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PubMed2000

Spatial determination of elements in green leaves of oak trees (Quercus robur) by laser ablation-ICP-MS.

Laser ablation inductively coupled plasma mass spectrometry (laser ablation-ICP-MS) has been applied to the spatially resolved determination of the elements Mg, Ca, Cu, Ni, Ba, Al, Pb, Sr and Mn in green leaves of oak trees. Instrument operating parameters such as the laser wavelength and the pulse energy have been optimized to provide the sensitivity and reproducibility required for the analysis. The method provides spatial resolution down to 300 microm with the use of the 355 nm wavelength (3rd harmonic of the 1,064 nm Nd:YAG laser wavelength) and the pulse energy of 50 mJ. Plant standards and cellulose, doped with multi element solution standards, dried and pressed to pellets were used as calibration samples. To compensate for signal fluctuations caused by the variation of the ablated sample mass 13C was used as a "natural" internal standard. The accuracy of the calibration was verified with selected samples analyzed by ICP-MS (high pressure digestion, 170 degrees C, 10(7) Pa, HNO3, 2 h) and by laser ablation-ICP-MS. Recovery rates between 93% (Cu) and 108% (Mn) were obtained. Leaves taken from oak trees (Quercus robur) were analyzed.

Calibration↗
PubMed2006

Leading knowledge producers within the biomedical informatics community.

OBJECTIVES: To present findings on academic leadership within the biomedical informatics community based upon the number of research articles produced by authors, institutions, and countries within five biomedical informatics journals. METHODS: Five biomedical informatics journals were analyzed for the most producing author, institution, and country for two time periods: 1995-1999 and 2000-2004. RESULTS: Results show that an overall trend exists whereby the academic leadership for author, institution, and country is the U.S. The results exist for both time periods of 1995-1999 and 2000-2004. CONCLUSIONS: Even though individual institutional and author rankings may have fluctuated within the two time periods (1995-1999 and 2000-2004), U.S. dominance at the institutional and author level remains significant within the five biomedical journals selected for this study.

Internationality↗
PubMedDate not supplied

Renal function and pituitary hormone release during cerebral osmostimulation and TRH in dogs.

The effects of increases in serum osmolality on renal function and plasma levels of radioimmunoassayable prolactin (PRL) and luteinizing hormone (LH) were examined during intracarotid (IC) infusions of hypertonic NaCl in conscious dogs with a sustained water diuresis (SWD). A 10 minute bilateral IC infusion of 45 mumole/kg X min X artery of NaCl during SWD which raised jugular osmolality by 10.1 mOsm/kg, without significantly altering peripheral venous osmolality, produced a significant decrease in free water clearance (CH2O) at 20 to 40 minutes postinfusion. IC infusions of 0.9% NaCl did not produce an antidiuretic response. No change in heart rate or blood pressure from preinfusion control values occurred during NaCl infusions. Elevations in cerebral osmolality did not result in changes in circulating levels of LH or PRL which qualitatively differed from levels of these hormones recorded during IC infusions of 0.9% NaCl. Although fluctuations in levels of LH occurred during experiments, renal function was not concomitantly affected. The results suggest that a specificity exists in the hormonal response to selective elevations of cerebral osmolality. The administration of TRH 3.8-4.2 micrograms/kg produced a transient increase in blood pressure and inhibited a water diuresis, the latter possibly as a result of releasing antidiuretic hormone.

Animals↗
PubMed1982

The inhibition of the serum-stimulated increase of ornithine decarboxylase by ionophores and local anesthetics.

The addition of fresh serum-containing growth medium to L1210 mouse leukemic cells in culture resulted in a 5-fold increase in ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity. The presence of microtubule disrupting agents (colchicine, vinblastine) or cations (5-10 mM K+, Na+ or Mg2+) abolishes this increase of ornithine decarboxylase activity. (Chen, K.Y., Heller, J.S. and Canellakis, E.S. (1976) Biochem. Biophys. Res. Commun. 70, 212-219). Based on these observations we proposed that fluctuation in cellular cation concentrations may act as a link between the membrane structure and ornithine decarboxylase. To test this proposal, we studied the effects of selective membrane perturbing agents such as ionophores and local anesthetics, on the serum-stimulated increase of ornithine decarboxylase activity in L1210 cells. Among the six ionophores tested, valinomycin was the most potent one, with I50 value (concentration that gives 50% inhibition of ornithine decarboxylase activity) of 6.10(-9) M. Dibucaine and tetracaine were also effective inhibitors at 10(-4)-10(-5) M. The I50 values of valinomycin on the protein synthesis and RNA synthesis, however, were greater than 1.10(-6) M. These results substantiate the notion that ornithine decarboxylase activity can be regulated at plasma membrane level and such regulation is related to the perturbation of cellular cation pools.

Anesthetics, Local↗
PubMed2003

Variability of heat shock proteins and glutathione S-transferase in gill and digestive gland of blue mussel, Mytilus edulis.

Glutathione S-transferase (GST) and heat shock proteins (hsps) 40, 60, 70 and 90 were determined by immunoblotting using actin as an internal control in Mytilus edulis from one station outside (site1) and three stations within (sites 2-4) Cork Harbour, Ireland. Comparisons were made between gill and digestive gland and between sites. Gill shows generally higher hsp 60, 70 and 90 while digestive gland has higher hsp 40. Site 1 showed higher gill hsps 40 and 70 than sites 2-4 while gill GST was higher in sites 3 and 4 than 1 and 2. Comparison with sites in the North Sea (site 5: outside Tjärnö in The Koster archipelago in the Skagerack) and Baltic Sea (site 6: Askö island) also revealed lower hsps 40 and 70 in site 6 (low salinity) than site 5 (high salinity) although hsps 60, 70 and 90 were detectable in digestive gland unlike sites 1-4. Previously, only hsp 70 had been studied at these sites [Mar. Environ. Res. 39. (1995), 181]. At the mRNA level, gill hsp 70 is 80-fold higher at Tjärnö than Askö. These data suggest that, while salinity may slightly decrease hsp 40 and 70, both hsp 70 and GST are selectively up-regulated by approx. 10- and 3-fold, respectively, at Tjärnö compared to the other sites which we attribute to exposure to more widely fluctuating pollution levels.

Animals↗
PubMed2003

Emotional arousal does not affect delay eyeblink conditioning.

Arousal can modulate information processing, including associative learning. However, there are conflicting results as to whether arousal affects eyeblink conditioning in humans. One potential problem with previous studies is that they have not taken into account factors that are known to affect conditioning. One such factor is the strength of the unconditioned response (UR). Despite evidence that greater UR leads to greater conditioned responses (CR), prior studies have not examined the role of the UR in CR performance. Prior studies have also usually classified subjects into low and high arousal groups based on a priori categorization without reliance on objective measures of arousal. The present study was designed to examine the impact of arousal on delay eyeblink conditioning. Changes in arousal levels were obtained by having participants view pictures selected for their a priori emotional and arousal values as being pleasant/arousing, unpleasant/arousing, or neutral/not arousing. Each subject viewed pictures of only one category. The spontaneous fluctuation of the skin conductance was taken as an index of physiological arousal. Subjects were divided into low and high arousal groups according to a median-split. Results showed that the rate of CR was positively related to the amplitude of the UR, but was not affected by emotional pictures or by physiological arousal. It is argued that changes in CR during arousal could be due to differences in unconditioned eyeblink strength rather than to changes in associative processes.

Adult↗
PubMedDate not supplied

Study of physical and biological factors involved in the disruption of E. coli by hydrodynamic cavitation.

Hydrodynamic cavitation results in flow restriction in a flow system causing rapid pressure fluctuations and significant fluid forces. These can be harnessed to mediate microbial cell damage. Hydrodynamic cavitation was studied for the partial disruption of E. coli and selective release of specific proteins relative to the total soluble protein. The effects of the cavitation number, the number of passes, and the specific growth rate of E. coli on the release of periplasmic and cytoplasmic proteins were studied. At the optimum cavitation number of 0.17 for this experimental configuration, 48% of the total soluble protein, 88% of acid phosphatase, and 67% of beta-galactosidase were released by hydrodynamic cavitation in comparison with the maximum release attained using multiple passes through the French Press. The higher release of the acid phosphatase over the total soluble protein suggested preferred release of periplasmic compounds. This was supported by SDS-PAGE analysis. The absence of micronization of cell material resulting in the potential for ease of solid-liquid separation downstream of the cell disruption operation was confirmed by TEM microscopy. E. coli cells cultivated at a higher specific growth rate (0.36 h(-1)) were more easily disrupted than slower grown cells (0.11 h(-1)). The specific activity of the enzyme of interest released by hydrodynamic cavitation, defined as the units of enzyme in solution per milligram of total soluble protein, was greater than that obtained on release by the French Press, high-pressure homogenization, osmotic shock, and EDTA treatment. The selectivity offered indicates the potential of enzyme release by hydrodynamic cavitation to ease the purification in the subsequent downstream processing.

Acid Phosphatase↗
PubMed2000

Evolution, stress, and longevity.

The disposable soma theory suggests that longevity is determined through the setting of longevity assurance mechanisms so as to provide an optimal compromise between investments in somatic maintenance (including stress resistance) and in reproduction. A corollary is that species with low extrinsic mortality are predicted to invest relatively more effort in maintenance, resulting in slower intrinsic ageing, than species with high extrinsic mortality. We tested this prediction in a comparative study of stress resistance in primary skin fibroblasts and confirmed that cells from long-lived species are indeed more resistant to a variant of stressors. A widely studied example of within-species variation in lifespan is the rodent calorie restriction model. Food-restricted animals show elevations in a range of stress response mechanisms, and it has been suggested that this is an outcome of natural selection for life history plasticity. We have developed a theoretical model for dynamic optimisation of the allocation of effort to maintenance and reproduction in response to fluctuations in food availability. The model supports the suggestion that the response to calorie restriction may be an evolutionary adaptation, raising interesting questions about the hierarchy of genetic control of multiple stress response systems. The model identifies ecological factors likely to support such an adaptation that may be relevant in considering the likely relevance of a similar response to calorie restriction in other species. Comparative and theoretical studies support the role of somatic maintenance and stress response systems in controlling the rate of ageing.

Animals↗
PubMed1987

Abrupt transitions in physics and biophysics: van der Waals revisited.

An iteration procedure that relates pressure and volume changes in the condensation of a gas by means of two independent relations of the volume and the effective pressure predicts abrupt volume transitions similar to those experimentally observed. Similar abrupt transitions are predicted for a molecular association in which the association free energy is dependent upon the extent of reaction. The pressure, or the concentration, at which the abrupt transition occurs depends upon the volume, or the extent of reaction, used to initiate the iteration procedure and selection of the transition that corresponds to the equilibrium requires additional conditions. For the gas condensation, assumption of the symmetry of the effects of the pressure fluctuations at equilibrium gives results that coincide with those obtained by application of the Maxwell rule. From these observations it is concluded that abrupt transitions arise naturally when independent conditions cannot be simultaneously satisfied.

Journal Article↗
PubMed2006

Aged garlic extract maintains cardiovascular homeostasis in mice and rats.

Nitric oxide (NO) plays an important role in controlling the physiological functions of the cardiovascular system. However, toxic peroxynitrite is produced by the reaction of NO with superoxide. We investigated the effect of aged garlic extract (AGE) on NO production, and on oxidative stress induced by peroxynitrite. A single dose of AGE temporarily increased NO production by 30-40% between 15 and 60 min after administration to mice. The time course of the fluctuation in NO levels in the AGE-treated group clearly differed from that in a group treated with an inducible NO synthase (iNOS) inducer. A selective constitutive NOS (cNOS) inhibitor overcame the effect of AGE. These results indicate that AGE increases NO production by activating cNOS, but not iNOS. In another experiment, the addition of AGE to a rat erythrocyte suspension reduced the rate of peroxynitrite-induced hemolysis in a concentration-dependent manner, suggesting that AGE protects erythrocytes from membrane damage induced by peroxinitrite. Because an increase in NO derived from cNOS and protection against peroxynitrite are important factors in the prevention of cardiovascular disease, our data strongly suggest that AGE could be useful in preventing cardiovascular diseases associated with oxidative stress or dysfunctions of NO production.

Animals↗
PubMed2003

Flow phase diagrams for concentration-coupled shear banding.

After surveying the experimental evidence for concentration coupling in the shear banding of wormlike micellar surfactant systems, we present flow phase diagrams spanned by shear stress Sigma (or strain rate gamma) and concentration, calculated within the two-fluid, non-local Johnson-Segalman (d-JS-phi) model. We also give results for the macroscopic flow curves Sigma(gamma,phi) for a range of (average) concentrations phi. For any concentration that is high enough to give shear banding, the flow curve shows the usual non-analytic kink at the onset of banding, followed by a coexistence "plateau" that slopes upwards, dSigma/dgamma>0. As the concentration is reduced, the width of the coexistence regime diminishes and eventually terminates at a non-equilibrium critical point [Sigmac,phic,gammac]. We outline the way in which the flow phase diagram can be reconstructed from a family of such flow curves, Sigma(gamma,phi), measured for several different values of phi. This reconstruction could be used to check new measurements of concentration differences between the coexisting bands. Our d-JS-phi model contains two different spatial gradient terms that describe the interface between the shear bands. The first is in the viscoelastic constitutive equation, with a characteristic (mesh) length l. The second is in the (generalised) Cahn-Hilliard equation, with the characteristic length xi for equilibrium concentration-fluctuations. We show that the phase diagrams (and so also the flow curves) depend on the ratio r congruent with l/xi, with loss of unique state selection at r=0. We also give results for the full shear-banded profiles, and study the divergence of the interfacial width (relative to l and xi) at the critical point.

Journal Article↗
PubMed2002

Travoprost--a new prostaglandin analogue for the treatment of glaucoma.

Travoprost, a highly selective and potent analogue of the prostaglandin PGF(2)(alpha), has recently been approved and marketed as a topical ocular hypotensive agent for the treatment of ocular hypertension and glaucoma. Following absorption into the eye, the free acid form of travoprost interacts with the endogenous FP prostanoid receptor to enhance aqueous humor outflow and lower intraocular pressure (IOP). Travoprost is distinguished from other marketed prostaglandin analogues in that it is a full agonist at the prostaglandin receptor. It is also highly selective with little or no affinity for other prostanoid or non-prostanoid receptors in the eye. Travoprost provides robust lowering of IOP with little diurnal fluctuation and results in low target pressures in a large percentage of patients. In controlled clinical trials, travoprost 0.004% o.d. used as monotherapy produced greater IOP reduction than timolol 0.5% b.i.d. and equal or greater reduction than latanoprost 0.005%o.d. Travoprost 0.004% was also shown to be an effective adjunctive agent offering an additional 5 - 7 mmHg IOP reduction in patients inadequately controlled on timolol 0.5%. Subgroup analysis of a large Phase III trial revealed travoprost 0.004% to be significantly more effective at lowering IOP in African American patients by almost 2 mmHg compared to non-African Americans. Moreover, a higher percentage of African American patients responded to travoprost 0.004% and reached lower target pressures than with either latanoprost 0.005% or timolol 0.5%. Travoprost is a very stable compound, maintaining its efficacy following exposure to extremely low and high temperatures, repeated freezing and thawing and exposure to light. Throughout all clinical trials, travoprost was found to be safe and well-tolerated with very few (< 5%) discontinuations due to adverse events. Travoprost 0.004% represents a clinically significant advance for the treatment of glaucoma and ocular hypertension, offering superior IOP reduction and diurnal control, especially among African American patients, in a safe, well-tolerated, stable formulation.

Adrenergic beta-Antagonists↗
PubMed1981

Protein-bound cyclic AMP and steroidogenesis in the adrenal gland of the rat.

Adrenocortical cyclic AMP (both total and protein-bound), and adrenal and plasma concentrations of corticosterone were measured in male rats killed at selected intervals throughout the day. The animals had previously been synchronized for 3 weeks in natural lighting. Adrenal and plasma levels of corticosterone showed similar circadian fluctuations and the onset of their ascending phases started at 13.00 h, maximum concentrations being reached at 21.00 h. On the other hand, a time-lag between the circadian variations of total cyclic AMP and protein-bound cyclic AMP could be seen in adrenocortical tissue. The onset of an increase in adrenocortical protein-bound cyclic AMP was apparent at 15.00 h and the peak occurred at 21.00 h, while total adrenocortical cyclic AMP did not begin to rise before 19.00 h and was maximal at 04.00 h. No direct link between total cyclic AMP and protein-bound cyclic AMP could be seen during the dark phase, suggesting a functional compartmentalization of cyclic AMP in the adrenal gland of the rat. While the ascending phase of the rhythm in steroidogenesis preceded the rise in total adrenocortical cyclic AMP by about 4 h an excellent synchrony between the respective patterns of corticosterone concentration and protein-bound cyclic AMP was noticed.

Adrenal Cortex↗
PubMed1975

Clinical presentation of infection in granulocytopenic patients.

Inability to accurately diagnose infection in granulocytopenic patients is a major cause for morbidity and mortality, and prompted this study of 344 infections (pharyngitis, skin infection, pneumonia, anorectal infection, and urinary tract infection) in a select group of cancer patients. Strikingly similar alterations in clinical presentation were found for all infections that developed in profoundly granulocytopenic patients. Physical findings of exudate, fluctuation, ulceration or fissure, local heat, swelling, and regional adenopathy were all less prevalent in the granulocytopenic patient, while fever was much more common. Only erythema and local pain or tenderness were present in practically all patients regardless of site of infection or level of granulocyte count. A better understanding of how granulocytopenia affects the presentation of infection should lead to earlier and more accurate diagnosis and potentially to more successful therapy.

Adolescent↗
PubMed1995

Mathematical modelling of electrostatic fluctuations in subtilisin active site.

The intensities of electrostatic fluctuations in subtilisin active site generated by conformational motion of charged side chains, polar side chains and peptide bonds of the main chain are calculated. The comparative analysis of all these fragments reveals that there are few of them which make the main contribution to the total value of the intensity, which has been found to be approximately 10(7) g.cm-1.s-2. These are Ser 125, Thr 220 and peptide bonds of aminoacids 125-126, 218-219. Our present analysis enables us to compare the relative contribution of different fragments but we do not pretend to obtain precise absolute values. The reason for this is the lack of the detailed selective information on the mean-square amplitudes and correlation times of conformational motion of the fragments and on the values of local dielectric constants in the interior of subtilisin. The possibility for electrostatic fluctuations in enzyme active site to be an efficient nonspecific source of substrate activation is discussed.

Binding Sites↗
PubMed2002

Transcriptional profiling of a human papillomavirus 33-positive squamous epithelial cell line which acquired a selective growth advantage after viral integration.

Alterations in gene expression represent key events in carcinogenesis. We have studied HPV-induced cervical carcinogenesis, using an HPV-33-positive cell line (UT-DEC-1) established from a low-grade vaginal dysplasia (VAIN-I). Early-passage cells contained HPV-33 in episomal form, but these were superseded at later passages by cells carrying only integrated virus. To gain insight into the biologic significance of HPV integration, we compared the level of gene expression in normal vaginal keratinocytes, early-passage and late-passage UT-DEC-1 cells, using cDNA microarrays. Total RNA was isolated from cells by CsCl-gradient centrifugation, reverse-transcribed with MMLV reverse transcriptase and labeled with alpha-(32)P ATP. A cDNA microarray expression profile analysis was performed with Clontech's Human Cancer 1.2 cDNA expression array kit. The 16 upregulated genes (cut-off 2-fold), identified by comparing both cell types to control keratinocytes, appeared to support cell-cycle progression or to be functional in mitosis. These included, e.g., MCM4 DNA replication licensing factor, cdc2p34 and chromatin assembly factor 1 p48 subunit. Downregulated genes (44 altogether) interfered with apoptosis and cell adhesion, including the apoptosis-inducing genes FRAP, Bik and caspase-9 precursor. The most significant differences between the late and early passages (29 and 46 constantly up- and downregulated genes without any fluctuation) were overexpression of the transcription factors E2F5 with its dimerization partner DP1, NF-kappa B and serine/threonine kinases and underexpression of enzymes of the MAPK pathway. Acquisition of a selective growth advantage after viral integration might be explained by a major shift from a MAPK pathway to cell-cycle dysregulation (G(2)/M).

Cell Cycle↗
PubMed2003

Emergency and early carotid endarterectomy in patients with acute ischemic stroke selected with a predefined protocol. A prospective pilot study.

AIM: The appropriateness of early carotid endarterectomy (CEA) in patients with acute ischemic stroke is still unsettled. The aim of this study was to verify the safety and feasibility of early CEA in a consecutive series of patients with acute ischemic stroke observed in an emergency Department Stroke Unit. METHODS: During a 24-month study, out of 756 patients with acute ischemic stroke 33 (4.4%) were scheduled for early CEA. Endarterectomy procedures were distinguished according to the time between the onset of stroke and operation as emergency (within 8 hours), early CEA (1-18 days). Patients with impaired consciousness or an infarct larger than 2.5 cm on computed tomographic (CT) or magnetic resonance (MR) scans or both were excluded from surgery. All patients underwent spiral CT, echo-color-Doppler (ECD) sonography, transcranial Doppler (TCD) sonography and, when necessary, MR angiography within 6 hours of admission. No patient underwent conventional angiography. Most patients were operated on under cervical block (CB) anesthesia; general anesthesia (GA) was used only for those with an unstable neurological deficit. Selective shunting was used on the basis of intra-operative transcranial Doppler in patients under GA and the onset or worsening of neurological deficit under CB anesthesia. RESULTS: Of the 6 patients operated on within a median 6 hours after the onset of stroke, 1 (16.5%) had a fatal hemorrhagic transformation of the infarct, while the remaining 5 (83.5%) stopped fluctuating or progressing and had a favourable neurological outcome. Of the 16 patients operated on within a median 36 hours and of the 11 patients operated on within 7 days, none deteriorated after operation. CONCLUSION: Emergency CEA is feasible for acute ischaemic stroke provided that strict selection criteria are applied and the door-to-surgery interval is kept short (within 8 hours). Early CEA for secondary prevention is feasible and safe, confirming that a delayed operation is in most cases unwarranted. Large randomized trials are warranted before implementing emergent and early CEA in routine clinical practice.

Acute Disease↗
PubMed2006

The loss of adaptive plasticity during long periods of environmental stasis.

Adaptive plasticity allows populations to adjust rapidly to environmental change. If this is useful only rarely, plasticity may undergo mutational degradation and be lost from a population. We consider a population of constant size N undergoing loss of plasticity at functional mutation rate m and with selective advantage s associated with loss. Environmental change events occur at rate theta per generation, killing all individuals that lack plasticity. The expected time until loss of plasticity in a fluctuating environment is always at least tau, the expected time until loss of plasticity in a static environment. When mN > 1 and N theta >> 1, we find that plasticity will be maintained for an average of at least 10(8) generations in a single population, provided tau > 18/theta. In a metapopulation, plasticity is retained under the more lenient condition tau > 1.3/theta, irrespective of mN, for a modest number of demes. We calculate both exact and approximate solutions for tau and find that it is linearly dependent only on the logarithm of N, and so, surprisingly, both the population size and the number of demes in the metapopulation make little difference to the retention of plasticity. Instead, tau is dominated by the term 1/(m+s/2).

Adaptation, Biological↗