Biomedical subjects

Christian Kohler

Publications and source records attributed to Christian Kohler.

At least 19 recordsLinked to original sources

PubMed2006

Self-face recognition and theory of mind in patients with schizophrenia and first-degree relatives.

OBJECTIVE: The hypothesized relationship between theory of mind (ToM) and self-face recognition as well as its potential genetic associations has not been previously explored in patients with schizophrenia and in first-degree relatives with schizotypal personality traits. METHOD: Ten patients diagnosed with schizophrenia, 10 of their first-degree relatives and 10 healthy controls were included. To assess self-face recognition (SFR), participants were presented images of faces of themselves and others and asked to make rapid 'unfamiliar', 'familiar' and 'self' judgments. As a measure of ToM, subjects were administered the Revised Mind in the Eyes Test (MET [Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y., and Plumb, I., 2001. The "Reading the Mind in the Eyes" Test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. J Child Psychol Psychiatry 42(2), 241-251.]). Schizotypal characteristics in relatives and controls were assessed using a modified version of the Schizotypal Personality Questionnaire (SPQ [Raine, A., 1991. The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophrenia Bulletin 17(4), 555-564.]). RESULTS: Patients took longer and were less accurate on the SFR task than their relatives who in turn performed worse than healthy controls. Specific ToM deficits in schizophrenia were replicated. There was a relationship between accuracy rates on the MET and SFR tasks. High levels of schizotypal traits such as social anxiety, constricted affect and no close friends were important for both tasks. CONCLUSIONS: Face recognition deficits and ToM deficits in schizophrenia are apparent. The critical influence of high levels of select schizotypal traits is also highlighted. A deficit in relatives of schizophrenia patients raises the possibility that ToM and face recognition deficits may be candidate endophenotypes for schizophrenia. Support for the hypothesized link between ToM and face recognition is provided.

Adult↗

PubMed2006

Staphylococcus aureus carriers neutralize superantigens by antibodies specific for their colonizing strain: a potential explanation for their improved prognosis in severe sepsis.

Staphylococcus aureus is one of the most common causes of hospital-acquired infections. At the same time, 25% of healthy persons are symptom-free S. aureus carriers, and they have an increased risk of developing nosocomial S. aureus septicemia. Paradoxically, their prognosis is much better than that of noncarriers. We compared the antibody profiles for carriers and noncarriers toward S. aureus superantigens. In carriers, we found high titers of neutralizing antibodies specific for those superantigens that are expressed by their colonizing strain. The results show that carriage status confers strain-specific humoral immunity, which may contribute to protection during S. aureus septicemia.

Antibodies, Bacterial↗

PubMed2006

Fast digital hologram generation and adaptive force measurement in liquid-crystal-display-based holographic tweezers.

Computer-generated holograms in conjunction with spatial light modulators (SLMs) offer a way to dynamically generate holograms that are adapted to specific tasks. To use the full dynamic capability of the SLM, the hologram computation should be very fast. We present a method that uses the highly parallel architecture of a consumer graphics board to compute analytical holograms in video real time. A precice characterization of the SLM (Holoeye LC-R-2500) and the adaption of its settings to our near-infrared application is necessary to guarantee an efficient hologram reconstruction. The benefits of a fast computation of adapted holograms and the application of an efficient SLM are demonstrated by measuring the trapping forces of holographic tweezers.

Journal Article↗

PubMed2006

Optimally tuned spatial light modulators for digital holography.

Digital holography and comparative digital holography are applications that require computer-addressable modulators for the optical reconstruction of digital holograms. The quality of the reconstructed holograms depends on the modulator's properties. Therefore a characterization of the modulators is required. We show the result of a modulator characterization and the modulator's influence on the quality of the reconstructed hologram. We then compare qualitatively and quantitatively the optical reconstruction of phase and amplitude holograms by considering their level of detail and their diffraction efficiency.

Journal Article↗

PubMed2006

Levels-of-processing effect on internal source monitoring in schizophrenia.

BACKGROUND: Recognition can be normalized in schizophrenia by providing patients with semantic organizational strategies through a levels-of-processing (LOP) framework. However, patients may rely primarily on familiarity effects, making recognition less sensitive than source monitoring to the strength of the episodic memory trace. The current study investigates whether providing semantic organizational strategies can also normalize patients' internal source-monitoring performance. METHOD: Sixteen clinically stable medicated patients with schizophrenia and 15 demographically matched healthy controls were asked to identify the source of remembered words following an LOP-encoding paradigm in which they alternated between processing words on a 'shallow' perceptual versus a 'deep' semantic level. A multinomial analysis provided orthogonal measures of item recognition and source discrimination, and bootstrapping generated variance to allow for parametric analyses. LOP and group effects were tested by contrasting recognition and source-monitoring parameters for words that had been encoded during deep versus shallow processing conditions. RESULTS: As in a previous study there were no group differences in LOP effects on recognition performance, with patients and controls benefiting equally from deep versus shallow processing. Although there were no group differences in internal source monitoring, only controls had significantly better performance for words processed during the deep encoding condition. Patient performance did not correlate with clinical symptoms or medication dose. CONCLUSIONS: Providing a deep processing semantic encoding strategy significantly improved patients' recognition performance only. The lack of a significant LOP effect on internal source monitoring in patients may reflect subtle problems in the relational binding of semantic information that are independent of strategic memory processes.

Adult↗

PubMed2005

Proteome analyses of Staphylococcus aureus in growing and non-growing cells: a physiological approach.

Staphylococcus aureus is a versatile human pathogen causing a wide variety of diseases ranging from wound infection to endocarditis, osteomyelitis, and sepsis. In order to investigate this pathogen, we sought to analyze the cytoplasmic proteome of S. aureus COL by using two different approaches: two-dimensional (2D) gel analyses combined with matrix-assisted laser ionization-time of flight mass spectrometry and a gel-free system using multidimensional liquid chromatography followed by mass spectrometry. By combining both analyses we identified 1123 cytoplasmic proteins that represent two-thirds of the cytoplasmic proteome of the organism. With our standard 2D gel setup (pI 4-7) we identified 473 proteins that cover about 40% of the cytoplasmic proteome predicted for this proteomic window. The identified proteins belong to a variety of cellular functions ranging from the transcriptional and translational machinery, tricarboxylic acid cycle (TCC), glycolysis, and fermentation pathways to biosynthetic pathways of nucleotides, fatty acids, and cell wall components. While most of the metabolic pathways predicted for S. aureus were covered by this gel-based proteomics 650 additional proteins were identified by the gel-free approach, among them alkaline or hydrophobic proteins. In our work, we established a master 2D gel that enabled us to study the regulation of core carbon metabolism in S. aureus cells grown in a complex medium. Our comparison of the protein pattern of exponentially growing cells with that of stationary-phase cells revealed a higher amount of enzymes involved in protein synthesis, transcription, and glycolysis in exponentially growing cells. In contrast, enzymes of the TCC and gluconeogenesis are increased at the stationary phase. With this comprehensive proteome map we have an essential tool for a better understanding of cell physiology of the human pathogen, S. aureus.

Adaptation, Physiological↗

PubMed2005

Global-local visual processing in schizophrenia: evidence for an early visual processing deficit.

BACKGROUND: Abnormalities in early-stage visual processing might contribute to observed higher neurocognitive deficits in schizophrenia, but to date no clear link has been established. Schizophrenia has been associated with deficits in the magnocellular visual pathway, suggesting a relative bias for processing elemental (local) as opposed to configural (global) aspects of a hierarchical stimulus; however, global-local paradigm studies in schizophrenia have yielded mixed results. METHODS: In the current study, global-local and event-related potential (ERP) procedures were concomitantly used to assess temporal and spatial characteristics of hierarchical visual stimulus processing abnormalities. RESULTS: Patients (n = 24) had slower and less accurate responses to global stimuli than a healthy comparison group (n = 29). They exhibited a marked decrement in N150 ERP amplitude, which correlated with speed of response to global stimuli. They also failed to show an augmented P300 response to local stimuli. CONCLUSIONS: Behavioral and physiological data are consistent and support a global visual processing deficit in schizophrenia. This is manifest at a relatively early stage of visual processing and might relate to physiological disturbances in areas V3/V3a of the extrastriate cortex.

Adolescent↗

PubMed2005

Quantification of facial expressions using high-dimensional shape transformations.

We present a novel methodology for quantitative analysis of changes in facial display as the intensity of an emotion evolves from neutral to peak expression. The face is modeled as a combination of regions and their boundaries. An expression change in a face is characterized and quantified through a combination of non-rigid (elastic) deformations, i.e., expansions and contractions of these facial regions. After elastic interpolation, this yields a geometry-based high-dimensional 2D shape transformation, which is used to register regions defined on subjects (i.e., faces with expression) to those defined on the reference template face (a neutral face). This shape transformation produces a vector-valued deformation field and is used to define a scalar valued regional volumetric difference (RVD) function, which characterizes and quantifies the facial expression. The approach is applied to a standardized database consisting of single images of professional actors expressing emotions at predefined intensities. We perform a detailed analysis of the deformations generated and the regional volumetric differences computed for expressions. We were able to quantify subtle changes in expression that can distinguish the intended emotions. A model for the average expression of specific emotions was also constructed using the RVD maps. This method can be applied in basic and clinical investigations of facial affect and its neural substrates.

Adolescent↗

PubMed2005

Levels-of-processing effect on frontotemporal function in schizophrenia during word encoding and recognition.

OBJECTIVE: Patients with schizophrenia improve episodic memory accuracy when given organizational strategies through levels-of-processing paradigms. This study tested if improvement is accompanied by normalized frontotemporal function. METHOD: Event-related blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) was used to measure activation during shallow (perceptual) and deep (semantic) word encoding and recognition in 14 patients with schizophrenia and 14 healthy comparison subjects. RESULTS: Despite slower and less accurate overall word classification, the patients showed normal levels-of-processing effects, with faster and more accurate recognition of deeply processed words. These effects were accompanied by left ventrolateral prefrontal activation during encoding in both groups, although the thalamus, hippocampus, and lingual gyrus were overactivated in the patients. During word recognition, the patients showed overactivation in the left frontal pole and had a less robust right prefrontal response. CONCLUSIONS: Evidence of normal levels-of-processing effects and left prefrontal activation suggests that patients with schizophrenia can form and maintain semantic representations when they are provided with organizational cues and can improve their word encoding and retrieval. Areas of overactivation suggest residual inefficiencies. Nevertheless, the effect of teaching organizational strategies on episodic memory and brain function is a worthwhile topic for future interventional studies.

Adult↗

PubMed2004

A sexually dimorphic ratio of orbitofrontal to amygdala volume is altered in schizophrenia.

BACKGROUND: Neuroanatomic sexual dimorphisms have been correlated with behavioral differences between healthy men and women. We have reported higher orbitofrontal cortex to amygdala ratio (OAR) in women than men. Although gender differences in schizophrenia are evident clinically and correlate with neuroanatomic measures, their relationship to OAR has not been examined. METHODS: Magnetic resonance imaging was performed in 31 neuroleptic-naïve schizophrenic patients (16 men) and 80 healthy volunteers (34 men), aged less than 50 years. An automated tissue segmentation procedure was combined with expert-guided parcellation of orbitofrontal and amygdala volumes. RESULTS: Men with schizophrenia had increased OAR relative to healthy men, whereas women had decreased OAR. Increased OAR in men with schizophrenia reflected abnormally low amygdala volumes, whereas decreased OAR in women reflected abnormally low orbitofrontal volumes. Less severe negative symptoms were associated with increased OAR in men but with decreased OAR in women. In men, increased amygdala volume was associated with greater symptom severity, whereas in women higher volumes of both amygdala and orbitofrontal regions were associated with lesser severity of negative symptoms. CONCLUSIONS: These opposite OAR abnormalities, whereby men show feminization and women masculinization, suggest gender-mediated effects of the underlying neuropathologic processes. The correlations with symptom severity suggest that neuroanatomic abnormalities in OAR reflect compensatory brain changes.

Adult↗

PubMed2004

Chronic antidepressants reverse cerebrocortical allopregnanolone decline in the olfactory-bulbectomized rat.

Olfactory bulbectomy is one of the most validated models of depression. We demonstrate that bilateral removal of the olfactory bulbs in rats produced a significant decline of allopregnanolone content in a select cerebrocortical area which was reversed by chronic (3-week) treatment with three different classes of antidepressant (desipramine, fluoxetine, and sertraline, and venlafaxine). The effects of the chronic antidepressant treatments on allopregnanolone cortical content are observed at a time which typically coincides with the drug's abilities to reverse the behavioral deficits of the bulbectomy syndrome. We therefore propose that normalization of allopregnanolone cerebrocortical levels may contribute to the antidepressant-like profile of these drugs in the olfactory-bulbectomized rat model of depression.

Animals↗

PubMed2004

Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia.

OBJECTIVE: Neuropsychological studies have demonstrated verbal episodic memory deficits in schizophrenia during word encoding and retrieval. This study examined neural substrates of memory in an analysis that controlled for successful retrieval. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation during word encoding and recognition in 14 patients with schizophrenia and 15 healthy comparison subjects. An unbiased multiple linear regression procedure was used to model the BOLD response, and task effects were detected by contrasting the signal before and after stimulus onset. RESULTS: Patients attended during encoding and had unimpaired reaction times and normal response biases during recognition, but they had lower recognition discriminability scores, compared with the healthy subjects. Analysis of contrasts was restricted to correct items. Previous findings of a deficit in bilateral prefrontal cortex activation during encoding in patients were reproduced, but patients showed greater parahippocampal activation rather than deficits in temporal lobe activation. During recognition, left dorsolateral prefrontal cortex activation was lower in the patients and right anterior prefrontal cortex activation was preserved, as in the authors' previous study using positron emission tomography. Successful retrieval was associated with greater right dorsolateral prefrontal cortex activation in the comparison subjects, whereas orbitofrontal, superior frontal, mesial temporal, middle temporal, and inferior parietal regions were more active in the patients during successful retrieval. CONCLUSIONS: The pattern of prefrontal cortex underactivation and parahippocampal overactivation in the patients suggests that functional connectivity of dorsolateral prefrontal and temporal-limbic structures is disrupted by schizophrenia. This disruption may be reflected in the memory strategies of patients with schizophrenia, which include reliance on rote rehearsal rather than associative semantic processing.

Adult↗

PubMed2003

Region-specific dysregulation of allopregnanolone brain content in the olfactory bulbectomized rat model of depression.

Allopregnanolone (ALLO) is one of the most potent positive endogenous allosteric modulators of the type A gamma-aminobutyric acid (GABA(A)) receptors. While the robust anxiolytic profile of ALLO has been extensively characterized in rodents and its antidepressant-like effect was recently demonstrated in mice, there have been only few reports on alterations of brain ALLO levels in putative animal models of depression and anxiety. Removal of the olfactory bulbs of rats produces one of the most predictive animal models with which to screen for drugs with potential antidepressant activity following repeated treatment. We therefore investigated whether the olfactory bulbectomized (OB) rat model of depression may be associated with alterations of ALLO levels in whole brain tissue and in different brain regions. We determined ALLO levels in whole brain, amygdala, frontal cortex, hippocampus, and whole cerebral cortex of OB or sham-operated rats at 7, 14, or 28 days following bulbectomy or sham surgery. We observed a significant increase of whole brain ALLO content at 7 and 28 days post-surgery in the OB rats. At days 7 and 14 following olfactory bulb removal, ALLO levels were significantly decreased in amygdala and frontal cortex and significantly increased in whole cerebral cortex. In the hippocampus we observed only a tendency for decreased ALLO levels at day 14. Our data indicates a strong region-specific dysregulation of ALLO homeostasis in brains of OB rats which may contribute to the formation of the bulbectomy syndrome via a sustained reduction in physiological GABA-ergic tone in amygdala and frontal cortex.

Animals↗

PubMed2003

Neurocognitive performance and clinical changes in olanzapine-treated patients with schizophrenia.

Diffuse cognitive impairment characterizes patients with schizophrenia throughout the course of illness. The deficits persist despite clinical improvement associated with neuroleptic intervention and are related to outcome. It is unclear whether treatment with atypical agents is associated with improved cognition that relates to symptoms and outcome. Using a set of computerized neurocognitive measures, we evaluated whether the effects of olanzapine are greater than practice effects for specific neurocognitive domains that could provide targets for large-scale randomized studies. We enrolled 19 patients with schizophrenia before initiation of treatment with olanzapine and 16 of them were examined at 6 weeks and 6 months of follow-up. They were compared to 34 healthy participants who enrolled, 24 of whom were evaluated longitudinally. Improvement exceeding practice effects was observed in patients for abstraction and spatial memory and the latter correlated with clinical improvement in negative symptoms. These results suggest that some effects of olanzapine may impact both symptoms and cognitive performance.

Adolescent↗

PubMed2003

Physiological characterization of a heme-deficient mutant of Staphylococcus aureus by a proteomic approach.

The high-resolution two-dimensional (2D) protein gel electrophoresis technique combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry was used for identification of proteins whose levels were changed by a mutation in hemB. Cytoplasmic protein extracts obtained from the mutant and the wild type (strain COL) at different stages of growth in tryptone soya broth (exponential, transitional, and stationary growth phases) were separated on 2D protein gels. Comparison of the 2D patterns of the protein extracts of the two strains revealed major differences. Because the electron transport chain of the mutant is interrupted due to the deficiency of heme, this organism should be unable to use oxygen or nitrate as a terminal electron acceptor. Consistent with this hypothesis, proteins involved in the glycolytic pathway and related pathways (glyceraldehyde-3-phosphate dehydrogenase, enolase, and phosphoglycerate kinase) and in fermentation pathways (lactate dehydrogenase, alcohol dehydrogenase, and pyruvate formate lyase) were induced in exponentially growing cells of the mutant. These results strongly indicate that the hemB mutant generates ATP from glucose or fructose only by substrate phosphorylation. Analyses of the fermentation reactions showed that the main product was lactate. Although pyruvate formate lyase (Pfl) and pyruvate dehydrogenase were present, neither ethanol nor acetate was detected in significant amounts. Presumably, Pfl was not activated in the presence of oxygen, and pyruvate dehydrogenase might have very low activity. Transcriptional analysis of citB, encoding the aconitase, revealed that the activity of the citrate cycle enzymes was down-regulated in the hemB mutant. The arginine deiminase pathway was also induced, and it could provide ATP as well. Furthermore, the amounts of most of the extracellular virulence factors were significantly reduced by a mutation in hemB, which is consistent with previous reports.

Acetyltransferases↗

PubMed2003

Impairment of odor hedonics in men with schizophrenia.

OBJECTIVE: Olfactory deficits in patients with schizophrenia, including those of odor identification, detection threshold sensitivity, discrimination, and memory, have been well described. Deficits in emotional perception, processing, and experience have also been reported, with anhedonia being one of the core features. While anatomical connections testify to the relationship between olfaction and emotion, there has been little investigation of the hedonic properties of odors in schizophrenia. This study examined intensity and hedonic judgments in patients with schizophrenia to determine whether these functions were differentially impaired. METHOD: Suprathreshold scaling of odor intensity and pleasantness was acquired by using the Suprathreshold Amyl Acetate Odor Intensity and Odor Pleasantness Rating Test given to 30 patients (15 men and 15 women) with a DSM-IV diagnosis of schizophrenia and 30 age- and sex-matched healthy comparison subjects. RESULTS: Despite virtually identical ratings of odor intensity, male patients were impaired in the assignment of odor pleasantness to amyl acetate. This gender-specific diagnostic group difference was not explained by variability in symptom severity or negative/positive symptoms. The impact of smoking status and general cognitive impairment on this deficit was also insignificant. CONCLUSIONS: Findings reveal a gender-specific disruption in the ability to attribute appropriate hedonic valence to odors in male patients with schizophrenia. This difficulty in identifying the hedonic valence of odors, despite intact intensity ratings, is consistent with clinical observations of anhedonia and points to a neural substrate that might contribute to the emotional disturbances seen in patients with schizophrenia.

Adult↗

PubMed2003

Societal dimensions of third-party evaluation of Internet health content.

Rating and certification of Internet health content have been suggested as strategies to guide citizens to high quality information. Attempts to rate Internet content, however, have been criticised for being unfeasible or undesirable. We created and tested a novel concept and technology to evaluate online health resources. In this paper, we view various societal issues and suggest solutions whenever possible. Rating and certification of Internet content should be preceded by a consideration and discussion that has many societal dimensions.

Access to Information↗

PubMed2002

Development of an abbreviated schizophrenia quality of life scale using a new method.

The goal of the study was to develop and apply a predictive model approach to reduce the number of items collected for scales that yield a total summary score. A parsimonious subset of items from the 21-item Quality of Life Scale (QLS) that can accurately predict the total scale score was sought and evaluated in 198 patients with schizophrenia, using a statistical modeling approach. Two additional data sets were used for model validation: the subset of 101 patients used in the model construction who had the QLS administered approximately 1 year later and a new sample of 37 patients. Using only seven QLS items as predictors, the correlation was 0.9831 between the predicted and true QLS totals. Applying the model based for these seven QLS items, the correlations from the first and second validation data sets were 0.9791 and 0.9637, respectively. The study demonstrates that a small subset of items of the QLS predicts the entire 21-item scale with high accuracy. Two validation samples have confirmed the finding. This reduces the effort associated with scale administration and is likely to increase the assessment of an important functional domain. Such models can guide efforts for item reduction in other rating instruments.

Adolescent↗