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Biomedical subjects

Z Janka

Publications and source records attributed to Z Janka.

At least 19 recordsLinked to original sources

Unchanged rat brain amyloid precursor protein levels after exposure to benzodiazepines in vivo.

BACKGROUND AND OBJECTIVE: Recent studies emphasize a positive correlation between (cardiac) surgical interventions and increased risk for developing Alzheimer's disease in the late postoperative period. Since amyloid precursor protein and its neurotoxic derivatives play key roles in the development of Alzheimer's dementia, the impact of several agents used in the intra- and perioperative period is examined. METHOD: Amyloid precursor protein concentrations were assessed by semi-quantitative Western-immunoblot in brains of rats following intraperitoneal treatment with diazepam and midazolam. RESULTS: There were no significant changes in the amyloid precursor protein concentrations. CONCLUSION: Both diazepam and midazolam are considered to be relatively safe with respect to amyloid precursor protein metabolism.

Alzheimer Disease↗

Gene expression profile analysis of lymphocytes from Alzheimer's patients.

Since the function and metabolism of peripheral lymphocytes is known to be altered in Alzheimer's disease (AD), a pilot study was carried out to examine differences in gene expression profiles of these cells in 16 AD patients and aged control probands. Using a cDNA microarray representing 3200 distinct human genes, we identified 20 candidate genes whose expression is altered in AD lymphocytes compared with the control probands. Among these were the alpha2C-adrenoreceptor gene, known to regulate blood pressure and learning, the defensin, histocompability complex enhancer-binding protein, carboxypeptidase M, and the Fc fragment of IgE known to be involved in cellular and humoral immune responses. Others, like human cell death protein, TRAIL, and galectin-4 participate in the regulation of apoptosis. Real-time quantitative reverse transcription-polymerase chain reaction analysis was performed in order to confirm the expression changes in AD lymphocytes, and it could detect down-regulation of defensin and alpha2c-adrenoceptor genes, while other genes seemed unaltered in their expression, including heat-shock protein (hsp90), cholesteryl ester transfer protein, and apolipoprotein B100 (apoB). The altered expression profile of these genes might be connected with the previously reported AD-specific lymphocyte abnormalities. It remains to be elucidated, however, how these genes are related to the pathomechanism of dementia and whether the gene expression differences of AD lymphocytes reflect disease traits or stage processes.

Aged↗

Patients with schizophreniform disorder use verbal descriptions for the representation of visual categories.

BACKGROUND: Neuropsychological impairment is a common finding in schizophrenia. However, a significant proportion of patients are not impaired in conventional neuropsychological tests. In this study, we investigated whether remitted patients with schizophreniform disorder exhibited dysfunctions in specific cognitive tasks. METHOD: Twenty remitted, highly functioning patients with schizophreniform disorder and 20 control subjects participated in the study. In addition to background neuropsychological evaluation (WAIS-R IQ, Wisconsin Card Sorting Test (WCST), Trail Making B, Rey Osterrieth Complex Figure), subjects received a category learning task. The categories consisted of geometric shapes systematically changing in shape and size. Training included the sequential presentation of category members (visual learning) and verbal description of categories. RESULTS: The patients with schizophreniform disorder had normal IQ, executive functions/psychomotor speed (WCST and Trail Making B) and visual memory (Rey-Osterrieth Complex Figure). In contrast, they displayed impaired categorization performances after visual learning. The performance of the patients improved markedly after verbal description of categories. Verbal knowledge about categories positively correlated with categorization performance in the patients, but not in the controls. CONCLUSIONS: Category learning functions, which include decision-making under uncertainty and feature integration, are impaired in patients with schizophreniform disorder who display normal executive functions and visual memory. These patients may use verbal knowledge as a compensatory strategy in visual tasks.

Adult↗

No evidence for impaired 'theory of mind' in unaffected first-degree relatives of schizophrenia patients.

OBJECTIVE: The aim of this study was to investigate the possibility that 'theory of mind' (ToM) impairments are associated with schizophrenia liability. METHOD: Forty healthy control subjects and 79 first-degree biological relatives of schizophrenia patients (32 siblings and 47 parents) received the Eyes Test, during which subjects are asked to choose the word best describes the mental state of a person whose eyes are depicted on a photograph. RESULTS: The affected relatives (n = 14) performed worse on the Eyes Test compared with the controls (P = 0.0001), whereas the unaffected relatives (n = 65) showed intact performances (P = 0.4). The Eyes Test values did not correlate with age and IQ. There was no significant difference between male and female participants. CONCLUSION: ToM deficits, as measured by the Eyes Test, are not associated with schizophrenia liability.

Adult↗

Critical evaluation of cognitive dysfunctions as endophenotypes of schizophrenia.

OBJECTIVE: Cognitive dysfunctions are potential endophenotypes of schizophrenia. The aim of this study was to investigate whether recent evidence indeed suggests that cognitive dysfunctions are potent indicators of specific genetic traits that represent susceptibility for schizophrenia. METHOD: Studies including large, well-defined samples and controlled cognitive assessment have been reviewed. RESULTS: Evidence suggests that schizophrenia patients and their unaffected biological relatives are impaired in several cognitive domains, including working memory, executive functions, sustained attention, verbal episodic memory, processing of visual and auditory stimuli, and smooth pursuit eye movements. However, these impairments are present only in a limited proportion of subjects, showing low specificity and sensitivity and high variability. Linkage with specific genes is weak. CONCLUSION: Although some results are promising, at present cognitive dysfunctions cannot be considered as highly sensitive and specific endophenotypes of schizophrenia.

Case-Control Studies↗

Dopaminergic contributions to the visual categorization of natural scenes: evidence from Parkinson's disease.

Recent evidence raised the possibility that dopaminergic mechanisms in the neostriatum play an important role in categorization. In this study, we examined the electrophysiological correlates of natural scene categorization in Parkinson's disease (PD), which is characterized by the depletion of dopamine in the neostriatum. Event-related potentials (ERPs) were recorded in PD patients and age-matched control subjects using a natural scene categorization task. Subjects had to decide whether a briefly presented image contained animals or non-animals. In the control group, the mean amplitudes of N1 (150-250 ms) and N2 components (400-600 ms) were more negative for non-animal scenes as compared with stimuli containing animals, whereas P2 (250-350 ms) was more positive for animals. In contrast, in the PD group the mean amplitudes of N1 and N2 components were similar for both animal and non-animal stimuli, and the P2 amplitudes were reduced. In the case of N1 peak latency, there was no between-group difference, whereas the N2 and P2 components were significantly delayed in the PD group. These results suggest that both perceptual (N1) and semantic (N2) processes related to the categorization of natural scenes are specifically impaired in PD. In the temporal domain, the slowed semantic processing is preceded by a relatively normally paced perceptual analysis. These findings are in agreement with the hypothesis emphasizing the importance of striatal dopaminergic mechanisms in classification functions.

Aged↗

Codon 311 (Cys --> Ser) polymorphism of paraoxonase-2 gene is associated with apolipoprotein E4 allele in both Alzheimer's and vascular dementias.

The gene of an esterase enzyme, called paraoxonase (PON, EC.3.1.8.1.) is a member of a multigene family that comprises three related genes PON1, PON2, and PON3 with structural homology clustering on the chromosome 7.(1,2) The PON1 activity and the polymorphism of the PON1 and PON2 genes have been found to be associated with risk of cardiovascular diseases such as hypercholesterolaemia, non-insulin-dependent diabetes, coronary heart disease (CHD) and myocardial infaction.(3-8) The importance of cardiovascular risk factors in the pathomechanism of Alzheimer's disease (AD) and vascular dementia (VD)(9-13) prompted us to examine the genetic effect of PON2 gene codon 311 (Cys-->Ser; PON2*S) polymorphism and the relationship between the PON2*S allele and the other dementia risk factor, the apoE polymorphism in these dementias. The PON2*C and PON2*S allele frequencies were similar in both AD (25% and 75%) and VD groups (23% and 77%), respectively, compared with the controls (27% and 73%). The ratio of the PON2*S carriers was significantly higher among the apoE4 allele carrier AD (27%) and VD (25%) groups than in the control (12%). Our results indicate that the PON2*S and apoE4 alleles have interactive effect on the development of the two most common forms of dementias AD and VD, and further support the hypothesis that cardiovascular factors contribute to the development of AD.

Aged↗

Intact prototype learning in schizophrenia.

In this study, we examined executive functions and visual prototype learning in patients with schizophrenia (n=22) and matched healthy control subjects (n=20). The patients demonstrated marked perseveration in the Wisconsin Card Sorting Test (WCST), whereas they successfully learned prototypes of dot-pattern category exemplars. These findings are against the hypothesis of a pure generalized cognitive dysfunction in schizophrenia, providing preliminary evidence for intact neocortical mechanisms related to perceptual classification functions.

Adult↗

[Impaired visual information processing in unaffected siblings of schizophrenia patients].

Recent research has provided evidence that certain psychophysiological dysfunctions are present in non-psychotic biological relatives of schizophrenia patients. A new candidate for such studies is the visual backward masking (VBM) dysfunction. In this study, the authors compared the VBM and Wisconsin Card Sorting Test (WCST) performances of unaffected siblings of schizophrenia patients with that of normal volunteers with a negative family history. In the BM test, a briefly presented target letter must be recognized, which is followed by an irrelevant stimulus (mask). The WCST assesses higher-level cognitive (prefrontal) functions of categorization and attentional set-shifting. Despite their intact psychosocial and general intellectual functions, the unaffected relatives of schizophrenia patients showed lower BM performances in comparison with the controls, which was restricted to short interstimulus intervals (< 60 ms). In the controls, there was a non-linear (N-shaped) masking function, whereas in the relatives no similar effects were found. There was no significant difference in the WCST performances. These results suggest that the dysfunction of early sensory-perceptual processes is a trait marker of schizophrenia.

Adolescent↗

Remitted schizophrenia-spectrum patients with spared working memory show information processing abnormalities.

Working memory and information processing abnormalities are often reported in schizophrenia. The aim of this study was to examine visual backward masking (BM) functions in remitted schizophrenia-spectrum patients with spared working memory functions. Seventy-two patients with DSM-IV schizophrenia-spectrum disorders were screened using the Wisconsin Card Sorting Test (WCST) and the digit span forward/backward tasks. Patients with spared WCST and digit span performances were selected and administered a spatial working memory test and two BM procedures (target identification and location). The schizophrenia-spectrum group with spared WCST and digit span performances included individuals with schizophreniform disorder (N=11), schizophrenia (N=2), and schizoaffective disorder (N=2). These patients were clinically remitted and demonstrated spared IQ, normal spatial working memory, and relatively high psychosocial functioning. However, there was a significant impairment in the BM procedure, most prominently in the target location task and at short interstimulus intervals. These results suggest that the BM dysfunction is a trait marker of schizophrenia-spectrum disorders and may be present in the absence of working memory abnormalities.

Adult↗

Are Alzheimer's disease patients able to learn visual prototypes?

Recently, controversial results emerged regarding visual prototype learning in Alzheimer's disease (AD). The aim of this study was to elucidate this issue in a larger population of AD patients. The AD patients (N=72) and age-matched healthy control subjects (N=25) learned to recognize and to categorize visual dot patterns. In comparison with the control subjects, the AD patients as a group showed dysfunctions in the recognition task, whereas categorization was relatively spared in their case. Recognition was impaired in patients with mild AD (Mini-Mental score: 18-23) and moderate AD (Mini-Mental score<18), whereas categorization was impaired only in patients with moderate AD. These results suggest that while the medio-temporal/diencephalic explicit memory system is markedly affected even in early AD, the sensory neocortical areas mediating implicit category learning display a sufficient degree of functional capacity until later stages of the disease.

Aged↗

Event-related potentials from a visual categorization task.

Investigation of the neural bases of human perceptual categorization is a continuously growing territory of visual sciences. Recently, several papers appeared on the cortical bases of human categorization performance, using functional brain imaging techniques such as positron emission tomography (PET) or functional magnetic resonance imaging (fMRI). However, the cheaper commercially available laboratory tests are not always the best methods to study multiple aspects of visual categorization. In this study, we describe the electrophysiological correlates of natural scene categorization in humans. The subject's task was to decide whether briefly presented natural scenes contained animal or non-animal items. Analysis of event-related potentials (ERPs) recorded during the categorization task, revealed more negative potentials for non-animal stimuli (NAS) in the time windows of 150-250 ms (N1) and 350-500 ms (N2), and more positive potentials for animal stimuli (AS) in the time window of 250-350 ms (P2). Our work provides an inexpensive noninvasive method to study both early perceptual and late phases of semantic information processing by recording ERPs during the categorization of natural scenes.

Evoked Potentials, Visual↗

Different trait markers for schizophrenia and bipolar disorder: a neurocognitive approach.

BACKGROUND: The aim of this study was to assess visual information processing and cognitive functions in unaffected siblings of patients with schizophrenia, bipolar disorder and control subjects with a negative family history. METHODS: The siblings of patients with schizophrenia (N = 25), bipolar disorder (N = 20) and the controls subjects (N = 20) were matched for age, education, IQ, and psychosocial functioning, as indexed by the Global Assessment of Functioning scale. Visual information processing was measured using two visual backward masking (VBM) tests (target location and target identification). The evaluation of higher cognitive functions included spatial and verbal working memory, Wisconsin Card Sorting Test, letter fluency, short/long delay verbal recall and recognition. RESULTS: The relatives of schizophrenia patients were impaired in the VBM procedure, more pronouncedly at short interstimulus intervals (14, 28, 42 ms) and in the target location task. Marked dysfunctions were also found in the spatial working memory task and in the long delay verbal recall test. In contrast, the siblings of patients with bipolar disorder exhibited spared performances with the exception of a deficit in the long delay recall task. CONCLUSIONS: Dysfunctions of sensory-perceptual analysis (VBM) and working memory for spatial information distinguished the siblings of schizophrenia patients from the siblings of individuals with bipolar disorder. Verbal recall deficit was present in both groups, suggesting a common impairment of the fronto-hippocampal system.

Adult↗

Comparative studies on [Ca2+]i-level of fibroblasts from Alzheimer patients and control individuals.

The accumulation of the beta-amyloid peptide (betaAP) in the brain, produced from the ubiquitously expressed amyloid precursor protein (APP) is a defining feature of Alzheimer's disease (AD). Consistent with studies demonstrating the importance of skin biopsy in the diagnosis of neurodegenerative disorders, we investigated whether differences in intracellular free calcium levels ([Ca2+]i) of cultured cutaneous fibroblasts derived from sporadic AD patients and from age-matched control individuals might be present. [Ca2+]i was measured in Fura-2AM-loaded human fibroblasts by dual wavelength spectrofluorimetry. AD cells exhibited lower [Ca2+]i as compared to the control cultures. Exposure of fibroblasts to betaAP resulted in increased [Ca2+]i of the control cells, but not of AD fibroblasts. Our test could prove useful in supporting the diagnosis of (sporadic) AD in patients suspected of suffering from the disease.

Aged↗

Visual information processing in patients with schizophrenia: evidence for the impairment of central mechanisms.

Patients with schizophrenia are especially impaired in the detection of spatial location if the briefly presented target stimulus is followed by a mask in a close temporal proximity (target location backward masking (BM) paradigm). It has been suggested that this phenomenon is related to the impairment of low spatial and high temporal frequency-sensitive transient (magnocellular) visual channels. To test this hypothesis, we measured target location BM and visual contrast sensitivity (CS) in clinically remitted patients with schizophrenia. In the BM task, subjects were asked to indicate the position of letters appearing at four possible spatial locations. In the CS test, a two-alternative forced choice method was used to measure the minimal contrast level required for the detection of horizontal gratings set at low spatial and high temporal frequencies (0.5 cycle/degree and 8 Hz, respectively). We found that the schizophrenia patients with normal CSs (spared transient channel functions) showed a marked deficit in the target location BM task. This suggests that the abnormality of subcortical transient channels does not explain some visual information processing dysfunctions in schizophrenia. Instead, deficient cortical interactions of rapidly changing environmental signals may be involved.

Adult↗

P300 component of visual event-related potentials distinguishes patients with idiopathic parkinson's disease from patients with essential tremor.

A considerable rate of misdiagnosis has recently been reported in movement disorders. One of the most difficult clinical problems is the differentiation of Parkinson's disease and essential tremor. In this study, we have examined whether event-related potentials (ERPs) could aid in the solution of this differential diagnostic problem. Visual ERPs were obtained by using an "oddball" paradigm in 20 patients with idiopathic Parkinson's disease (IPD), 20 patients with essential tremor (ET), and 20 age-matched control subjects. We found that the P300 amplitudes were selectively reduced in the IPD group at the midline (Fz, Cz, Pz) electrode sites, whereas the ET group exhibited selectively elevated P300 amplitudes at the left parietal and frontal (F3, P3) recording sites. The patients with IPD, but not ET, showed a significant prolongation of the P300 latency at each electrode site. Similarly, only the IPD patients were significantly slower in responding to the target stimulus. The primary visual evoked potential (P100) did not distinguish among the IPD, ET, and control subjects. These results suggest that visual ERPs might provide a useful diagnostic method for differentiating IPD from ET.

Aged↗

Early and late components of visual categorization: an event-related potential study.

We examined the characteristics of early and late components of event-related potentials (ERPs) accompanying the visual categorization of natural scenes. In the first experiment, ERPs were recorded in an animal-non-animal categorization task (CT), whereas the second experiment included a spatial frequency discrimination task (DT). In the CT, there were more negative potentials for non-animals in the time windows of 150-250 ms (N1) and 350-500 ms (N2), and a more positive potential for animals in the time window of 250-350 ms (P2). In the DT, spatial frequency gratings evoked only a short-duration difference N1 at the frontal sites. Our results suggest that N1 may be related to higher-level categorization processes.

Adult↗