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PubMed1993

The effect of verbal instructions on blood pressure measurement.

AIM: To determine whether orally delivered instructions can modify the intensity and direction of blood pressure and heart rate fluctuation. METHODS: The blood pressure of 120 subjects, 60 hypertensive and 60 normotensive, was measured before and after oral instructions. The normotensive subjects were selected from a sample of university students and the hypertensive patients were selected at a routine medical screening. Each sample of 60 subjects was randomly divided into four groups of 15. Each subject was left seated alone in a room for 5 min. The researcher then measured the subjects' blood pressure and heart rate. Following this, each group of normotensives and hypertensives was told that their blood pressure would diminish, or that it would not change or that it would increase. The control group was given no instructions. After 5 min the blood pressure and heart were measured again. RESULTS: In the normotensive and hypertensive groups who were told that their blood pressure would increase, systolic blood pressure increased by 4.3 and 2.5 mmHg, respectively. In the groups who were told that their blood pressure would decrease, systolic pressure fell by 7.8 and 7.4 mmHg, respectively. Those who were told that no change would occur showed a systolic pressure decrease of 3.5 and 1.8 mmHg, respectively. In the control groups systolic blood pressure decreased by 5.6 and 4.2 mmHg, respectively. CONCLUSIONS: These results show that oral instructions are a source of variation in the assessment of blood pressure and emphasize the need for 24-h blood pressure monitoring to eliminate this type of variation.

Blood Pressure↗

PubMed2001

Chaotic behavior in lemon-shaped billiards with elliptical and hyperbolic boundary arcs.

Chaotic properties of a new family, ellipse hyperbola billiards (EHB), of lemon-shaped two-dimensional billiards, interpolating between the square and the circle, whose boundaries consist of hyperbolic, parabolic, or elliptical segments, depending on the shape parameter delta, are investigated classically and quantally. Classical chaotic fraction is calculated and compared with the quantal level density fluctuation measures obtained by fitting the calculated level spacing sequences with the Brody, Berry-Robnik, and Berry-Robnik-Brody distributions. Stability of selected classical orbits is investigated, and for some special hyperbolic points in the Poincaré sections, the "blinking island" phenomenon is observed. Results for the EHB billiards are compared with the properties of the family of generalized power-law lemon-shaped billiards.

Journal Article↗

PubMed1992

Deprenyl in Parkinson's disease: mechanisms, neuroprotective effect, indications and adverse effects.

Deprenyl is a synthetic, selective inhibitor of the monoamine oxidase-B enzyme system. The mechanism of its beneficial effect in early and advanced Parkinson's disease is not settled. Increased striatal dopamine accumulation, sensitization of surviving dopamine neurons with increased dopamine production and reduced nigro-striatal toxicity may all contribute. The standard daily dose of deprenyl is 10 mg. Selectivity may be lost at higher doses. Deprenyl is especially indicated in untreated patients, improving up to 50 percent of patients with mild motor fluctuations. Major symptomatic benefit also occurs in occasional levodopa treated patients. Adverse effects are common, however. Increase dyskinesias, confusion and hallucinations, nausea and postural hypotension may necessitate drug withdrawal or the use of low dose regimens. Caution should be exercised with older patients, those with ulcer disease, which may be worsened by deprenyl, and individuals with active ischemic heart disease where the safety of this drug is not yet clear.

Humans↗

PubMed1991

Increased stability of nucleolin in proliferating cells by inhibition of its self-cleaving activity.

Nucleolin is the major nucleolar phosphoprotein of exponentially growing eukaryotic cells and is presumably involved in pre-rRNA transcription and ribosome biogenesis. Monoclonal antibodies against nucleolin were selected by a differential dot-immunobinding assay. Nucleolin expression during T lymphocyte activation was monitored by the specific antibody. Results showed that nucleolin fluctuated in parallel to DNA synthesis. The intact 105-kDa nucleolin molecule was the major species in actively dividing cells, whereas the degraded forms were relatively abundant in nondividing cells. These results imply that stability of nucleolin molecule is cell proliferation-dependent. When affinity purified nucleolin containing undetectable contaminants was incubated at 37 degrees C, the majority of 105-kDa nucleolin was cleaved by 6 h and completely degraded within 24 h. This purified nucleolin was further separated from possible copurified protease, if any, on a reducing sodium dodecyl sulfate-polyacrylamide gel. After renaturation, the 105-kDa nucleolin immobilized in the gel was also cleaved at 37 degrees C. These data have confirmed that nucleolin protein autocatalyzes its own degradation. The self-cleaving activity of nucleolin was inhibited by nuclear extracts prepared from proliferating cells. Apparently, a proteolytic inhibitor(s) in the nuclei of proliferating cells stabilized the nucleolin molecule. It provides an unique regulatory mechanism for nucleolin expression.

Antibodies, Monoclonal↗

PubMed1994

Activity and activation of the complement system in patients being operated on for cancer of the colon.

OBJECTIVE: To find out if there was any local activation of complement in the vicinity of a colonic cancer, and any fluctuation in the function of the complement system during operation. DESIGN: Prospective study. SETTING: One university and two district hospitals in Denmark. SUBJECTS: 29 selected patients undergoing emergency and elective operations for colonic cancer. INTERVENTIONS: Measurements of systemic and local complement fixation capacity and complement activation in samples of serum or plasma taken before, during, and after operation. MAIN OUTCOME MEASURES: Changes in complement fixation capacity and complement activation during operation. RESULTS: Haemodilution during operation caused a significant reduction in the complement fixation capacity of serum and in the activation of the complement system as measured by generation of C3c. We were unable to confirm the presence of complement inhibitors during operation. Haemodilution caused a 30% reduction in fixation capacity of C3b (12/29 samples of serum had values more than 2SD below the mean of the reference range compared with 4/29 before operation). The activity of C4 was reduced by 25% during operation and the capacity of the complement system to fix C3b and C4b was restored to baseline nine days postoperatively. Concentration of C3d was significantly higher in serum from tumour venous blood compared with that from peripheral blood during operation. CONCLUSION: The presence of complement activation products in the general circulation reflects local activation of the complement system in the vicinity of the tumour, but this may have been influenced by tissue necrosis or subclinical infection. Haemodilution causes a significant reduction in the capacity of the complement system during operation, whereas inhibitory factors associated with the cancer or operation and anaesthesia could not be demonstrated. We found no correlation between complement activity and clinical data.

Adult↗

PubMed1991

Adhesion-related molecules in the central nervous system. Upregulation correlates with inflammatory cell influx during relapsing experimental autoimmune encephalomyelitis.

The expression of a battery of adhesion-related molecules and cytokines was investigated by immunocytochemistry in the central nervous system (CNS) of SJL/J mice sensitized for experimental autoimmune encephalomyelitis (EAE). These molecules consisted of the ligands MECA-325, intercellular adhesion molecule-1, and major histocompatibility complex molecules I and II, plus the receptors lymphocyte function-associated antigen-1, CD8, and CD4. The cytokines comprised interferon-gamma and tumor necrosis factor-alpha. EAE was induced by the adoptive transfer of myelin basic protein-sensitized lymphocytes. MECA-325, a marker for murine high endothelial venules in lymph node tissue, was absent from normal CNS tissue, was expressed at low levels on venules 24 to 48 hours before the onset of clinical signs, rose to maximal levels during acute disease, decreased to preclinical levels during remissions, and rose again during relapses. Intercellular adhesion molecule-1, major histocompatibility antigen-I, and major histocompatibility antigen-II showed similar fluctuations around CNS vessels. The receptors lymphocyte function-associated antigen-1 and CD4 fluctuated in parallel with the above molecules, whereas CD8 remained at a similar low level. Interferon-gamma was present during the acute, remitting, and relapsing phases and was localized to inflammatory cells, whereas tumor necrosis factor occurred at low levels only. Thus, several molecules associated with lymphocyte traffic in lymphoid tissue are selectively expressed in a stage-specific manner within the target organ, the CNS, during EAE. This suggests that the CNS may act as an ancillary organ of the immune system, and that cellular traffic into the CNS during EAE is related to the fluctuating expression of several distinct adhesion-related molecules, frequently co-expressed on the same vessel. The findings may have relevance to the sequence of events in the developing CNS lesion of multiple sclerosis.

Animals↗

PubMed2004

Between-year variation of MHC allele frequencies in great reed warblers: selection or drift?

The major histocompatibility complex (MHC) genes are extremely polymorphic and this variation is assumed to be maintained by balancing selection. Cyclic interactions between pathogens and their hosts could generate such selection, and specific MHC alleles or heterozygosity at certain MHC loci have been shown to confer resistance against particular pathogens. Here we compare the temporal variation in allele frequencies of 23 MHC class I alleles with that of 23 neutral microsatellite markers in adult great reed warblers (a passerine bird) in nine successive cohorts. Overall, the MHC alleles showed a significantly higher variation in allele frequencies between cohorts than the microsatellite alleles, using a multi-variate genetic analysis (amova). The frequency of two specific MHC alleles, A3e (P = 0.046) and B4b (P = 0.0018), varied more between cohorts than expected from random, whereas none of the microsatellite alleles showed fluctuations exceeding the expectation from stochastic variation. These results imply that the variation in MHC allele frequencies between cohorts is not a result of demographic events, but rather an effect of selection favouring different MHC alleles in different years.

Analysis of Variance↗

PubMed1996

Statistical properties of the variation at linked microsatellite loci: implications for the history of human Y chromosomes.

It has recently been suggested that observed levels of variation at microsatellite loci can be used to infer patterns of selection in genomes and to assess demographic history. In order to evaluate the feasibility of these suggestions it is necessary to know something about how levels of variation at microsatellite loci are expected to fluctuate due simply to stochasticity in the processes of mutation and inheritance (genetic sampling). Here we use recently derived properties of the stepwise mutation model to place confidence intervals around the variance in repeat score that is expected at mutation-drift equilibrium and outline a statistical test for whether an observed value differs significantly from expectation. We also develop confidence intervals for the time course of the buildup of variation following a complete elimination of variation, such as might be caused by a selective sweep or an extreme population bottleneck. We apply these methods to the variation observed at human Y-specific microsatellites. Although a number of authors have suggested the possibility of a very recent sweep, our analyses suggest that a sweep or extreme bottleneck is unlikely to have occurred anytime during the last approximately 74,000 years. To generate this result we use a recently estimated mutation rate for microsatellite loci of 5.6 x 10(-4) along with the variation observed at autosomal microsatellite loci to estimate the human effective population size. This estimate is 18,000, implying an effective number of 4,500 Y chromosomes. One important general conclusion to emerge from this study is that in order to reject mutation-drift equilibrium at a set of linked microsatellite loci it is necessary to have an unreasonably large number of loci unless the observed variance is far below that expected at mutation-drift equilibrium.

Biological Evolution↗

PubMed1982

Poorly selective cation channels in the skin of the larval frog (stage less than or equal to XIX).

The abdominal skin of bullfrog larvae (Rana catesbeiana) was placed in an Ussing-type chamber, and its transepithelial electrical parameters were recorded with mucosal solutions of different ionic composition. With "K+-like" cations (K+, NH+4, RB+, Cs+) the power spectra of the fluctuations in short-circuit current displayed a Lorentzian component (fc = 30 - 40 Hz). The relaxation noise could be suppressed by addition of the K+ -channel blockers Ba2+ and TEA to the mucosal solution. Also, in presence of the ionophore antibiotic nystatin the Lorentizian noise was abolished. The Na+ -channel probes amiloride and benzimidazolyl-2-guanidine (BIG) both enhanced the relaxation noise obtained with the K+-like cations but, with Na+ and Li+, also caused the rise of a relaxation component above the background noise. In presence of amiloride or BIG, the addition of Ba2+, TEA and nystatin still abolished the Lorentizian noise. It can be concluded that the relaxation-noise source is located in the apical cell membranes of the tadpole skin. These spontaneously fluctuating cation channels do not seem to strictly discriminate between K+-like ions (K+, NH+4, Rb+, Cs+) and Na+-like ions (Na+, Li+). On the other hand, well-known specific probes for K+ channels (Ba2+, TEA) and for Na+ channels (amiloride, BIG) interact with this apical cation channel. It is possible that the poorly selective channel plays a role in the ontogenesis of the specific Na+ transport in the maturing frog skin.

Amiloride↗

PubMed2001

Selective inhibition of beta(2)-adrenergic receptor-mediated cAMP generation by activation of the P2Y(2) receptor in mouse pineal gland tumor cells.

Rhythmic noradrenergic signaling from the hypothalamic clock in the suprachiasmatic nucleus to the pineal gland causes an increase in intracellular cAMP which regulates the circadian fluctuation of melatonin synthesis. The activation of phospholipase C (PLC)-coupled P2Y(2) receptors upon treatment with ATP and UTP exclusively inhibited the isoproterenol-stimulated cAMP production in mouse pineal gland tumor cells. However, the activation of other PLC-coupled receptors including P2Y(1) and bombesin receptors had little or no effect on the isoproterenol-stimulated cAMP production. Also, ATP did not inhibit cAMP production caused by forskolin, prostaglandin E(2), or the adenosine analog NECA. These results suggest a selective coupling between signalings of P2Y(2) and beta(2)-adrenergic receptors. The binding of [(3)H]CGP12177 to beta(2)-adrenergic receptors was not effected by the presence of ATP or UTP. Ionomycin decreased the isoproterenol-stimulated cAMP production, whereas phorbol 12-myristate 13-acetate slightly potentiated the isoproterenol response. Chelation of intracellular Ca(2+), however, had little effect on the ATP-induced inhibition of cAMP production, while it completely reversed the ionomycin-induced inhibition. Treatment of cells with pertussis toxin almost completely blocked the inhibitory effect of nucleotides. Pertussis toxin also inhibited the nucleotide-induced increase in intracellular Ca(2+) and inositol 1,4,5-trisphosphate production by 30-40%, suggesting that the ATP-mediated inhibition of the cAMP generation and the partial activation of PLC are mediated by pertussis toxin-sensitive G(i)-protein. We conclude that one of the functions of P2Y(2) receptors on the pineal gland is the selective inhibition of beta-adrenergic receptor-mediated signaling pathways via the inhibitory G-proteins.

1-Methyl-3-isobutylxanthine↗

PubMed2002

Pharmacology of systemic analgesics.

Systemic administration of analgesic drugs is still the most widely used method for providing pain relief in acute painful situations. Opioids may be selected on the basis of their physicochemical characteristics and their diffusion index to the brain. But in clinical practice, their very steep concentration-analgesic effect relationship remains a critical aspect of opioid therapy. Thus, small fluctuations in plasma concentrations of opioids may lead to profound fluctuations in analgesic effect when their plasma and effect-site concentrations are near the minimum effective analgesic concentration (MEAC). Combining drugs acting on different mechanisms of nociceptive modulation offers benefits from additive/synergistic effects and will decrease the incidence of their adverse effects. Evidence-based reviews showed that effective pain relief using non-opioid analgesics relied on paracetamol supplemented with non-steroidal anti-inflammatory drugs (NSAIDs). The role of COX-2 selective inhibitors (CSIs) in acute pain relief still requires further evaluation. NSAIDs, CSIs and paracetamol share the property of morphine sparing in situations of severe (post-operative) pain. CSIs may be beneficial in patients in whom post-operative bleeding is a major surgical risk as the effects of NSAIDs on coagulation may last for days. Finally, low-dose ketamine infusions remain a worthwhile addition to opioid therapy. Analgesic concentrations of ketamine are 1/5th to 1/10th the anaesthetic concentration and exert significant inhibition on N-methyl-d-aspartate (NMDA) receptor activation.

Acetaminophen↗

PubMed1977

Selective hyperalimentation: a new look at an old problem.

Safe and consistently reliable parenteral hyperalimentation in the care of the critically ill or injured remains an unrealized expectation. Our experience with critically ill patients managed with standard 25% dextrose/4.25% protein hyperalimentation solution (S.H.A.) delivered through a centrally placed catheter demonstrated that S.H.A. was associated with a high catheter infection rate, fluctuations in hyperosmolar tolerance, unstable insulin requirements, and a high discontinuation rate. In retrospect this unsatisfactory experience resulted from the inappropriate assumption that a single type of nutritional support and delivery system could meet the varying metabolic requirements of the critically ill or injured. In an effort to reduce these complications, we have recently utilized a system of selective hyperalimentation in managing 25 consecutive patients. We now identify specific risk factors for groups of patients and use these factors to select the appropriate rout and solution. Selective hyperalimentation has resulted in a lowering of infusion complications and an improvement in completion rate, with satisfactory weight gain and protein response. These results suggest that our approach is sucessful in meeting the nutritional requirements of differing groups of critically ill patients without exposing upsuitable candidates to the potential risks of standard hyperalimentation.

Adolescent↗

PubMed1998

Gingival crevicular pH in experimental gingivitis and occlusal trauma in man.

The purpose of this study was to investigate the fluctuation of gingival crevicular pH during experimentally evoked gingivitis and occlusal trauma, and to examine the relationship between the pH and periodontal health status using a newly developed pH sensor. Maxillary first premolars with clinically healthy gingiva were selected as test teeth in 10 volunteers. In the first study phase, experimental gingivitis was evoked, and gingival index, plaque index, and crevicular pH were recorded during the study period. In the second study phase, experimental occlusal trauma was created with metal onlays having occlusal interferences in lateral movements, and tooth mobility and pH were recorded during the study period. In the gingivitis phase, GI, PlI, and pH values fluctuated significantly during the study period (P < 0.01) and positive correlations were observed between both GI and pH values (P < 0.05), and PlI and pH values (P < 0.01). In the occlusal trauma phase, significant fluctuation was found among tooth mobilities (P < 0.05) during the study phase, but not in pH values. Statistically significant correlations were not observed between tooth mobilities and pH values. These data suggest that the crevicular pH level may not be influenced by experimental occlusal trauma, but shifts toward alkaline with experimental gingivitis.

Adult↗

PubMed1994

Effect of a nasogastric tube on esophageal pressure measurement in normal adults.

We studied the correspondence between fluctuations of esophageal pressure measured before and after placement of a nasogastric (NG) tube in six normal volunteers. Flow, airway pressure, and esophageal pressure data from at least 20 breaths were recorded in seven ventilatory conditions in two body postures: 0 degree (supine) and 60 degrees (upright). The conditions studied included normal quiet breathing, added resistance, reduced compliance, increased frequency, increased tidal volume, continuous positive airway pressure, and volume-cycled ventilation with positive pressure. During recording with the NG tube in place, the subject targeted the same tidal volume (VT), respiratory rate, and inspiratory time fraction (TI/TTOT) recorded before NG tube placement. A computer program selected for analysis only those recorded breaths with and without an NG tube that were "matched" within 5 percent for both VT and TI. We calculated average VT, TI, and esophageal pressure fluctuation (delta Pes) for the matched breaths from each subject during every condition. The delta Pes values with and without NG tube were not statistically different in any tested condition (p > 0.05). Our data indicate that the presence of an NG tube does not invalidate the accuracy of delta Pes measurements made using a well-positioned balloon catheter in the tested conditions.

Adult↗

PubMed1994

Clinical use of ambulatory blood pressure monitoring: a critical appraisal.

Traditional sphygmomanometric techniques are heavily affected by the 'white-coat' effect and cannot be used to assess blood pressure variability over the 24h period. These limitations can be overcome in part using ambulatory monitoring, which (1) quantifies both the mean and the variability of blood pressure over 24h, including blood pressure fluctuations between day and night, (2) does not trigger any alerting reaction in the patient, (3) provides reproducible 24h blood pressure means and (4) allows the action of antihypertensive drugs to be assessed over 24h without interference from a placebo effect. Moreover, ambulatory blood pressure values are more closely related to the end-organ damage associated with hypertension than are isolated clinic readings. However, the limited accuracy of ambulatory monitoring in ambulant individuals, the lack of normal reference values for 24h blood pressure and the need for a longitudinal demonstration of the prognostic value of the technique do not permit the recommendation of its widespread use in clinical hypertension. Although the clinical use of ambulatory monitoring should be restricted to selected cases, there is general agreement on its usefulness in clinical pharmacology trials and in studies aimed at assessing cardiovascular regulation through the analysis of 24h blood pressure and heart rate fluctuations.

Antihypertensive Agents↗

PubMed2005

Four-mode quantum calculations of resonance states in complex-forming bimolecular reactions: C- + CH3Br.

The vibrational resonance states of the complexes formed in the nucleophilic bimolecular substitution (S(N)2) reaction Cl(-)+CH(3)Br-->ClCH(3)+Br(-) were calculated by means of the filter diagonalization method employing a coupled-cluster potential-energy surface and a Hamiltonian that incorporates an optical potential and is formulated in Radau coordinates for the carbon-halogen stretching modes. The four-dimensional model also includes the totally symmetric vibrations of the methyl group (C-H stretch and umbrella bend). The vast majority of bound states and many resonance states up to the first overtone of the symmetric stretching vibration in the exit channel complex have been calculated, analyzed, and assigned four quantum numbers. The resonances are classified into entrance channel, exit channel, and delocalized states. The resonance widths fluctuate over six orders of magnitude. In addition to a majority of Feshbach-type resonances there are also exceedingly long-lived shape resonances, which are associated with the entrance channel and can only decay by tunneling. The state-selective decay of the resonances was studied in detail. The linewidths of the resonances, and thus the coupling to the energetic continuum, increase with excitation in any mode. Due to the strong mixing of the many progressions in the intermolecular stretching modes of the intermediate complexes, this increase as a function of the corresponding quantum numbers is not monotonic, but exhibits pronounced fluctuations.

Journal Article↗

PubMed2000

Denaturing gradient gel electrophoresis analysis of 16S ribosomal DNA amplicons to monitor changes in fecal bacterial populations of weaning pigs after introduction of Lactobacillus reuteri strain MM53.

The diversity and stability of the fecal bacterial microbiota in weaning pigs was studied after introduction of an exogenous Lactobacillus reuteri strain, MM53, using a combination of cultivation and techniques based on genes encoding 16S rRNA (16S rDNA). Piglets (n = 9) were assigned to three treatment groups (control, daily dosed, and 4th-day dosed), and fresh fecal samples were collected daily. Dosed animals received 2.5 x 10(10) CFU of antibiotic-resistant L. reuteri MM53 daily or every 4th day. Mean Lactobacillus counts for the three groups ranged from 1 x 10(9) to 4 x 10(9) CFU/g of feces. Enumeration of strain L. reuteri MM53 on MRS agar (Difco) plates containing streptomycin and rifampin showed that the introduced strain fluctuated between 8 x 10(3) and 5 x 10(6) CFU/g of feces in the two dosed groups. Denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rDNA fragments, with primers specific for variable regions 1 and 3 (V1 and V3), was used to profile complexity of fecal bacterial populations. Analysis of DGGE banding profiles indicated that each individual maintained a unique fecal bacterial population that was stable over time, suggesting a strong host influence. In addition, individual DGGE patterns could be separated into distinct time-dependent clusters. Primers designed specifically to restrict DGGE analysis to a select group of lactobacilli allowed examination of interspecies relationships and abundance. Based on relative band migration distance and sequence determination, L. reuteri was distinguishable within the V1 region 16S rDNA gene patterns. Daily fluctuations in specific bands within these profiles were observed, which revealed an antagonistic relationship between L. reuteri MM53 (band V1-3) and another indigenous Lactobacillus assemblage (band V1-6).

Animals↗

PubMed1992

Selective translational control and nonspecific posttranscriptional regulation of ribosomal protein gene expression during development and regeneration of rat liver.

Mammalian liver development is accompanied by a transition from rapid growth in the fetus to a quiescent state in the adult. However, extensive proliferation can be induced in the adult liver by partial hepatectomy. In this study, we examined the regulation of ribosomal protein (rp) gene expression in the developing and regenerating rat liver. Our results indicate that the translation of rp mRNAs is selectively repressed by about 70% upon development from fetal to adult life, as illustrated by the decrease in ribosomal loading. In addition, the relative abundance of these mRNAs, like that of several other, but not all, housekeeping mRNAs, declines during development through a posttranscriptional mechanism. When liver cells commence growth following partial hepatectomy, translation of rp mRNAs is resumed to near-maximal capacity, as judged by their very efficient recruitment into polysomes. The concomitant increase in the abundance rp mRNAs under these circumstances is achieved by a posttranscriptional mechanism. The apparent fluctuations in the translation efficiency of rp mRNAs are accompanied by parallel changes in the expression of the genes encoding the initiation factors eIF-4E and eIF-4A. Our results indicate that selective translational control of rp mRNAs in mammals is not confined to manipulated cells in culture but constitutes an important regulatory mechanism operating in vivo in the course of liver development and regeneration.

Animals↗