ALTERED BOLD RESPONSE WITHIN THE CORE FACE-PROCESSING NETWORK IN CONGENITAL PROSOPAGNOSIA.

BACKGROUND AND PURPOSE: Congenital prosopagnosia is a life-long disorder of face perception. To study the neural backgrounds of congenital prosopagnosia we measured the blood oxygen level-dependent response of congenital prosopagnosic participants, using functional magnetic resonance imaging. METHODS: We tested three persons of the family (father, daughter and son), having symptoms of congenital prosopagnosia, as well as healthy controls, using combined neuropsychological and functional magnetic resonance imaging methods. To reveal the neural correlates of the impairments, blood oxygen level-dependent responses within the occipito-temporal cortex were measured to faces and nonsense object images in a block-design experiment. RESULTS: Neuropsychological tests demonstrated significant impairments of face perception/recognition in each subject. We found that the activity of the fusiform and occipital face areas as well as of the lateral occipital cortex was significantly reduced in congenital prosopagnosic participants when compared to controls. Analysis of the hemodynamic response function revealed a lower peak response, but also a significantly faster and stronger decay of the blood oxygen level-dependent response in the occipito-temporal areas in congenital prosopagnosic participants when compared to controls. CONCLUSION: Our results emphasize the dysfunction of the core face processing system, as well as the lateral occipital complex, in congenital prosopagnosia. Further, the functional impairment of these areas is signalled best by the altered hemodynamic response function, showing abnormally low initial peak and stronger and faster decay in the later parts of the blood oxygen level-dependent response.

Neural correlates of after-effects caused by adaptation to multiple face displays.

Adaptation to a given face leads to face-related, specific after-effects. Recently, this topic has attracted a lot of attention because it clearly shows that adaptation occurs even at the higher stages of visual cortical processing. However, during our every-day life, faces do not appear in isolation, rather they are usually surrounded by other stimuli. Here, we used psychophysical and fMRI adaptation methods to test whether humans adapt to the gender properties of a composite multiple face stimulus as well. As adaptors we used stimuli composed of eight different individual faces, positioned peripherally in a ring around a fixation mark. We found that the gender discrimination of a subsequent centrally presented target face is significantly biased as a result of long-term adaptation to either male or female multiple face stimuli. Similar to our previous results with single-face adaptors (Kovács et al. in Neuroimage 43(1):156-164, 2008), a concurrent functional magnetic resonance imaging adaptation experiment revealed the strongest blood oxygen level-dependent signal adaptation bilaterally in the fusiform face area. Our results suggest that humans extract the statistical features of the multiple face stimulus and this process occurs at the level of occipito-temporal face processing.

[Functional polymorphism of genes inactivating catecholamines and emotional deficits in paranoid schizophrenia]. / Funkcjonalny polimorfizm genów enzymów inaktywujacych katecholaminy a deficyty procesów emocjonalnych w schizofrenii paranoidalnej.

AIM: The aim of our work was to assess qualitatively and quantatively emotional deficits in patients diagnosed with schizophrenia following ICD-10 criteria in early and late stages of the schizophrenic process and the evaluation of the relationship between genes polymorphism of enzymes influencing dopaminergic, serotoninergic, and noradrenergic transfer and emotional functioning of the examined patients. METHOD: In our study the following methods have been used: Short Recognition Memory test for Faces (TPRT), Facial Expression Recognition Test (FERT), "Reading the mind in the eyes" Test and psychiatric scales (SAPS, SANS, BDI) and molecular techniques (PCR reaction, RFLP and VNTR techniques). 100 paranoid schizophrenia patients (43 female and 57 man) and 50 healthy controls (30 female and 20 man) were invited to participate in the study. RESULTS: Our results revealed an association between polymorphism of Val158Met COMT and emotional deficits in schizophrenic patients. Furthermore, the relationship between polymorphism of MAO-A and empathy/theory of mind deficit was found. No relationship was elicited between polymorphism of Val158Met COMT and VNTR MAO-A in the promoter area and schizophrenia onset. Allelic distribution of polymorphism of Val158Met COMT and VNTR MAO-A in the promoter area did not differ between the groups. The patients with genotype Val/Val of polymorphism Val158Met COMT showed major emotional deficits. The patients with genotype of 4/4 of polymorphism VNTR MAO-A showed deeper empathy/theory of mind deficits.

Adaptation duration affects the spatial selectivity of facial aftereffects.

Adaptation processes in human early visual cortical areas are sensitive to the exposure time of the adaptor stimulus. Here we investigated the effect of adaptation duration at the higher, shape-specific stages of visual processing using facial adaptation. It was found that long-term (5s) adaptation evokes facial aftereffects consisting of a position invariant as well as a position-specific component. As a result of adaptation to a female face, test faces were judged more masculine when they were displayed in the same location as the female adaptor face, as compared to that when they were presented in the opposite visual hemifield. However, aftereffects evoked by short-term (500 ms) adaptation were found to be entirely position invariant. In accordance with these behavioral results, we found that the adaptation effects, measured on the amplitude of the N170 ERP component consisted of a position-specific component only after long-term, but not after short-term adaptation conditions. These results suggest that both short and long exposure to a face stimulus leads to adaptation of position invariant face-selective processes, whereas adaptation of position-specific neural mechanisms of face processing requires long-term adaptation. Our findings imply that manipulating adaptation duration provides an opportunity to specifically adapt different neural processes of shape-specific coding and to investigate their stimulus selectivity.

[Activity of matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9) and content of their tissue inhibitors in endometrial cancer--a preliminary study]. / Aktywnosc metaloproteaz macierzowych -2 i -9 (MMP-2 i MMP-9) oraz zawartosc ich tkankowych inhibitorów w raku blony sluzowej macicy--doniesienie wstepne.

OBJECTIVES: Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) are enzymes degrading collagen type IV and other components of the basement membrane. Their activity is suppressed by tissue inhibitors of metalloproteinases--TIMP-1 and TIMP-2. Substantial evidence indicates that MMP2 and MMP-9 play an important role in the spread of malignant tumours. The aim of the study was to evaluate the activity of MMP-2 and MMP-9 and contents of their inhibitors: TIMP-1 and TIMP-2 in endometrial cancer and normal endometrium. MATERIAL AND METHODS: Material for the study comprised 28 samples of endometrial cancers and 15 samples of normal endmetrium. A two-step method for extraction of MMPs was applied. The activity of MMP-2 and MMP-9 was measured with semi-quantitative zymography. TIMP-1 and TIMP-2 contents were measured with ELISA method. RESULTS: Mean activity and activation ratio of MMP-9 was significantly higher in endometrial cancers compared with normal myometrium, whereas mean activity and activation ratio of MMP-2 did not differ significantly between investigated groups. Mean content of TIMP-1 and TIMP-2 did not differ between cancer and control tissues. No unequivocal association between activity of investigated MMPs or contents of their inhibitors and clinicopathological features of endometrial cancers was observed. CONCLUSIONS: Results of the study suggest that MMP-9 may play an important role in the progression of endometrial cancer, whereas MMP-2 does not seem to be involved in this process. Action of MMP-9 may be further enhanced by relative deficiency of TIMP-1.

Cathodal transcranial direct current stimulation over the parietal cortex modifies facial gender adaptation.

Previous studies have observed that prolonged adaptation to a face will bias the perception of a subsequent one. This phenomenon is known as figural or face after-effect. Although currently the topic of face adaptation enjoys utmost popularity, we still don't know much about the neural process underlying it. The aim of the present study was to determine, using transcranial direct current stimulation (tDCS), how the retinotopically organised primary visual cortex (V1) and higher-level, non-retinotopic right lateral temporo-parietal areas interact with facial adaptation processing. Seventeen healthy subjects received 10 min anodal, cathodal or sham stimulation over these areas during a facial adaptation task. Cathodal stimulation of the right temporo-parietal cortex reduces the magnitude of facial adaptation while stimulation over the V1 results in no significant effects. These data imply that mainly lateral temporo-parietal cortical areas play role in facial adaptation and in facial gender discrimination, supporting the idea that the observed after-effects are the result of high-level, configurational adaptation mechanisms.

[Stress oxidative in schizophrenia]. / Stres oksydacyjny w schizofrenii.

Etiopathogenesis of schizophrenia development is unknown yet in 1% of human population. There is damaged metabolism of biological membranes, abused production of free radicals and altered activity of antioxidant enzymes in patients with schizophrenia. Recently, a study showed that many of the genes and proteins whose expression is modified in the schizophrenic brain are related to glutathione and oxidative stress pathways. According to the researchers changes in permeability of biological membranes in brain could involve the pathophisiology of all--subtypes of schizophrenia as a result of oxidative stress. Brain is particularly sensitive to oxidative damage. There is a lot of phospholipids and polyunsaturated fatty acids in brain tissue under physiological conditions. The changes in polyunsaturated fatty acids metabolism, increased lipid peroxidation and the presence of oxidative stress are found in schizophrenia. They can course to appear instabilities of neuron membranes or even cell death owing to oxidative stress. Mainly to getting to know the molecular disease mechanism is associated with a disorder of the brain. The results suggest that at least some of the schizophrenia disease process can be traced in peripheral tissue like plasma, blood cells or liver. In various types of schizophrenia antipsychotic treatment affects oxidative state of erythrocyte membranes in a different way. Research into changes of antioxidant enzymes level during the treatment of typical and atypical neuroleptic drugs could contribute to widening the knowledge on the reasons of undesirable effects during pharmacotherapy with typical neuroleptic drugs.

[Genetic polymorphism of a MAO in mental disorders]. / Polimorfizm genu MAO w zaburzeniach psychicznych.

Amin oxydase (monoaminoxydase, MAO) is an enzyme which catalyses chemical reactions of biogenic amines. It plays a crucial role in pathogenesis of mental disorders associated with the dysfunction of the central monoaminergic systems (schizophrenia, affective disorders, some forms of alcohol dependence, and personality disorders). MAO has got two isoforms such as MAO-A and MAO-B. The genes coding of MAO are localised at the short arm of chromosome Xp11. In each sequence of genes there is a probability of functional polymorphism occurrence which leads to a variable expression or a change of MAO activity and it exerts an impact on the onset of some mental disorders, such as: schizophrenia, affective disorders, some forms of alcohol dependence, and personality and behavioural disorders. Dynamic development of psychiatric genetics may have crucial impact on considerable progress in understanding molecular background of mental disorders.

[Genetic polymorphism of COMT in mental disorders]. / Polimorfizm genu COMT w zaburzeniach psychicznych.

Many neurobiochemical studies show abnormalities within dopaminergic neuropathways, particularly altered dopamine transmission in etiopathogenesis of mental disorders. Evaluation of genes associated with the dopaminergic system include five well known subtypes of dopaminergic receptors, dopamine transporter and enzymes associated with the synthesis and degradation of dopamine, such as tyrosine hydroxylase, dopa decarboxylase, monoamine oxidase (MAO) and catechol O-methyltransferase (COMT). None of these genes is 'a' pathognomonic factor of schizophrenia onset. In each sequence of the following genes 'a' functional polymorphism can occur. The polymorphisms of genes MAO-A and COMT have been described in relation to various expression or altered activity of these enzymes, their influence on cognitive functions, affective and anxiety disorders, learning disabilities, aggressive behaviour, eating disorders or gender differences.

The electrophysiological correlates of integrated face and body-part perception.

Previous studies have suggested that the human visual system processes faces and bodies holistically-that is, the different body parts are integrated into a unified representation. However, the time course of this integrative process is less known. In the present study, we investigated this issue by recording event-related potentials evoked by a face and two hands presented simultaneously and in different configurations. When the hands were rotated to obtain a biologically implausible configuration, a reduction of the P2 amplitude was observed relative to the condition in which the face and hands were retained in their veridical configuration and were supplemented with visual cues to highlight further the overall body posture. Our results show that the P2 component is sensitive to manipulations affecting the configuration of face and hand stimuli and suggest that the P2 reflects the operation of perceptual mechanisms responsible for the integrated processing of visually presented body parts.

[The role of matrix metalloproteinases and tissue inhibitors of metalloproteinases in invasion of tumours of neuroepithelial tissue]. / Rola metaloproteaz macierzy i tkankowych inhibitorów metaloproteaz w inwazji nowotworów pochodzenia neuroepitelialnego.

Tumour invasion requires degradation of extracellular matrix components and migration of cells through degraded structures into surrounding tissues. Matrix metalloproteinases (MMP) constitute a family of zinc and calcium-dependent endopeptidases that play a key role in the breakdown of extracellular matrix, and in processing of cytokines, growth factors, chemokines and cell surface receptors. Their activity is regulated at the levels of transcription, activation and inhibition by tissue inhibitors of metalloproteinases (TIMP). Changes in expression of MMP and TIMP are implicated in tumour invasion, because they may contribute to both migration of tumour cells and angiogenesis. Alterations of MMP expression observed in brain tumours arouse interest in the development and evaluation of synthetic matrix metalloproteinase inhibitors as antitumour agents.

[Lack of prognostic significance of carcinoembryonic antigen (CEA) preoperative serum levels in patients with advanced larynx cancer]. / Brak wartosci diagnostycznej przedoperacyjnego oznaczania steienia antygenu rakowo-plodowego (CEA) w surowicy pacjentów z zaawansowanym rakiem krtani.

The purpose of this study was to identify the relationship between preoperative serum levels of carcinoembryonic antigen (CEA) and clinicopathological features in advanced stage of larynx cancer. The mean CEA serum concentrations were below cutoff value, which exclude the CEA as a serum marker in diagnosis of larynx cancer. However, significant correlations were found between CEA levels and tumor size, lymph node metastasis and clinical stage of the disease. The pretreatment CEA level was increased above cut-off value only in 6% of tested patients and thereby is not a prognostic factor in larynx cancer.

Position-specificity of facial adaptation.

We investigated the representation of objects' position at the higher, shape-selective stages of visual processing by testing the position-specificity of the behavioural and neural effects of facial adaptation. Here, we show that facial after-effects evoked by adaptation to both upright and upside-down faces are significantly larger when the adaptor and test faces are presented on the same retinal position than when they are displayed in different hemifields. Our event-related potential recordings revealed that adaptation effects measured on the amplitude of the N170 event-related potential component over the hemisphere that was contralateral to the test face stimulus also show strong position-specificity. These findings suggest that face adaptation effects are only partially translation invariant and facial after-effects measured with peripheral test stimuli primarily reflect the adaptation processes in the contralateral hemisphere.

[Histone deacetylase inhibitors as a new generation of anti-cancer agents]. / Inhibitory deacetylaz histonów jako potencjalne cytostatyki nowej generacji.

The acetylation and deacetylation of histones mediated by histone acetylases and deacetylases influence DNA accessibility to factors regulating replication, repair, and transcription. Histone deacetylases inhibitors (HDI) are inducers of growth arrest, differentiation, and/or apoptosis of many tumors cells by altering the transcription of a small number of genes. The selective tumor specificity of these compounds underscores their potential as new agents for the treatment of cancer. Several HDI have shown anti-tumor activity in vitro and in vivo with remarkably low toxicity in preclinical studies and are currently in phase I and II clinical trials. This review summarizes the molecular mechanism of action of HDI and its clinical application in the treatment of cancer.

[Role of matrix metalloproteinases in the pathogenesis of multiple sclerosis]. / Rola metaloproteinaz macierzy zewnatrzkomórkowej w patogenezie stwardnienia rozsianego.

Multiple sclerosis (MS) is an autoimmune disease whose features include a massive lymphocyte recruitment into the central nervous system and segmental demyelinization of the white matter. One of the MS development factors is an increase of matrix metalloproteinases (MMPs) activity with a coincidental decrease of tissue inhibitors of MMPs (TIMPs) activity. Investigations of serum, cerebrospinal fluid and brain tissue of patients showed an increase of MMP-1, -2, -3, -7, -9 and MMP-12 activity. MMPs disrupt the blood-brain barrier (BBB), increase lymphocyte migration into the central nervous system and are involved in degradation of myelin proteins. MMPs induce the appearance of an active form of tumor necrosis factor alpha, a strong proinflammatory cytokine. The drugs used in MS treatment decrease MMPs expression. Multiple actions of MMPs prove their involvement in the pathogenesis and treatment of MS.

[Diagnostic value of tissue polypeptide antigen in serum of larynx cancer patients]. / Wartosc diagnostyczna oznaczania tkankowego antygenu polipeptydowego w surowicy chorych na raka krtani.

UNLABELLED: Tissue polypeptide antigen (TPA) is a serological tumour marker used in the diagnosis, management and follow-up of patients with head and neck cancer. The aim of this study was to evaluate the diagnostic and prognostic significance of pretreatment TPA serum levels in patients with larynx cancer. The predicting ability of this tumour marker with respect to histological type, pathological state and lymph node metastasis was also assessed. MATERIALS AND METHOD: Concentrations of the TPA in the serum from 35 patients were measured by immunoradiometric assay. RESULTS: The results showed the sensitivity value for the group of 35 patients was 29.4%, but in clinical stage IV was 70%. TPA levels correlate with T classification and lymph node metastasis. In T4 tumors it was significantly higher than in T2 (p=0.047). TPA levels were significantly higher in patients with nodal invasion and were generally lower in patients with spinocellular carcinoma (p=0.0048). CONCLUSION: Our date indicate that TPA is of limited usefulness in the primary diagnosis in patients with larynx cancer, but is useful in detecting lymph node metastasis.

[Squamous cell carcinoma antigen levels in patients with laryngeal cancer]. / Antygen raka plaskonablonkowego w surowicy krwi pacjentów z rakiem krtani.

Squamous cell carcinoma antigen (SCCAg) is one of the most common markers used in diagnosis of head and neck cancer and larynx cancer. We tested correlations between level of SCC Ag and tumor size, presence of lymph node metastasis, clinical advances of tumour and histopathological diagnosis. Pretreatment level of SCC antigen was evaluated in 34 patients with squamous cell carcinoma of the larynx. Microparticle enzyme immunoassay was used to measure the SCCAg level. Elevated SCCAg serum levels were found in 41% of patients. The magnitude of the marker elevations were correlated with lymph node metastases (N0 versus N2, and N1 versus N2). Our date indicate that in patients with larynx cancer SCCAg does not appear to be a sensitive marker in the primary diagnosis. However, seem to be useful marker for monitoring nodal invasion.

Adaptation Duration Dissociates Category-, Image-, and Person-Specific Processes on Face-Evoked Event-Related Potentials.

Several studies demonstrated that face perception is biased by the prior presentation of another face, a phenomenon termed as face-related after-effect (FAE). FAE is linked to a neural signal-reduction at occipito-temporal areas and it can be observed in the amplitude modulation of the early event-related potential (ERP) components. Recently, macaque single-cell recording studies suggested that manipulating the duration of the adaptor makes the selective adaptation of different visual motion processing steps possible. To date, however, only a few studies tested the effects of adaptor duration on the electrophysiological correlates of human face processing directly. The goal of the current study was to test the effect of adaptor duration on the image-, identity-, and generic category-specific face processing steps. To this end, in a two-alternative forced choice familiarity decision task we used five adaptor durations (ranging from 200-5000 ms) and four adaptor categories: adaptor and test were identical images-Repetition Suppression (RS); adaptor and test were different images of the Same Identity (SameID); adaptor and test images depicted Different Identities (DiffID); the adaptor was a Fourier phase-randomized image (No). Behaviorally, a strong priming effect was observed in both accuracy and response times for RS compared with both DiffID and No. The electrophysiological results suggest that rapid adaptation leads to a category-specific modulation of P100, N170, and N250. In addition, both identity and image-specific processes affected the N250 component during rapid adaptation. On the other hand, prolonged (5000 ms) adaptation enhanced, and extended category-specific adaptation processes over all tested ERP components. Additionally, prolonged adaptation led to the emergence of image-, and identity-specific modulations on the N170 and P2 components as well. In other words, there was a clear dissociation among category, identity-, and image-specific processing steps in the case of longer (3500 and 5000 ms) but not for shorter durations (< 3500 ms), reflected in the gradual reduction of N170 and enhancement of P2 in the No, DiffID, SameID, and RS conditions. Our findings imply that by manipulating adaptation duration one can dissociate the various steps of human face processing, reflected in the ERP response.

Influence of metallothioneins on zinc and copper distribution in brain tumours.

Metallothioneins take part in the homeostasis of the ions of the metals which are necessary for the proper metabolism of the organism (zinc, copper), in biosynthesis regulation of the zinc-containing proteins and also in the detoxication of metals from the tissues. They also protect the tissue from the effects of free radicals, radiation, electrophilic pharmacological agents used in the cancer therapy and from mutagens. The experimental materials were brain astrocytomas, benign gliomas and malignant gliomas. The levels of the metallothionein were determined by cadmium-haemoglobin affinity assay using the cadmium isotope (109Cd). The values of zinc and copper were determined by means of atomic absorption spectrophotometry. In our studies, the level of metallothioneins in the group of malignant neoplasms was slightly higher than the level of these proteins in the group of benign neoplasms. The correlation coefficient of the studied parameters proved an interrelation between the levels of zinc and copper and the content of metallothioneins. In malignant neoplasms, the level of zinc showed a positive relationship with the metallothionein level, whereas the copper content showed an inverse relationship. There was a statistical difference, but no significant difference, in the levels of copper between malignant and benign groups.

Activity of matrix metalloproteinases-2 and -9 in advanced laryngeal cancer.

OBJECTIVES: Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) are proteolytic enzymes that digest collagen type IV and other components of the basement membrane. They play a key role in local invasion and the formation of distant metastases by malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and MMP-9 in stage III and IV laryngeal cancers. STUDY DESIGN: In the study we used specimens of laryngeal cancer and surrounding normal mucosa obtained from 23 patients undergoing surgical treatment as a primary therapy. After extraction of MMP-2 and MMP-9 from tissue samples, their activity was assessed with zymography. RESULTS: Greater activity of MMP-2 and MMP-9 and a higher active/latent MMP-2 ratio were found in cancer compared with normal mucosa. Moreover, N2 tumors revealed greater activity of MMP-2 in comparison with N1 and N0 tumors. CONCLUSIONS: Results of the study indicate that both MMP-2 and MMP-9 may be involved in the expansion of laryngeal cancer. MMP-2 may also play an important role in the lymphatic spread of some laryngeal tumors.