by mechanical disruption, centrifugation, dialysis and lyophilization. Yeast growth phase was assessed by sequential colony counts and optical density measurements. Patterns of IgG immunoreactivity in high (n = 3) and low (n = 3) titre sera were compared using extracts prepared at each time point by sodium dodecyl sulphate polyacrylamide gel electrophoresis and western immunoblotting. Protein bands of 62 and 49 kDa were recognized by all sera, and 98 and 68 kDa bands were recognized by five sera. Proteins of 188, 66, 58, 57, 38, 28 and 17 kDa were only recognized by high titre sera. All high titre sera used recognized more bands in exponential phase (d2) extracts when compared with decline phase (d8-d10) extracts, and two of these sera showed most bands in stationary phase (d4-d6) extracts. Bands of 62 and 57 kDa were primarily detected in exponential and early stationary phase extracts. There is variation in antigenic expression in different growth phases of M. pachydermatis, which might explain discrepancies between previous laboratory studies of canine immunity to this yeast.

Animals↗

PubMed1980

Nuclear division cycle in Neurospora crassa hyphae under different growth conditions.

Treatment with picolinic acid blocked Neurospora crassa nuclei in G1, and recovery from the treatment allowed a synchronous wave of deoxyribonucleic acid synthesis to occur. Nuclei, which appeared as compact globular bodies during the period of blockage, assumed a ring shape during the following S phase, which was also maintained in the G2 phase. The proportion of compact globular nuclei was much higher in hyphae growing at lower rates, whereas that of ring nuclei increased when the hyphae were growing at higher rates. Horseshoe nuclei (probably mitotic nuclei) and double ring nuclei were also observed in growing hyphae, but their frequencies were low and fairly independent of the rate of growth. The length of the S phase of the Neurospora nuclear division cycle was determined to be about 30 min. From the frequencies of the phase-specific nuclear shapes, the durations of the G1 phase and the combined S plus G2 phases were calculated. The results showed that variations in the growth rates of the mycelia were mainly coupled with variations in the G1 phase of the nuclear division cycle. For mycelia growing in minimal sucrose, the lengths of all of the phases of the nuclear division cycle were estimated.

Cell Division↗

PubMed2001

Growth hormone secretion after baclofen administration in different phases of the menstrual cycle in healthy women.

AIM: The aim of this study was to investigate the effect of baclofen administration on growth hormone (GH) secretion during different phases of the menstrual cycle. METHODS: Twelve healthy women (33.6 +/- (SD) 2.8 years; range 23-40 years) with regular menstrual cycles were enrolled. The phases of the menstrual cycle were determined using transvaginal ultrasonography (TV-US) and detecting hormonal serum levels. Plasma GH levels were evaluated during the early follicular, periovulatory and luteal phases of the cycle before and after the baclofen challenge test. RESULTS: After acute baclofen administration, GH levels increased significantly (p < 0.001) compared to basal values during the periovulatory and luteal phases, while no significant variation was detected during the early follicular phase. In addition, plasma GH levels resulted significantly (p < 0.001) higher during the luteal phase than during the periovulatory phase. CONCLUSION: Acute baclofen administration induces a significant increase in plasma GH levels in healthy females during the periovulatory and luteal phases, but not during the early follicular phase. These data suggest a modulator role of plasma sex steroids levels on GH release induced by baclofen.

Administration, Oral↗