Biomedical subjects

H Hecht

Publications and source records attributed to H Hecht.

At least 19 recordsLinked to original sources

PubMed2001

Recombinant tyrosine aminotransferase from Trypanosoma cruzi: structural characterization and site directed mutagenesis of a broad substrate specificity enzyme.

The gene encoding tyrosine aminotransferase (TAT, EC 2.6.1.5) from the parasitic protozoan Trypanosoma cruzi was amplified from genomic DNA, cloned into the pET24a expression vector and functionally expressed as a C-terminally His-tagged protein in Escherichia coli BL21(DE3)pLysS. Purified recombinant TAT exhibited identical electrophoretic and enzymatic properties as the authentic enzyme from T. cruzi. Both recombinant and authentic T. cruzi TATs were highly resistant to limited tryptic cleavage and contained no disulfide bonds. Comprehensive analysis of its substrate specificity demonstrated TAT to be a broad substrate aminotransferase, with leucine, methionine as well as tyrosine, phenylalanine, tryptophan and alanine being utilized efficiently as amino donors. Valine, isoleucine and dicarboxylic amino acids served as poor substrates while polar aliphatic amino acids could not be transaminated. TAT also accepted several 2-oxoacids, including 2-oxoisocaproate and 2-oxomethiobutyrate, in addition to pyruvate, oxaloacetate and 2-oxoglutarate. The functionality of the expression system was confirmed by constructing two variants; one (Arg389) being a completely inactive enzyme; the other (Arg283) retaining its full activity, as predicted from the recently solved three-dimensional structure of T. cruzi TAT. Thus, only one of the two strictly conserved arginines which are essential for the enzymatic activity of subfamily Ialpha aspartate and aromatic aminotransferases is critical for T. cruzi's TAT activity.

Amino Acids↗

PubMed2001

Heterocyclic ortho-quinones, a novel type of Photosystem II inhibitors.

Members of the new chemical class of 7-substituted 6-bromo-benzo[4,5]imidazo[1,2alpha]pyridin-8,9-diones were found to be excellent inhibitors at the Q(B) site of the photosystem II D1 reaction center protein. The best inhibitors with pI(50)-values of >7 are: dimethyl-propyl, 7.05; i-pentyl, 7.36; t. butyl, 7.47; and i-propyl, 7.51. Displacement experiments with [14C]atrazine revealed that the 8,9-diones behave non-competitively in respect of Photosystem II herbicides and, hence, have to be considered as a new type of Photosystem II inhibitors. This notion is further corroborated by their inhibitory activity in D1 mutants of Chlamydomonas reinhardtii.

Animals↗

PubMed2001

Motor learning enhances perceptual judgment: a case for action-perception transfer.

Transfer from perception to action is well documented, for instance in the form of observational learning. Transfer from action to perception, on the other hand, has not been researched. Such action-perception transfer (APT) is compatible with several learning theories and has been predicted within the framework of common coding of perceptual and motor events (Prinz, 1992, 1997). Our first experiment aimed at an empirical evaluation of APT and involved motor practice of timed two-cycle arm movements on verbal command without visual feedback. In a transfer test, visual judgments of similar patterns had to be made. In addition, transfer from the visual to the motor task was studied. In Experiment 2 we separated kinesthetic aspects of motor practice from preparatory and efferent contributions to APT. The experiments provide evidence that transfer between perception and action is bi-directional. Transfer from perception to action and, more importantly, from action to perception was found. Furthermore, APT was equally pronounced for participants who had actively practiced movements during training and for passive participants who had received merely kinesthetic feedback about the movement. This kinesthetic-visual transfer is likely to be achieved via visuomotor-kinesthetic matching or via timekeeping mechanisms that are involved in both motor and visual performance.

Adult↗

PubMed2001

Regularities of the physical world and the absence of their internalization.

The notion of internalization put forth by Roger Shepard continues to be appealing and challenging. He suggests that we have internalized, during our evolutionary development, environmental regularities, or constraints. Internalization solves one of the hardest problems of perceptual psychology: the underspecification problem. That is the problem of how well-defined perceptual experience is generated from the often ambiguous and incomplete sensory stimulation. Yet, the notion of internalization creates new problems that may outweigh the solution of the underspecification problem. To support this claim, I first examine the concept of internalization, breaking it down into several distinct interpretations. These range from well-resolved dynamic regularities to ill-resolved statistical regularities. As a function of the interpretation the researcher selects, an empirical test of the internalization hypothesis may be straightforward or it may become virtually impossible. I then attempt to cover the range of interpretations by drawing on examples from different domains of visual event perception. Unfortunately, the experimental tests regarding most candidate regularities, such as gravitational acceleration, fail to support the concept of internalization. This suggests that narrow interpretations of the concept should be given up in favor of more abstract interpretations. However, the latter are not easily amenable to empirical testing. There is nonetheless a way to test these abstract interpretations by contrasting internalization with the opposite concept: externalization of body dynamics. I summarize evidence for such a projection of body constraints onto external objects. Based on the combined evidence of well-resolved and ill-resolved regularities, the value of the notion of internalization has to be reassessed.

Biomechanical Phenomena↗

PubMed2001

Time-to-passage judgments on circular trajectories are based on relative optical acceleration.

Current theories of arrival time have difficulty explaining performance in the common but neglected case of nonlinear approach. Global tau, a variable supposed to guide time-to-passage (TTP) judgments of objects approaching on linear trajectories, does not apply to circular movement. However, TTP judgments are surprisingly accurate in such cases. We simulated movement through a three-dimensional cloud of point-lights on various circular trajectories. Arrival-time judgments were found to be above chance when observers had to determine which of two expansionless targets would pass them first. Similar to the inside bias observed in heading studies on circular trajectories, observers showed a strong bias to select the target on the inside of their own curved motion path as passing by first. Analysis of the projected target motion revealed that targets on the inside had lower optical velocities and relatively high optical acceleration rates. Empirical TTP judgments agreed best with a strategy based on relative optical velocity changes.

Adult↗

PubMed2001

Laser-evoked potentials to noxious stimulation during hypnotic analgesia and distraction of attention suggest different brain mechanisms of pain control.

Psychological accounts of hypnosis have hypothesized that hypnosis and attention might share similar mechanisms and that hypnosis simply represents an extensive state of reduced attention. This assumption implies that reports of pain and electrocortical brain responses to painful stimulation should be similarly reduced when subjects are exposed to suggestions of hypnotic analgesia (HA) or requested to distract their attention from painful stimuli (distraction of attention: DA) as compared to a control condition (CC). To test this hypothesis, we recorded event-related electrical brain potentials to noxious laser-heat stimuli and pain reports during HA, DA, and CC from subjects highly susceptible to hypnotic suggestions. Pain reports were significantly reduced during HA and DA as compared to CC. The amplitudes of the late laser-evoked brain potential (LEP) components N200 and P320 were also significantly smaller during DA than during CC. However, no significant difference of these late LEP amplitudes was obtained for HA as compared to CC. Results indicate that hypnotic analgesia and distraction of attention represent different mechanisms of pain control and involve different brain mechanisms.

Adult↗

PubMed2001

Orientation illusions and heart-rate changes during short-radius centrifugation.

Intermittent short-radius centrifugation is a promising countermeasure against the adverse effects of prolonged weightlessness. To assess the feasibility of this countermeasure, we need to understand the disturbing sensory effects that accompany some movements carried out during rotation. We tested 20 subjects who executed yaw and pitch head movements while rotating at constant angular velocity. They were supine with their main body axis perpendicular to earth gravity. The head was placed at the centrifuge's axis of rotation. Head movements produced a transient elevation of heart-rate. All observers reported head-contingent sensations of body tilt although their bodies remained supine. Mostly, the subjective sensations conform to a model based on semicircular canal responses to angular acceleration. However, some surprising deviations from the model were found. Also, large inter-individual differences in direction, magnitude, and quality of the illusory body tilt were observed. The results have implications for subject screening and prediction of subjective tolerance for centrifugation.

Adult↗

PubMed2000

Understanding projectile acceleration.

Throwing and catching balls or other objects is a generally highly practiced skill; however, conceptual as well as perceptual understanding of the mechanics that underlie this skill is surprisingly poor. In 5 experiments, we investigated conceptual and perceptual understanding of simple ballistic motion. Paper-and-pencil tests revealed that up to half of all participants mistakenly believed that a ball would continue to accelerate after it left the thrower's hand. Observers also showed a remarkable tolerance for anomalous trajectory shapes. Perceptual judgments based on graphics animations replicated these erroneous beliefs for shallow release angles. Observers' tolerance for anomalies tended to decrease with their distance from the actor. The findings are at odds with claims of the naive physics literature that liken intuitive understanding to Aristotelian or medieval physics theories. Instead, observers seem to project their intentions to the ball itself (externalization) or even feel that they have power over the ball when it is still close.

Acceleration↗

PubMed1999

X-ray structure determination of a vanadium-dependent haloperoxidase from Ascophyllum nodosum at 2.0 A resolution.

The homo-dimeric structure of a vanadium-dependent haloperoxidase (V-BPO) from the brown alga Ascophyllum nodosum (EC 1.1.11.X) has been solved by single isomorphous replacement anomalous scattering (SIRAS) X-ray crystallography at 2.0 A resolution (PDB accession code 1QI9), using two heavy-atom datasets of a tungstate derivative measured at two different wavelengths. The protein sequence (SwissProt entry code P81701) of V-BPO was established by combining results from protein and DNA sequencing, and electron density interpretation. The enzyme has nearly an all-helical structure, with two four-helix bundles and only three small beta-sheets. The holoenzyme contains trigonal-bipyramidal coordinated vanadium atoms at its two active centres. Structural similarity to the only other structurally characterized vanadium-dependent chloroperoxidase (V-CPO) from Curvularia inaequalis exists in the vicinity of the active site and to a lesser extent in the central four-helix bundle. Despite the low sequence and structural similarity between V-BPO and V-CPO, the vanadium binding centres are highly conserved on the N-terminal side of an alpha-helix and include the proposed catalytic histidine residue (His418(V-BPO)/His404(V-CPO)). The V-BPO structure contains, in addition, a second histidine near the active site (His411(V-BPO)), which can alter the redox potential of the catalytically active VO2-O2 species by protonation/deprotonation reactions. Specific binding sites for the organic substrates, like indoles and monochlordimedone, or for halide ions are not visible in the V-BPO structure. A reaction mechanism for the enzymatic oxidation of halides is discussed, based on the present structural, spectroscopic and biochemical knowledge of vanadium-dependent haloperoxidases, explaining the observed enzymatic differences between both enzymes.

Amino Acid Sequence↗

PubMed1999

A perception experiment with time-critical graphics animation on the World-Wide Web.

The World-Wide Web offers a potentially interesting tool to collect data from a large and heterogeneous audience. While questionnaires have become rather common on the Internet, its potential reaches far beyond text processing. In principle, it is possible not only to perform interactive, dynamic experiments on the Web, but also to include graphical animation and time-critical responses, such as reaction times. We implemented a visual motion extrapolation task on the Web using the programming language Java, which can be interpreted by standard Web browsers such as Netscape or Internet Explorer. The data collected with this method turned out to be reliable and differed little from data obtained in a controlled laboratory setting, with the exception of conditions with fixation instruction. Thus, the Web can, generally speaking, be used for data collection of large sample sizes. The strengths and weaknesses of dynamic visual simulation experiments on the Internet are discussed.

Adult↗

PubMed1999

Compression of visual space in natural scenes and in their photographic counterparts.

Classical theories of space perception posit continuous distortions of subjective space. These stand in contrast to the quantitatively and qualitatively different distortions experienced in space that is represented pictorially. We challenge several aspects of these theories. Comparing real-world objects with depictions of the same objects, we investigated to what extent distortions are introduced by the photographic medium. Corners of irregularly shaped buildings had to be judged in terms of the vertical dihedral angles subtended by two adjacent walls. Across all conditions, a robust effect of viewing distance was found: Building corners appear to flatten out with distance. Moreover, depictions of corners produce remarkably similar results and should not receive a different theoretical treatment than do real-world scenes. The flattening of vertical angles cannot be explained by a linear distortion of the entire visual space. We suggest that, for natural scenes, compression of space is local and dependent on contextual information.

Adult↗

PubMed1998

Rapidly alternating chemotherapy and radiotherapy instead of cystectomy for the treatment of muscle-invasive carcinoma of the urinary bladder: long term results of a pilot study.

BACKGROUND: The authors studied rapidly alternating chemotherapy and radiotherapy as the initial treatment for patients with muscle-invasive transitional cell carcinomas of the urinary bladder whose advanced age and lack of strength precluded cystectomy. METHODS: Twenty-one patients with T2 (28%) or T3 (72%) NXM0 carcinomas were treated by transurethral resection followed by chemoradiotherapy. Their median age was 73 years. The chemotherapy (consisting of methotrexate, vinblastine, doxorubicin, and cisplatin) was given during Weeks 1, 4 and 7. Radiotherapy (1.8-2 Gray [Gy] twice a day, to a total dose of 18-20 Gy per week) was given during Weeks 2, 5 and 8, for a final dose of 40 Gy to the pelvis plus 14-20 Gy boost to the affected bladder. RESULTS: There was 1 treatment-related death (5% of patients), but otherwise the acute toxicity was relatively mild. Cystoscopy 1 month after chemoradiotherapy did not reveal invasive cancer in any patient. Subsequent cystoscopies detected recurrent invasive cancer in 3 patients after 30, 44, and 82 months, respectively. The observed survival rate after 5 years was 37%, the cause specific survival rate was 63%, the metastasis free rate was 71%, and the local control rate was 80%. Eighty-four percent of patients had normal bladder function. CONCLUSIONS: Transurethral resection plus chemoradiotherapy was successful in preserving bladder function in the majority of the patients. The survival and progression free rates compared favorably with what has been reported recently after radical cystectomy and chemotherapy, and they add to the growing body of evidence that chemoradiotherapy might be a safe, effective alternative to cystectomy for many patients with muscle-invasive carcinoma of the urinary bladder.

Aged↗

PubMed1998

Perceiving topological structure of 2-D patterns.

Four experiments investigated observers' sensitivity to the topological structure of visual stimuli. Three factors were taken to capture the topological structure of 2-D patterns: The number of disconnected components, the number of holes (connections), and inclusion relationships. If studied in isolation, any given topological property is typically confounded with the presence of particular features such as line terminations and contour length, or with Gestalt principles of perceptual organization. We went beyond existing studies and attempted to systematically remove potential confounds from the stimulus displays. Results showed that processing speeds for two-dimensional patterns are a function of their topological properties. The more patterns differ in their topological structure the easier they can be discriminated. Not only do all three topological factors contribute to pattern discriminability, they also can be combined to provide an overall measure of structural complexity. Forced choice comparison techniques agreed well with similarity judgments. Topological structure thus contributed to discriminability above and beyond many confounding variables. Claims suggesting a general topological analyzer in visual processing are discussed.

Adult↗

PubMed1998

Personality in patients with affective disorders and their relatives.

BACKGROUND: In studies of both patients and high-risk subjects, particular patterns of personality have been found to be associated with affective disorders. Neuroticism and features of the melancholic type of personality seem to be risk factors for depression while premorbid features of the manic type of personality predominate in patients with more manic than depressive episodes. While neuroticism prevails in the majority of mental disorders, the 'affective' personality variants appear to be more specifically associated with affective disorders. METHODS: Personality features were investigated in 122 recovered patients with affective disorders, 58 first-degree relatives (high-risk subjects (HR)) and in the respective control groups (n=48; n=29). Patients were subdivided into: unipolar depression (melancholic subtype); bipolar II; bipolar I with more depressive episodes and bipolar I with more manic episodes. Personality measures were based on the Biographical Personality Interview (BPI) and the Munich Personality Test (MPT). RESULTS: The melancholic personality type (BPI) decreased from the unipolar depressives to the mainly manic group, while features of the manic type increased. MPT scores failed to discriminate between subgroups of patients. HR were significantly more introverted and had a stronger orientation towards social norms than controls according to the MPT, and showed a tendency towards the melancholic type according to the BPI. LIMITATIONS: The sizes of some groups or subgroups are relatively small. Therefore, they have to be enlarged in the continuation of the study so as to increase the power of the statistical tests and thus to ascertain the robustness of the results. CONCLUSION: Features of the typus melancholicus seem to be a risk factor for depression. The identification of highly predictive risk factors provides an opportunity for the development of prevention programs.

Adult↗

PubMed1997

Premorbid personality in patients with uni- and bipolar affective disorders and controls: assessment by the Biographical Personality Interview (BPI).

The relationship between premorbid personality and subtypes of affective disorder was investigated by means of the Biographical Personality Interview (BPI) and by a self-rating scale. Interviewer and rater (BPI) were blind to diagnosis. A total of 52 patients with unipolar depression or bipolar II disorder (D/Dm), 32 bipolar-I patients (DM) and 39 control subjects (C) were examined. Expert rating of "typus melancholicus" features (BPI) were found to be more pronounced in D/Dm than in DM and C. "Typus manicus" features were also distinguished between both clinical groups, whereas anxious-insecure features were not significantly different between the groups of patients. In contrast to the expert-rated personality variants, self-rating of personality features did not reveal any significant differences between the two clinical groups. Potential sources of the discrepancies between the questionnaire data and the interview data are discussed. It is concluded that premorbid features of "typus manicus" and "typus melancholicus" predicted, respectively, a predominant manic and a predominant depressive course of an affective disorder.

Adult↗

PubMed1997

Response programming in dementia of the Alzheimer type: a kinematic analysis.

Although planning is important for the functioning of patients with dementia of the Alzheimer Type (DAT), little is known about response programming in DAT. This study used a cueing paradigm coupled with quantitative kinematic analysis to document the preparation and execution of movements made by a group of 12 DAT patients and their age and sex matched controls. Participants connected a series of targets placed upon a WACOM SD420 graphics tablet, in response to the pattern of illumination of a set of light emitting diodes (LEDs). In one condition, participants could programme the upcoming movement, whilst in another they were forced to reprogramme this movement on-line (i.e. they were not provided with advance information about the location of the upcoming target). DAT patients were found to have programming deficits, taking longer to initiate movements, particularly in the absence of cues. While problems spontaneously programming a movement might cause a greater reliance upon on-line guidance, when both groups were required to guide the movement on-line, DAT patients continued to show slower and less efficient movements implying declining sensori-motor function; these differences were not simply due to strategy or medication status.

Aged↗

PubMed1997

[Limits of perceptual robustness in perspective distortion].

Pictures often do not appear distorted even when viewed at oblique angles. Three hypotheses have been put forth to explain this robustness of virtual space toward affine transformations. First, array specificity holds that the perception of depicted space is fully specified by the information available at the point of observation. Second, the notion of a compensatory mechanism involves an unconscious recreation of the scene according to the original viewpoint. Third, the indiscrimination hypothesis denies the ability of the visual system to resolve or detect affine transformations up to a certain degree. Three experiments were conducted to investigate these claims. Using a double projection technique devised by Cutting (1987), Experiment I showed that observers are able to discriminate and compensate, to some degree, for affine transformations if information about the projection surface is available. However, observers relied on relative image velocities rather than reconstructing the object. In Experiment 2 additional observer motion was simulated. In single and double projection trials that required more difficult judgments of object rotation, compensation was poor and observers seemed to rely on local cues. Finally, real and simulated rotation of the projection surface revealed that observers are able to compensate for only one primary projection surface slant. The results reject the indiscrimination hypothesis and support the notion of array specificity.

Adult↗

PubMed1996

Increased sensitivity of the inositol-phospholipid system in neutrophils from patients with acute major depressive episodes.

Evidence from in vitro and in vivo studies suggests that the therapeutic and prophylactic effects of lithium in recurrent affective disorders are due to an attenuation of the inositol-phospholipid (IPL) second messenger system. An increased sensitivity of this signal transduction system might therefore constitute a risk factor for affective illness. The extent of the agonist-induced release of intracellular Ca2+ (Ca2+ response) can be used as an indicator of the sensitivity of the IPL system. Using this paradigm, we have measured the agonist-induced Ca2+ response in neutrophils of 17 unmedicated patients who were experiencing an acute major depressive episode. The neutrophils were stimulated by the chemotactic peptide formylmethionylleucylphenylalanine, which activates the IPL system in the cells. The sensitivity of the IPL system in these patients was significantly greater (dose-response curve shifted to the left) compared with its sensitivity in healthy age- and sex-matched control subjects. The results indicate that acute episodes of major depression are associated with an increased sensitivity of the IPL system.

Adult↗