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PubMed1985

[Intravenous labetalol in normotensive coronary patients. Effects on hemodynamics and myocardial metabolism].

The haemodynamic and myocardial metabolic effects of intravenous Labetalol were studied in 7 normotensive coronary patients with at least one significant stenosis on the left anterior descending artery. The study consisted of 5 successive observation periods: basal (I); during atrial pacing at the theoretical maximal heart rate or when anginal pain occurred (II); return to basal conditions (III); 20 minutes after an injection of 1.5 mg/kg of Labetalol over 3 minutes into the pulmonary artery (IV); during repeat atrial pacing at the rate achieved during phase II (V). There was no significant difference between phases I and III except for a slightly faster heart rate in phase III. The effects of Labetalol were assessed by comparing the results during phases III and IV between phases II and V and by analysing the variations between phases I, II, IV and V. In comparison with basal conditions (phase III), Labetalol (phase IV) induced a slight decrease in cardiac output (p less than 0.05), a decrease in aortic pressure and systemic arterial resistances (p less than 0.01) and of the double product. Coronary sinus flow did not change but myocardial oxygen consumption fell by an average of 11% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1976

Lunarperiodic variation of the phase-angle difference in nocturnal animals under natural Zeitgeber-conditions near the equator.

Several months' studies under natural illumination conditions in the vicinity of the equator show that night monkeys (Aotus trivirgatus), and leaf-nosed bats (Artibeus lituratus) exhibit species-specific lunarperiodic changes of the phase position of their activity rhythm to the Zeitgeber rhythm (Figures 1-3). These changes are closely to nightly illumination conditions. In Aotus the phase-angle differences (p.a.ds) of the onset and end of the activity phase, and in Artibeus the p.a.ds of the midpoint and end of the activity phase are significantly dependent upon the phases of the moon. In the African fruit bat Rousettus aegyptiacus, and in the leaf-nosed bat Phyllostomus hastatus no statistically significant lunarperiodic changes of the p.a.ds could be detected. These results cannot be explained by means of current models concerning the mechanism of synchronisation of biological oscillation. They appear to be, instead, expressions of a periodic masking of the real phase-position due to direct effects of light intensity on the level of activity which which itself is determined by the circadian rhythm. Aschoff's rule, which states that the earlier a species or an individual awakes the later it terminates its daily phase of activity, is partly confirmed for the nocturnal mammals examined in the present study.

Animals↗
PubMed1981

Small-angle neutron scattering study of lipid phase diagrams by the contrast variation method.

A small-angle neutron scattering (SANS) study of slightly sonicated liposomes of binary lipid mixtures is presented. It is demonstrated that the neutron scattering of lipid lamellae may be analyzed in terms of the Kratky--Porod model of scattering by two-dimensional systems. The contrast variation technique may thus be applied in order to study the structure and phase diagrams of lipid layers not disturbed by heavy sonication. The thickness of isolated bilayers is measured, and molar volumes of pure lipid phases are determined. Mixtures of deuterated dimyristoylphosphatidylcholine with (1) protonated dipalmitoylphosphatidylcholine and (2) protonated distearoylphosphatidylcholine, respectively, are studied. Excess volumes of lipid mixtures are determined by the contrast variation. For the first mixture positive excess volumes of +86 A3 in the crystalline phase (5 degrees C) and of +49 A3 in the fluid phase (35 degrees C) are obtained. These large positive excess volumes are interpreted in terms of free volume creation at the interface between the monolayers, which indicates that the polar head groups are rather fixed with respect to the lipid--water interface. We show that the phase boundaries at a given temperature may be determined by performing contrast variation experiments for two mixtures with different initial composition. Good agreement with existing experimental data is observed for the first mixture. A miscibility gap is established in the crystalline state of the second mixture. A most interesting result is the finding of an immiscibility in the fluid state. This is interpreted in terms of critical concentration fluctuations caused by the critical demixing point of the solid-state miscibility gap hidden below the liquidus line.

Deuterium↗
PubMed1992

[Quantification of tricuspid insufficiency--comparison of Doppler echocardiography and radionuclide ventriculography].

In 40 patients (pts) (ages 34-83 years) the severity of tricuspid regurgitation (TR) was graded by pulsed Doppler echocardiographic determination of regurgitant jet extension. Mild TR was assessed in seven pts (group I), mode-rate TR in 20 pts (group II), and severe TR in 13 pts (group III). The enddiastolic diameter of the left ventricle as measured by M-mode-echocardiography was 55 +/- 16 mm in group I, 48 +/- 6 mm in group II, and 50 +/- 10 mm in group III. The regurgitant index (RI), i.e., the ratio of left-to-right-ventricular stroke counts (normal range 0.89-1.97) and the time-activity curve over the liver area were measured by equilibrium radionuclide ventriculography (RNV). The RI differed significantly between group I (1.6 +/- 0.5), II (1.0 +/- 0.3), and III (0.8 +/- 0.3) (p less than 0.01). An RI-value below 0.89 as an index of right-ventricular volume overload was found in 14% (group I), 45%, (group II) and 77% (group III). The time-activity curve over the liver area, as graded by count variation in phase with the right atrium from 1 (no count variation) to 4 (typical count variation) showed all grades in groups I and II, but only grade 2 to 4 in group III. The RI resp. the time-activity curve over the liver is a sensitive parameter for the detection of moderate to severe TR. If TR is ascertained, severe regurgitation can be differentiated from mild regurgitation by RNV-derived RI as an index of right-ventricular volume overload.

Adult↗
PubMed1989

Reassortment of pilin genes in Neisseria gonorrhoeae occurs by two distinct mechanisms.

Phase and antigenic variation of pilin expression in Neisseria gonorrhoeae result from recombination events in which variant sequences from one of the silent loci (pilS) are transferred to the expression locus (pilE). Such rearrangements were originally thought to be gene conversions, but findings showing that phase variation is partially inhibited by DNase I, that piliated (P+) cells are highly competent for DNA uptake and that gonococci readily undergo autolysis in culture, led to the suggestion that pilin variation occurs through transformation by exogenous DNA. We have developed a simple method for the selection of non-piliated (P-) cells and have evaluated naturally occurring P+ to P- transitions. Two primary pathways of pilin variation can be distinguished--transformation-mediated recombination, which is influenced by culture conditions and inhibited by DNase I, and intragenomic reciprocal recombination, which is unaffected by DNase I. Furthermore, we demonstrate that both piliated and revertible P- cells are competent for DNA uptake, an essential prerequisite of the first pathway.

Bacterial Outer Membrane Proteins↗
PubMed1986

Motor and cognitive performances of parkinsonian patients in the on and off phases of the disease.

Twenty-one Parkinsonian patients were tested in on and off phases during chronic levodopa therapy for cognitive function, affective status, and evaluation of motor performance with reaction and movement times. A worsening of mood was observed from the on to the off phase. No variation in cognitive performance was observed from the on to the off phase in spite of evident motor changes. Mood changes during on-off variations may reflect involvement of mesocortical and mesolimbic dopaminergic systems.

Affect↗
PubMed2001

Gender influence on jejunal migrating motor complex.

The role of gender and the menstrual cycle in small bowel motility has not been clearly elucidated. Jejunal motility was recorded with a nasojejunal catheter incorporating five solid-state pressure transducers in ambulatory menstruating women and men of comparable age over 24 h. All women were studied twice, in the early follicular (early-F) and midluteal (mid-L) phases of the menstrual cycle, verified by determining serum levels of gonadal steroids and gonadotropins. The propagation velocity of phase III was slow and the contraction amplitude was high in both menstrual cycle phases compared with men, and these parameters were correlated with serum estrogen levels in the mid-L phase. In the early-F phase, migrating motor complex (MMC) cycle duration during sleep was long compared with other groups and positively correlated with estrogen concentrations, whereas in the mid-L phase MMC cycle duration during sleep was negatively correlated with serum progesterone levels. In all groups, the frequency of phase III contractions was low and the intercontractile interval measured from pressure peak to peak was long during sleep compared with the awake state. Postprandial motility did not display gender difference in any parameter examined. The results demonstrate that the majority of patterns of motility are similar in menstruating women and men, whereas certain aspects of the MMC, most conspicuously propagation velocity and phase III contraction amplitude, differ. We have also documented circadian variation of phase III contraction frequency in both women and men.

Adult↗
PubMed1992

Integration of thyroid hormones with hypothalamic factors on pituitary TSH secretion.

A study employing a newly developed fourth generation immunometric serum TSH assay (assay limit 0.001 mu/l was performed to determine the temporal pattern of inhibition of serum TSH in response to a maximal suppressive dose of thyroid hormone (T3, T4 and TRIAC) as compared to the pattern produced by dopamine (DA) and dexamethasone (DEX). Mean onset of inhibition was 24, 48 and 68 minutes for thyroid hormone, DA and DEX, respectively. The inhibitory pattern was uniform and reproducible for the same or different individuals if data were normalized respective to basal TSH values. Inhibitory pattern with thyroid hormone formed two distinct log linear functions: A rapid phase (phase 1) spanning 48 minutes to 24 hours and a slower phase (phase 2) bridging 24 to 1,000 hours. A diurnal variation in phase 1, but not in phase 2 suppression, was observed. A phase 1 response was also produced by DA and DEX but not phase 2. Low dose TRH infusion studies indicated that thyroid hormone and DEX inhibited thyrotroph response at or beyond the TRH receptor, while DEX appeared to inhibit endogenous TRH secretion. No additive effects of DA or DEX on T3 inhibition were seen in phase 1. These studies provide new insight into the mechanism by which these endocrine factors complementarily regulate TSH secretion in man.

Dexamethasone↗
PubMed1993

Ki-S1, a novel proliferative marker: flow cytometric assessment of staining in human breast carcinoma cells.

There is considerable interest in immunohistochemical markers of proliferation which are suitable for use on routinely fixed clinical material. The novel proliferation-associated antibody Ki-S1 shows promise in this respect. In this study we have: (i) defined the pattern of Ki-S1 labelling relative to the cell cycle phase; (ii) investigated the labelling pattern with Ki-S1 on a human breast cell line (ZR75) under varying proliferative conditions induced by serum deprivation and refeeding; (iii) examined in a flow cytometric study Ki-S1 staining in archival, clinical breast carcinoma samples. In exponentially growing cells Ki-S1 showed a marked cell cycle phase-specific variation in staining intensity which increased linearly through the S-phase, was high in G2 and reached its peak in mitosis. Ki-S1 staining intensity mirrored the changes in proliferative activity of ZR75 cells during serum deprivation and refeeding. In a small series of human breast carcinoma, Ki-S1 staining intensity correlated with S-phase fraction (SPF) derived from DNA profiles. The antigen labelled by Ki-S1 is extremely robust, resisting degradation by fixation and by an aggressive enzymic tissue disaggregation method. Ki-S1 warrants further investigation as a proliferation-related marker, particularly for routine clinical application.

Animals↗
PubMed2006

Optimized HREM imaging of objects supported by amorphous substrates using spherical aberration adjustment.

High Resolution Electron Microscopy (HREM) is often used to characterize objects supported by amorphous substrates, usually amorphous carbon. HREM is currently undergoing step change in performance due to aberration correctors. This paper examines the aberration corrected imaging of objects supported by amorphous substrates. In particular, we show that a substantial increase in the ratio of the object contrast to the substrate contrast can be achieved by utilizing the strong variation of phase contrast with height, which is present when the spherical aberration has been adjusted to a small value. This variation is examined using the familiar Weak Phase Object Approximation model from which it is determined that the contrast ratio achieves a maximum at a small nonzero value of the spherical aberration. This result is confirmed by multislice modelling which allows for deviations from the Weak Phase Object Approximation and delocalization effects. One important practical result of this study is the need to place the object of interest on the correct side of the amorphous carbon substrate.

Journal Article↗
PubMed1996

The pilA regulatory gene modulates the pilus-mediated adhesion of Neisseria meningitidis by controlling the transcription of pilC1.

Adherence to eukaryotic cells is essential in the pathogenesis of Neisseria meningitidis. Pilus-mediated adhesion has been shown to play an essential role in this process. Pilin, the pilus major subunit, and two pilus associated proteins, PilC1 and PilC2, are key components in meningococcal adhesiveness. Phase and/or antigenic variation of these molecules are the only identified means by which N. meningitidis modulates pilus-mediated adhesion. PilA/PilB is a pleiotropic regulatory system first characterized in Neisseria gonorrhoeae where it controls pilin gene transcription. Similar alleles are found in N. meningitidis. To address the role of this regulatory pathway in N. meningitidis, we engineered a meningococcal pilA mutant strain and analysed the consequences of this mutation on pilus-mediated adhesion using epithelial Hec-1-B cells. This mutation resulted in a threefold reduction in adhesiveness. As no change in the amount of pilin nor in pilin gene mRNA was detected, we compared the expression of the pilC genes in both pilA and parental strains. Two transcriptional fusions pilC1-lacZ and pilC2-lacZ were constructed. A threefold reduction in beta-galactosidase activity was observed in the pilA mutant strain harbouring the pilC1-lacZ fusion. No effect of the pilA mutation on beta-galactosidase activity was observed in the strain carrying the pilC2-lacZ fusion. Gel retardation experiments confirmed that the PilA protein binds to the promoter region of pilC1 but not of pilC2. Taken together, these data demonstrate that PilA modulates meningococcal adhesiveness via the transcription of pilC1. Thus, in addition to phase variation, a more co-ordinate and responsive system may allow a fine adaptation of adhesiveness of meningococci to various environmental signals.

Bacterial Adhesion↗
PubMed2002

Metabolic specialization associated with phenotypic switching in Candidaalbicans.

Phase and antigenic variation are mechanisms used by microbial pathogens to stochastically change their cell surface composition. A related property, referred to as phenotypic switching, has been described for some pathogenic fungi. This phenomenon is best studied in Candida albicans, where switch phenotypes vary in morphology, physiology, and pathogenicity in experimental models. In this study, we report an application of a custom Affymetrix GeneChip representative of the entire C. albicans genome and assay the global expression profiles of white and opaque switch phenotypes of the WO-1 strain. Of 13,025 probe sets examined, 373 ORFs demonstrated a greater than twofold difference in expression level between switch phenotypes. Among these, 221 were expressed at a level higher in opaque cells than in white cells; conversely, 152 were more highly expressed in white cells. Affected genes represent functions as diverse as metabolism, adhesion, cell surface composition, stress response, signaling, mating type, and virulence. Approximately one-third of the differences between cell types are related to metabolic pathways, opaque cells expressing a transcriptional profile consistent with oxidative metabolism and white cells expressing a fermentative one. This bias was obtained regardless of carbon source, suggesting a connection between phenotypic switching and metabolic flexibility, where metabolic specialization of switch phenotypes enhances selection in relation to the nutrients available at different anatomical sites. These results extend our understanding of strategies used in microbial phase variation and pathogenesis and further characterize the unanticipated diversity of genes expressed in phenotypic switching.

Base Sequence↗
PubMed1998

Ultrasonic tissue characterization for coronary care unit patients with acute myocardial infarction.

The ultrasonic integrated backscatter of myocardium changes in infarction and ischemia. On the third day after acute myocardial infarction, 30 patients underwent ultrasonic tissue characterization from the parasternal short-axis view. With a composite parameter, the phase-weighted variation, sensitivity, specificity, and accuracy for diagnosing multivessel coronary artery disease were 84.6%, 52.9% and 66.6%, respectively. Using 67 degrees as the cutoff value for the phase deviation of the backscatter power curve, the recanalization of the infarct-related artery could be detected with a positive predictive value of 77.7% and a negative predictive value of 66.6%. Ultrasonic tissue characterization is a feasible technique for detecting the multivessel coronary artery diseases and the recanalization of infarct-related artery for patients with acute myocardial infarction. The diminished cardiac cycle-dependent variation in integrated backscatter and increased phase deviation can differentiate patent coronary arteries from those coronary arteries with anatomically significant stenoses.

Aged↗
PubMed2005

High-performance liquid chromatographic enantioseparation of alpha-substituted glycine analogs on a quinine-based anion-exchanger chiral stationary phase under variable temperature conditions.

The retention of enantiomers of chiral analytes, i.e. alpha-substituted glycine analogs, on a quinine-based anion-exchanger chiral stationary phase was studied in the temperature range of 5-70 degrees C and at different mobile phase compositions, using isocratic elution in the reversed-phase mode. By variation of both mobile phase composition and temperature, baseline separations could be achieved for these enantiomers. Separation could be optimized more quickly by adjusting the column temperature rather than the mobile phase composition. The dependence of the natural logarithms of retention and selectivity factors (lnk' and lnalpha) on the inverse of temperature, 1/T (van't Hoff plots) was used to determine thermodynamic data on the enantiomers. Calculated thermodynamic constants (Delta(DeltaH degrees ), Delta(DeltaS degrees ) and Delta(DeltaG degrees )) were applied to promote an understanding of the thermodynamic driving forces for retention in this chromatographic system. The elution sequence of the enantiomers in most cases was determined.

Anion Exchange Resins↗
PubMed1998

Effect of temperature on retention of enantiomers of beta-methyl amino acids on a teicoplanin chiral stationary phase.

The isocratic retention of enantiomers of beta-methyl amino acids (beta-methyltyrosine, beta-methylphenylalanine, beta-methyl-tryptophan and beta-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) was studied on a teicoplanin-containing chiral stationary phase at different temperatures and at different mobile phase compositions, using the reversed-phase mode. With variation of both mobile phase composition and temperature, almost baseline separations could be achieved for all four enantiomers of sterically hindered amino acids. The retention factors and selectivity factors for the enantiomers of all investigated compounds decreased with increasing temperature. The natural logarithms of the retention factors (ln k) of the investigated compounds depended linearly on the inverse of temperature (1/T). van 't Hoff plots afforded thermodynamic parameters, such as the apparent change in enthalpy (delta H degree), the apparent change in entropy (delta S degree) and the apparent change in Gibbs free energy (delta G degree) for the transfer of analyte from the mobile to the stationary phase. The thermodynamic constants (delta H degree, delta S degree and delta G degree) were calculated in order to promote an understanding of the thermodynamic driving forces for retention in this chromatographic system.

Amino Acids↗
PubMed1990

Hormonal regulation of prostaglandin production by rhesus monkey endometrium.

Although there have been numerous studies on the production of prostaglandins (PGs) by human endometrium in vitro during the menstrual cycle, considerable variation exists in the levels reported during the proliferative vs. the secretory phase. Such variation may be due in part to the difficulty in obtaining endometrium from a precisely known hormonal environment and in part to the use of the different culture systems employed. The aim of the present study was to develop a non-human primate model in which precisely dated endometrial tissue could be obtained reliably. Moreover, PG levels in the endometrium of the rhesus monkey or other primates have not previously been reported during the artificial menstrual cycle. An important objective in establishing such a model was to permit future manipulations of the cycle in vivo [e.g. by omitting the midcycle estradiol (E) peak] to further dissect specific roles of E and progesterone (P) in regulating PG synthesis during the menstrual cycle. Ovariectomized rhesus monkeys were maintained on a standard artificial menstrual cycle via the insertion and removal of Silastic capsules containing E or P. Samples of endometrium (approximately 50 mg) were obtained by hysterotomy under sterile conditions at predetermined stages of separate menstrual cycles: day 9 (midproliferative; n = 5), day 13 (E peak; n = 3), day 14 (1 day post-E peak; n = 5), and day 23 (midsecretory; n = 8). Measurement of the primary PGs in unextracted medium by RIA over 4 days of organ culture indicated PGF2 alpha greater than 6-keto-PGF1 alpha greater than PGE2 greater than thromboxane-B2, PGD2 greater than leukotrienes. PGF2 alpha, the most abundant PG produced on the first day of culture, was low on day 9 and increased dramatically on day 13 (P less than 0.01). On day 14, PGF2 alpha levels fell significantly only 1 day post-E peak (P less than 0.01), while on day 23, after exposure to P in vivo, PGF2 alpha was 10-fold higher (P less than 0.01) than on cycle days 9 and 14. The other PGs measured showed a lower but similar profile at the cycle stages examined. Physiological concentrations of P (5.0 ng/mL) added to cycle day 23 cultures in both the absence and presence of low or high E markedly inhibited the high levels of PGs found in day 23 cultures (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Arteries define the position of the thyroid gland during its developmental relocalisation.

During vertebrate development, the thyroid gland undergoes a unique relocalisation from its site of induction to a distant species-specific position in the cervical mesenchyme. We have analysed thyroid morphogenesis in wild-type and mutant zebrafish and mice, and find that localisation of growing thyroid tissue along the anteroposterior axis in zebrafish is linked to the development of the ventral aorta. In grafting experiments, ectopic vascular cells influence the localisation of thyroid tissue cell non-autonomously, showing that vessels provide guidance cues in zebrafish thyroid morphogenesis. In mouse thyroid development, the midline primordium bifurcates and two lobes relocalise cranially along the bilateral pair of carotid arteries. In hedgehog-deficient mice, thyroid tissue always develops along the ectopically and asymmetrically positioned carotid arteries, suggesting that, in mice (as in zebrafish), co-developing major arteries define the position of the thyroid. The similarity between zebrafish and mouse mutant phenotypes further indicates that thyroid relocalisation involves two morphogenetic phases, and that variation in the second phase accounts for species-specific differences in thyroid morphology. Moreover, the involvement of vessels in thyroid relocalisation sheds new light on the interpretation of congenital thyroid defects in humans.

Animals↗