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At least 19 recordsLinked to original sources

[Clinical, immunophenotypic and cell cyclic analysis in chronic lymphocytic leukemia].

15 cases of chronic lymphocytic leukemia (CLL) were immunophenotyped with a panel of monoclonal antibodies. 13 cases were B-CLL, which was characterized by CD20+, HLA-Dr+, SmIg+ and CD5+/Em+. 2 cases were T-CLL, one with Ts phenotype and HLA-Dr+ T-Cll in the other. The ratio of G0 + G1 cells in bone marrow of CLL was 91.1 +/- 2.3% (76.0 +/- 5.1% in controls), while S + G2M cells was 8.9 +/- 2.3% (23.9 +/- 5.1% in controls). The ratios of various cyclic cells were similar in bone marrow and in peripheral blood. Prolymphocytoid transformation developed in the late stage in 3 CLL patients. The clinical course, cytochemistry and immunologic changes in CLL were also analysed.

Aged↗

Backbone modifications in cyclic peptides. Conformational analysis of a cyclic pseudopentapeptide containing a thiomethylene ether amide bond replacement.

NMR and X-ray crystallographic studies have shown that cyclic pentapeptides of the general structure cyclo(D-Xxx-Pro-Gly-Pro-Gly) possess beta- and gamma-turn intramolecular hydrogen bonds. As part of our continuing series surveying the compatibility of various amide bond replacements on peptide structure, we have synthesized cyclo(D-Phe-Pro psi[CH2S]Gly-Pro-Gly). The pseudopeptide was prepared by solid phase methods and cleaved from the resin by a new procedure involving phase transfer catalysis using K2CO3 and tetrabutylammonium hydrogen sulfate. Cyclization was carried out with the use of DPPA, HOBt, and DMAP to afford the product in 69% yield. The conformational behavior of the pseudopeptide was analyzed by 1H and 13C (1D and 2D) NMR techniques. The backbone modification replaced the amide bond that is involved in a gamma-turn intramolecular hydrogen bond in the all-amide structure. In CDCl3, the pseudopeptide adopted the same all-trans conformation as its parent, although the remaining beta-turn hydrogen bond was weaker according to delta delta/delta TNH measurements. In DMSO-d6, the all-trans conformer and a second conformer were observed in a ratio of 55:45. These conformers, which slowly interconverted on the NMR time scale, could be separately assigned; peaks due to chemical exchange were readily distinguishable by the ROESY technique as reported earlier by others. 13C and ROESY experiments suggested the minor conformer contained one cis amide bond at the Gly1-Pro2 position. Thus, both the location and type of amide surrogate are important determinants affecting the compatibility of the replacement with a particular conformational feature.

Amino Acid Sequence↗

Conformational analysis of cyclic peptides in solution.

The strategy and tactics of conformational analysis of cyclic peptides in solution is demonstrated by the example of cyclo(-D-Pro-Phe-Thr-Phe-Trp-Phe-). Spin-locked experiments like rotating frame nuclear Overhauser enhancement spectroscopy (ROESY), ROTO, and TOCSY are successfully applied to assign all proton signals and to obtain distance information. A crude conformational model was built using the nmr data. This starting model was refined by restrained molecular dynamics (MD) calculations using ROE derived distances and fixed bond angles as determined from homo- and heteronuclear coupling constants. To mimic the solvent and to reduce artifacts in an in vacuo calculation the charges of the solvent-exposed NH protons were gradually reduced according to the temperature gradients. The thus obtained "conformation" (mean of a 40 ps MD trajectory) shows very close similarity to x-ray structures in an orthorhombic and in two monoclinic crystal modifications of the same compound. The main difference is the breaking of an intermolecular hydrogen bond of the threonine hydroxyl group on dissolution of the crystal and forming an intramolecular hydrogen bond in solution.

Models, Molecular↗

Seasonal and latitudinal occurrence of cerebral vasospasm and subarachnoid hemorrhage in the northern hemisphere.

Using patient data obtained from the International Cooperative Aneurysm Study that evaluated clinical records from 68 neurosurgical centers in 14 countries, we evaluated the data as to the monthly occurrence of cerebral vasospasm and subarachnoid hemorrhage relative to the latitude of the medical center where the data were gathered. Using the Edwards analysis for cyclic patterns, we examined peak to trough ratios and months of peak to assess the strength and nature of the cyclic variations between December 1980 and July 1983. Of the 3,521 subarachnoid hemorrhage patient records examined, 685 developed some grade of vasospasm as defined symptomatically, angiographically, and by the Fisher Grading Scale. Cyclic analysis demonstrated a strong seasonal occurrence for the incidence of subarachnoid hemorrhage, with a peak in February, in the northern hemisphere. Cerebral vasospasm incidence, after controlling for subarachnoid hemorrhage occurrence, exhibited only a small peak to trough ratio (1.15) relative to the larger ratio (1.74) seen with unadjusted vasospasm data. Age was related to both incidence and location. In populations at high risk for cerebrovascular diseases, climatic conditions may act as synchronizers of pathologic vascular events.

Adolescent↗

Analysis of cyclic nucleotide phosphodiesterase by isoelectric focusing coupled to a specific activity stain.

The procedure described allowed a convenient analysis of cyclic nucleotide phosphodiesterase. The different phosphodiesterase forms present in a crude cytosolic preparation from rat heart were separated by isoelectric focusing on a polyacrylamide gel plate. Phosphodiesterase activity bands were rendered evident by a specific staining method. They were then characterized by means of their substrate specificity and their sensitivity to selective phosphodiesterase inhibitors. The correspondence between the stain bands and the previously described activity peaks, obtained by a preparative technique and detected by radioisotopic enzyme assay, was also investigated.

Animals↗

Simulation and optimization of cyclic activation analysis of short-lived isotopes with 14MeV neutron generator.

A program of simulation and optimization is developed for the case of cyclic activation analysis of short-lived isotopes with 14-MeV neutrons. The background line under the photopeaks of interest is simulated using Zikovsky's model. The reliability of the program is checked on real conditions with a geological reference sample "Soil 5" provided by the IAEA. Optimum experimental conditions (timing parameters, number of cycles) are determined, and corresponding detection limits calculated. A systematic study of short-lived isotopes with half-lives lower than 5 min is done for Soil 5, and the results are discussed.

Activation Analysis↗

Individual differences in vocal activity rhythm: fourier analysis of cyclicity in amount of talk.

Speakers in informal conversations tend to alternate regularly between lower and higher amounts of talking; the periods of these low/high activity cycles are on the order of 3, 6, and 15 minutes. Statistically significant periodicities occurred in 55% of the conversations studied. The periodograms that describe the partition of variance among periodic components show consistent individual differences in the cyclic patterning of vocal activity. Discriminant analysis used the amount of variance accounted for by each of the 12 lowest-frequency periodic components as discriminating variables to see whether speakers could be identified on the basis of the cyclic patterns in vocal activity. Speakers were discriminated and classified at levels well above chance. This suggests that there are consistent individual differences among speakers in the length of cycles in amount of talk.

Activity Cycles↗

Analysis of cyclic feed intake in rats fed on a zinc-deficient diet and the level of dihydropyrimidinase (EC 3.5.2.2).

The body weight and feed intake of rats fed on a Zn-deficient diet for 28 d were reduced compared with those of control rats. The feed intakes of the Zn-deficient and control groups during the period were 10.2 (SE 0.3) and 15.7 (SE 0.2) g/d respectively. Cyclic variations in feed intake and body-weight changes were found in analysis not only of all the data for five rats but also that in each individual rat. Cosinor analysis revealed that the cyclical period of both the feed intake and body-weight change in the Zn-deficient rats was 3.5 (SE 0.1) d. The mesor and amplitude value of the feed intake in the Zn-deficient rats was 10.1 (SE 0.4) g/d and 3.5 (SE 0.5) g/d respectively, and that of body-weight change was 1.4 (SE 0.1) g/d and 7.9 (SE 1.3) g/d respectively. Among pyrimidine-catabolizing enzymes, dihydropyrimidinase (EC 3.5.2.2) activity showed significant retardation in the Zn-deficient rat liver with decrease of the enzyme protein. The ratio of apo-form to holo-form dihydropyrimidinase in the liver was not affected by the Zn-deficient diet.

Amidohydrolases↗

Fluorescence decay time distribution analysis of cyclic enkephalin analogues; influence of solvent and Leu configuration in position 5 on conformation.

Lifetime distribution analysis were performed to study the influence of Leu configuration in position 5 on changes of the peptide chain of cyclic analogues of enkephalins containing a fluorescence donor and acceptor in different solvents. The configuration change of Leu5 in all the analogues of enkephalins studied which contain donor-acceptor pairs has no apparent influence on Trp lifetime distributions. In contrast, there is a significant solvent effect on the shape of lifetime distribution.

Enkephalins↗

The effect of continuous G-CSF application in human cyclic neutropenia: a model analysis.

Human cyclic neutropenia (CN) is a rare haematological disorder characterized by oscillations of blood neutrophils at subnormal levels with a stable period of approximately 21 d. During the phase of severe neutropenia (neutrophils < 250 cells/microliters), which last 4-10 d, the patients are endangered by serious infections. Several authors report that continuous G-CSF application can elevate the blood neutrophils to such a level that the risk of infections is significantly reduced. Although the characteristic cycles are not eliminated by G-CSF, the period of the oscillations is shortened to 12-14 d. Based on a previously proposed computer-simulation model of human CN, the effects of continuous G-CSF application on CN are studied. It is shown how the known different cell-kinetic effects of G-CSF on granulopoiesis explain the clinical data in CN. The reduced length of the cycles emerges as a result of the transit time reduction of the post-mitotic granulopoietic cells by G-CSF. The measured increase of the neutrophil maxima is reproduced by the additional mitoses of the immature granulopoietic bone marrow cells induced by G-CSF. The slight elevation of the neutrophil nadirs can be attributed to a weak effect of G-CSF on the assumed underlying defect in CN (an abnormally small variance of the granulopoietic bone-marrow transit time).

Cell Cycle↗

Cyclic stress analysis of flexor tendon repair.

A method of evaluating flexor tendon repair techniques with the use of cyclic testing is presented. This type of evaluation complements the presently used load-to-failure tests by providing more detailed information about gap formation at the repair site. During load-to-failure testing in this study, core sutures alone demonstrated initial gap formation at 0.85 kg tensile force or more; yet on cyclic testing all techniques demonstrated gap formation of 1.9 mm or greater at 0.5 kg tensile force. Thus cyclic testing demonstrated gap formation not readily apparent on load-to-failure testing. An epitenon stitch placed circumferentially around the laceration site added strength in both load-to-failure and cyclic tests, and significantly reduced gap formation regardless of the core suture technique.

Hand↗

Static and cyclical biomechanical analysis of pedicle screw spinal constructs.

Biomechanical evaluation of twelve different spinal devices in vitro employing pedicle screws was performed using static (n = 5) and cyclical testing (n = 3) parameters. In general, the rank order of implant failures was similar between static and cyclical tests, performed at 600 N compressive load, 5 Hz, and 1 million cycles. The mean number of cycles to failure was higher for spinal instrumentation systems employing longitudinal rods than those using plates (ANOVA F = 16.94, P < .001). At 600 N, the compact Cotrel-Dubousset, TSRH, and ISOLA rod systems demonstrated mean cycles to failure ranging from 200,000 to 800,000 cycles. The remaining devices including Dyna-lok, Kirschner plate, and VSP devices had failures ranging from 50,000 to 210,000 cycles. Polyethylene cylinders representing vertebral bodies were used to eliminate the problems of biologic deterioration encountered with cadaveric spines (a full cyclical test to 1 million cycles required 56 hours), and thus to provide analysis of the weak portion of each spinal system. The failure of eleven of the twelve spinal systems occurred by fracture of a pedicle screw, most commonly at the junction of the upper screw thread and the collar (Kirschner, AO fixator, standard CD, ISOLA, and TSRH). However, in Dynalok and VSP systems, fracture of the threaded portion of the screw just posterior to the integral nuts was the most common screw fracture location. The compact CD system was the only spinal implant that consistently failed by fracture of the longitudinal spinal member (rod). The fatigue life of rod based systems was longer than plate based systems. These studies confirm the importance of anterior column load sharing (vertebral body, corpectomy bone graft) as the mean bending strength demonstrated by these implant systems was not inordinately high using this "worst case scenario" model.

Biomechanical Phenomena↗

Patch- and voltage-clamp analysis of cyclic AMP-stimulated inward current underlying neurone bursting.

The second messenger cyclic AMP has been variously reported to affect the electrical activity of different neurones by decreasing outward potassium current, increasing outward current and increasing inward current. The recently developed patch clamp method of recording single ionic channels allows direct measurement of the action of cyclic AMP on membrane conductances. Using the patch clamp, the closure of potassium channels by cyclic AMP has previously been documented on the single channel level. We report here that in a bursting molluscan neurone, intracellular iontophoresis of cyclic AMP under voltage clamp elicits an inward current of maximal amplitude in the pacemaker voltage region. Patch-clamp analysis reveals inward channels whose opening frequency is augmented by cyclic AMP stimulation and whose activity accompanies burst episodes. Channel opening frequency is significantly increased by depolarization of the whole soma, but not by focal depolarization of the patch; this may reflect the action of another second messenger that acts in concert with cyclic AMP to confer voltage sensitivity.

Animals↗

Analysis of cyclic nucleotide-related enzymes by continuous-flow fast-atom bombardment mass spectrometry.

Continuous-flow fast-atom bombardment mass spectrometry has been developed to directly monitor cyclic nucleotide (substrate) and its product levels from an on-going phosphodiesterase reaction. Analysis of cAMP and cCMP phosphodiesterase incubates have been performed where the temporal evolution of the enzymic reaction is monitored and the effect of enzyme concentration upon the rate of reaction determined. Quantitative data on the enzyme kinetics have been obtained, in the form of Lineweaver-Burke plots, that are shown to correlate well with well-established radiometric methods.

Animals↗

Analysis of cyclic enzyme reaction schemes by the graph-theoretic method.

The development of the graph-theoretic method is proposed particularly for the analysis of closed cycles of elementary stages in enzyme reaction schemes. Some simplifications of the graph structure may be based on the application of Kirchhoff's laws to enzyme reaction graphs in the steady-state. The importance of the cyclic processes for enzyme regulations and a principle non-equilibrium of this phenomenon are emphasized. As an example of the regulatory role of cycles "the liberation" from substrate inhibition by substrate analogues is considered. The modification of the graph-theoretic method in the pre-steady-state kinetics for arbitrary initial conditions (for pre-mixing procedures) is also discussed. The necessary and sufficient conditions for damped oscillations in the pre-steady state are formulated which are the equality conditions for some of the rate constants along the cycle (both for reversible and irreversible stages).

Enzyme Inhibitors↗

Spectral analysis of cyclic symptoms in late luteal phase dysphoric disorder.

Fifty-eight subjects self-referred for premenstrual difficulty were evaluated for late luteal phase dysphoric disorder through a spectral analysis technique applied to prospective symptom ratings. Data from the Schedule for Affective Disorders and Schizophrenia--Life-time Version were used to group the subjects according to the absence or presence of past or present psychiatric disorders. The two psychiatric groups were compared with regard to both patterns of significant symptom change and premenstrual symptom severity. Differences between the groups are used to discuss issues regarding the reliable identification of late luteal phase dysphoric disorder and the impact of other psychiatric disorders on this syndrome.

Adult↗

Kinetic analysis of cyclic CMP-specific and multifunctional phosphodiesterases by quantitative positive-ion fast-atom bombardment mass spectrometry.

Two enzymes, cyclic CMP-specific phosphodiesterase and multifunctional phosphodiesterase, are responsible for the hydrolysis of cytidine 3',5'-cyclic monophosphate in living cells. Quantitation of both enzymes has been carried out by positive-ion fast-atom bombardment mass spectrometric analysis of the enzyme incubates after termination of the reaction. The kinetic data obtained are in close agreement with parallel data obtained by the conventional radiometric assay. The extra facility of the mass spectrometry based assay to monitor several incubation components simultaneously has been exploited to study the concurrent hydrolysis of alternate cyclic nucleotide substrates and provides kinetic parameters of significance in interpreting substrate-enzyme interactions. This is extended by the use of collisionally-induced dissociation of the protonated molecules of the liberated products to identify the mononucleotide isomers resulting from the cyclic nucleotide hydrolysis.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗