Effect of 13-cis violaxanthin on organization of light harvesting complex II in monomolecular layers.

Lutein, neoxanthin and violaxanthin are the main xanthophyll pigment constituents of the largest light-harvesting pigment-protein complex of photosystem II (LHCII). High performance liquid chromatography analysis revealed photoisomerization of LHCII-bound violaxanthin from the conformation all-trans to the conformation 13-cis and 9-cis. Maximally, the conversion of 15% of all-trans violaxanthin to a cis form could be achieved owing to the light-driven reactions. The reactions were dark-reversible. The all-trans to cis isomerization was found to be driven by blue light, absorbed by chlorophylls and carotenoids, as well as by red light, absorbed exclusively by chlorophyll pigments. This suggests that the photoisomerization is a carotenoid triplet-sensitized reaction. The monomolecular layer technique was applied to study the effect of the 13-cis conformer of violaxanthin and its de-epoxidized form, zeaxanthin, on the organization of LHCII as compared to the all-trans stereoisomers. The specific molecular areas of LHCII in the two-component system composed of protein and exogenous 13-cis violaxanthin or 13-cis zeaxanthin show overadditivity, which is an indication of the xanthophyll-induced disassembly of the aggregated forms of the protein. Such an effect was not observed in the monomolecular layers of LHCII containing all-trans conformers of violaxanthin and zeaxanthin. 77 K chlorophyll a fluorescence emission spectra recorded from the Langmuir-Blodgett (L-B) films deposited to quartz from monomolecular layers formed with LHCII and LHCII in the two-component systems with all-trans and 13-cis isomers of violaxanthin and zeaxanthin revealed opposite effects of both conformers on the aggregation of the protein. The cis isomers of both xanthophylls were found to decrease the aggregation level of LHCII and the all-trans isomers increased the aggregation level. The calculated efficiency of excitation energy transfer to chlorophyll a from violaxanthin assumed to remain in two steric conformations was analyzed on the basis of the chlorophyll a fluorescence excitation spectra and the mean orientation of violaxanthin molecules in LHCII (71 degrees with respect to the normal to the membrane), determined recently in the linear dichroism experiments [Gruszecki et al., Biochim. Biophys. Acta 1412 (1999) 173-183]. The calculated efficiency of excitation energy transfer from the violaxanthin pool assumed to remain in conformation all-trans was found to be almost independent on the orientation angle within a variability range. In contrast the calculated efficiency of energy transfer from the form cis was found to be strongly dependent on the orientation and varied between 1.0 (at 67.48 degrees ) and 0 (at 70.89 degrees ). This is consistent with two essentially different, possible functions of the cis forms of violaxanthin: as a highly efficient excitation donor (and possibly energy transmitter between other chromophores) or purely as a LHCII structure modifier.

Nucleotide sequences flanking dinucleotide microsatellites in the human, mouse and Drosophila genomes.

We extracted nucleotide sequences from the EMBL database that flank dinucleotide microsatellites in the long sequenced parts of the human, mouse and drosophila genomes. Comparison of the flanking sequences showed that the microsatellites were mostly connected to the bulk of genomic DNA through conserved, highly non-random and mostly (A+T)-rich sequences having many dozens of nucleotides in length. In many cases, the connectors were mutated versions of the flanked microsatellites whose sequence pattern gradually vanished with the distance from the microsatellite center. Hence many microsatellites have hundreds rather than dozens of nucleotides in length, and their ends are diffuse. In contrast, some microsatellites containing predominantly C and/or G, did not influence their neighborhood at all. These results make us change notions about the microsatellite nature. They also indicate that the microsatellites are the dominant part of eukaryotic genomes.

Xanthophyll pigments in light-harvesting complex II in monomolecular layers: localisation, energy transfer and orientation

Monomolecular layers of the largest light-harvesting pigment-protein complex of Photosystem II (LHCII) were formed at the argon-water interface. The molecular area of the LHCII monomer in monomolecular layers determined from the isotherms of compression is found to be close to 14 nm2, which corresponds well to the molecular dimensions of the protein evaluated on the basis of crystallographic studies. Monolayers of LHCII were deposited on a glass support by means of the Langmuir-Blodgett technique and subjected to spectroscopic studies: electronic absorption spectrophotometry and spectrofluorometry. The fluorescence excitation spectra of chlorophyll a in monolayers of LHCII were analysed using gaussian deconvolution. Comparison of the absorption and fluorescence excitation spectra enabled calculation of the rate of excitation energy transfer in the system. Excitation energy was found to be transferred to chlorophyll a from chlorophyll b with 97% efficiency, from neoxanthin with 85%, from lutein with 62% and from violaxanthin with at least 54% efficiency. The analysis of the position of the 0-0 absorption band of the xanthophylls revealed that neoxanthin is located in the same protein environment as lutein but in a different environment than violaxanthin. The analysis of fluorescence excitation spectra of chlorophyll a in LHCII, recorded with the excitation light beam polarised in two orthogonal directions, enabled the determination of the mean orientation angle of the accessory xanthophyll pigments with respect to the plane of the sample. The mean orientation of lutein found in this study (approx. 51 degrees ) corresponds well to the crystallographic data. Neoxanthin was found to adopt a similar orientation to lutein. The transition dipole moment of violaxanthin was found to form a mean angle of 71 degrees with the axis spanning two polar regions of the protein, perpendicular to the plane of the monolayer, suggesting planar orientation of this pigment with respect to the plane of the thylakoid membrane. These experimentally determined xanthophyll orientations are discussed in terms of importance of peripheral xanthophyll pigments in supramolecular organisation of LHCII and the operation of the xanthophyll cycle within the thylakoid membrane.

Biphasic waveforms for ventricular defibrillation: optimization of total pulse and second phase durations.

Waveform parameters may affect the efficacy of ventricular defibrillation. Certain biphasic pulse waveforms are more effective for ventricular defibrillation than monophasic waveforms, but the optimal biphasic waveform parameters have not been identified. The purpose of this study was to investigate the effects of total pulse duration and the duration of the second (negative) phase on voltage and energy defibrillation requirements using biphasic waveforms. Defibrillation efficacy was evaluated in an isolated rabbit heart model using the Langendorff technique. The biphasic waveform was a truncated exponential with the initial voltage of the second phase equal to 50% of the final voltage of the first phase. An up/down protocol was used to determine the 50% probability-of-success levels (E50) for delivered energy and initial voltage. First, using pulse waveforms with equal positive and negative phase durations, test waveforms with total durations of 4 ms (2 ms positive + 2 ms negative), 6 ms (3 + 3 ms), and 16 ms (8 + 8 ms) were compared to the control waveform of 8 ms (4 + 4 ms) in 30 experiments. Defibrillation voltage requirements with 4 ms (174 +/- 56 V) were higher (P = 0.001) compared to 8 ms (127 +/- 49 V). Defibrillation voltage requirements for the 6-ms and 16-ms waveforms were similar to the 8-ms control waveform. Delivered energies tended to be higher with the 4-ms waveform. A second series of 40 experiments were performed to compare monophasic (4 + 0 ms) and three asymmetric biphasic waveforms (4 + 2 ms, 4 + 8 ms, and 4 + 16 ms) to the symmetric control waveform (4 + 4 ms). The monophasic (2.15 +/- 1.21 J) and the 4 + 16 ms waveform (1.86 +/- 1.09 J) required higher energies (P < or = 0.05) than the control waveform (1.24 +/- 0.41 J and 0.87 +/- 0.7 J, respectively). The monophasic waveform also resulted in greater voltage requirements (223 +/- 64 V) compared to the control waveform (160 +/- 26 V) (P = 0.02). Energy and voltage requirements were similar for the 4 + 2 ms and 4 + 8 ms waveforms compared to the control. Defibrillation requirements with biphasic waveforms were affected by total and second phase duration. For waveforms with equal phase durations, total durations between 6-16 ms resulted in the lowest values for defibrillation. For waveforms with variable second (negative) phase durations, durations ranging from 50%-200% of the first phase did not affect defibrillation efficacy.

Activity controlled cardiac pacemakers during stairwalking: a comparison of accelerometer with vibration guided devices and with sinus rate.

Activity controlled pacemakers are the most widely used rate adaptive systems. We studied second-generation activity controlled systems (accelerometer) in 21 patients with such an accelerometer controlled system implanted during walking level and stairs. We compared them to the rate of vibration controlled, first-generation activity pacemakers and to the sinus rate of a healthy control group. A metronome directed the speed during walking and climbing stairs at 92, 108, and 120 steps/min. At 92 steps/min, the new accelerometer controlled systems showed a significant (P < or = 0.001) pacing rate increase from 107 +/- 8 beats/min during walking level to 124 +/- 8 beats/min during climbing stairs, and a significant decrease to 105 +/- 12 beats/min during walking downstairs. In contrast, first-generation activity controlled pacemakers showed a less physiological rate behavior with higher pacing rate (113 +/- 7 beats/min) walking downstairs than walking upstairs (97 +/- 9). For everyday activities at normal walking speed, accelerometer controlled pacemakers show a more physiological rate behavior than first-generation pacemakers, but they lose this physiological response with faster walking.

[Heart rate changes in a new generation of activity controlled pacemakers during stair climbing]. / Frequenzverhalten einer neuen Generation aktivitätsgesteuerter Herzschrittmacher beim Treppengehen.

OBJECTIVE: A study was undertaken to determine whether a new generation of accelerometer controlled rate adaptive pacemakers has advantages over the older type of activity controlled pacemaker. PATIENTS AND METHODS: Pacemaker rates of 21 patients (15 women, six men; mean age 64.1 [44-85] years) with the new pacemakers were compared with those of a control group of patients free of cardiac disease (four women, six men; mean age 50.5 [39-75] years) in whom a vibration controlled pacemaker system had been attached to the right pectoral area. Heart rate was monitored by a rate analyser, data recorder and rate watch throughout the period of activity. Step frequencies of 92, 108 and 120 steps/min were fixed by metronome. RESULTS: The new pacemaker responded with a rate increase at a step rate of 92/min (P < 0.001): from 106.6 +/- 7.9 beats/min on walking on the even, to 123 +/- 8.4 beats/min on stair climbing. There was a significant fall in frequency, to 105 +/- 11.7 beats/min, when descending steps. The conventional pacemakers responded with a decrease in frequency on stair climbing (97.2 +/- 8.7 beats/min compared with 112.6 +/- 7.4 when descending). CONCLUSIONS: The results indicate that the new system provides for a more physiological rate response. However, this difference between the older and the new generation of pacemakers is less marked on walking at higher step rates.

Intrinsic heart rate response as a predictor of rate-adaptive pacing benefit.

OBJECTIVE: More than half of the pacemaker systems now being implanted can be rate adaptively paced. Our objective was to determine which patients benefit from rate-adaptive pacing in terms of improvement in maximum performance and aerobic capacity. METHODS: Thirty patients with implanted accelerometer-driven, rate-adaptive pacemakers underwent a standardized, ergospirometrically and maximally symptoms = limited cardiopulmonary exercise (CPX) stress test with both rate-adaptive and fixed-rate stimulation in a randomized order. The patients were divided into three groups depending on the intrinsic heart rate achieved during maximum workload: group 1 achieved < or = 90 beats per minute (bpm), group 2 achieved 90 to < or = 110 bpm, and group 3 achieved > 110 bpm. RESULTS: Group 1 demonstrated a significant increase (p < or = 0.01) in maximum oxygen uptake from 16.4 +/- 5.6 mL/kg/min with fixed-rate pacing to 23.2 +/- 11.1 mL/kg/min (+ 41.5%) with rate-adaptive pacing. At the anaerobic threshold, oxygen uptake significantly increased (p < or = 0.01) from 11.8 +/- 2.7 mL/kg/min to 15.7 +/- 5 mL/kg/min (+33.1%). Group 2 patients showed an increase in maximum oxygen uptake from 23.3 +/- 5.4 mL/kg/min to 25.3 +/- 4.9 mL/kg/min (+8.5%, p < or = 0.05) as well as an increase in oxygen uptake at the anaerobic threshold from 15.9 +/- 2.6 mL/kg/min to 18.1 +/- 2.9 mL/kg/min (+13.8%, p < or = 0.05) with rate-adaptive pacing. Group 3 demonstrated no significant difference between the two pacing methods (from 25.6 +/- 9.4 mL/kg/min to 25.9 +/- 9.3 mL/kg/min and from 15.8 +/- 5.5 mL/kg/min to 16.3 +/- 6 mL/kg/min). No difference in maximum oxygen uptake and in oxygen uptake at the anaerobic threshold was evident among the three groups when paced rate adaptively (not significant). CONCLUSION: The second-generation, accelerometer controlled rate-adaptive pacemakers used in testing enabled a stress-oriented heart rate increase and an age- and gender-dependent adequate matching of maximum performance. The benefit from a rate-adaptive system to the patient increases as his or her chronotropic reserve limitation became more pronounced.

[Improvement in oxygen consumption by frequency-adjusted pacemaker stimulation: effect of intrinsic heart rate]. / Verbesserung der Sauerstoffaufnahmekapazität durch frequenz-adaptive Schrittmacherstimulation: Einfluss der Herzeigenfrequenz.

More than half of all pacemaker systems currently implanted function rate-adaptively. Our objective was to determine which patients benefit from rate-adaptive pacing in terms of improvement in maximum performance and aerobic capacity. Thirty patients with implanted accelerometer-driven, rate-adaptive pacemakers were examined ergospirometrically and patient symptom-limited while walking on a treadmill. The patients were divided into three groups depending on the intrinsic heart rate achieved during maximum workload: Group I achieved < or = 90 bpm, Group II achieved 90 to < or = 110 bpm, Group III achieved > 110 bpm. Group I demonstrated a significant increase (p < or = 0.01) in maximum oxygen uptake from 16.4 +/- 5.6 ml/kg/min with fixed-rate pacing to 23.2 +/- 11.1 ml/kg/min (+41.5%) with rate-adaptive pacing. At the anaerobic threshold, oxygen uptake significantly increased (p < or = 0.01) from 11.8 +/- 2.7 ml/kg/min to 15.7 +/- 5 ml/kg/min (+33.1%). Group II showed an increase in maximum oxygen uptake from 23.3 +/- 5.4 ml/kg/min to 25.3 +/- 4.9 ml/kg/min (+8.5%, p < or = 0.05) as well as an increase in oxygen uptake at the anaerobic threshold from 15.9 +/- 2.6 ml/kg/min to 18.1 +/- 2.9 ml/kg/min (+13.8%, p < or = 0.05) with rate-adaptive pacing. Group III demonstrated no significant difference between the two pacing methods (from 25.6 +/- 9.4 ml/kg/min to 25.9 +/- 9.3 ml/kg/min and from 15.8 +/- 5.5 ml/kg/min to 16.3 +/- 6 ml/kg/min). No difference in maximum oxygen uptake and in oxygen uptake at the anaerobic threshold was evident between the three groups when paced rate-adaptively (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Behavior of different activity-based pacemakers during treadmill exercise testing with variable slopes: a comparison of three activity-based pacing systems.

A new generation of activity-based pacemakers incorporates an accelerometer sensitive to low frequency acceleration signals in the anteroposterior direction for sensing of bodily stress. The purpose of our investigation was to test a representative model of these new activity-based pacemakers (Relay) and compare it with current vibration- and housing pressure-sensing systems. We tested ten pacemaker patients with implanted Activitrax, Sensolog, and Relay systems during treadmill exercise testing with variable slopes. Devices from the three systems were also strapped externally to the chest of each patient and to ten normal test subjects in the control group. Exercise tests were conducted with changes of treadmill speed and/or treadmill slope. For comparable workloads during constant speed/variable slope and constant slope/variable speed, Relay had similar rate responses (difference not significant). Significant differences (P < 0.05) in rate adaptation attributable to the kind of treadmill exercise (change in treadmill speed or slopes) were observed in the housing pressure- and vibration-based pacemakers. Activity-based pacemakers with an acceleration sensor adapt pacing rates during treadmill exercises independent of treadmill speed or slope better than those controlled by a conventional housing pressure or vibration sensor.

[Behavior of various activity-controlled cardiac pacemakers in treadmill stress tests with variable slopes]. / Verhalten verschiedener aktivitätsgesteuerter Herzschrittmacher bei Laufbandbelastungen mit unterschiedlichen Steigungen.

New activity pacemaker systems with the principle of sensing low-frequency acceleration in the anterior-posterior axis are currently under clinical evaluation. We compared the pacemaker system Relay, which represents this new generation of accelerometer controlled devices, with conventional activity systems sensing pressure and vibration. Ten pacemaker patients with implanted Activitrax, Sensolog or Relay pacemakers and 10 healthy volunteers with externally strapped-on pacemakers were studied. The aim was to evaluate the systems' ability to distinguish different workloads during graded treadmill testing with changes in speed and/or slope. The rate adaption of the new acceleration sensing pacemakers was found to be more adequate compared to vibration and pressure-sensing pacemakers when only the slope of the treadmill was varied. The acceleration-sensing pacemaker adjusted its rate according to the workload largely independent from the type of stress (n.s.). With the vibration and pressure-sensing pacemakers, however, significant differences (p < 0.05) were seen between rate adaption in the two stress test modes. The new generation of acceleration-sensing pacemakers has certain advantages over conventional vibration-sensitive systems in terms of a higher sensitivity to varying workloads and higher specificity to the type of exercise performed.

Comparison of two activity-controlled rate-adaptive pacing principles: acceleration versus vibration.

Activity-guided rate-adaptive pacing is currently the most widely used principle for rate adaptation. Broad experience has been gathered from several hundred thousand pacemakers that adjust the pacing rate according to vibrational forces detected by a piezosensor bonded to the inner side of the pacemaker can. A new generation of accelerometer-based pacemakers has been introduced into clinical practice. The vibrational type detects vibration, pressure, and shock waves traveling through the body with physical stress and using the pacemaker can as a resonator. In contrast, the accelerometer is insulated from the pacemaker housing and is incorporated into electronic hybrid circuitry. The forces detected by an accelerometer are motion and acceleration of the body in an anterior-posterior direction. Clinical studies conducted to date have shown that the accelerometer to be superior to the conventional vibration activity pacemakers, as far as the discrimination of different workloads and rejection of unwanted environmental noise are concerned.

[Initial studies of the possibility of selective ablation of arteriosclerotic vascular changes using laser-induced shock waves]. / Erste Untersuchungen zur Möglichkeit einer selektiven Ablation arteriosklerotischer Gefässveränderungen mit Hilfe laserinduzierter Stosswellen.

We studied the effect of laser-induced shock waves in 94 arterial segments from freshly obtained autopsy material. In analogy to the well-established method of shock-wave based lithotripsy, the new principle of our treatment depends on an indirect interaction of the laser energy with the arterial wall via laser-induced mechanical shock waves (angiotripsy). We used a Nd:YAG laser, 1064 nm, 8-20 ns pulse-length to create shock waves that effected smooth craters in arteriosclerotically affected arteries. The histological examination found no thermal damage. Shock waves applied to the healthy and normal arterial wall only resulted in focal intimal ablation and in a minor loosening of the medial structures. The examination of the irrigation solution by means of a laser-guided, high-resolution analysis of the particles revealed that, in 97%, the particles created by our shock wave angiotripsy showed a diameter of less than 5 mm and an area of less than 25 mm2. Based on these first in vitro results, it seems possible to ablate arteriosclerotically affected tissue without significant damage to normal wall segments. Further in vitro and in vivo studies are required to evaluate the clinical implications of this new therapeutic approach.

[A new mechanical sensor for activity controlled and body position dependent frequency adaptive pacemaker stimulation]. / Ein neuer mechanischer Sensor für aktivitätsgesteuerte und körperpositionsabhängige frequenzadaptive Schrittmacherstimulation.

In the past, the most important feature in the development of rate-responsive pacemaker systems was ensuring an adequate rate response to physical exercise. But there are other variables that modulate the rate of the healthy heart; examples include postural changes in heart rate in order to prevent orthostatic reactions, and the nightly decrease in intrinsic pacemaker rate. Therefore, we developed a sensor that could distinguish, not only rest and activity, but also discriminate between a supine and an upright position. This sensor is a multicontact tilt switch, which contains a small mercury ball. By measuring the number of openings and closures within the sensor as the ball touches the numerous sensor contacts it is possible to discriminate between different levels of exercise; the contact pins are circled around the base plate. There is an almost linear increase in the number of changes per time with increasing exercise. Besides measuring body activity from the number of contact changes per time, it is also possible to determine the body's posture from the count and positioning of the closed contacts within the casing. Based upon the results of 12 volunteers and nine pacemaker patients, a new algorithm is being prepared which enables the pacemaker to decrease stimulation rate in the supine position, to increase it in the upright position, and to correlate pacing rate with the increase in physical exercise. There is a good correlation between number of contact changes and the intrinsic heart rate (r = 0.87).

The basis for activity controlled rate variable cardiac pacemakers: an analysis of mechanical forces on the human body induced by exercise and environment.

We conducted tests on six healthy volunteers and six pacemaker patients. With the aid of three straight line frequency acceleration pickups attached to the body, the mechanical signals were recorded on the three axes during different activities. Along with standardized exercise on bicycle and treadmill ergometers, we tested the influence of household activities and interference influences. The results were analyzed in terms of the amplitude and frequency content of the signals. For walking activities, we found a signal amplitude increasing in a largely linear fashion with the walking speed, the signal amplitudes being approximately twice as high on the vertical axis as on the other two axes. Exercise on the bicycle ergometer produced mechanical signals of clearly lower amplitude than comparable walking activities. The Fast-Fourier analysis showed amplitude peaks in the low frequency range of 1 to 4 Hz for all forms of physiological exercise, while interference influences showed amplitude peaks mainly in the range above 8 Hz. The use of a straight line-frequency acceleration pickup and a corresponding low pass filter might be a way of reducing the effect of unphysiological interference influences on an activity controlled pacemaker system. A sensor measuring on the horizontal axis appears to be the most favorable compromise for the various types of exercise. However, due to the considerable difference in signal amplitude for different types of exercise of the same intensity, an activity controlled pacemaker system cannot entirely meet metabolic conditions and requirements.

[Principle of the activity-controlled rate-adaptive cardiac pacemaker: analysis of stress and environment-induced mechanical effects on the human body]. / Grundlage aktivitätsgesteuerter frequenzvariabler Herzschrittmacher: Analyse von belastungs- und umweltbedingten mechanischen Einflüssen am menschlichen Köper.

Rate-adaptive pacemakers are increasingly becoming part of clinical routine, the most widespread systems being activity-controlled. In order to shed more light on the foundations of mechanical forces which can possibly be utilized for controlling rate-adaptive systems, we conducted tests on six healthy volunteers and six pacemaker patients. With the aid of three orthogonal wide-band linear acceleration pick-ups attached to the body, the mechanical signals were recorded from the three axes during different activities. Along with standardized exercise on bicycle and treadmill ergometers, we tested the influence of household activities and interference influences. The results were analyzed in terms of the amplitude and frequency content of the signals. For walking activities we found a signal amplitude increasing in largely linear fashion with the walking speed, the signal amplitudes being approximately twice as high on the vertical axis as on the other two axes. Exercise on the bicycle ergometer produced mechanical signals of clearly lower amplitude than comparable walking activities. The Fast-Fourier analysis showed amplitude peaks in the low frequency range of 1 to 4 Hz for all forms of physiological exercise, while interference influences showed amplitude peaks mainly in the range above 8 Hz. The use of an acceleration pickup and a corresponding low pass filter might be a way of reducing the effect of nonphysiological interference influences on an activity-controlled pacemaker system. A sensor measuring in the horizontal axis appears to be the most favorable compromise for the various types of exercise. However, due to the considerable difference in signal amplitude for different types of exercise of the same intensity, an activity-controlled pacemaker system cannot entirely meet metabolic conditions and requirements.

A new mechanical sensor for detecting body activity and posture, suitable for rate responsive pacing.

In the past, thought about rate responsive pacing mainly focused on rate increase with exercise but did not consider that a rate increase with postural changes also is mandatory in order to prevent orthostatic reactions. A nightly decrease in pacemaker rate when the body is at rest and in a supine position is a further advantage for the patient's sleep and recovery. Therefore, we developed a sensor that could detect not only rest and body activity but also discriminate between a supine and an upright position. This sensor is a multicontact tilt switch containing a small mercury ball, as shown in the left panel of the figure below. The principle of discrimination between rest and low and high body activity is realized by the movement of the mercury ball resulting from body motion, which causes openings and closures within the sensor as the ball touches the numerous sensor contacts. In the upright position, a distinct number of contacts at the bottom of the tilt switch are closed. In the supine position, there is no closure of the bottom contacts and a postural discrimination can be achieved. We studied 12 volunteers and 10 pacemaker patients with this new device both at rest and during physical exercise. The right panel of the figure illustrates that the contacts per second correlate to the increase of physical exercise, such as walking on the treadmill. Further studies with an external pacemaker containing a small sensor suitable to fit into the pacemaker are in preparation.

A new rate-modulated pacemaker system optimized by combination of two sensors.

A new rate-modulated pacemaker system optimized by combination of two sensors is described. The parameter body activity and central venous blood temperature control the pacemaker rate. The specific characteristic of each parameter determines its role within the algorithm. While the motion sensor yields a fast reaction following the onset or a change of stress intensity, central venous blood temperature corresponds better to body metabolism. An indication of increased exercise from the motion sensor results in an accordingly rapid increase in the pacing rate. Unless this increased exercise is confirmed by an increase in central venous blood temperature within 2 or 3 minutes, the new motion level will be assumed to be the new baseline motion value and the pace rate will return to a basic pacing rate. Prolonged inappropriate responses are therefore avoided. Longer lasting exercise, fever and nonphysiological signals are recognized and handled safely. Exercise tests with five volunteers under various conditions showed pacing rate behavior that was close to normal.

Partial purification and properties of a highly specific trehalose phosphate phosphatase from Mycobacterium smegmatis.

A specific trehalose phosphate phosphatase was purified approximately 50-fold from Mycobacterium smegmatis. The enzyme had a pH optimum of about 7.0 and was stimulated by Mg(2+). The optimum concentration of Mg(2+) was about 1.5 x 10(-3)m. Of other divalent cations tested, only Co(2+) showed some activity. The K(m) for trehalose phosphate was found to be about 1.5 x 10(-3)m. The enzyme showed slight activity toward mannose-6-P and fructose-6-P but was inactive on a large number of other phosphorylated compounds. Citrate was a competitive inhibitor of the enzyme both with respect to trehalose phosphate concentration and Mg(2+) concentration. This inhibition appears to be due to chelation of Mg(2+) by this compound. Ethylenediaminetetraacetic acid and NaF were also inhibitors of the enzyme, but these inhibitions were noncompetitive.