[COGNITIVE DISORDERS IN PATIENTS WITH TRAUMATIC ENCEPHALOPATHY].

As a result of examination 147, patients with traumatic encefalopatìû (TE) were explained the features of cognitive disorders, selected major psihopatologìcnì syndromes. The moderate cognitive disorders (KP) in patients THOSE, were observed in 40%bolnykh with the psikhorganicheskim syndrome, in 90.6% of patients with the asthenic syndrome, in 90.4%--by likvorodistsirkulyatornym syndrome and 76.1% in patients are cerebral--by focus syndrome. CD complicates, the progress of any post traumatic syndrome, in which they were presented. Moderate cognitive disorders are included in the structure of post traumatic psihorganìcnoo syndrome and is a significant dezadaptuûcim factor for the patient.

[FEATURES OF PTSD IN THE PARTICIPANTS OF THE ANTI-TERRORIST OPERATION--UKRAINIAN SYNDROME].

The article gives information about the results of research of characteristics of post traumatic stress disorder (PTSD) in the participants of the anti-terrorist operation (ATO), and refugees. Drawn attention to the fact that the demonstration took place in the study of PTSD patients, in the form of the following options: invasion (penetration); avoiding (displacement); hyperactivation. In the study took part 71 serviceman (69 men and 2 women) aged from 22 to 35 years (average age 26,2 years) that have closed traumatic brain injury , in the form of a brain concussions, contusions and suffered on PTSD (main group), studies conducted in 3-6 months after received closed traumatic brain injury. In the group of comparison included 37 patients (34 women and 3 men) aged 27-42 years (average age 32,2 years) that have had PTSD. In a group that included military personnel, in which in addition to PTSD, the clinical picture had existing consequences of craniocerebral injury observed in asthenic symptom complex--27 patients (38.1%); the anxious-phobic--in 19 patients (26.7%); hysterical--in 8 patients (11.3%); a depressive--in 17 patients (23.9%). In a group of patients and refugees from the ATO was: asthenic symptom complex--in 12 patients (32.4%), the anxious-phobic--in 11 patients (29.7%), hysterical--in 6 patients (16.2%), a depressive--in 8 patients (21.7%).

Mechanisms of stimulation of granulocytopoiesis with neupogen in patients with breast cancer during chemotherapy.

The mechanisms of granulocytopoiesis stimulation with granulocytic CSF (neupogen), added to chemotherapy protocol (adriablastine+taxotere) in patients with stages III-IV breast cancer, were studied. The hemostimulatory effect of granulocytic CSF preparation is based on stimulation of proliferation and differentiation of granulomonocytopoisis precursor cell in the hemopoietic tissue, due to neupogen effects on hemopoietic elements and on the hemopoiesis-inducing microenvironment cells.

State of central and peripheral pools of hemopoietic precursor cells in patients with malignant neoplasms during chemotherapy.

We studied toxic effects of various schemes of cytostatic treatment on central and peripheral pools of hemopoietic precursor cells in patients with III-IV stages of lung cancer and breast cancer. It was found that erythro- and granulomonocytopoietic precursors are characterized by high resistance to cytostatic treatment compared to morphologically discernible bone marrow elements, which is probably a evolutionary developed property of this cell type aimed at rapid recovery of the hemopoietic tissue.

GABA(A)-receptor expression in glioma cells is triggered by contact with neuronal cells.

The expression of functional GABA(A)-receptors in glioma cells correlates with low malignancy of tumours and cell lines from glioma lack these receptors. Here we show that contact with neurons induces the expression of functional GABA(A)-receptors. C6 and F98 glioma cell lines were labelled by recombinant expression of enhanced green fluorescent protein injected into rat brain and studied in acute slices after two to three weeks of tumour growth. The cells responded to GABA or the specific agonist, muscimol with a current typical for GABA(A)-receptors, as studied with the patch-clamp technique. To get insight into the mechanism of GABA(A) receptor induction, the C6 or F98 cells were co-cultured with neurons, astrocytes, oligodendrocytes and microglia. Glioma cells expressed functional GABA(A) receptors within 24 h only in cultures where physical contact to neurons occurred. Activation of GABA(A)-receptors in the co-cultures attenuated glioma cell metabolism while blockade of the receptors increased metabolism. We conclude that with this form of interaction, neurons can influence tumour behaviour in the brain.

Compensatory reactions during impairment of granulocytic stem in patients with lung cancer receiving antitumor chemotherapy.

We compared changes in the granulocytic hemopoietic stem in patients with stage III-IV lung cancer receiving cytostatic therapy by the original CVC and standard CAM schemes. In patients treated with the CVC regimen, the granulocytic hemopoietic stem possessed more potent compensatory capacities.

GFAP promoter-controlled EGFP-expressing transgenic mice: a tool to visualize astrocytes and astrogliosis in living brain tissue.

We have generated transgenic mice in which astrocytes are labeled by the enhanced green fluorescent protein (EGFP) under the control of the human glial fibrillary acidic protein (GFAP) promoter. In all regions of the CNS, such as cortex, cerebellum, striatum, corpus callosum, hippocampus, retina, and spinal cord, EGFP-positive cells with morphological properties of astrocytes could be readily visualized by direct fluorescence microscopy in living brain slices or whole mounts. Also in the PNS, nonmyelinating Schwann cells from the sciatic nerve could be identified by their bright green fluorescence. Highest EGFP expression was found in the cerebellum. Already in acutely prepared whole brain, the cerebellum appeared green-yellowish under normal daylight. Colabeling with GFAP antibodies revealed an overlap with EGFP in the majority of cells. Some brain areas, however, such as retina or hypothalamus, showed only low levels of EGFP expression, although the astrocytes were rich in GFAP. In contrast, some areas that were poor in immunoreactive GFAP were conspicuous for their EGFP expression. Applying the patch clamp technique in brain slices, EGFP-positive cells exhibited two types of membrane properties, a passive membrane conductance as described for astrocytes and voltage-gated channels as described for glial precursor cells. Electron microscopical investigation of ultrastructural properties revealed EGFP-positive cells enwrapping synapses by their fine membrane processes. EGFP-positive cells were negative for oligodendrocyte (MAG) and neuronal markers (NeuN). As response to injury, i.e., by cortical stab wounds, enhanced levels of EGFP expression delineated the lesion site and could thus be used as a live marker for pathology.

Mechanisms of myelopoiesis stimulation with pantohematogen and granulocyte colony-stimulating factor during cytostatic myelosuppression.

We compared hemopoiesis-stimulating activities of dry pantohematogen and recombinant granulocyte colony-stimulating factor under conditions of cyclophosphamide-induced myelosuppression. These preparations stimulated regeneration of bone marrow granulomonocytopoiesis by various mechanisms.

Analysis of myeloid-associated genes in human hematopoietic progenitor cells.

The distribution of myeloid lineage-associated cytokine receptors and lysosomal proteins was analyzed in human CD34+ cord blood cell (CB) subsets at different stages of myeloid commitment by reverse-transcriptase polymerase chain reaction (RT-PCR). The highly specific granulomonocyte-associated lysosomal proteins myeloperoxidase (MPO) and lysozyme (LZ), as well as the transcription factor PU.1, were already detectable in the most immature CD34+Thy-1+ subset. Messenger RNA (mRNA) levels for the granulocyte-colony stimulating factor (G-CSF) receptor, granulocyte-macrophage (GM)-CSF receptor alpha subunit and tumor necrosis factor (TNF) receptors I (p55) and II (p75) were also detected in this subset in addition to c-kit and flt-3, receptors known to be expressed on progenitor cells. By contrast, the monocyte-macrophage colony stimulating factor (M-CSF) receptor was largely absent at this stage and in the CD34+Thy-1-CD45RA- subsets. The M-CSF receptor was first detectable in the myeloid-committed CD34+Thy-l-CD45RA+ subset. All other molecules studied were found to be expressed at this stage of differentiation. Different cocktails of the identified ligands were added to sorted CD34+Thy-1+ single cells. Low proliferative capacity was observed after 1 week in culture in the presence of stem cell factor (SCF) + Flt-3 ligand (FL) + G-CSF. Addition of GM-CSF to this basic cocktail consistently increased the clonogenic capacity of single CD34+Thy-1+ cells, and this effect was further enhanced (up to 72.3 +/- 4.3% on day 7) by the inclusion of TNF-alpha. In conclusion, the presence of myeloid-associated growth factor receptor transcripts in CD34+ CB subsets does not discriminate the various stages of differentiation, with the exception of the M-CSF receptor. In addition, we show that TNF-alpha is a potent costimulatory factor of the very immature CD34+Thy-1+ CB subset.

Efficient retrovirus-mediated gene transfer of dendritic cells generated from CD34+ cord blood cells under serum-free conditions.

A retroviral-vector encoding the low affinity nerve growth factor receptor (LNGFR) was used to transduce dendritic cells (DCs) generated from CD34+ cord blood (CB) progenitor cells under serum-free conditions. Transduction efficiency was monitored by flow cytometry (FACS) using a specific monoclonal antibody. Prior to retroviral infections, CD34+ CB cells were stimulated for 60 h in a serum-free medium containing a DC differentiation inducing cytokine cocktail: stem cell factor (SCF), granulocyte/macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFalpha), and transforming growth factor beta 1 (TGF-beta1). Addition of flt3-ligand (FL) to the aforementioned growth factors significantly enhanced cell expansion (41.7+/-11.5 fold vs. 22.5+/-4.7 fold without FL) and generation of CD1a+ DCs (mean 45.7+/-9.8% vs. 28+/-6.5% without FL, n = 4,p = 0.01). Furthermore, FL significantly increased the proportion of CD1a+LNGFR+ cells (mean 10%+/-4.4% vs. 6%+/-2.4 without FL n = 4, p = 0.03). When serum-free viral supernatants were used to infect DCs progenitors under entirely serum-free conditions and with the most potent cytokine combination, approximately one-third of the CD1a+ DCs generated co-expressed the LNGFR gene. Moreover, the transduced gene was also identified in more mature CD1a+CD80+ and CD1a+CD86+ DCs after 12-14 days of culture. In addition, transduced CD1a+ DCs maintained their functional properties, stimulating allogeneic T cells with similar efficiency as nontransduced CD1a+ DCs. Thus, the serum-free system described allows efficient generation and transduction of CD1a+ DCs derived from CD34+ progenitor cells and may be very useful for future therapeutic applications of DCs.

Activation of the skeletal muscle ryanodine receptor by suramin and suramin analogs.

Ca2+ release from skeletal muscle sarcoplasmic reticulum is activated by adenine nucleotides and suramin. Because suramin is known to interact with ATP-binding enzymes and ATP receptors (P2-purinergic receptors), the stimulation by suramin has been postulated to occur via the adenine nucleotide-binding site of the ryanodine receptor/Ca2+-release channel. We tested this hypothesis using suramin and the following suramin analogs: NF037, NF018, NF023, and NF007. The suramin analogs stimulate the binding of [3H]ryanodine binding to sarcoplasmic reticulum membranes with the following rank order of potency: suramin (EC50 = approximately 60 microM) > NF037 (EC50 = approximately 150 microM) > NF018 > NF023 > NF007. The suramin-induced stimulation occurs via a myoplasmic binding site on the ryanodine receptor as confirmed by binding experiments and single-channel recordings with the purified protein. This binding site is different than that for ATP, a conclusion that is supported by the following observations: (i) Suramin stimulates the association rate and inhibits the dissociation rate of [3H]ryanodine, whereas ATP analogs increase only the on-rate. (ii) In the presence of suramin but not of ATP analogs, [3H]ryanodine binding is resistant to the inhibitory effect of millimolar Mg2+ and Ca2+. (iii) ATP analogs and suramin have an additive effect on [3H]ryanodine binding. (iv) Affinity labeling of the purified ryanodine receptor with 2',3'-dialdehyde [alpha-32P]ATP or after in situ oxidation of [gamma-32P]ATP is not affected by suramin. Thus, our results show that suramin acts as a direct and potent stimulator of the ryanodine receptor but that this action is mediated via a binding site different from that for adenine nucleotides.

Metamorphic modifications and EPR dosimetry in tooth enamel.

It is shown that metamorphic modifications in tooth enamel have an essential influence on the results of EPR dosimetry. The metamorphic modifications in minerals of biological origin proceed more quickly than in usual natural minerals. The approaches which at present are applied for reconstruction of doses connected with Chernobyl accident need additional investigation.