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Biomedical subjects

T Eggert

Publications and source records attributed to T Eggert.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative sensory testing in cluster headache: increased sensory thresholds.

To determine if recently reported changes in sensory thresholds during migraine attacks can also be seen in cluster headache (CH), we performed quantitative sensory testing (QST) in 10 healthy subjects and in 16 patients with CH. Eight of the patients had an episodic CH and the other eight a chronic CH. The tests were performed on the right and left cheeks and on the right and left side of the back of the hands to determine the subjects' perception and pain thresholds for thermal (use of a thermode) and mechanical (vibration, pressure pain thresholds, pin prick, von Frey hairs) stimuli. Six patients were examined in the attack-free period. Three were also willing to repeat the tests a second time during an acute headache attack, which was elicited with nitroglycerin. The healthy subjects performed the experiments in the morning and evening of the same day to determine if sensory thresholds are independent of the time of day. If they were, this would allow estimation of the influence of the endogenous cortisone concentration on these thresholds. The control group showed no influence of the time of day on the thresholds. There was a significant difference in pain sensitivity between the back of the hands and the cheeks (P<0.05): higher thresholds were found on the back of the hands. The thresholds generally exhibited little intersubject variability, indicating that QST is a reliable method. There was also a significant difference between the test areas in the patient group (P<0.001): the cheeks were also more sensitive than the back of the hands. In comparison with reference data of healthy volunteers, the detection thresholds were increased in the patients on both test areas. These were statistically significant for warmth, thermal sensory limen (TSL), heat and pressure on the back of the hands (P<0.04) and for the warmth and TSL thresholds on the cheeks (P<0.05). There were no differences in the thresholds regardless of whether the patients were examined in or outside of a cluster bout. Furthermore, we found no cutaneous allodynia in the three patients tested during an attack. The increased sensory thresholds on the cheeks as well as on the back of the hands are in agreement with an increased activation of the patients' antinociceptive system. The seasonal variation and the temporal regularity of single attacks as well as the findings in imaging studies indicate that the hypothalamus is involved in the pathophysiology of CH. In view of the strong connectivity between the hypothalamus and areas involved in the antinociceptive system in the brainstem, we hypothesize that this connection is the reason for the increased sensory thresholds in CH patients found in our study.

Adaptation, Physiological↗
PubMed2005

Initial characterization of a blue-light sensing, phototropin-related protein from Pseudomonas putida: a paradigm for an extended LOV construct.

The open reading frame PP2739 from Pseudomonas putida KT2440 encodes a 151 amino acid protein with sequence similarity to the LOV domains of the blue-light sensitive protein YtvA from Bacillus subtilis and to the phototropins (phot) from plants. This sensory box LOV protein, PpSB2-LOV, comprises a LOV core, followed by a C-terminal segment predicted to form an alpha-helix, thus constituting a naturally occurring paradigm for an extended LOV construct. The recombinant PpSB2-LOV shows a photochemistry very similar to that of YtvA and phot-LOV domains, yet the lifetime for the recovery dark reaction, taurec=114 s at 20 degrees C, resembles that of phot-LOV domains (5-300 s) and is much faster than that of YtvA or YtvA-LOV (>3000 s). Time-resolved optoacoustics reveals phot-like, light-driven reactions on the ns-micros time window with the sub-nanosecond formation of a flavin triplet state (PhiT=0.46) that decays into the flavin-cysteine photoadduct with 2 micros lifetime (Phi390=0.42). The fluorescence spectrum and lifetime of the conserved W97 resembles the corresponding W103 in full-length YtvA, although the quantum yield, PhiF, is smaller (about 55% of YtvA) due to an enhanced static quenching efficiency. The anisotropy of W97 is the same as for W103 in YtvA (0.1), and considerably larger than the value of 0.06, found for W103 in YtvA-LOV. Different to YtvA and YtvA-LOV, the fluorescence for W97 becomes larger upon photoproduct formation. These data indicate that W97 is located in a similar environment as W103 in full-length YtvA, but undergoes larger light-driven changes. It is concluded that the protein segment located C-terminally to the LOV core (analogous to an interdomain linker) is enough to confer to the conserved tryptophan the fluorescence characteristics typical of full-length YtvA. The larger changes experienced by W97 upon light activation may reflect a larger conformational freedom of this protein segment in the absence of a second domain.

Bacillus subtilis↗
PubMed2005

Saccades to moving targets.

The metrics and dynamics of saccades to stationary and moving targets were observed in monkeys (Macaca mulatta). To isolate the effects of target speed on the saccade from contributions of smooth pursuit, saccade velocity was corrected for intrasaccadic pursuit velocity on a trial-by-trial basis prior to analysis. The effects of presaccadic retinal error and target speed on the saccadic velocity profile were determined by analyzing the partial correlations computed as a function of time after saccade onset. The main results are: (1) Saccade amplitude is determined not only by the retinal error sampled before the saccade, but also by the speed of the target during the latency period. (2) The dynamics of saccades, even if compensated for smooth-pursuit components, differ between forward- and backward-moving targets. (3) Whereas the presaccadic retinal error affects the eye velocity throughout the saccade, target speed has no effect before peak velocity. These results are discussed in the context of current models of saccade generation and their physiological substrates, in particular the role of the cerebellum in the local feedback loop.

Animals↗
PubMed2003

[Transrectal ultrasound-guided punch biopsies of the prostate. Indication, technique, results, and complications].

The golden standard for diagnosis of prostate cancer is transrectal ultrasound-guided systematic biopsy (TRUS-Bx). The optimal number of cylinders, sampling design, and indications for repeat biopsy are still in a state of flux. At the beginning of the 1980s, considerable doubts persisted regarding the benefit of ultrasound-guided punch biopsy for the diagnosis of prostate cancer. The examination on a chair with a fixed ultrasound head caused the patient substantial discomfort. Besides, in the pre-PSA era, most prostate carcinomas were detected by palpation and digitally guided biopsies were easily obtained. Indeed, the DRU procedure alone exhibited low sensitivity. Keetch et al. found that in only 25% of patients with abnormal palpatory findings and PSA between 4 and 20 ng/ml was a carcinoma revealed upon biopsy. On the other hand, patients with suspicious palpatory findings and proven malignancy suffered more frequently from locally advanced and systemic metastasizing tumors. As a result of restaging based on PSA, in most series more than half of the detected carcinomas presented normal palpatory findings. Ultrasound examination made precise imaging of zonal structures possible and thus offered the advantage of precision guidance for tissue biopsy despite lower sensitivity and specificity for diagnosis of suspicious lesions. Furthermore, calculation of prostate volume was possible. At the end of the 1980s, Hodge defined the systematic sextant biopsy as the first golden standard for early detection of prostate cancer. This meant the systematic removal of three punch cylinders from both lateral lobes of the prostate in the parasagittal midline at various levels (apex, middle, and base).

Adult↗
PubMed2003

[Functional results of various surgical techniques for radical prostatectomy].

Radical prostatectomy for the treatment of prostate cancer can be performed by various techniques using a retropubic, perineal, or laparoscopic approach. Besides tumor control, the postoperative urinary continence rates and potency rates impact patients' quality of life after radical prostatectomy. This paper shows the results of our own center and compares the data in the literature regarding functional results of radical prostatectomy with respect to various operative techniques.

Aged↗
PubMed2003

Anterior canal failure: ocular torsion without perceptual tilt due to preserved otolith function.

A patient with anterior semicircular canal dehiscence syndrome underwent surgical patching that caused an isolated dysfunction of the left anterior semicircular canal postoperatively. He exhibited significant ocular torsion toward the side of the affected labyrinth (17 degrees excyclotropia of the ipsilateral eye), but no displacement of the subjective visual vertical. This dissociation suggests that an isolated ocular torsion may occur after an anterior semicircular canal lesion. A combined ocular torsion and subjective visual vertical tilt, which is usually seen with vestibular lesions, requires an associated otolith dysfunction.

Eye Diseases↗
PubMed2003

Three-dimensional eye position and slow phase velocity in humans with downbeat nystagmus.

Downbeat nystagmus (DN), a fixation nystagmus with the fast phases directed downward, is usually caused by cerebellar lesions, but the precise etiology is not known. A disorder of the smooth-pursuit system or of central vestibular pathways has been proposed. However, both hypotheses fail to explain why DN is usually accompanied by gaze-holding nystagmus, which implies a leaky neural velocity-to-position integrator. Because three-dimensional (3-D) analysis of nystagmus slow phases provides an excellent means for testing both hypotheses, we examined 19 patients with DN during a fixation task and compared them with healthy subjects. We show that the presentation of DN patients is not uniform; they can be grouped according to their deficits: DN with vertical integrator leakage, DN with vertical and horizontal integrator leakage, and DN without integrator leakage. The 3-D analysis of the slow phases of DN patients revealed that DN is most likely neither caused by damage to central vestibular pathways carrying semicircular canal information nor by a smooth pursuit imbalance. We propose that the observed effects can be explained by partial damage of a brain stem-cerebellar loop that augments the time constant of the neural velocity to position integrators in the brain stem and neurally adjusts the orientation of Listing's plane.

Adult↗
PubMed2002

Effects of intravenous opioids on eye movements in humans: possible mechanisms.

Oculomotor symptoms such as downbeat nystagmus can be due to side effects of drugs. We investigated the clinical effects as well as the eye movement symptoms after intravenous administration of opiates (pethidine and fentanyl). Eye movements were recorded with the magnetic search coil technique. All four normal subjects showed a transient disturbance of eye fixation with downbeat nystagmus, a range of saccadic intrusions and oscillations, including square wave jerks and saccadic pulses, lasting from 10 to 15 minutes. The gain of sinusoidal VOR and smooth pursuit was moderately decreased; in particular the vertical pursuit showed an upward velocity offset. On the basis of the clinical findings and of recent diprenorphine PET findings in humans, which detected opiod binding sites in the cerebellum and the known inhibitory action of opiates, we hypothesized that a cerebellar dysfunction occurs after opiate administration which could possibly be mediated by inhibition of the parallel fiber activation of the Purkinje cells. Furthermore, opiate binding sites in the vestibular nuclei could be responsible for the vertical vestibular tonus imbalance involved in the pathophysiolgy of downbeat nystagmus.

Analgesics, Opioid↗
PubMed2002

Differential effect of a distractor on primary saccades and perceptual localization.

A distractor presented nearby the target of a goal-directed short latency saccade leads to spatial averaging, that is, the saccade lands between the target and the distractor. This so-called global effect is a characteristic feature of the spatial processing underlying the programming of saccadic eye movements. To determine whether this effect of near distractors on saccade metrics is also reflected in perceptual localization, subjects performed a saccade task and a perceptual localization task using identical, briefly flashed visual stimuli. To make the available visual processing time for saccades and perception more similar, we followed the target with a mask. Without the mask, primary saccades with short latency landed between target and distractor. The distractor had less effect on primary saccades with longer latencies (>200 ms) and did not affect the final eye position after late secondary saccades in the dark. This indicates that the oculomotor system can correctly use information about the target location 200 ms after the target flash even if no visual stimulus is present during this period. Likewise the presence of a distractor did not affect perceptual localization. Under the masking condition a similar global effect occurred for primary saccades with short latencies, but the latency dependence of the global effect was weakened. Secondary saccades and perceptual localization still did not show a global effect. The results suggest that the primary saccade is based on a specific target acquisition process that differs from that used for spatial perception and for the programming of memory-guided corrective saccades.

Adult↗
PubMed2001

Cerebellar lesions impair rapid saccade amplitude adaptation.

This study investigated whether the cerebellum is essential for rapid saccade adaptation. Saccade adaptation was elicited by 30% backward target steps during the primary saccade. Patients with cerebellar lesions adapted less than normal subjects, but saccade adaptation was most impaired in the group of patients with cerebellar degeneration. As the variability of the saccade gain in patients with cerebellar degeneration did not significantly differ from that in the other patients, the increased variability in motor performance due to a cerebellar lesion cannot alone explain this impaired adaptation.

Adult↗
PubMed2001

Lipolytic enzymes LipA and LipB from Bacillus subtilis differ in regulation of gene expression, biochemical properties, and three-dimensional structure.

Bacillus subtilis secretes the lipolytic enzymes LipA and LipB. We show here that they are differentially expressed depending on the composition of the growth medium: LipA is produced in rich and in minimal medium, whereas LipB is present only in rich medium. A comparison of biochemical characteristics revealed that LipB is thermostable at pH 11 but becomes thermolabile at pH 5. However, construction of a variant carrying the substitution A76G in the conserved lipase pentapeptide reversed these effects. The atomic coordinates from the LipA crystal structure were used to build a three-dimensional structural model of LipB, which revealed that 43 out of 45 residues different from LipA are surface-located allowing to rationalize the differences observed in the substrate preferences of the two enzymes.

Bacillus subtilis↗
PubMed2001

The crystal structure of Bacillus subtilis lipase: a minimal alpha/beta hydrolase fold enzyme.

The X-ray structure of the lipase LipA from Bacillus subtilis has been determined at 1.5 A resolution. It is the first structure of a member of homology family 1.4 of bacterial lipases. The lipase shows a compact minimal alpha/beta hydrolase fold with a six-stranded parallel beta-sheet flanked by five alpha-helices, two on one side of the sheet and three on the other side. The catalytic triad residues, Ser77, Asp133 and His156, and the residues forming the oxyanion hole (backbone amide groups of Ile12 and Met78) are in positions very similar to those of other lipases of known structure. However, no lid domain is present and the active-site nucleophile Ser77 is solvent-exposed. A model of substrate binding is proposed on the basis of a comparison with other lipases with a covalently bound tetrahedral intermediate mimic. It explains the preference of the enzyme for substrates with C8 fatty acid chains.

Acyltransferases↗
PubMed2001

Elliptic flow in Au+Au collisions at square root(S)NN = 130 GeV.

Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at square root(S)NN = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.

Journal Article↗
PubMed2001

Directed evolution and the creation of enantioselective biocatalysts.

Directed evolution has emerged as a key technology to generate enzymes with new or improved properties that are of major importance to the biotechnology industry. A directed evolution approach starts with the identification of a target enzyme to be optimized and the cloning of the corresponding gene. An efficient expression system is needed before the target gene is subjected to random mutagenesis and/or in vitro recombination, thereby creating molecular diversity. Subsequently, improved enzyme variants are identified, preferably after being secreted into culture medium, by screening or selection for the desired property. The genes encoding the improved enzymes are then used to parent the next round of directed evolution. Enantioselectivity is a biocatalyst property of major biotechnological importance that is, however, difficult to deal with. We discuss recent examples of creating enantioselective biocatalysts by directed evolution.

Amidohydrolases↗
PubMed2001

Mislocalization of peripheral targets during fixation.

To investigate the effect of the visual stimulus configuration on localization when oculomotor performance is excluded, we evaluated the errors made when subjects compare the horizontal location of two sequentially presented peripheral targets while looking at a visual or memorized fixation spot. Eye position was monitored by means of an infrared eye tracker. Significant localization errors were observed. As long as the fixation spot stayed on or off during the entire presentation time of both peripheral targets, the localization error did not depend on the presence or absence of the fixation spot. A significant change in the localization error was observed only if the fixation spot was presented together with the first peripheral target but disappeared before the presentation of the second one. The localization error did not depend on: (1) the visual asymmetry (unilateral versus bilateral target presentation); (2) the distribution of visual attention (cued versus non-cued test location); or (3) the time interval between the two targets. These results suggest that the mislocalization observed during fixation is partially due to a mismatch between egocentric and exocentric localization mechanisms.

Analysis of Variance↗
PubMed2001

Improving the homogeneity of the magnetic field in the magnetic search coil technique.

The magnetic search coil technique is used to obtain accurate eye-movement measurements. For the data analysis it must be assumed that the magnetic field does not change over time (apart from the required modulation). To comply with this assumption either no translational movements of the eye coil(s) are allowed or the magnetic field has to be perfectly homogeneous. Both are normally not the case, i.e., measurement errors occur. These errors can be minimized by keeping the magnetic field as homogeneous as possible. Larger field coils are typically chosen to achieve this aim. However, sometimes the experimental setup imposes limitations on the size of the configuration. We present a method for improving the homogeneity of the magnetic field by adding supplementary field coils without changing the size of the configuration.

Equipment Design↗
PubMed2001

DsbA and DsbC affect extracellular enzyme formation in Pseudomonas aeruginosa.

DsbA and DsbC proteins involved in the periplasmic formation of disulfide bonds in Pseudomonas aeruginosa were identified and shown to play an important role for the formation of extracellular enzymes. Mutants deficient in either dsbA or dsbC or both genes were constructed, and extracellular elastase, alkaline phosphatase, and lipase activities were determined. The dsbA mutant no longer produced these enzymes, whereas the lipase activity was doubled in the dsbC mutant. Also, extracellar lipase production was severely reduced in a P. aeruginosa dsbA mutant in which an inactive DsbA variant carrying the mutation C34S was expressed. Even when the lipase gene lipA was constitutively expressed in trans in a lipA dsbA double mutant, lipase activity in cell extracts and culture supernatants was still reduced to about 25%. Interestingly, the presence of dithiothreitol in the growth medium completely inhibited the formation of extracellular lipase whereas the addition of dithiothreitol to a cell-free culture supernatant did not affect lipase activity. We conclude that the correct formation of the disulfide bond catalyzed in vivo by DsbA is necessary to stabilize periplasmic lipase. Such a stabilization is the prerequisite for efficient secretion using the type II pathway.

Alkaline Phosphatase↗