Dimebon and Tacrine Inhibit Neurotoxic Action of β-Amyloid in Culture and Block L-type Ca2+ Channels

Dimebon, a Russian-made drug, inhibited toxic effects of beta -amyloid on cultured neurons. Excessive accumulation of beta-amyloid in the brain is characteristic of Alzheimer dementias. Antialzheimer preparations tacrine and dimebon improve survival of cerebellar granule cells during long-term incubation with Ab25-35, the neurotoxic fragment of beta-amyloid. Both preparations can block potential-dependent Ca²⁺ entry into neurons by about 20%, which is explained by their selective action on L-type Ca²⁺ channels. It was assumed that the neuroprotective effect of dimebon and tacrine against Ab25-35 partially depends on inhibition of potential-dependent Ca²⁺ entry.     

IL-4 and IL-10 modulate autoimmune haemolytic anaemia in NZB mice

New Zealand Black (NZB) mice spontaneously develop autoimmune haemolytic anaemia (AIHA). Here the effect of injecting NZB mice with plasmids encoding IL-4 (pIL-4) or IL-10 (pIL-10) on NZB disease was tested. Both constructs delayed the development of anaemia as judged by increased haematocrit values as compared with controls, but neither altered the IgG1 to IgG2 red blood cell (RBC) bound autoantibody levels. The increased haematocrit value was associated temporally with increased RBC bound IgG in NZB mice treated with pIL-10, but not pIL-4. By contrast, up-regulation of splenic macrophage FcgammaRIIb2 mRNA was associated temporally with increased haematocrit values in NZB mice given pIL-4. However, no such increase occurred in NZB mice that inhaled a peptide containing a dominant T-cell epitope, although this treatment is known to bias the autoimmune response towards Th2 and to reduce the severity of anaemia. It is considered that IL-4 treatment, in part, ameliorates NZB anaemia by increasing the expression of the inhibitory FcgammaRIIb2 and thereby reducing the capacity of splenic macrophages to phagocytose autoantibody coated RBC, but that this mechanism does not explain the beneficial effects of the inhaled peptide.     

结核性脑膜炎的CT诊断(附16例分析)

目的：通过分析16例结核性脑膜炎的CT表现及其产生的病理基础，提高对本病的认识和诊断水平。方法：16例结核性脑膜炎病人采用常规头颅CT扫描，对其影像及临床资料进行回顾性分析。结果：脑基底池、侧裂池变窄12例(75％)，合并密度增高8例(50％)；不同程度的脑积水14例(88％)；脑梗塞8例(50％)；结核瘤1例(6％)。结论：结核性脑膜炎的主要CT征象是脑基底池、侧裂池变窄，同时有不同程度的脑积水。如同时伴有脑结核瘤，可作出诊断。     

Roles of tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and IL-10 in the modulation of intercellular adhesion molecule-1 (ICAM-1) expression by macrophages during mycobacterial infection

Profiles of ICAM-1 expression on cultured murine peritoneal macrophages infected with Mycobacterium avium complex (MAC) were examined, with special reference to modulating roles of TNF-alpha, TGF-beta, and IL-10. When macrophages were infected with MAC, ICAM-1 expression, measured by microscopic counting of ICAM-1+ macrophages stained with anti-ICAM-1 antibody, ELISA, and flow cytometric analysis, was rapidly increased, peaking at day 3 (early-phase up-regulation) due to endogenous TNF-alpha, and thereafter gradually declined to the normal level within 1 week or more (late-phase down-regulation). The late-phase ICAM-1 down-regulation was also seen in macrophages phagocytosing heat-killed MAC and those stimulated with lipopolysaccharide but not in macrophages phagocytosing latex beads. ICAM-1 mRNA expression was augmented markedly at day 1 after MAC infection and thereafter decreased. While TNF-alpha and IL-10 production by MAC-infected macrophages was observed during the first 3 days, TGF-beta production was initiated from day 3 and continued until day 14. Exogenously added TGF-beta strongly inhibited the early-phase increase in ICAM-1 expression by infected macrophages, and the blockade of endogenous TGF-beta with anti-TGF-beta antibody markedly inhibited late-phase ICAM-1 down-regulation. Moderate blocking effect was also observed for anti-IL-10 antibody. On the other hand, late-phase ICAM-1 down-regulation was not prevented by the addition of exogenous TNF-alpha. Therefore, TGF-beta and IL-10, especially the former, appear to play active roles in the late-phase down-regulation of ICAM-1 in MAC-infected macrophages during long-term cultivation.     

The need-informational theory of emotions

As an evolvement of Pavlov ideas on higher nervous (psychic) activity 'the need-informational theory of emotions' was suggested by the author in 1964. According to it an emotion is a function of two major factors: (1) power and quality of actual need (or drive, or motivation) and (2) estimation of probability (possibility) of need satisfaction on the basis of phylo- and ontogenetic experience. In the process of experimental testing of 'the need-informational theory of emotions' the role of different cerebral structures (frontal neocortex, hippocampus, amygdala, hypothalamus) in the genesis of emotional states and in the organization of goal-directed behavior was elucidated. The experimental data showed that these 4 brain structures play the major role in estimation of signals coming from environment and in the choice of subject's reactions. The individual characteristics of the interaction between the 4 brain structures must be taken into consideration in discussing neurophysiological backgrounds of different types of the higher nervous activity (temperaments), parameters of extra-introversion and neurotism (emotionality), the formation of main types of neurosis.     

Characterization of hepatitis B virus (Dane particle)

Hepatitis B virions (Dane particles) were purified from the sera of chronic HBsAg carriers by consecutive rate-zonal and isopycnic centrifugations in sucrose gradients using HBsAg, HBcAg and endogenous DNA polymerase activities as specific markers. Purified Dane particles, radiolabelled with Na ¹²⁵I by the chloramine-T procedure, had a higher buoyant density in CsCl (1.28 g/cm³) than unlabelled particles (1.26 g/cm³) and an estimated sedimentation coefficient of 280 s. ¹²⁵I-Dane particles were fully precipitated by anti-HBs and not by anti-HBc sera. Heavy and light density core particles were purified from heavy and light density populations of Dane particles and radioiodinated. The iodinated polypeptides of Dane particles and HBcAg were compared with those of the iodinated 22-nm form of HBsAg by SDS-PAGE. Iodinated Dane particles contained seven polypeptides with molecular weights of 18,000, 23,000, 26,000, 34,000, 43,000, 48,000 and 115,000. Heavy and light core particles contained three polypeptides with molecular weights of 18,000, 25,000 and 37,000.     

Immunocytochemical characterization of lymphocytes in benign and malignant lymphocyte - rich serous effusions

Summary The cytological diagnosis of malignant Lymphoma in serous effusions can be difficult because reactive lymphocytes may be morphologically indistinguishable from malignant cells in lymphocytic and other low grade Non-Hodgkin's lymphomas. As a result of the present study, diagnostic accuracy can be improved by means of B- and T-cell enumeration using an immunoalkaline-phosphatase method (IAP). 30 cytological specimens, including 28 pleural, 1 pericardial and 1 ascitic fluids, were studied with a panel of monoclonal anti B- and anti T-cell antibodies (PAN B, kappa, lambda, T1, T2, OKT4, T8). Reactive lymphocytic effusions were characterized by a predominance of T cells constituting 80% of all lymphocytes with an excess of helper/inducer cells (mean helper to suppressor ratio 3.0) and by a surface kappa to surface lambda ratio of 1.6 on B-cells. Tuberculous effusions showed a similar distribution of lymphocyte-subpopulations whilst most of the carcinomatous fluids showed a lower percentage of T cells (lowest value 67%) and lower Th:Ts ratio (mean 2.0). Lymphoid cells in samples of five B-cell lymphomas were characterized by T-cell depression ( 70%). B-cells in three cases expressed clear cut light chain monoclonality which was at least suggested in the other two cases.Lymphoid cells from two cases of Hodgkin's disease expressed an indistinct immunological pattern. Labelling of cytoplasmic immunoglobulins (heavy and light chains) using the peroxidase antiperoxidase method (PAP) may be important to characterize neoplasms of the plasma cell series.It is concluded that the chosen panel of antibodies in combination with IAP labelling method may be of great value in identifying B-cell lymphomas. The technique can be used in the routine laboratory and storage of unlabelled and labelled slides over long periods is possible.Dedicated to Professor K. Lennert, Kiel, on the occasion of his 65th birthdayThis study was supported by the Krebsliga St. Gallen/Appenzell     

Potent depressant effects of adenosine analogs on hippocampal slow-wave activity in the unanesthetized rat

Summary Adenosine and its analogs have previously been shown to exert a depressant effect on several measures of hippocampal excitability in the hippocampal slice and intact anesthetized preparation. In the present report, we examined the effects of intraventricular injections of adenosine analogs on hippocampal slow-wave activity in the freely moving rat. Each of three adenosine analogs— 5-N-ethylcarboxamidoadenosine (NECA) and N⁶-(phenylisopropyl) adenosine (L- and D-PIA) — were found to strongly suppress hippocampal electroencephalographic (EEG) activity. For instance, low doses of NECA (0.5 g) produced an 80–90% decrease in the amplitude of the hippocampal EEG. NECA was approximately 20-fold more potent than L-PIA, and L-PIA was twice the potency of D-PIA. In separate experiments in the anesthetized rat, NECA and L-PIA were found to block completely the activation of the hippocampal theta rhythm elicited with brainstem stimulation. The effects of adenosine analogs on both the hippocampal EEG and theta rhythm were very effectively reversed with methylxanthine, 8-para-sulphophenyl-theophylline (8-PSPT). The present findings demonstrate that adenosine analogs exert a powerful depressant effect on the hippocampal EEG in the natural unanesthetized state, and suggest that changes in the levels of endogenous adenosine may play a significant role in modulating the normal activity and function of the hippocampus.This work was supported in part by National Science Foundation grant BNS-8403544 to RPV     

Immunochemical characterization of mouse brain-associated theta (Thy-1) antigen.

The Thy-1 antigens or rat brain and thymus have been isolated and chemically characterized, but those of mice have not been identified. Moreover, it is uncertain whether the antigens are glycolipids or glycoproteins. This study with highly purified preparations of gangliosides GM₁, ¹GD_1a, GD_1b and GT_1b from bovine brain and several ganglioside fractions from mouse brain showed that Thy-1 activity does not reside in gangliosides, but rather in the chloroform-methanol-insoluble residue of brain remaining after extraction of gangliosides. The antigen could be solubilized from this residue with a non-ionic detergent. The antigenic activity of the solubilized preparation was heat-labile but resistant to periodate. The chemical properties of the Thy-1 antigen of mouse brain are discussed.