[Grisel's syndrome after otoplasty]. / Grisel-Syndrom nach Anthelixplastik.

Grisel's syndrome is known as a very rare complication of ENT surgery. It is described as non-traumatic atlantoaxial rotatory subluxation, often seen after tonsillectomy or adenoidectomy in children. Therapy is staged according to the Fielding classification. We report the case of a 9-year-old female patient with Grisel's syndrome after otoplasty. The diagnosis was confirmed by CT scan. Manual reposition was performed under general anaesthesia, followed by temporary immobilization with a Minerva orthesis.

[Management and prognosis of patients with squamous cell carcinomas of the nasal cavity and the paranasal sinuses]. / Management und Prognose von Patienten mit Plattenepithelkarzinomen der Nasenhaupt- und Nasennebenhöhlen.

Squamous cell carcinomas (SCC) of the nasal cavity and the paranasal sinuses are a very rare and poorly understood tumor entity. To date, no consistent management strategy exists. The purpose of our study was to demonstrate our therapeutic strategy and to correlate clinicopathological features with clinical follow-up data.45 patients with primarily resected SCC of the nasal cavity (n=35) and the paranasal sinuses (n=10) between 1994 and 2010 were reviewed retrospectively (mean follow-up period 2.6 years; range 0.3 to 14.9 years).Tumors of the nasal cavity were diagnosed at an early stage (97% T1 and T2) whereas tumors of the parasinuses were found at an advanced stage (90% T3 and T4). Lymph node metastases were only found 2 patients. 13 patients (29%) had a local tumor progress, 2 patients showed lymph node metastases and 4 patients had distant metastases in follow up. The prognosis of tumors of the nasal cavitiy or the paranasal sinuses was bad (31% 5-year overall survival) especially by patients with a relapse.Reconstructive surgery was performed after 12 months, when early local relapse could be excluded. There was no positive correlation between clinicopathological features and survival data.The prognosis of tumors of the nasal cavity and paranasal sinuses depends mainly on the control of local tumor growth. Modern strategies of surgical treatment in combination with radiotherapy need to be implemented in an effort to achieve continuous tumor-free survival.

Role of molecular phonons and interfacial-temperature discontinuities in water evaporation.

During steady-state water evaporation, when the vapor phase is heated electrically, the temperature on the vapor side of the interface has been reported to be as much as 27.83 degrees C greater than that on the liquid side. The reported interfacial temperatures were measured with thermocouple beads that were less than 50 microm in diameter and centered 35 microm from the interface in each phase. We examine the reliability of these measurements by using them with a theory of kinetics to predict the interfacial-liquid temperature. The predicted temperature discontinuities are found to be in agreement with those measured up to a temperature discontinuity of 15.69 degrees C , but larger discontinuities cannot be confirmed because of uncertainties in the vapor-phase pressure measurements. The theory of kinetics used in the analysis includes molecular phonons in the expression for the evaporation flux. We show it is essential to include these terms if the theory is to be used to predict the temperature discontinuities.

[Repeated dual-probe pH monitoring as a diagnostic tool to control therapy for laryngopharyngeal reflux]. / Therapiekontrolle bei laryngopharyngealem Reflux durch wiederholte 2-Kanal-pH-Metrie.

OBJECTIVES: The most effective current treatment option for patients suffering from laryngopharyngeal reflux (LPR) is the use of proton pump inhibitors (PPIs). Compared to other PPIs, esomeprazole seems to provide best 24-h control of intragastric acid. However, some patients remain resistant to medical acid suppression with PPIs. The aim of this investigation was to identify the number of non-responders among patients suffering from LPR being treated by esomeprazole 40 mg once daily (officially approved maximum dosage). PATIENTS AND METHODS: Between June 2004 and January 2006, 27 patients suffering from LPR diagnosed by dual-probe pH monitoring were treated with esomeprazole 40 mg once daily. After 13-54 days (mean 28 days) while still under PPI-treatment, the 24-h pH-study was repeated in order to control the effectiveness of therapy. Patients with at least a reduction of the reflux area index (RAI) compared to the result before treatment were categorized as responders. Furthermore, the number of patients with a measurable reduction of proximal reflux episodes under PPI-treatment was quantified. RESULTS: Repeated pH monitoring during PPI therapy revealed a reduction of the RAI in 22 of 27 patients. Five patients, however, showed a higher RAI despite medical treatment (19%). In 13 patients (48%), treatment with 40 mg esomeprazole once daily reduced the RAI to a normal value (<6.3). In 18 of 27 patients, the number of proximal reflux episodes has decreased (67%). CONCLUSION: In a number of patients suffering from LPR, treatment with esomeprazole 40 mg once daily did not provide any measurable proximal acid reduction. Repeated pH monitoring during treatment is an adequate diagnostic tool to control the therapeutic effect of PPIs objectively and to identify non-responders at an early point.

Regioselectivity of a plant lauric acid omega hydroxylase. Omega hydroxylation of cis and trans unsaturated lauric acid analogs and epoxygenation of the terminal olefin by plant cytochrome P-450.

The study of the stereochemistry and regioselectivity of plant fatty acid hydroxylases is hampered by the difficulty to purify plant cytochrome P-450 enzymes. To provide an alternative, we have now defined an experimental plant system which expresses only one hydroxylase activity towards lauric acid: microsomes from clofibrate-induced Vicia sativa seedlings hydroxylate this fatty acid exclusively at the methyl terminus. To explore the catalytic capabilities of this laurate oxidase, a series of 1-14C-radiolabeled unsaturated lauric acid analogs (7-, 8-, 9-, 10- and 11-dodecenoic acids) were synthesized. Microsomes from clofibrate induced Vicia sativa seedling catalyzed the omega-oxidation of the lauric acid analogs in the presence of O2 and NADPH. The cis and trans forms of the four in-chain unsaturated analogs of lauric acid were 12-hydroxylated with similar efficiency. The terminal olefin was readily converted to the epoxide with only marginal autocatalytic inactivation of the enzyme. The formation of each metabolite was inhibited to the same extend when microsomes were incubated in presence of carbon monoxide or a suicide-substrate for omega LAH, suggesting that a single cytochrome P-450 isoenzyme from Vicia sativa microsomes is able to omega hydroxylate lauric acid and in-chain unsaturated analogs, and to epoxygenate 11-dodecenoic acid.

Methyl jasmonate induces lauric acid omega-hydroxylase activity and accumulation of CYP94A1 transcripts but does not affect epoxide hydrolase activities in vicia sativa seedlings

Treatment of etiolated Vicia sativa seedlings by the plant hormone methyl jasmonate (MetJA) led to an increase of cytochrome P450 content. Seedlings that were treated for 48 h in a 1 mM solution of MetJA stimulated omega-hydroxylation of 12:0 (lauric acid) 14-fold compared with the control (153 versus 11 pmol min-1 mg-1 protein, respectively). Induction was dose dependent. The increase of activity (2.7-fold) was already detectable after 3 h of treatment. Activity increased as a function of time and reached a steady level after 24 h. Northern-blot analysis revealed that the transcripts coding for CYP94A1, a fatty acid omega-hydroxylase, had already accumulated after 1 h of exposure to MetJA and was maximal between 3 and 6 h. Under the same conditions, a study of the enzymatic hydrolysis of 9,10-epoxystearic acid showed that both microsomal and soluble epoxide hydrolase activities were not affected by MetJA treatment.

Regulation of the Cinnamate 4-Hydroxylase (CYP73A1) in Jerusalem Artichoke Tubers in Response to Wounding and Chemical Treatments.

trans-Cinnamate 4-hydroxylase (C4H) is a plant-specific cytochrome (P450) that is encoded by the gene CYP73A and catalyzes the second step of the multibranched phenylpropanoid pathway. Increases in C4H activity in response to physical and chemical stresses have been well documented, but the mechanism of these increases has never been studied in detail. This paper reports on the regulatory mechanism controlling C4H activity in Jerusalem artichoke (Helianthus tuberosus) tubers in response to wounding and chemical treatments. We compared induction of C4H and other P450-catalyzed activities. C4H was moderately induced by chemicals relative to other P450s. Increases in enzyme activity, C4H protein, and transcripts were quantified and compared in tuber tissue 48 h after wounding and chemical treatments. Our data suggest that induction of the enzyme activity results primarily from gene activation. Time-course experiments were performed after wounding and aminopyrine treatment. Compared with wounded tissues, aminopyrine triggered an additional and delayed peak of transcript accumulation. The timing of the induced changes in activity, protein, and transcripts confirms that C4H induction results primarily from an increase in CYP73A1 mRNA, in both wounded and aminopyrine-treated tissues. However, posttranscriptional mechanisms might also contribute to the regulation of C4H activity.

[omega]-Hydroxylation of Oleic Acid in Vicia sativa Microsomes (Inhibition by Substrate Analogs and Inactivation by Terminal Acetylenes).

Oleic acid (18:1) is hydroxylated exclusively on the terminal methyl by a microsomal cytochrome P-450-dependent system ([omega]-OAH) from clofibrate-induced Vicia sativa L. (var minor) seedlings (F. Pinot, J.-P. Salaun, H. Bosch, A. Lesot, C. Mioskowski, F. Durst [1992] Biochem Biophys Res Commun 184: 183-193). This reaction was inactivated by two terminal acetylenes: (Z)-9-octadecen-17-ynoic acid (17-ODCYA) and the corresponding epoxide, (Z)-9,10-epoxyoctadecan-17-ynoic acid (17-EODCYA). Inactivation was mechanism-based, with an apparent binding constant of 21 and 32 [mu]M and half-lives of 16 and 19 min for 17-ODCYA and 17-EODCYA, respectively. We have investigated the participation of one or more [omega]-hydroxylase isoforms in the oxidation of fatty acids in this plant system. Lauric acid (12:0) is [omega]-hydroxylated by the cytochrome P-450 [omega]-hydroxylase [omega]-LAH (J.-P. Salaun, A. Simon, F. Durst [1986] Lipids 21: 776-779). Half-lives of [omega]-OAH and [omega]-LAH in the presence of 40 [mu]M 17-ODCYA were 23 and 41 min, respectively. Inhibition of oleic acid [omega]-hydroxylation was competitive with linoleic acid (18:2), but noncompetitive with lauric acid (12:0). In contrast, oleic acid did not inhibit [omega]-hydroxylation of lauric acid. Furthermore, 1-pentadecyltriazole inhibited [omega]-hydroxylation of oleic acid but not of lauric acid. These results suggest that distinct monooxygenases catalyze [omega]-hydroxylation of medium- and long-chain fatty acids in V. sativa microsomes.

Thermocapillary transport of energy during water evaporation.

When evaporation occurs at a spherical water-vapor interface maintained at the circular mouth of a small funnel, studies of the energy transport have indicated that thermal conduction alone does not provide enough energy to evaporate the liquid at the observed rate. If the Gibbs model of the interface is adopted and the "surface-thermal capacity" is assigned a value of 30.6+/-0.8 kJ/(m2 K), then for evaporation experiments with the interfacial temperature in the range -10 degrees C< or =TLV< or =3.5 degrees C and Marangoni number (Ma) in the range 100

Stereochemistry of oxidized fatty acids generated during catalytic oxygenation of lauric acid and unsaturated analogs by plant microsomes.

The capacity of microsomes from aminopyrine-induced Jerusalem artichoke (Helianthus tuberosus L.) to oxidize saturated and unsaturated fatty acids has been investigated using lauric acid and a series of unsaturated lauric acid analogs (7-, 8-, 9- and 10-dodecenoic acids) as radiolabeled substrates. In the presence of NADH, lauric acid was mono-hydroxylated principally at carbon 9. Steric analysis of this product showed a low enantiomeric excess of 28%. Mono-hydroxylated and mono-epoxidated reaction products were formed from the unsaturated analogs. The epoxidation/hydroxylation ratio was related to the position of the double bond in the aliphatic chain. The oxidation of 7-dodecenoic acid (7-DDNA) and 10-DDNA produced mainly 9-hydroxy-7-DDNA and 9-hydroxy-10-DDNA plus minor amounts of 7,8-epoxy- or 10,11-epoxylauric acid, respectively. In contrast, 8- and 9-DDNAs yielded essentially 8,9-epoxy- and 9,10-epoxylauric acids and smaller amounts of 10-hydroxy-9-DDNA and 8-hydroxy-9-DDNA, respectively. The optical purity and the absolute configuration of the major metabolites were investigated. Epoxidation of Z 8-DDNA and Z 9-DDNA occurs with high enantiomeric excesses. When the double bond was in the Z configuration, (8S,9R)/(8R,9S) 8,9-epoxylauric acid (93/7) or (9R,10S)/(9S,10R) 9,10-epoxylauric acid (89/11) were produced. In contrast, when the double bond was in the E configuration, steric analysis showed an enantiomeric ratio of 52/48 for E 8,9-epoxide and of 59/41 for E 9,10-epoxide. Z 7-DDNA led to the formation of 98% of the 9(S)-hydroxy-Z 7-DDNA enantiomer, while 9-hydroxy-Z 10-DDNA derived from Z 10-DDNA was 35% (R) and 65% (S).

Development of microsomal cytochrome P-450 monooxygenases during the last larval instar of the locust, Locusta migratoria: correlation with the hemolymph 20-hydroxyecdysone titer.

Several enzyme activities were measured in microsomes from Malpighian tubules and from fat body of the locust, Locusta migratoria, during the last larval instar and the 20-hydroxyecdysone titer was determined in the hemolymph. Ecdysone 20-monooxygenase, the cytochrome P-450 dependent monooxygenase which converts ecdysone to the active molting hormone 20-hydroxyecdysone had a low activity in the beginning of the instar, but showed a peak in both Malpighian tubules and fat body which coincided with the peak of 20-hydroxyecdysone in the hemolymph. The varying ratios of ecdysone and 20-hydroxyecdysone in L. migratoria hemolymph may therefore be accounted for by these changes in ecdysone 20-monooxygenase activity. The amounts of cytochrome P-450 and the activity of NADPH-cytochrome c reductase also showed a peak on day 5 of the instar, as did the activity of cytochrome P-450 linked lauric acid omega-hydroxylase in fat body microsomes. In larvae experimentally deprived of molting hormone, the activities of the cytochrome P-450 monooxygenases were low. The possible role of ecdysteroids in the control of developmental changes of cytochrome P-450 monooxygenases is discussed.

Assessment of spatial and temporal velocity profiles distal of normally functioning Björk-Shiley prosthesis by the Doppler method.

By Doppler echocardiography, the performance of heart valve prostheses is assessed with the aid of maximal transprosthetic velocities, which, however, may not be representative for the full spatial velocity profile in the vicinity of mechanical valve substitutes due to flow separation by the open occluder. The purpose of this study was to determine characteristics of velocity profiles downstream of a normally functioning Björk-Shiley prosthesis. In a pulsatile flow apparatus, different flow rates of 6.3 and 8.4 l/min were delivered. Using a spatially and temporally resolving ultrasonic Doppler method, velocity profiles 20 and 30 mm distal from the prosthesis were registered and displayed in a three-dimensional grid. The spatial velocity profile was found to deviate substantially from a flat profile at these transducer positions at the two flow conditions. Distal to the minor orifice, velocities measured only 70 and 80% of those downstream of the major orifice. In between, a region of relatively slow moving flow was present. The shape of the profiles remained essentially unchanged during acceleration and deceleration of flow. Thus, spatially resolved velocity profiles downstream of mechanical prostheses can be registered by an ultrasonic Doppler device. These findings may be useful for the detection of beginning malfunction both in the experimental and the clinical setting.

Reynolds stress under a change of frame of reference.

In this paper, we study the characteristics of the Reynolds stress under a change of frame, as defined by the Euclidean group of transformation. We show that being subject to the dynamical processes induced from the mean Navier-Stokes equations, the invariance group of the fluctuating velocity and the Reynolds stress is no longer the Euclidean group of transformation, which is merely a kinematical aspect, but reduces to the extended Galilean group of transformation. As a consequence, in contrast to developing the constitutive equations for the Cauchy stress in continuum mechanics, wherein the principle of material frame-indifference is a guiding principle, the frame-dependent kinematical quantities, e.g., the mean spin tensor, may be allowed to play an effective role as the constitutive variable in turbulence modeling.

Subterminal hydroxylation of lauric acid by microsomes from a marine fish.

Microsomes from the liver of sea bass (Dicentrarchus labrax) were shown to hydroxylate lauric acid at subterminal positions. The cytochrome P-450 system converted lauric acid to several mono-hydroxylated metabolites including omega-1 hydroxylaurate, which was the major metabolite (44% of total products). In addition, omega-2, omega-3, omega-4 and a small amount (2.3%) of omega hydroxylaurates were found. Reaction products were identified using thin-layer chromatography (TLC) and gas chromatography/mass spectrometry (GC/MS). Oxidation reactions were dependent upon O2 and NADPH, and did not occur with boiled microsomes or in the presence of a mixture of CO/O2. Hydroxylation proceeded linearly up to 20 min at 28 degrees C for protein concentrations below 380 micrograms. Treatment of fish with benzo(a)pyrene (BP) (20 mg/kg) drastically increased xenobiotic metabolism (ECOD, EROD and BPMO activities), but no difference in laurate hydroxylase activity was observed between untreated and treated fish. Starvation strongly enhanced laurate hydroxylase activity, and resumption of feeding reduced by half this increase of activity. In all of the experiments we did not observe any modification of the regioselectivity of lauric acid hydroxylation by this microsomal in-chain hydroxylating system. We suggest that cytochrome P-450 enzymes involved in lauric acid and xenobiotics metabolism are regulated independently.

Bi-directional flow sensor with a wide dynamic range for medical applications.

This paper describes a novel three-wire thermal flow sensor for medical applications. The present innovation for low-frequency measurements involves the use of a pulsed-wire anemometer with a comparatively large wire diameter (12.5 microm and larger) together with a novel signal processing approach. A small wire is heated using a sinusoidal alternating current, and two sensing wires, acting as resistance thermometers, are set parallel to, and at a small distance on either side of, the pulsed wire. The thermal wake of the pulsed wire is convected downstream to one of the two receiving wires which detect its delayed arrival. This arrangement allows the sensing of both the direction and the flow velocity component normal to the three probes. By appropriate signal processing, the present sensor can be operated such that the phase shift between the periodic current that drives the central wire and the detected signal by either the upstream or downstream wire takes into account a combination of convection, diffusion and the finite thermal response time of both the pulsed wire and the receiving wire. Because the time constants increase as the flow velocity decreases, the time lag due to thermal inertia supplements the time lag due to the true time of flight, thus yielding an effective operating range of 0.05 m/s

Plant cytochromes P450: an overview.

Cytochromes P450 from higher plants share many general characteristics with those from animals and microorganisms. There are now 20 known P450 gene families in plants, with the number rapidly increasing. Many of these enzymes catalyze reactions in the secondary metabolic pathways of higher plants. The sheer number of plant species and the variety of these many pathways together result in the diverse enzyme chemistry available from P450s in the plant kingdom. Highlights of recent findings and of the contents of this journal issue are summarized.

Xenobiotics: Substrates and inhibitors of the plant cytochrome P450.

The ability of a plant cytochrome P450 to bind and metabolise plant endogenous molecules and xenobiotics was investigated. The work was performed on the yeast-expressed CYP73A1, a cinnamate 4-hydroxylase isolated from Helianthus tuberosus. CYP73 controls the general phenylpropanoid pathway and is likely to be one of the most abundant sources of P450 in the biosphere. The enzyme shows a high selectivity toward plant secondary metabolites. Nevertheless, it oxygenates several small and planar xenobiotics with low efficiency, including an herbicide (chlorotoluron). One xenobiotic molecule, 2-naphthoic acid, is hydroxylated with an efficiency comparable to that of the physiological substrate. This reaction was used to devise a fluorimetric test for the rapid measurement of enzyme activity. A series of herbicidal molecules (hydroxybenzonitriles) are shown to bind the active site without being metabolised. These molecules behave as strong competitive inhibitors of CYP73 with a K(i) in the same micromolar range as the K(m) for the physiological substrate. It is proposed that their inhibition of the phenylpropanoid pathway reinforces their other phytotoxic effects at the level of the chloroplasts. All our results indicate a strong reciprocal interaction between plant P450s and xenobiotics.

The C-terminus of p63 contains multiple regulatory elements with different functions.

The transcription factor p63 is expressed as at least six different isoforms, of which two have been assigned critical biological roles within ectodermal development and skin stem cell biology on the one hand and supervision of the genetic stability of oocytes on the other hand. These two isoforms contain a C-terminal inhibitory domain that negatively regulates their transcriptional activity. This inhibitory domain contains two individual components: one that uses an internal binding mechanism to interact with and mask the transactivation domain and one that is based on sumoylation. We have carried out an extensive alanine scanning study to identify critical regions within the inhibitory domain. These experiments show that a stretch of ∼13 amino acids is crucial for the binding function. Further, investigation of transcriptional activity and the intracellular level of mutants that cannot be sumoylated suggests that sumoylation reduces the concentration of p63. We therefore propose that the inhibitory function of the C-terminal domain is in part due to direct inhibition of the transcriptional activity of the protein and in part due to indirect inhibition by controlling the concentration of p63.