Cerebrovascular reactivity during the Valsalva maneuver in migraine, tension-type headache and medication overuse headache.

The aim of this study was to investigate, by means of transcranial Doppler ultrasound (TCD), cerebrovascular reactivity during the Valsalva maneuver (VM) during the headache-free interval in patients with migraine (M), migraine plus tension-type headache (M+TTH), and migraine plus medication overuse headache (M+MOH). A total of 114 patients (n=60 M, n=38 M+TTH, n=16 M+MOH) and n=60 controls were investigated; diagnoses were made according to the International Headache Society criteria. All subjects underwent TCD monitoring and, simultaneously, non-invasive assessment of arterial blood pressure and end-tidal CO2. Two indices were determined: the cerebrovascular Valsalva ratio (CVR) was calculated as the maximum end-diastolic flow velocity acceleration during the late straining phase of the VM [cm/s2] and the centroperipheral Valsalva ratio (CPVR) was defined as the quotient of CVR to the concomitant arterial blood pressure acceleration [cm/mmHg x s]. The dynamic cerebrovascular autoregulatory response to the VM, measured as CVR, was increased in patients with M and M+TTH compared to age-matched healthy subjects. By contrast, CPVR (i.e. the quotient of the cerebrovascular to the peripheral autonomic response), was increased in M patients compared to healthy subjects and all other headache conditions tested. Cerebrovascular autoregulatory response during the VM was increased in M patients compared to age-matched normal healthy subjects, indicating a disturbed autonomic control of cerebral vasoreactivity. The CPVR seems to be a sensitive parameter for distinguishing between M patients and M+TTH or M+MOH patients.

JAK3 associates with the human interleukin 4 receptor and is tyrosine phosphorylated following receptor triggering.

In human B cells, interleukin 4 (IL4) acts in regulating proliferation, antigen expression, isotype switching and differentiation. These different effects are mediated through the IL4R complex including the IL2R gamma chain (gamma c) and a specific p130/140 binding unit referred below as human Interleukin 4 Receptor (IL4-R). Here, we studied the signal transduction events following IL4R activation and leading to CD23 expression on resting B cells. We demonstrate that IL4R triggering induced the tyrosine phosphorylation of JAK3 and of a p170 protein. Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. Orthovanadate treatment, while having no effect on IL4-induced p130 phosphorylation, leads to the hyperphosphorylation of the p170 and inhibits IL4-induced CD23 expression. These suggest that two mandatory steps exist in early IL4 signaling: one controlled by JAK3 activation and the other by the p170 phosphoprotein.

Psychophysics of reading--XIV. The page navigation problem in using magnifiers.

Most people with low vision require magnification to read. A magnifier's field of view often contains only a few letters at a time. Page navigation is the process by which the reader moves the magnifier from word to word, and from the end of one line to the beginning of the next line. Page navigation takes time and reduces reading speed. The major questions addressed in this paper are: (1) What role does page navigation play in limiting reading speed? and (2) Are the window width requirements for reading (number of characters in the field for a criterion performance level) increased by the need for page navigation? We measured the reading speeds of three normal-vision and seven low-vision subjects in two ways: with drifting-text requiring no page navigation, and with a closed-circuit TV (CCTV) magnifier which required page navigation. We built special hardware to record the location of the CCTV's magnified field in the text. These recordings were used to separate forward-reading time (left-to-right movement through the text) from retrace time (navigational movement). For normal-vision subjects, forward-reading and retrace times were about equal. For low-vision subjects, retrace times were shorter than forward-reading times, indicating that the forward-reading performance was limited by visual, not navigational, demands. The retrace time did have an impact, however, ranging from 17 to 50% of the overall time. The window requirements for reading with page navigation (CCTV) were larger than those for reading without page navigation (drifting-text). The difference was more than a factor of three for normal-vision subjects and close to a factor of two for low-vision subjects (10 characters for CCTV vs 5.2 characters for drifting-text for 85% of maximum reading speed.

Nonlinear analysis of sleep EEG data in schizophrenia: calculation of the principal Lyapunov exponent.

The generating mechanism of the electroencephalogram (EEG) points to the hypothesis that EEG signals derive from a nonlinear dynamic system. Hence, the unpredictability of the EEG might be considered as a phenomenon exhibiting its chaotic character. The essential property of chaotic dynamics is the so-called sensitive dependence on initial conditions. This property can be quantified by calculating the system's first positive Lyapunov exponent, L1. We calculated L1 for sleep EEG segments of 13 schizophrenic patients and 13 control subjects that corresponded to sleep stages I, II, III, IV and REM (rapid eye movement), as defined by Rechtschaffen and Kales, for the lead positions Cz and Pz. During REM sleep, for both electrode positions, the principal Lyapunov exponent L1 was significantly increased in schizophrenic patients compared with control subjects. This finding points to altered nonlinear brain dynamics during REM sleep in schizophrenia.

[Automatic classification of liver segments according to Couinaud: development of a new algorithm and evaluation spiral CT data]. / Automatische Klassifikation der Lebersegmente nach Couinaud: Entwicklung eines neuen Algorithmus und Evaluierung an Spiral-CT-Datensätzen.

PURPOSE: To develop a software tool that analyzes the anatomy of the portal vein branches and assigns segmental and subsegmental branches according to Couinaud's classification system and to evaluate its accuracy. MATERIALS AND METHODS: The algorithm was developed in C++ on a PC. The algorithm recognizes the three major branching patterns of the portal vein. Segmental and subsegmental branches are assigned to 8 segments following Couinaud and encoded by 8 colors. The software was evaluated using CT data sets of 39 patients. After the individual segmental anatomy of each patient was determined by an experienced radiologist, automatic classification was performed and the results were compared on a branch by branch basis. RESULTS: The numbering was accurate according to Couinaud's system in 358 of 409 segmental and subsegmental branches (88 %). The assignment failed in 51 of 409 branches due to unexpected anatomy or software problems. CONCLUSION: Automatic classification of portal vein branches and their appendant parenchyma is possible. The automatic designation of liver segments enables the three-dimensional visualization of the segmental anatomy. In the future, automatic analysis might facilitate the reporting and communication of CT findings.

The calculation of the first positive Lyapunov exponent in sleep EEG data.

To help determine if the EEG is quasiperiodic or chaotic we performed a new analysis by calculating the first positive Lyapunov exponent L1 from sleep EEG data. Lyapunov exponents measure the mean exponential expansion or contraction of a flow in phase space. L1 is zero for periodic as well as quasiperiodic processes, but positive in case of chaotic processes expressing the sensitive dependence on initial conditions. We calculated L1 for sleep EEG segments of 15 healthy male subjects corresponding to sleep stages I, II, III, IV and REM (according to Rechtschaffen and Kales). Our investigations support the assumption that EEG signals are neither quasiperiodic waves nor simple noise. Moreover, we found statistically significant differences between the values of L1 for different sleep stages.

Unusual proton Zeeman spin relaxation in an organic solid: several crystal polymorphs or different glass structures?

Solid state proton Zeeman relaxation rate R1z measurements in two isomers of an organic solid (1- and 2-ethylnaphthalene) are reported. The samples are liquids at room temperature and the temperature T and Larmor frequency omega dependence of R1z depends strongly on how the sample is solidified. Methyl group (CH3) rotation is responsible for the proton spin relaxation and the methyl groups serve as probes of the local environment. The R1z measurements clearly distinguish between different solid states due to the differences in local structure at the several-molecule level. The experiments cannot be used to determine the states of these Van der Waals solids although interpreting the relaxation rate data suggests the states are unusual. We propose that these systems might exist in two (2-ethylnaphthalene) or more (1-ethylnaphthalene) polycrystalline polymorphs or that we are observing distinguishable glassy states, or, both. A phase transition is observed in 1-ethylnaphthalene. Variable temperature X-ray studies of organic systems that solidify well below room temperature are difficult, or at least not routine, and proton spin relaxation measurements serve as a convenient starting point for investigating such systems.

Deterministic chaos and the first positive Lyapunov exponent: a nonlinear analysis of the human electroencephalogram during sleep.

Under selected conditions, nonlinear dynamical systems, which can be described by deterministic models, are able to generate so-called deterministic chaos. In this case the dynamics show a sensitive dependence on initial conditions, which means that different states of a system, being arbitrarily close initially, will become macroscopically separated for sufficiently long times. In this sense, the unpredictability of the EEG might be a basic phenomenon of its chaotic character. Recent investigations of the dimensionality of EEG attractors in phase space have led to the assumption that the EEG can be regarded as a deterministic process which should not be mistaken for simple noise. The calculation of dimensionality estimates the degrees of freedom of a signal. Nevertheless, it is difficult to decide from this kind of analysis whether a process is quasiperiodic or chaotic. Therefore, we performed a new analysis by calculating the first positive Lyapunov exponent L1 from sleep EEG data. Lyapunov exponents measure the mean exponential expansion or contraction of a flow in phase space. L1 is zero for periodic as well as quasiperiodic processes, but positive in the case of chaotic processes expressing the sensitive dependence on initial conditions. We calculated L1 for sleep EEG segments of 15 healthy men corresponding to the sleep stages I, II, III, IV, and REM (according to Rechtschaffen and Kales). Our investigations support the assumption that EEG signals are neither quasiperiodic waves nor a simple noise. Moreover, we found statistically significant differences between the values of L1 for different sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonlinear analysis of sleep EEG in depression: calculation of the largest lyapunov exponent.

Conventional sleep analysis according to Rechtschaffen and Kales (1968) has provided meaningful contributions to the understanding of disturbed sleep architecture in depression. However, there is no characteristic alteration of the sleep cycle, which could serve as a highly specific feature for depressive illness. Therefore, we started to investigate nonlinear properties of sleep electroencephalographic (EEG) data in order to elucidate functional alterations other than those obtained from classical sleep analysis. The application of methods from nonlinear dynamical system theory to EEG data has led to the assumption that the EEG can be treated as a deterministic chaotic process. Chaotic systems are characterized by a so-called sensitive dependence on initial conditions. This property can be quantified by calculating the system's Lyapunov exponents, which measure the exponential separation of nearby initial states in phase space. For 15 depressive inpatients (major depressive episodes according to DSM-III-R criteria) and 13 healthy controls, matched in gender, age, and education, we computed the principal Lyapunov exponents L1 of EEG segments corresponding to sleep stages, I, II, III, IV, and rapid eye movement (REM), according to Rechtschaffen and Kales, for the lead positions CZ and PZ. We found statistically significant decreased values of L1 during sleep stage IV in depressives compared with a healthy control group.

[Physical factors in animal experiments for testing antimasspsychotic drugs]. / Physikalische Faktoren bei Tierversuchen zur Testung anti-massenpsychotisch wirkender Pharmaka

Lemmingson et al. have observed that the movement of masspsychotic lemmings (Lemmus lemmus) shows a distinct preference for the left direction. They suggested that this is due to the influence of the Coriolis force. According to this proposition the influence of the Coriolis force on a group of masspsychotic animals has been investigated quantitatively. The results suggest the following model: Normally the influence of the Coriolos force, which on the northern hemisphere acts to the right, is compensated by a neuromuscular feedback mechanism. The tendency towards the left under masspsychotic conditions corresponds to overcompensation. The tendency to the left should also be observed on the southern hemisphere, if the direction of this compensation is determined genetically. Therefore, the test proposed by Lemmingson et al. is not suited to distinguish between the influence of the Coriolis force and the influence of biologically active left-isomer molecules.

Determination of the orientations of tryptophan analogues bound to the trp repressor and the relationship to activation.

The antirepressor indole 3-propanoate has been shown by X-ray crystallography to bind in a different orientation compared with the natural corepressor for the tryp repressor, L-tryptophan (Lawson, C.L. & Sigler, P. B. (1988) Nature 333, 869-871). This suggests a simple difference between what constitutes a corepressor versus an antirepressor. We have used visible absorption and 1H-NMR spectroscopy to characterise the nature of several ligand-repressor complexes and DNA-binding assays to assess the relative operator binding affinities. 5-Fluorotryptophan binds with similar affinity and in the same orientation as L-tryptophan, and is an equally effective corepressor. In contrast, the tight-binding antirepressor indole 3-acrylate binds in the same orientation as indole 3-propanoate. Indole, also an antirepressor, also binds in the indole-3-propanoate orientation. 5-Methyltryptamine, a corepressor, shows spectroscopic characteristics of both tryptophan and indoleacrylate, though NOEs indicate that the tryptophan orientation is preferred. These results indicate that the ammonium group in the side chain is essential both for activation and binding in the L-tryptophan orientation. Antirepressors, lacking the ammonium group, bind in the more favourable indole-3-propanoate orientation. Differences in the NMR signatures of the different repressor-ligand complexes indicate that the details of the conformations depend on the nature of the ligands and their orientation within the binding site. Despite any conformational rearrangement of the protein on binding, dissociation of ligands is facile: 5-fluorotryptophan dissociates rapidly at 313 K. These findings complement and extend the X-ray and thermodynamic analyses of ligand binding.

Relationship between saliva and serum quinidine concentrations and suppression of ventricular premature beats.

Saliva and serum quinidine concentrations were determined in six cardiac patients after twice-daily dosing with 324 or 648 mg quinidine gluconate and the relationship of these concentrations to the degree of suppression of ventricular premature beats (VPB) was evaluated. Mixed saliva and corresponding serum samples were obtained at various times after the 1st, 9th, and 19th doses. With serum quinidine concentrations ranging from 0.05 to 0.83 micrograms/ml after the first dose, the average saliva/serum ratios for quinidine varied between 0.25 and 1.35 (0.54 +/- 0.43). At steady state with the serum quinidine concentrations ranging between 0.36 and 3.35 micrograms/ml, the average saliva/serum ratios ranged from 0.27 to 1.79 (0.81 +/- 0.72) and from 0.19 to 1.84 (0.90 +/- 0.85) for the 9th and 19th doses, respectively. The interpatient variations in the saliva/serum ratio were large for the three doses (approximately 90%). On the other hand, the intrapatient variations were smaller and diminished with each succeeding sampled dose (from 31 to 18 to 12% for the 1st, 9th, and 19th doses, respectively). Moreover, the value for the quinidine saliva/serum ratio for a given patient was similar for all three doses. No significant correlation between the extent of VPB suppression and the concentrations of quinidine in the saliva or serum was observed. The data suggest that salivary quinidine concentrations may be clinically useful to monitor serum drug concentrations in a given patient. However, the relationship between saliva and serum quinidine concentrations and suppression of VPB measured by Holter monitoring is not clear-cut.

Interaction of the trp repressor with trp operator DNA fragments.

The interaction of the trp repressor with several trp operator DNA fragments has been examined by DNA gel retardation assays and by circular dichroism, in the absence and presence of the corepressor L-tryptophan. The holorepressor binds stoichiometrically to both the trpO and aroH operators, forming 1:1 complexes. In the presence of excess protein, additional complexes are formed with these operator fragments. The relative electrophoretic mobilities of the 1:1 complexes differ significantly for trp and aroH operators, indicating that they differ substantially in gross structure. A mutant trp operator, trpOc, has low affinity for the holorepressor, and forms only complexes with stoichiometries of 2:1 (repressor: DNA) or higher, which have a very low electrophoretic mobility. Specific binding is also accompanied by a large increase in the intensity of the near ultraviolet circular dichroism, with only a small blue shift, which is consistent with significant changes in the conformation of the DNA. Large changes in the chemical shifts of three resonances in the 31P NMR spectrum of both the trp operator and the aroH operator occur on adding repressor only in the presence of L-tryptophan, consistent with localised changes in the backbone conformation of the DNA.

Sequence-specific NMR assignments of the trp repressor from Escherichia coli using three-dimensional 15N/1H heteronuclear techniques.

Sequence-specific 15N and 1H assignments for the trp holorepressor from Escherichia coli are reported. The trp repressor consists of two identical 107-residue subunits which are highly helical in the crystal state [Schevitz, R., Otwinowski, Z., Joachimiak, A., Lawson, C. L. & Sigler, P. B. (1985) Nature 317, 782-786]. The high helical content and the relatively large size of the protein (Mr = 25,000) make it difficult to assign even the main-chain resonances by conventional homonuclear two-dimensional NMR methods. However, we have now assigned the main-chain resonances of 94% of the residues by using three-dimensional 15N/1H heteronuclear experiments on a sample of protein uniformly labelled with 15N. The additional resolution obtained by spreading out the signals into three dimensions proved indispensable in making these assignments. In particular, we have been able to resolve signals from residues in the N-terminal region of the A helix for the first time in solution. The observed NOE results confirm that the repressor is highly helical in solution, and contains no extended chain conformations.

[Registration and analysis of airway pressure and gas flow in ventilated patients. The "Hyper-DAQ Respiration Mechanics Recorder"]. / Registrierung und Analyse von Atemwegsdruck und Gasfluss beatmeter Patienten. Der "Hyper-DAQ Atmungsmechanikrekorder."

Respiratory data monitored in ventilated patients commonly consists of monitoring some inspiratory and expiratory pressures and volumes. For a more sophisticated analysis of respiratory mechanics in ventilated patients, a combined hardware and software system is presented that allows for continuous monitoring of airway pressure and gas flow. Gas flow is measured using a pneumotach. The "Hyper-DAQ" is an 8-channel 12-bit analog to a digital converter that can be connected to IBM PCs as well as to Macintosh computers using a standard RS 232 link. A special module consisting of three pressure transducers (airway pressure, differential pressure for a Fleisch head and ambient pressure) and five additional analog inputs is used for recording respiratory data. Once set up, the Hyper-DAQ records all the data in real time, independently of the host system that can query the data via the RS 232 link. The software runs on IBM and compatible PCs, as well as on Macintosh computers. The software simulates a strip-chart recorder and can be controlled by the keyboard and the mouse. We developed special software for the calibration of pressure and flow. Using models of the gas distribution in the lung compliance, resistance and lung time constants can be calculated from the raw data. For special purposes the data can be transferred to spread-sheet software. A mainstream CO2-detector connected to one of the additional analog inputs allows for additional data: alveolar ventilation, series deadspace, etc. The system presented can be recommended in routine work as well as for scientific studies in ventilated patients.

Methyl reorientation in solid 3-ethylchrysene and 3-isopropylchrysene.

We have measured the proton spin-lattice relaxation rate as a function of temperature in polycrystalline 3-ethylchrysene at nuclear magnetic resonance Larmor frequencies of 53.0 and 22.5 MHz and in polycrystalline 3-isopropylchrysene at 53.0, 22.5 and 8.50 MHz. The syntheses of these new compounds are presented. The relatively large chrysene backbone creates an ideal and unique environment for the alkyl groups such that methyl group rotation is the only motion on the nuclear magnetic resonance Larmor frequency timescale over a large temperature range. The relaxation rate data are interpreted in terms of the simplest possible dynamical model: that of random hopping for the methyl group(s), all of which are equivalent in the solid state. The barriers of 11-12 kJ mol-1 are typical for methyl groups in 'isolated' ethyl and isopropyl groups.

A new mechanism for spin--lattice relaxation of heavy nuclei in the solid state: 207Pb relaxation in lead nitrate.

A detailed investigation of the spin-lattice relaxation time, T1, for 207Pb in solid lead nitrate has been undertaken in an effort to understand the mechanism of relaxation. The results show that the 207Pb T1 is independent of magnetic field strength and inversely proportional to the square of the temperature. These are signatures of relaxation by a spin-phonon Raman scattering mechanism. Nuclear spin-lattice relaxation in solid lead salts is more efficient for sites with smaller magnetic shielding anisotropy. A coupling mechanism is proposed whereby phonons create a local magnetic field by modulating the valence electron shell motion relative to the nuclear/electron core. Literature data suggest that spin-phonon scattering is a common relaxation pathway for other spin-1/2 heavy nuclei in solids.