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PubMed1998

Monitoring conformational dynamics of a single molecule by selective fluorescence spectroscopy.

A recently developed, real-time spectroscopic technique, burst-integrated fluorescence lifetime (BIFL), is shown to be well suited for monitoring the individual molecular conformational dynamics of a single molecule diffusing through the microscopic, open measurement volume (approximately 10 fl) of a confocal epi-illuminated set-up. In a highly diluted aqueous solution of 20-mer oligonucleotide strand of DNA duplex labeled with the environment-sensitive fluorescent dye tetramethylrhodamine (TMR), fluorescence bursts indicating traces of individual molecules are registered and further subjected to selective burst analysis. The two-dimensional BIFL data allow the identification and detection of different temporally resolved conformational states. A complementary autocorrelation analysis was performed on the time-dependent fluctuations in fluorescence lifetime and intensity. The consistent results strongly support the hypothesized three-state model of the conformational dynamics of the TMR-DNA duplex with a polar, a nonpolar, and a quenching environment of TMR.

Kinetics↗
PubMed2004

Wet-days: are they better indicators of Ascaris infection levels?

Seasonal variation in a particular area may influence the occurrence of helminth infections and determining such fluctuations may help to maximize the beneficial effects of mass treatment. This study determined the seasonal variations in infection levels of Ascaris lumbricoides between March 2000 and June 2001 in two selected low-country plantations. Four hundred and seventy seven persons aged between 2 and 74 years (median 13) participated. Stools were tested using the Kato-Katz method and the prevalence and intensity of infection determined. All persons were treated with a single dose of mebendazole. Monthly follow-ups were undertaken with similar stool examinations and treatment given if found positive. Infection and re-infection rates were calculated each month. Rainfall and temperature were recorded each day. Total rainfall, number of wet-days and mean temperature was calculated for each month. The prevalence of Ascaris infection was 53.4% and 51.0% at Maliboda and Ayr estates respectively. Highest infection and re-infection rates at Maliboda (37.7%, 37.2%) occurred in June and at Ayr (13.3%, 25.9%) in October 2000 respectively. During the study period, the mean rainfall was 28.1 cm (range 7.4-63.9 cm) and mean temperature 27.6 degrees C (range 22.1 degrees -34.4 degrees C). Significant correlations (P<0.05) were found between the re-infection rate and rainfall, temperature and the number of wet-days. Similar correlations were observed with the infection rate and temperature and the number of wet-days. Ascaris infections were found to correlate significantly only with the number of wet-days in a month (P<0.01). Thus, the number of wet-days appears to be a better indicator of Ascaris infections than total rainfall or mean temperature.

Adolescent↗
PubMed1994

The menopause: when it is all over or is it?

The menopause is defined rigorously as the cessation of menstruation as a result of ovarian follicular depletion. Although in common clinical usage, the term is used to encompass the menopausal transition, a period which may average 4 years in duration, and during which alterations in menstrual regularity and/or flow may be accompanied by somatic or psychological symptoms. Measurement of serum follicle-stimulating hormone (FSH) with or without oestradiol (E2) is frequently advocated as providing a useful indicator of menopausal status. Several studies have shown an increase in serum FSH, with or without decrease in E2, in women over the age of 40 years who continue to cycle regularly. Abrupt fluctuations in serum FSH and E2 may be observed, with typically post menopausal levels subsequently returning to the normal reproductive range. In a cross sectional study, of regularly cycling women randomly selected from the Melbourne community, and over the age of 45 years, 7% had FSH levels typical of the post menopause, and 39% had levels above those found during the follicular phase in women aged less than 35 years. It is concluded that serum FSH is of little diagnostic value in the assessment of menopausal status, which can currently be made only on clinical grounds. An elevated serum FSH level cannot tell us reliably 'when it is all over'.

Adult↗
PubMed2002

Electromagnetic articulograph based on a nonparametric representation of the magnetic field.

Electromagnetic articulograph (EMA) devices are capable of measuring movements of the articulatory organs inside and outside the vocal tract with fine spatial and temporal resolutions, thus providing useful articulatory data for investigating the speech production process. The position of the receiver coil is detected in the EMA device on the basis of a field function representing the spatial pattern of the magnetic field in relation to the relative positions of the transmitter and receiver coils. Therefore, the design and calibration of the field function are quite important and influence the accuracy of position detection. This paper presents a nonparametric method for representing the magnetic field, and also describes a method for determining the receiver position from the strength of the induced signal in the receiver coil. The field pattern in this method is expressed by using a multivariate spline as a function of the position in the device's coordinate system. Because of the piecewise property of the basis functions and the freedom in the selection of the rank and the number of the basis functions, the spline function has a superior ability to flexibly and accurately represent the field pattern, even when it suffers from fluctuations caused by the interference between the transmitting channels. The position of the receiver coil is determined by minimizing the difference between the measured strength of the received signal and the predicted one from the spline representation of the magnetic field. Experimental results show that the error in estimating the receiver position is less than 0.1 mm for a 14 x 14-cm measurement area, and this error can be further reduced by using a spline-smoothing technique.

Electromagnetic Fields↗
PubMed1991

Angiotensin II does not contribute to rapid reflex control of arterial pressure.

Pharmacological blockade of the renin-angiotensin converting enzyme reportedly alters the heart rate (HR) power spectrum in conscious dogs, suggesting that these hormones contribute to the short-term regulation of arterial blood pressure. We tested this possibility using four independent procedures. First, HR power spectrum was determined in seven awake dogs before and after administration of enalaprilat (300 ng/kg), a converting-enzyme inhibitor. There were no significant changes in the average amplitude for the spectral peak between 0.003 and 0.1 Hz (i.e., the "low-frequency peak"). Second, the HR power spectrum was measured in 11 awake rabbits before and after treatment with deoxycorticosterone acetate (1 mg.kg-1.day-1) and salt (0.9% saline ad libitum) for 7 days to depress plasma renin levels. There were no significant changes in the amplitude of the HR power spectrum, although mean HR decreased from 206 +/- 3 to 184 +/- 4 beats/min after treatment. In the third experiment, another group of rabbits (n = 8) was tested after 2 wk on a low-salt diet to elevate plasma angiotensin levels and then after 2 wk on a normal salt diet. Once again there were no significant effects on the HR power spectrum. Finally, tranquilized dogs (n = 9) were subjected to sinusoidally varying lower body negative pressure at selected frequencies of 0.008-0.12 Hz. Tests were conducted in the control state and after administration of an angiotensin receptor antagonist (saralasin, 1 microgram.kg-1.min-1). Lower body negative pressure-induced fluctuations in arterial blood pressure were similar in both states. We find no evidence for the role of the renin-angiotensin system in the moment-to-moment regulation of arterial pressure and HR.

Angiotensin II↗
PubMed1998

Oscillatory nuclear movement in fission yeast meiotic prophase is driven by astral microtubules, as revealed by continuous observation of chromosomes and microtubules in living cells.

Using a computerized fluorescence microscope system to observe fluorescently stained cellular structures in vivo, we have examined the dynamics of chromosomes and microtubules during the process of meiosis in the fission yeast Schizosaccharomyces pombe. Fission yeast meiotic prophase is characterized by a distinctive type of nuclear movement that is led by telomeres clustered at the spindle-pole body (the centrosome-equivalent structure in fungi): the nucleus oscillates back and forth along the cell axis, moving continuously between the two ends of the cell for some hours prior to the meiotic divisions. To obtain a dynamic view of this oscillatory nuclear movement in meiotic prophase, we visualized microtubules and chromosomes in living cells using jellyfish green fluorescent protein fused with alpha-tubulin and a DNA-specific fluorescent dye, Hoechst 33342, respectively. Continuous observation of chromosomes and microtubules in these cells demonstrated that the oscillatory nuclear movement is mediated by dynamic reorganization of astral microtubules originating from the spindle-pole body. During each half-oscillatory period, the microtubules extending rearward from the leading edge of the nucleus elongate to drive the nucleus to one end of the cell. When the nucleus reversed direction, its motion during the second half of the oscillation was not driven by the same microtubules that drove its motion during the first half, but rather by newly assembled microtubules. Reversible inhibition of nuclear movement by an inhibitor of microtubule polymerization, thiabendazole, confirmed the involvement of astral microtubules in oscillatory nuclear movement. The speed of the movement fluctuated within a range 0 to 15 micron/minute, with an average of about 5 microm/minute. We propose a model in which the oscillatory nuclear movement is mediated by dynamic instability and selective stabilization of astral microtubules.

Cell Division↗
PubMed2002

Estimation of cancer deaths in Korea for the upcoming years.

Since the cancer has been the leading cause of deaths in Korea, estimation of the cancer deaths for the upcoming years in the population using the vital statistics is considered to be necessary. The aim of this study was to estimate the number and trends of cancer deaths in Korea. The expected numbers of cancer deaths were calculated by a time series model fitting the actual numbers of cancer deaths for each of the years 1983 through 2000 reported by Korea National Statistical Office. The options selected for the time series model included a quadratic time trend, which incorporated long-term information into the model and an autoregressive component which incorporated information about short-term fluctuations. The forecasting numbers of cancer deaths and their 95% confidence intervals were estimated for both genders and primary sites. The forecasting number of deaths from all cancers is increasing so that the cumulative number of expected cancer deaths between 2001 and 2005 would be about 309 thousand persons. Cancers of the lung, stomach, liver, and colorectum continue to be the most common causes of cancer deaths. While the numbers of expected cancer deaths in the stomach and liver show a decreasing trend, the cancer in the lung, colorectum, pancreas, breast, and oral cavity have an increasing trend. These observations indicate that cancer deaths in the near future would be increasing through the early 2000s, and there should be some urgent government's policy on the cancer management.

Colorectal Neoplasms↗
PubMed1997

[Guidelines of drug therapies for Parkinson's disease].

Treatment of Parkinson's disease has progressed steadily for the last decades after introduction of levodopa. For recovery of striatal dysfunction caused by loss of projecting nigral cells, supplementation of neurotransmitter dopamine (DA), facilitation of neural transmission by DA agonists and amantadine, suppression of acetyl-choline neurons, having antagonistic action to DA cells, are all effective especially at the early to middle stages of illness. As prevention of neuronal cell death in parkinsonian brain has not yet been succeeded, difficulties in treatment with symptom fluctuation and CNS side effects such as dyskinesia or psychic symptoms develop inevitably in the long course of evodopa treatment. Proper choice of drugs for parkinsonian core and accompanying symptoms and selection of methods of medication for maintenance of natural daily life activities are necessary for attainment of good QOL for whole time course of the disease.

Anxiety↗
PubMed1994

A statistical theory of cell killing by radiation of varying linear energy transfer.

A theory is presented that provides an explanation for the observed features of the survival of cultured cells after exposure to densely ionizing high-linear energy transfer (LET) radiation. It starts from a phenomenological postulate based on the linear-quadratic form of cell survival observed for low-LET radiation and uses principles of statistics and fluctuation theory to demonstrate that the effect of varying LET on cell survival can be attributed to random variation of dose to small volumes contained within the nucleus. A simple relation is presented for surviving fraction of cells after exposure to radiation of varying LET that depends on the alpha and beta parameters for the same cells in the limit of low-LET radiation. This relation implies that the value of beta is independent of LET. Agreement of the theory with selected observations of cell survival from the literature is demonstrated. A relation is presented that gives relative biological effectiveness (RBE) as a function of the alpha and beta parameters for low-LET radiation. Measurements from microdosimetry are used to estimate the size of the subnuclear volume to which the fluctuation pertains.

Cell Death↗
PubMed1993

Ca(2+)-blockable, poorly selective cation channels in the apical membrane of amphibian epithelia. Tetracaine blocks the UO2(2+)-insensitive pathway.

We examined the effect of the local anesthetic tetracaine on the Ca(2+)-blockable, poorly selective cation channels in the isolated skin of Rana temporaria and the urinary bladder of Bufo marinus using noise analysis and microelectrode impalements. Experiments with frog skin demonstrated that mucosal concentrations of the compound up to 100 microM did not affect the Na+ current through type S channels (slowly fluctuating, UO2(2+)-blockable channels) and the associated noise. On the other hand, 20 microM mucosal tetracaine already suffices to inhibit approximately 50% of the current carried by Cs+ and Na+ through channel type F (fast fluctuating, UO2(2+)-insensitive channel) and So of the associated Lorentzian component. With 100 microM of the inhibitor the current and So values were reduced by at least 70-80%. The time course of the response to serosal tetracaine was markedly slower and the effects on the current and So were smaller. Possible effects on the basolateral K+ conductance were excluded on the basis of the lack of response of transepithelial K+ movements to 100 microM tetracaine. UO2(2+) and tetracaine together blocked the poorly selective cation pathways almost completely. Moreover, both agents retain their inhibitory effect in the presence of the other. In toad urinary bladder, the Ca(2+)-blockable channel is also tetracaine blockable. The concentration required for half-maximal inhibition is approximately 100 microM in SO4(2-) and approximately 20 microM in Cl-. The data with tetracaine complement those obtained with UO2(2+) and support the idea that the Ca(2+)-blockable current proceeds through two distinct classes of cation channels. Using tetracaine and UO2(2+) as channel-specific compounds, we demonstrated with microelectrode measurements that both channel types are located in the granulosum cells.

Animals↗
PubMed2002

Renal aspects of the term and preterm infant: a selective update.

This review discusses new aspects of normal and abnormal renal development that expand insight into the adaptation of the neonatal kidneys to the stress of extrauterine life. Highlighted are some pitfalls in measuring glomerular filtration rate in the neonate mainly caused by postnatal fluctuations in serum creatinine levels. Serum creatinine levels are correlated with the authors' recent finding of tubular reabsorption of creatinine in the immature neonatal kidney. Renal maldevelopment in premature and small-for-date babies has been shown related to serious medical problems in adult life, including hypertension. This finding presents the pediatrician with a new role in the time-honored vocation of preventing disease. Mutations in several genes may be responsible for most cases of congenital or hereditary renal aberrations. Two renal disorders, congenital nephrotic syndrome and neonatal acute renal failure, and one form of treatment modality of newborn infants, renal replacement therapy, are discussed in detail. These conditions are rare in general pediatric practice, but they illustrate some of the new developments in the renal care of the newborn. A word of caution is offered about the use of nonsteroidal anti-inflammatory drugs during pregnancy and the newborn period. All nonsteroidal anti-inflammatory drugs administered indirectly to the unborn fetus and directly to the young newborn impair renal structure (fetus) and function (both fetus and newborn). The new data have been obtained with genetic and molecular biology techniques and with established methods of developmental renal physiology. A better understanding of the pathogenesis of neonatal renal disorders will result in new diagnostic procedures and improved preventive and therapeutic possibilities relevant to the neonate with a renal disorder.

Acute Kidney Injury↗
PubMed1990

Selective hearing in the aged with regard to speech perception in quiet and in noise.

Most listening environments contain some noise which is mixed up with the speech. The effects of noise on speech perception depend on the parameters of the noise (long term spectrum, fluctuations of the intensity in time and average intensity relative to the intensity of speech) and on the speech material (sentences, monosyllables, CV-, CVC-, VC-syllables). The most effective at masking are noises with spectra similar to the speech spectrum, such as the speech simulating noise (CCITT-noise) or cocktail-party-noise. The cocktail-party situation is judged to be a difficult communication situation not only by the hearing impaired but also by patients with presbycusis. We examined different age-dependent changes of the speech discrimination in noise ability. Using sentences and CV-syllables (rhyme test) the critical signal-to-noise ratios (S/N-dB) for a speech discrimination of 35%-45% were investigated for monaural and binaural noise representations for different age groups. The results are compared to several types of hearing loss and to those of similar studies in literature. The data of this study prove that hearing impaired and elderly patients are greatly affected by noise. While younger patients with moderate high-tone hearing loss may profit from a special hearing aid device with an integrated noise suppression-system, an improvement of speech discrimination in noise for the elderly can be achieved only by enhancing the signal-to-noise ratio by more than 10 dB. This is possibly because of the reduced capacity for frequency-, intensity- and time-resolution in the peripheral and central pathways of the hearing organ of the aged.

Adult↗
PubMed2000

Non-NMDA receptor-mediated mechanisms are involved in levodopa-induced motor response alterations in Parkinsonian rats.

Chronic dopaminomimetic administration to parkinsonian animal models or Parkinson's disease patients leads to characteristic alteration in motor response. Previous studies suggested that the nonphysiologic stimulation of dopaminergic receptors on striatal medium spiny neurons enhances the synaptic efficacy of juxtaposed glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype. Resultant NMDA receptor sensitization due to differential changes in subunit phosphorylation appears to favor alterations in striatal output in ways that influence motor function. To detail the involvement of NMDA receptors further as well as to determine whether similar functional changes might develop in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, the effects of selective antagonist of AMPA receptors (6-nitro-7-sulfamoyl-benzo[f]-quinoxaline-2,3 (1H,4H)-dione sodium salt, NBQX, 10 mg/kg) on levodopa-induced response alterations in 6-hydroxydopamine (6-OHDA) lesioned rats were compared with drugs which act competitively (3-(+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonicacid, CPP, 6.25 mg/kg) or noncompetitively (dextromethorphan, 40 mg/kg) to block NMDA receptors, or a nonselective inhibitor of glutamatergic transmission (2-amino-6-trifluoromethoxy benzothiazole, riluzole, 5 mg/kg). We found that the shortened duration of the motor response to levodopa, which underlies human wearing-off fluctuations, was reversed to a similar degree by the acute coadministration of CPP, NBQX, or riluzole (n = 4-6) but dextromethorphan did not. These observations strengthen the possibility that a reduction in levodopa-associated changes in motor response by inhibitors of glutamatergic transmission acting generally or selectively at the glutamate binding-sites may relate to their ability to attenuate pathologic gain in striatal glutamatergic function. The capacity of NBQX to reverse these altered responses suggests that an enhanced synaptic efficacy of striatal AMPA receptors may also participate in the generation of these motor response changes in levodopa-treated parkinsonian rats.

Animals↗
PubMed2000

Surgical treatments for Parkinson's disease.

OBJECTIVE: This article reviews surgical treatments for Parkinson's disease, emphasizing aspects pertinent to family physicians: rationale for and description of surgeries, patient selection issues, and outcome expectations. QUALITY OF EVIDENCE: No published series describes long-term follow up of a randomized controlled study of any surgery for Parkinson's disease. Some reports, however, describe thorough but brief follow up of functioning in small numbers of patients following surgery. MEDLINE articles were identified using Parkinson's disease, surgery, pallidotomy, thalamotomy, stimulation, grafting, and transplantation as search words. Articles chosen for this paper described patients with systematic follow up using accepted validated rating scales. MAIN MESSAGE: Reported series show impressive improvements to patients undergoing lesioning, stimulation, and grafting surgery for Parkinson's disease. These patients are typically severely disabled but highly selected, and follow up is brief. Stereotactic lesioning (pallidotomy and thalamotomy), deep brain stimulation (thalamic, and elsewhere) and grafting (striatal) can be performed safely, but results vary greatly among centres. CONCLUSIONS: Certain Parkinson's disease patients might benefit from surgery. Ideal candidates for pallidotomy experience motor fluctuations with disabling levodopa-induced dyskinesias. Tremors resistant to antiparkinsonian medications sometimes respond to thalamotomy or thalamic stimulation. Other parkinsonian syndromes, dementias, and difficulties with gait and balance respond poorly to unilateral pallidotomy. Bilateral deep brain stimulation procedures could benefit "midline" dysfunction.

Brain Tissue Transplantation↗
PubMed1976

Selective concentration and localization of gold in macrophages of synovial and other tissues during and after chrysotherapy in rheumatoid patients.

Gold distribution was studied in the tissues of 7 rheumatoid patients who had died from 0 to 23 years after stopping chrysotherapy (sodium aurothiomalate) and in 23 samples of synovial tissue removed surgically at intervals during chrysotherapy in 5 patients. After the application of a highly specific staining technique, the cellular localization of gold was examined microscopically in various tissues: the amounts of gold in selected areas of the same specimens which had been examined microscopically were then measured by neutron activation analysis. During active chrysotherapy gold was abundant in synovial lining cells except where a fibrin layer was present on the surface; after stopping chrysotherapy, gold disappeared from the synovial lining cells. Gold accumulated progressively in the subsynovial connective tissues during chrysotherapy, but was not uniformly distributed, and bore no relationship to fluctuations in serum gold levels. Gold deposition was not confined to joint tissue, but was found within the macrophages of many organs, renal tubular epithelium, and, after recent chrysotherapy, in seminiferous tubules, hepatocytes, and adrenal cortical cells. Gold persisted in synovial and other tissues for up to 23 years after chrysotherapy was stopped. The overall findings indicated that gold is selectively concentrated within inflamed synovial tissues during chrysotherapy.

Aged↗
PubMed1999

Correlations of structure, dynamics and function in the gramicidin channel by solid-state NMR spectroscopy.

The high resolution structure of the gramicidin A channel has been determined in a lamellar phase environment using solid-state NMR spectroscopy. While the fold is similar to previous characterizations, channel function is exquisitely dependent on structural detail. There is essentially no structural change upon cation binding and no significant change in dynamics. The cations appear to be adequately solvated in their binding site by no more than two carbonyls and no fewer than three water molecules at any one time. The relatively large number of water molecules allows for geometric flexibility and little selectivity among monovalent cations. However, the dehydration energies of cations clearly explain the selectivity for monovalent versus divalent cations. Moreover, the binding site is shown to be delocalized, resulting in a shallow potential energy well so that efficient cation conductance can be realized. The potential energy barrier at the bilayer centre has been shown to be rate limiting under certain circumstances through a correlation between conductance and the electrostatic interactions between cations at the gramicidin monomer-monomer junction and the indole dipole moments at the lipid-water interface. The dynamics are functionally important. The time-scale for carbonyl fluctuations about the C alpha-C alpha axis and kinetic rates for cation movement in the channel are the same, suggesting a correlation between molecular dynamics and kinetics. These functional correlations will be described in light of the recent K+ channel structure and the biological challenge to achieve both selectivity and efficiency.

Amino Acid Sequence↗
PubMed2002

Sinoaortic denervation abolishes pressure resetting for daily physical activity in rabbits.

It has been speculated that if baroafferent signals are only related to the negative feedback control of arterial pressure (AP), then physical activity would increase the range of AP fluctuation in baroafferent-denervated animals. Mean AP (MAP), heart rate (HR), and cardiac output (CO) were measured for 24 h in free-moving conscious rabbits. On the basis of hydrostatic pressure and electromyogram, MAP data taken during periods of physical activity and rest were selected from the overall 24-h MAP data and then converted into histograms. During physical activity, the mode of MAP histogram increased in intact rabbits and was unchanged in sinoaortic-denervated (SAD) rabbits. Movement increased the mode of total peripheral resistance (TPR) but did not significantly change CO in intact rabbits. Conversely in SAD rabbits, movement slightly decreased TPR and slightly increased CO. These findings indicate that arterial baroafferent signals are required to shift MAP to a higher pressure level by an increase in TPR but not in CO during a moving phase. These results suggest that baroafferent signals may not only minimize the fluctuating range of MAP through negative feedback control but also be involved in actively resetting MAP toward a higher pressure level during daily physical activity.

Animals↗
PubMed2004

Maintenance of clonal diversity in Dipsa bifurcata (Fallén, 1810) (Diptera: Lonchopteridae). II. Diapause stabilizes clonal coexistence.

We analyze a selection model analogous to a one-locus, two-allele haploid system that can explain recurrent seasonal changes in diversity for communities with diapausing species or populations with diapausing clones. The model demonstrates the potential influence of differential diapause on the stability of species and clonal coexistence and, by extension, on the maintenance of genetic polymorphism in general. Using estimates of clonal fitness values from populations of the parthenogenetic spear-winged fly Dipsa bifurcata (Fallén, 1810) (Diptera: Lonchopteridae), the model explains the long-term stable oscillation of clonal frequencies exhibited by these populations. In general, clones or species that share the same spatial habitat can persist in stable coexistence if there are differences not only in their temporarily fluctuating fitness values but also in their dormancy patterns.

Animals↗