Search

The aim of this randomized phase-II study was to evaluate the effect of substituting cytarabine by azacitidine in intensive induction therapy of patients with acute myeloid leukemia (AML). Patients were randomized to four induction schedules for two cycles: STANDARD (idarubicin, cytarabine, etoposide); and azacitidine given prior (PRIOR), concurrently (CONCURRENT), or after (AFTER) therapy with idarubicin and etoposide. Consolidation therapy consisted of allogeneic hematopoietic-cell transplantation or three courses of high-dose cytarabine followed by 2-year maintenance therapy with azacitidine in the azacitidine-arms. AML with CBFB-MYH11, RUNX1-RUNX1T1, mutated NPM1, and FLT3-ITD were excluded and accrued to genotype-specific trials. The primary end point was response to induction therapy. The statistical design was based on an optimal two-stage design applied for each arm separately. During the first stage, 104 patients (median age 62.6, range 18–82 years) were randomized; the study arms PRIOR and CONCURRENT were terminated early due to inefficacy. After randomization of 268 patients, all azacitidine-containing arms showed inferior response rates compared to STANDARD. Event-free and overall survival were significantly inferior in the azacitidine-containing arms compared to the standard arm (p< 0.001 and p= 0.03, respectively). The data from this trial do not support the substitution of cytarabine by azacitidine in intensive induction therapy.

Abstract:: We report results of a time resolved X-ray Absorption Spectroscopy (XAS) experiment on the oxidation process of epitaxial Y1(Nd0.05Ba1.95)Cu3Ox superconducting thin films. For the first time Cu K-edge XAS technique has been used to explore local structural changes around the Cu ions during the oxidation process of a high critical temperature superconducting film. The results show that during the oxygenation of a tetragonal Y1(Nd0.05Ba1.95)Cu3Ox additional local transitions appear in the orthorhombic I phase, which are not linked to long range order transformations as shown by in situ X-ray diffraction experiment. New questions concerning the dynamic microscopic process leading to the oxygenation and eventually to superconductivity of the complex R1+xBa2-xCu3Ox (R = Y or rare earth) compounds arose from these results.

The widely studied macrophage scavenger receptor system is known to bind both acetylated low density lipoprotein and oxidized low density lipoprotein. Although only the latter ligand has been shown to occur in vivo, acetylated low density lipoprotein is often used to evaluate the contribution of scavenger receptors to different (patho)physiologic processes, assuming that all existing subtypes of scavenger receptors recognise both lipoproteins. In the present work, we identify human platelets as the first natural cell type to bind oxidized low density lipoprotein without showing specificity for acetylated low density lipoprotein. Consequently, platelets possess exclusive receptor(s) for oxidized low density lipoprotein distinct from the ‘classical’ scavenger receptor AI/AII. From the data presented in this work, we conclude that the class B scavenger receptor CD36 (GPIV) is responsible for this exclusive oxidized low density lipoprotein binding.

Flux flow instabilities at high current densities have been recently reported to occur in high temperature superconductors. Such flux flow instabilities were already predicted by Larkin and Ovchinnikov. However, other mechanisms may possibly also account for this behaviour, as for instance hot spots or thermal instabilities. To investigate the mechanism at the origin of these instabilities, we have carried out detailed I- V experiments, using short current pulses, on YBCO thin films grown on sapphire substrates. When the current density exceeds 2-3 times the conventional critical current density, we observe an extremely fast transition from a low dissipative state into a highly dissipative state. We present some indications that this transition does not originate from temperature instabilities but is driven by the current.

Type VI collagen is a transformation‐sensitive glycoprotein of the extracellular matrix of fibroblasts. We have isolated and sequenced several overlapping cDNA clones (4153 bp) which encode the entire alpha 2 subunit of chicken type VI collagen. The deduced amino acid sequence predicts that the alpha 2(VI) polypeptide consists of 1015 amino acid residues that are arranged in four domains: a hydrophobic signal peptide of 20 residues, an amino‐terminal globular domain of 228 residues, a collagenous segment of 335 residues and a carboxy‐terminal globular domain of 432 residues. The collagenous domain contains seven Arg‐Gly‐Asp tripeptide units, some of which are likely to be used as cell‐binding sites. The globular domains contain three homologous repeats with an average length of 180 amino acid residues. These repeats show a striking similarity to the collagen‐binding motifs found in von Willebrand factor and cartilage matrix protein. We therefore speculate that the globular domains of the alpha 2(VI) polypeptide may interact with collagenous structures.

In an experiment with the 30-inch Hybrid Spectrometer at Fermilab we have obtained the inclusive and semi-inclusive production cross sections of the ϱ0 meson using a conventional background subtraction technique. Production cross sections for the ϱ0 are derived as a function of the Feynman scaling variablex, and the transverse variablespt2 andEt=(pt2+M2)1/2. The longitudinal distributions are compared with the (1−x) dependence of the proton and meson valence quark structure functions, using various forms of recombination and fragmentation models. The transverse distributions are compared with thermodynamic models. We give density matrix elements for the ϱ0 production from pions in the extreme forward region.

The ratio of hadronic p+/p- production has been studied in the target fragmentation region of p+p, p-p,K+p andp p collisions at 147 GeV/c beam momentum. The difference between this ratio in the p+p and p-p data is less than at lower energies but still present. No difference exists anymore for the p+/p- ratio at this energy betweenK+p andpp collisions. Exclusion of diffraction dissociation and resonance production does not change the main conclusions. The energy dependence of the ratio for p+p and p-p collisions gives evidence for a universal asymptotic ratio for all beams. Thept-dependence at low-pt is in agreement with the expectation from geometrical correlation of the valence quarks.

Megestrol acetate (MA) is a progestational agent that has been used in the management of AIDS cachexia and several types of hormone-dependent cancers. An increasing number of reports have suggested that the drug also has corticosteroid effects. Specifically, adrenal suppression, impairment of glucose tolerance, and Cushing's syndrome have been observed. The severity of symptoms appears to correlate with integrated drug exposure (dose × duration). These findings are supported by in vitro binding studies and prolonged dosing studies in cats as well as by similar clinical findings with the related compound, medroxyprogesterone acetate. Because the clinical presentation may be insidious, and because patients receiving MA often are those with advanced disease, the iatrogenic association may not be recognized. Clinicians need to be aware of the potential for adrenal insufficiency in patients receiving or withdrawing from megestrol because these complications may be life-threatening.

The PML/RARa fusion RNA can be detected in acute promyelocytic leukemia (APL), cytogenetically characterized by the translocation t(15; 17). Our study included ten newly diagnosed patients with APL who were investigated during the course of their diseases using reverse transcription polymerase chain reaction (RT-PCR). At diagnosis, aberrant fragments with a size heterogeneity due to alternative spliced products were detected in all patients, we observed breakpoints within bcr3 (short type) in two patients and bcr1 and 2 breakpoints (long type) in eight patients. Treatment consisted of all-trans retinoic acid (ATRA) in all patients; six patients received simultaneous cytostatic therapy during remission induction. At the time of complete hematological remission (CR), only two patients showed a negative RT-PCR result; eight of the ten patients were still PCR positive when nested primers were used. Subsequently, eight patients received consolidation chemotherapy and became PCR negative. Seven of eight patients are in continuous complete remission (median remission duration: 21 months, range: 11+-26+ months). One patient of the chemotherapy group became PCR positive after 4 months in complete remission and relapsed after 6 months. The remaining two patients who were treated only with ATRA relapsed, received induction chemotherapy, and are in second and third complete remission, respectively. In conclusion, PCR negativity can be achieved only by chemotherapeutic consolidation; patients treated with ATRA alone remain PCR positive. Relapse is always preceded by a positive PCR result. Surprisingly, also patients without measurable PML/ RARa-mRNA in sequential analyses after cytostatic treatment became PCR positive and experienced relapse.

The study was carried out on ten triathletes, six sprinters and ten subjects not trained in running (controls) to assess the effects of training history on the co-ordination between breathing and running rhythms during running on a treadmill. Three exercise intensities were used: 50%, 80% and 110% of the subject's anaerobic threshold (AT). All three intensities were performed twice: once with spontaneous breathing and once with breathing intentionally co-ordinated to the running rhythm. Heart rate, respiratory parameters and leg movements were continuously recorded. Blood lactate concentrations were measured discontinuously. The degree of co-ordination between running and breathing was quantified as the percentage of inspirations and/or expirations starting during the same phase of step. The results showed that the degree of both spontaneous and intended co-ordination at aerobic exercise intensities was in all three groups the same and increased in all groups with increasing intensity from 50% to 80% of AT; further increase of intensity to 110% of AT was associated with a significant decrease of co-ordination in controls and sprinters, whereas triathletes were able to maintain the same high degree of co-ordination as at 80% of AT. It was concluded that running training of either type at aerobic work loads had no effect on the co-ordination between running and breathing rhythms. At anaerobic intensities, however, the degree of co-ordination between running and breathing rhythms was higher in the endurance trained athletes than in the sprinters or in the untrained subjects. The degree of co-ordination increased with increasing regularity of breathing. The ability to increase intentionally the degree of co-ordination by paced breathing was independent of running training and was lowest at anaerobic exercise intensities.

Summary The functional characteristics at rest in responding to stepwise acute exposure to simulated altitude (6000 m) were compared in 10 acclimatized mountaineers (highlanders), residents of Zermatt (1616 m) working at an altitude up to about 4000 m, and in 11 nonacclimatized control subjects (lowlanders) living and working in Zurich (450 m). In comparison with the lowlanders, the highlanders showed at altitude significantly greater hyperventilation, lower heart rate and systolic blood pressure, smaller haemoconcentration, lower urodilatin secretion and natriuresis, and a preserved neuropsychological ability (attentiveness) and vasomotor tone (diastolic blood pressure); the critical altitude at which hypoxic short-term adaptation became insufficient was 6000 m. The lowlanders, however, manifested reduced tolerance of hypoxia, i.e. insufficient short-term adjustment with subjective and objective distress coinciding with the first signs of hypoxia of the central nervous system, already apparent at and above 4000 m. It was concluded that the functional differences between highlanders and lowlanders in responding to acute gradual hypoxia indicated factors contributing to altitude acclimatization.

Diuresis at altitude was thought to be the result of chemoreceptor stimulation leading to a reduction of cardiac volume overload. This hypothesis was tested in ten young, healthy subjects by infusion of almitrine (0.5 mg · kg-1 body mass within 30 min) assuming analogous sites of action, i.e. arterial chemoreceptors and pulmonary vessels, for almitrine as for hypoxic hypoxia. The results show that almitrine increases ventilation, heart rate, systolic blood pressure, central venous pressure and natriuresis, but fails to increase significantly atrial natriuretic peptide plasma concentration and diuresis. It is concluded: (1) that almitrine has similar sites of action as hypoxic hypoxia at about 5000 m, (2) that natriuresis during arterial chemoreceptor stimulation might reduce cardiac volume overload, (3) that the volume excretion hypothesis, in particular the pathways from the cardiac volume overload to the water diuresis, need, for an understanding of the hypoxia-induced diuresis, further direct investigations at altitude.

Respiratory, circulatory and neuropsychological responses to stepwise, acute exposure at rest to simulated altitude (6,000 m) were compared in ten acclimatized recumbent mountaineers 24 days, SD 11 after descending from Himalayan altitudes of at least 4,000 m with those found in ten non-acclimatized recumbent volunteers. The results showed that hypoxic hyperpnoea and O2 consumption at high altitudes were significantly lower in the mountaineers, their alveolar gases being, however, similar to those of the control group. In the acclimatized subjects the activation of the cardiovascular system was less marked, systolic blood pressure, pulse pressure, heart rate and thus (calculated) cardiac output being always lower than in the controls; diastolic blood pressure and peripheral vascular resistance, however, were maintained throughout in contrast to the vasomotor depression induced by central hypoxia which occurred in the non-acclimatized subjects at and above 4,000 m [alveolar partial pressure of O2 < 55–50 mmHg (7.3–6.6 kPa)]. It was concluded that in the acclimatized subjects at high altitude arterial vasodilatation and neurobehavioural impairment, which in the non-acclimatized subjects reflect hypoxia of the central nervous system, were prevented; that acclimatization to high altitude resulted in a significant improvement of respiratory efficiency and cardiac economy, and that maintaining diastolic blood pressure (arterial resistance) at and above 4,000 m may represent a useful criterion for assessing hypoxia acclimatization.

As a result of our recently published studies we have thought that altitude diuresis resulting from hypoxic stimulation of the arterial chemoreceptors reduces the cardiac volume overload. To test this hypothesis, cardiovascular, endocrine and renal responses to stepwise acute exposure to simulated altitude (6,000 m) were compared in ten acclimatized recumbent mountaineers a mean of 24 days, SD 11, after descending from Himalayan altitudes of at least 4,000 m, with those found in ten non-acclimatized recumbent volunteers. The results showed that natriuresis and diuresis typified the renal responses to altitude exposure of both the acclimatized as well as non-acclimatized subjects, as long as altitude was well tolerated. It was concluded that the renal effects were mediated by atrial natriuretic peptide release and slight suppression of arginine-vasopressin (AVP) secretion, that the increased urine flow at altitude offset the cardiac (volume) overload resulting from hypoxic stimulation of the arterial chemoreceptors, and that enhanced AVP secretion, as found in the non-acclimatized subjects at and above 4,000 m, coincided with subjective and objective distress, i.e. with inadequate altitude adjustment owing to insufficient chemoreflex effects and central hypoxia.

Summary: The relationship between pedalling- and breathing rhythm was studied in 34 medical students (“non-cyclists”) and 10 racing cyclists on an electromagnetic bicycle-ergometer, the effective work load of which (50 W, 100 W, 150 W, 200 W) was independent of the pedalling rate. The criteria used were integer p/b ratios (pedalling rate being a multiple of breathing frequency) and phase coupling (the breathing phases starting preferentially at a certain angle of the pedalling cycle). Unconsciously occurring coordination of pedalling and breathing rhythm was found in the majority of the test persons; 70%–100% of the racing cyclists, 50%–63% of the regularly breathing and 25%–33% of the irregularly breathing non-cyclists showed integer p/b ratios. This tendency decreased with increasing work load. Phase coupling was even more frequent than integer p/b ratios and was not affected by increasing work load. The majority of racing cyclists (unlike the non-cyclists) coupled the inspiration-onset with the onset of either the left or the right leg movement. Expiratory phase coupling, however, was analogous in all groups; expiration began preferentially at mid-contraction of either leg. The results are discussed in terms of relative (nervous) coordination. It is concluded that the tendency to coordination between pedalling- and breathing rhythm increases with pedalling training and with regularity of breathing.

The role of the sympatho-adrenal system in the acute respiratory and cardiovascular responses to high altitude was studied in 20 volunteers during ascent to 6,000 m in a low pressure chamber, once without (control) and once with beta-adrenergic blockade. Special attention was paid to the hypoxia-induced ECG changes. Propranolol lowered the level of hypoxia-induced cardiovascular reactions, whereas it had no effect on hypoxic hyperventilation and alveolar gases. At altitude, ECG changes during myocardial depolarization occurred in both the propranolol and the control groups, probably due to the direct effects of hypoxia. During the repolarization phase, propranolol led to an almost complete abolition of S-T depression and to significant reduction of T wave flattening. The minor but still significant flattening of the T wave as well as the relative (to the heart rate) lengthening of Q-T is probably due to the direct effects of hypoxia. Propranolol abolishes or diminishes the signs of cardiac hypoxia by antagonizing the effects of catecholamine release and/or by reducing myocardial oxygen consumption, thus probably increasing the ability to withstand oxygen-want at altitude.

Changes of whole-body microvibrations (MV) were quantitatively analyzed in 123 voluntary subjects during two examination situations and compared with the results obtained during the ensuing vacation. The force oscillations in the three space directions were measured during quiet bipedal standing and simultaneously recorded as a time function with the rectified and integrated force-time function (= rectified impulse). The rectified impulses related to body weight were used as a measure for the MV.

The effects of the lipid-peroxidation product 4-hydroxynonenal on the formation of fluorescent chromolipids from microsomes, mitochondria and phospholipids were studied. Incubation of freshly prepared rat liver microsomes or mitochondria with 4-hydroxynonenal results in a slow formation of a fluorophore with an excitation maximum at 360 nm and an emission maximum at 430 nm. The rate and extent of the development of the 430 nm fluorescence can be significantly enhanced by ADP-iron (Fe3+). With microsomes, yet not with mitochondria. NADPH has a catalytic effect similar to that of ADP-iron. Fluorescent chromolipids with maximum excitation and emission at 360/430 nm are also formed during the NADPH-linked ADP-iron-stimulated lipid peroxidation. Phosphatidylethanolamine and phosphatidylserine react with 4-hydroxynonenal revealing a fluorophore with the same spectral characteristics as that obtained in the microsomal and mitochondrial system. The findings suggest that the fluorescent chromolipids formed by lipid peroxidation are not derived from malonaldehyde, but are formed from 4-hydroxynonenal or similar reactive aldehydes via a NADPH and/or ADP-iron-catalysed reaction with phosphatidylethanolamine and phosphatidylserine contained in the membrane.

In anaesthetized, thoracotomized and artificially ventilated rabbits, the location of pulmonary stretch receptors (SR) was established by means of local mechanical stimulation as well as by micro-injections of the local anaesthetic cinchocaine. Differences in SR activity were analyzed in relation to the receptor site during specific stimulation by lung inflation, as well as during nonspecific activation by ammonia inhalation.

Type VI collagen is a transformation‐sensitive glycoprotein of the extracellular matrix of fibroblasts. We have isolated and sequenced several overlapping cDNA clones (4153 bp) which encode the entire alpha 2 subunit of chicken type VI collagen. The deduced amino acid sequence predicts that the alpha 2(VI) polypeptide consists of 1015 amino acid residues that are arranged in four domains: a hydrophobic signal peptide of 20 residues, an amino‐terminal globular domain of 228 residues, a collagenous segment of 335 residues and a carboxy‐terminal globular domain of 432 residues. The collagenous domain contains seven Arg‐Gly‐Asp tripeptide units, some of which are likely to be used as cell‐binding sites. The globular domains contain three homologous repeats with an average length of 180 amino acid residues. These repeats show a striking similarity to the collagen‐binding motifs found in von Willebrand factor and cartilage matrix protein. We therefore speculate that the globular domains of the alpha 2(VI) polypeptide may interact with collagenous structures.

The influence of cardiac activity on the endogenous microvibrations of the body (MV) was studied in a total of 37 young, healthy subjects. The force oscillations and the rectified and integrated force-time function in the three space directions were simultaneously recorded with the ECG and the arterial pulse during quiet bipedal standing before (control) and after isoprenaline inhalation, a work load of 150 W, and mild cold stress.

Summary: Whole-body microvibrations (MV) in three dimensions were measured in 51 volunteers, all medical students, 26 without and 25 with beta-receptor blockade (propranolol), immediately before a practical physiology examination and during the ensuing vacation. Propranolol impeded the increase in MV values in all three axes, significantly those in the z axis (vertical), the differences in MV values between the two measurements being minimal in the beta-receptor blocked group. On the other hand, propranolol enhanced MV in the x axis (anteroposterior) and the y axis (transverse), the y axis difference being significant only in females. Propranolol obviously relieves examination stress: the majority of candidates (52%) felt “quieter≓ in the examination with than in other similar situations without beta-receptor blockade. Propranolol was, however, without effect on the examination results. The rectified impulse in the z axis when related to body weight (Jz) correlates linearly with the calculated cardiac output. Propranolol, however, reduced cardiac output more than Jz, pointing to a Jz component non-sensitive to beta-receptor blockade. The part played by muscle tonus, mainly reflected in the y axis, thus remains unknown. The large and slow oscillations in the x and y axes, observed particularly in beta-receptor blocked females, might be attributed to diminution in standing ability.

The influence of the degree of coupling between the breathing and cycling rhythms (K) on oxygen uptake was examined in 30 volunteers. They cycled on an ergometer with a load equal to 50% of their work capacity 170 in two experimental runs with spontaneous breathing rhythm, and in a further two runs with acoustically triggered breathing. K was continuously ascertained. and other respiratory parameters were measured by an automatic “breath-by-breath analysis” system.

In order to anlayse the respiratory, cardiovascular, and ECG responses to acute hypoxic hypoxia, three experimental series were carried out in a randomized manner on 11 healthy, unacclimatized volunteers at rest during standardized stepwise exposure to 6000 m (PAO2 35.2±2.9 mmHg/4.7±0.4 kPa) in a low-pressure chamber a) without (control), b) with propranolol, and c) with atropine combined with propranolol. The results, show that hypoxic hyperventilation and alveolar gases are not affected by activation of the sympatho-adrenal axis or by parasympathetic withdrawal. Sympathetic activity, however, increases heart rate, stroke volume (pulse pressure), estimated cardiac output and systolic blood pressure, whereas decreased parasympathetic activity increases heart rate and estimated cardiac output, but lowers stroke volume. The fall in peripheral resistance, observed during progressive hypoxia in all three groups, is thought to be due to hypoxia-induced depression of the vasomotor center. At altitude catecholamine secretion and vagal withdrawal synergistically account in the ECG for the R-R shortening, the relative Q-T lengthening, the elevation of the P wave and the ST-T flattening. Probable direct hypoxic effects on the heart are the increase in P-Q duration and the minor but still significant depression of the T wave. It is concluded that at altitude increased sympatho-adrenal and decreased parasympathetic activity is without effect on hypoxic hyperventilation, but accounts for most of the cardiovascular and ECG changes. Diminution of sympathetic activity and imminent vagotonia arising after acute ascent to 6000 m probably reflect hypoxia of the central nervous system.

In order to distinguish the effects of beta-receptor stimulation on the ECG from other factors during short-term adjustment to hypoxic aerohypoxia, the ECG of 19 volunteers were compared during moderately acute, stepwise exposure to high altitude (6,000 m) in a low pressure chamber, once with and once without beta-receptor blockade (propranolol), and after isoprenaline inhalation at ground level. The results show that beta-receptor stimulation accounts mainly for most ECG changes during altitude exposure, i.e., for the shortening of R-R interval, the lengthening of Q-T and in particular for the ST-T flattening, the latter therefore being only an indirect sign of hypoxia. After exclusion of the catecholamines, the minor but still significant ECG changes at altitude (shortening of R-R interval, increase of P wave, prolongation of P-Q, deviation of the R vector, T wave flattening in the left precordial leads) may be attributed to other, so far undefined factors, such as cardiac hypoxia, vagal withdrawal, or increase of pulmonary resistance.

The contribution presents the state of the art in Nuclear Magnetic Resonance (NMR) — applications developed in our institute in the last two years. We have started our investigations using spectral information for the determination of aging states of different commercial prepreg materialsOur NMR-system is a Broker MSL 400 solid state spectrometer with magic angle spinning device (MAS) and with micro imaging facilities which allow in a first step only the imaging of biological tissues. The system (superconducting coil) works with 9.4 T magnetic field corresponding to a resonance frequency of 400 MHz for 'H nucleus spins. The magnetic field gradient for imaging has a maximum strength of 70 G/cmIn order to optimize the system for solid state imaging applications different techniques were implimented. Beside the well known Fourier-Transform-Imaging-algorithm with frequency and phase information, a back-projection-algorithm and a Fourier-Transform-Imaging-algorithm using only phase information now are available which are more reliable for solid state imaging. All of these algorithms can be combined with special designed pulse sequences for the determination of the relaxation times and to reduce and decouple the dipole-dipole-interactions. By using these parameters the distribution of the spin density and the molecular mobility in a polymer can be determinedFor elastomeric materials the inhomogeneity of the crosslink density and aging processes (e.g. oxidation) result in a change of molecular mobility. These effects can be determined in a quantitative manner and spatially resolved by using NMR-imaging techniquesAlso the resistivity of polymers (elastomers, thermoplastics, biopolymers) against water or organic solvents (fuels, engine oil, etc.) can be characterized nondestructively by measuring the content and the diffusion velocity of the swelling liquid. The nondestructive characterization of changes in the molecular mobility of the polymer is also possible during swelling, which result in a decrease of the impact strength of the polymer. Measuring the Relaxation time T2 in fibre reinforced composites the aging state of duroplastic prepregs can be characterized.

To test whether glycosyl phosphatidylinositol-linked T-cadherin is a component of cell junctions like classical cadherins, we have examined its distribution and targeting in polarized epithelial cells. In vivo, T-cadherin was detected on the apical cell surface of the chick intestinal epithelium. In cultures of transfected Madin-Darby canine kidney cells, T-cadherin was also expressed apically, whereas classical N-cadherin resided basolaterally. Both cadherins were directly targeted to their respective membrane domains. Mutant proteins were expressed in Madin-Darby canine kidney cells to identify the regions responsible for differential cadherin localization. NDeltacyt, an N-cadherin cytoplasmic domain deletion mutant, was stably distributed basolaterally. This mutant was transported to both the apical and basolateral membrane compartments, followed by preferential removal from the apical surface. T-NDeltacyt, a T-cadherin mutant with the N-cadherin cytoplasmic domain deletion, was localized basolaterally, whereas N-TGPI, a GPI-anchored N-cadherin mutant, resided at the apical domain. The T-cadherin carboxyl-terminal 76 amino acids contain the apical targeting signal and include the signal for GPI anchor attachment. Basolateral localization of N-cadherin is achieved through targeting signals in the cytoplasmic domain. Thus, GPI-linked T-cadherin is not a component of cell junctions, consistent with a function as a recognition rather than a cell adhesion molecule.

The ageing of prepregs of and fiber reinforced duroplastic polymers (glassfiber and carbonfiber reinforced polymers; GFRP and CFRP) during storage before manufacturing and during the manufacturing process at elevated temperatures is an essential technical problem. The resulting mechanical properties of cured components are strongly influenced by the ageing state of the prepregs. Nondestructive techniques up to now are unsufficient or time consuming. Nuclear magnetic resonance (NMR) techniques have been well known for 40 years and applied in analytical chemistry in order to characterize the microstructure and binding state of organic chemical compounds in fluid states. In medical diagnostics NMR-imaging is used for tissue characterization. Publications on solid state NMR-imaging are rare in technical literature because of the fact that the strong spin-spin-interaction in solids results in a broadening of the spectral lines, i.e., very short transversal relaxation times, T2 (some μs), compared to fluids (up to some 100 ms). Therefore special electronics are needed in order to produce short pulses and to switch the gradient fields in short time periods.The emphasis of the following contribution will be on the presentation of first results on the application of NMR techniques at prepegs in order to characterize the crosslink state after exposition at room and elevated (50°C) temperature. The results correlate with results of destructive tests and document the potential of NMR as a NDT tool. The experiments were performed with a MSL-400 Bruker NMR-spectrometer and micro-imaging system which works at 400 MHz (1H resonance frequency at a magnetic field of 9.4 T).

During apneic periods elicited by high-frequency oscillatory ventilation (HFOV) a tonic diaphragmatic activity was observed, contrasting with the absence of diaphragmatic activity during apnea induced by lung inflation. To clarify the mechanism underlying the persistence of the diaphragmatic activity during HFOV-induced arrest of breathing the reflex responses to short periods of HFOV, and to periods of lung inflation with airway pressure (Paw) equal to the meanPaw and/or to maximalPaw during HFOV were examined both before and after the blockade of slowly adapting stretch receptors (SR) by inhalation of sulphur dioxide (SO2) in anaesthetized rabbits. In animals with intact SR, the HFOV-induced reflex apnea lasted longer than that induced by lung inflation, the associated diaphragmatic activity being in the most cases higher than the diaphragmatic activity during quiet expiration; inflation, however, completely inhibited diaphragmatic activity. After blockade of SR, spontaneous breathing continued during periods of lung inflation, i.e., the Hering-Breuer inflation reflex was abolished, whereas HFOV still led to a cessation of spontaneous breathing, the associated diaphragmatic activity even exceeding the level observed during quiet inspiration. From these results we conclude that only one part of the reflex response to HFOV is due to SR-stimulation and that in addition other vagal pulmonary receptors (irritant-and/or C-fibre-receptors) are involved. The stimulation of the latter counterbalances the concomitant stimulation of SR, giving rise to the tonic activity of the diaphragm.

In anaesthetized rabbits the effects of high frequency ventilation (HFV) on breathing pattern and on stretch receptor (SR) activity were examined in order to elucidate the mechanism underlying the inhibition of respiration during HFV. An attempt was undertaken to compare the effects of HFV with those of static lung inflations.

The contribution of pulmonary stretch receptor (SR) activity to the changes in breathing pattern (f,VT,tI,tE,tI:tE) following inhalation of ammonia vapour has been studied in rabbits at three levels of lung distension, i.e., three levels of SR activity, and during reversible SO2-blockade of SR.

The activity in single vagal fibres arising from lung stretch receptors was recorded in rabbits during normal breathing at rest and during tachypnoea caused by inhalation of histamine or ammonia. The rate of argon elimination from the lungs was analysed to estimate the accompanying changes of lung ventilation.

We report on the epitaxial growth of BaCuO2 infinite layer (stabilised with CO3 groups) thin films by rf magnetron sputtering on (100) SrTiO3 and (100) LaAlO3. Excellent (001) films with c~4Å are obtained at 540 °C in a sputtering atmosphere of 1–10 mTorr of Ar+O2 with some addition of CO2. Off axis x-ray analysis reveal perfect in plane ordering and a tetragonal structure with a=b~3.96 Å. For these deposition conditions the resistivity at room temperature is of the order of several Ocm and exhibits a strong semiconductor-like behaviour. When the deposition temperature is increased to 660 °C, a supercell along the c axis appears with a period of about 8Å. After an in-situ annealing of these films in 7 Torr of oxygen at 500 °C, ?(300K) falls to 800µOcm. The resistance versus temperature curve reveals then a metallic behaviour and a superconducting transitions with onsets between 10–40K.

As reported previously, homologous plasma lipoproteins specifically bind to the plasma membrane of human blood platelets. The two major lipoprotein-binding membrane glycoproteins were purified to apparent homogeneity and identified by their mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, both in the nonreduced and reduced state, by specific antibodies against glycoproteins IIb (GPIIb) and IIIa (GPIIIa), respectively, including the alloantibody anti-PlA1and monoclonal antibodies. Furthermore, lipoprotein binding to intact platelets is also inhibited in a dose-dependent fashion by preincubation of the platelets with antibodies against these glycoproteins. From these experiments it can be concluded that lipoproteins bind to both components of the glycoprotein IIb-IIIa complex in isolated membranes and intact platelets.

The correlation between pulmonary stretch receptor activity and inspiration-expiration duration quotient, as well as respiratory frequency (Hering-Breuer relfexes) has been established before and during an asthma attack in the guinea-pig

We have studied the reactionspp?ppp+p-,K+p?K+pp+p-p, p+p? p+,pp+p- and p-p ?p+p- at 147 GeV/c using the 30-inch Fermilab hybrid system. All four reactions were detected with the same apparatus and analyzed in the same way. The energy dependence of the channel cross section was found to beAp-0.6+B for thepp reaction andAp-1+B for the other three. About 90% of the cross section at 147 GeV/c can be accounted for by either beam or target diffraction. Some of the remaining cross section may come from double Pomeron exchange reactions which we tried to isolate. We have tested the hypothesis of a factorizable Pomeron and our data indicates a violation of this hypothesis. We show that the 3p mass enhancement in the mass region 1.2–1.4 GeV is diffractively produced in the p± beam reactions. Fourprong, four-constraint and six-prong, four-constraint cross sections are reported.

The gross features of the data are reviewed and the momentum tensor components, , and are studied. Evidence for coplanarity effects is observed. A probabilistic method to search for jets is proposed. The jets found by this method are seen to be similar to highpT jets frompp interactionse+e- annihilations andvp interactions. The effect of subtracting the leading particles and the effect of lowpT diffractive and non diffractive components are investigated.