Synaptic imbalances in endogenous psychoses

Based on the formalism of logical balance, imbalances of information processing in tripartite synapses are described as a possible explanation for the pathophysiology of endogenous psychoses like depression, mania and schizophrenia. A tripartite synapse consists of the presynapse, the synaptic cleft, the postsynapse (neuronal components) and the glia (glial components). According to the logic of balance in a living system, the number of values and the number of variables must be equal. In a tripartite synapse the neuronal components are interpreted as values, the glial components as variables. In line with this novel synaptic model, three elementary synaptic imbalances can be deduced. First, tripartite synapses are underbalanced if the variables outnumber the values. Such a system state may cause depression. Second, if the values outnumber the variables, the tripartite synapses are overbalanced which may be responsible for mania. Third, if no functional variables are available at all, tripartite synapses process information unbalanced which may cause schizophrenia. The basic symptoms of these psychobiological disorders can be deduced from this novel synaptic model.     

Polymorphism in the human serotonin transporter gene in endogenous psychoses

Associations of the VNTR-17 and 5-HTTLPR polymorphisms of the serotonin transporter gene with affective disorders, including depression, have been found. These polymorphisms were analyzed in two groups of Russian probands: patients with endogenous psychoses and control individuals without mental disorders (423 and 277 persons, respectively). No associations were found between VNTR-17 genotypes or alleles and the diseases. However, the frequency of 10/10 (VNTR-17) homozygotes increased with age in both patients and healthy persons. The results of the analysis of the 5-HTTLPR polymorphism suggest an association of the short (s) allele of the 5-HTTLPR polymorphism with schizophrenia and schizoaffective psychoses, but not with affective disorders.     

Association between the tryptophan hydroxylase (TpH) gene polymorphic markers and endogenous psychoses

Tryptophan hydroxylase is one of the key enzymes involved in serotonergic metabolism. In many studies, an association between the TpH gene and human mentality, as well as mental disorders was demonstrated. This study was designed to analyze the association between three TpH gene polymorphisms (A218C, T3792A, and (CT) _n (CA) _n (CT) _n ) and endogenous psychoses. The patients included into investigation were represented by those with manic-depressive psychosis (93 individuals) and those with the schizophrenia spectrum disorders (307 individuals). An association between the A218C polymorphism with the disorders of the schizophrenia spectrum was demonstrated. These findings confirmed the data obtained earlier for other populations. In addition, an association between the (CT) _n (CA) _n (CT) _n microsatellite repeats and bipolar disease was shown for the first time.     

TaqIB allele polymorphism of the dopamine receptor D2 gene in patients with endogenous psychoses

The genotype at theTaqIB locus of the dopamine receptor D2 (DRD2) gene was established by PCR in 113 healthy donors and 340 patients with endogenous psychoses. The allele and genotype frequencies in patients with affective psychoses significantly differed from those in controls and in patients with schizophrenia. The proportion of B2/B2 homozygotes decreased with increasing contribution of the affective component to the clinical manifestation of schizo-affective and affective disorders. TheTaqIB polymorphism was assumed to play a role in mood aberrations in patients with mental disorders.     

Structures of apomyoglobin's various acid-destabilized forms

The structures and the cold and hot melting thermodynamics of the acid- and salt-destabilized states of horse heart apomyoglobin (apoMb), including the E (extended) and various I forms, are studied using probes of tertiary structure (tryptophan fluorescence and FTIR spectroscopy) and secondary structure (far-UV CD and FTIR spectroscopy). These forms likely resemble early structures in the folding of the largely helical protein. Both the I and E forms retain the AGH core whereby the two ends of the protein are tied together with sufficient numbers of tertiary contacts, involving a number of hydrophobic residues, to show cooperative melting. The melting thermodynamics of E and I are distinctly different. E contains no other tertiary structure and probably little other secondary structure apart from the core. The more destabilized E form appears to contain "random" buried runs of polypeptide backbone which convert to alpha-helix in the I form(s). Most interestingly, E consists not of a single structure but is composed of a heterogeneous mixture of conformations, all showing corelike cooperative melting characteristics, and consisting presumably of varying contacts between the A portion of apomyoglobin and the G-H hairpin. These results bear on the energy landscape and structural features of the early part of apomyoglobin's folding pathway.     

Epidemiological models with prevalence dependent endogenous self-protection measure

A simple mathematical model for human disease epidemics that takes the human learning behaviour and self-protective measures into account is proposed and investigated. We have analysed the effect of endogenous self-protective measures with respect to the prevalence level of the disease and conversely. In the model it is assumed that people start reacting against contracting a disease with self-protective measures whenever they are informed about the disease and when the burden of the disease is in a recognizable stage. It is shown that increasing the average effectiveness of self-protective measures is more important in decreasing the prevalence of a disease than increasing the proportion of individuals in a population into which awareness is created.     

Mechanism of the generation of various forms of respiratory rhythm

The respiratory muscles and neurons activity in the transitional process from rhythmic respiration to its cessation and reappearance of the usual rhythmic breathing after the apnea was registered in the acute experiments on the anesthetized cats and rabbits under the action of extra intrapulmonary oxygen pressure or intravenous injection of sodium cyanide. Different forms of disturbances of respiratory rhythm (apneusis, hasping, the combination of hasping with apneusis and respiratory movements of usual form - eupnea) observed in the critical states of the organism are considered to be the result of changes in the character of activity of the medulla oblongata respiratory neurons which occur at a definite stage of hypoxia. Hasping mechanism differs essentially from the generation of eupnea and apneusis.     

Allele polymorphism of the dopamine transporter gene in patients with endogenous psychoses: Association with pathological syndromes

A study was made of the association of the allele polymorphism of the 3′VNTR locus of the dopamine transporter (DAT) gene with schizophrenia, schizo-affective psychosis, and affective disorders. Three alleles (440, 480, and 520 nt) were found and the allele and genotype frequencies estimated in all groups. The allele and genotype frequencies in patients with depression significantly differed from those in controls and in patients with bipolar affective psychosis and schizophrenia. The results were correlated with the averaged MMPI profiles of controls and affective patients. In the latter group, 480/480 homozygotes significantly differed from patients with the other genotypes in the mean score on Hypochondria and Hysteria scales. The possible association of the DAT-3′VNTR polymorphism and individual syndromes, which are related to different mechanisms of psychological defense, is discussed.     

Immunogenic properties of various forms of flagellin]

The authors obtained and studied immunologically flagellae of S. typhi and flagellins (monomeric and polymeric) obtained from them. Immunological activity of flagellin was the greater the higher the molecular weight of the preparation (the polymer molecules were the largest and the most immunogenic). There were revealed differences between the preparations according to the dependence of the immunizing effect on the dose and the capacity to induce synthesis of 19S- and 7S-antibodies. A sharp change of the immunogenicity of flagellin preparation following gel-filtration through sepharose 2B was demonstrated.     

A differential microdetermination for the various forms of biopterin.

Conditions for the quantitative oxidation and destruction of tetrahydrobiopterin and quinoid dihydrobiopterin and the separation of biopterin from its reduced forms by ECTEOLA-Sephadex column chromatography are described. A procedure for the quantitation of tetrahydrobiopterin plus quinoid dihydrobiopterin, 7,8-dihydrobiopterin, and biopterin using a Crithidia bioassay is presented. Using these procedures it was found that tetrahydrobiopterin plus quinoid dihydrobiopterin are the prevalent forms in liver and blood of mice and that biopterin was the predominant form in the tails of tadpoles. In human urine, approximately half of the biopterin was found as tetrahydrobiopterin plus quinoid dihydrobiopterin and the other half was 7,8-dihydrobiopterin. The presence of tetrahydrobiopterin and quinoid dihydrobiopterin was confirmed by a coenzyme assay for the hydroxylation of phenylalanine.     

Mass spectra of various deuterium-labelled forms of bis-O-trimethylsilyl-N-acetylsphinganine

The mass spectrum of the trimethylsilyl derivative of N-acetylsphinganine (dihydrosphingosine) has been studied in detail. Origins, structures and mechanisms of formation of the principal ions are supported by deuterium labelling and exact masses. The ions formed on electron impact ionization at 70 eV can be divided into two main categories with respect to electron abstraction from one of the oxygen atoms or the nitrogen atom on the long-chain carbon backbone.     

Leukocyte lysozymes in various forms of leukemia]

The amount of lysozyme in the leukocytes of 47 patients with different forms of leukaemia and 6 healthy persons was investigated. The lysozyme determination was carried out in the lysate of isolated leukocytes obtained after freezing and thawing it seven times. The results expressed in microgram per 10(6) cells were compared with the simultaneously determined lysozyme concentration of serum and urine. A substantial reduction of the lysozyme amount as compared with the normal value (3.1 microgram/10(6) cells) was determined in the leukocytes of patients suffering from chronic lymphatic leukaemia, acute lymphatic leukaemia and the blastic crisis of chronic myeloid leukaemia. Different amounts of lysozyme ranging from extremely low ones to strongly elevated ones were found in leukocytes taken from patients with acute myeloblastic and chronic monocytic leukaemia. In many cases there was a lack of correlation between the lysozyme content of leukocytes on the one hand and that of serum and urine on the other hand. Possible causes underlying this lack of correlation are discussed.     

Differential range and activity of various forms of the Hedgehog protein

Background  

The Hedgehog (Hh) family of secreted proteins act as extra cellular messengers to control and coordinate growth and differentiation. The mechanism by which Hh protein travels across a field of cells, and results in a range of specific effects relating to the distance from the source, has been the subject of much debate. It has been suggested that the range and activity of the pathway can be linked to modifications of the Hh protein, specifically the addition of lipid groups at N- and C-terminal sites.